AGRI 2018-4

AĞRI - Cilt Volume 30 - Sayı Number 4 - Ekim October 2018

Cilt - Volume 30

ISSN 1300-0012

Sayı - Number 4 Ekim - October 2018

A RI PAIN TÜRK ALGOLOJİ (AĞRI) DERNEĞİ’NİN YAYIN ORGANIDIR THE JOURNAL OF THE TURKISH SOCIETY OF ALGOLOGY

KARE

Index Medicus-Medline, Web of Science, ESCI, EMBASE/Excerpta Medica, Index Copernicus, Gale, EBSCO, CINAHL ve TÜBİTAK-ULAKBİM tarafından dizinlenmektedir.

(Included and Indexed in Index Medicus-Medline, Web of Science, ESCI, EMBASE / Excerpta Medica, Index Copernicus, Gale, EBSCO, CINAHL and the Turkish Medical Index).

www.agridergisi.com

Cilt - Volume 30 Sayı - Number 4 Ekim - October 2018

ISSN 1300-0012

A RI PAIN TÜRK ALGOLOJİ (AĞRI) DERNEĞİ’NİN YAYIN ORGANIDIR THE JOURNAL OF THE TURKISH SOCIETY OF ALGOLOGY

Index Medicus-Medline, Web of Science, ESCI, EMBASE/Excerpta Medica, Index Copernicus, Gale, EBSCO, CINAHL ve TÜBİTAK-ULAKBİM tarafından dizinlenmektedir.

(Included and Indexed in Index Medicus-Medline, Web of Science, ESCI, EMBASE / Excerpta Medica, Index Copernicus, Gale, EBSCO, CINAHL and the Turkish Medical Index).

www.agridergisi.com

A RI PAIN Editör (Editor-in-Chief ) Gül KÖKNEL TALU Yardımcı Editör (Associate Editor) Ruhiye REİSLİ Bilimsel Danışma Kurulu (Editorial Board) Akgün K Turkey Antonaci F Italy Babacan A Turkey Cahana A Switzerland Çamcı E Turkey Erdine S Turkey İnan L Turkey İnan N Turkey Ketenci A Turkey Kress H Austria Morlion B Belgium Oral E Turkey Özge A Turkey

Peker S Turkey Şentürk M Turkey Talu U Turkey Tan E Turkey Unal Çevik I Turkey Uyar M Turkey Vadalouca A Greece van Kleef M Netherlands Varrassi G Greece Vissers K Netherlands Yücel B Turkey

Cilt (Volume) 30, Sayı (Number) 4, Ekim (October) 2018 p-ISSN 1300 - 0012 e-ISSN 2458-9446 Türk Algoloji (Ağrı) Derneği’nin Yayın Organıdır (The Journal of the Turkish Society of Algology)

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Üç Ayda Bir Yayınlanır (Published Quarterly) Sahibi ve Yazı İşleri Müdürü (Ownership and Accountability for Contents) Gül KÖKNEL TALU Türk Algoloji (Ağrı) Derneği The Turkish Society of Algology Başkan (President)

N. Süleyman ÖZYALÇIN

Üyeler (Members)

N. Süleyman ÖZYALÇIN Sema TUNCER UZUN Kenan AKGÜN Levent Ertuğrul İNAN Güngör Enver ÖZGENCİL Hayri Tevfik ÖZBEK Meltem UYAR

İletişim (Correspondence) Editör ve Yazı İşleri Müdürü (Editor-in Chief)

Gül KÖKNEL TALU

Yardımcı Editör (Associate Editor)

Ruhiye REİSLİ

Yürütücü Sekreter (Executive Secretary)

Gül KÖKNEL TALU

Adres (Mailing Address)

Tel (Phone) Faks (Fax) e-posta (e-mail) web

İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Algoloji Bilim Dalı, Çapa 34390 İstanbul, Turkey +90 - 212 - 531 31 47 +90 - 212 - 631 05 41 gktalu@yahoo.com www.algoloji.org.tr

Index Medicus-Medline, Web of Science, ESCI, EMBASE/Excerpta Medica, Index Copernicus, Gale, EBSCO, CINAHL ve TÜBİTAK-ULAKBİM tarafından dizinlenmektedir.

(Included and Indexed in Index Medicus-Medline, Web of Science, ESCI, EMBASE / Excerpta Medica, Index Copernicus, Gale, EBSCO, CINAHL and the Turkish Medical Index).

Yayıncı (Publisher) KARE YAYINCILIK | karepublishing

KARE Concord İstanbul, Dumlupınar Mah., Cihan Sok., No: 15, B Blok 162, Kadıköy, İstanbul, Turkey Tel: +90 216 550 61 11 Faks (Fax): +90 216 550 61 12 e-posta (e-mail): kareyayincilik@gmail.com / kare@kareyayincilik.com www.kareyayincilik.com Yayın Türü (Type of Publication): Süreli Yayın (Periodical) Basım Tarihi (Press Date): Ekim 2018 (October 2018) Sayfa Tasarımı (Design): Ali CANGÜL Baskı (Press): Yıldırım Matbaacılık Online Dergi (Web): LookUs Baskı Adedi (Circulation): 300

www.agridergisi.com

Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur (This publication is printed on paper that meets the international standart ISO 9706: 1994)

İ Ç İ N D E K İ L E R C O N T E N T S 2018-4

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vi Editorial vii Yazarlara Bilgi x Information for the Authors

DERLEME R E V I E W 153-164 Headache in challenging and special circumstances: Pregnancy and lactation

Zorlu ve özel koşullarda baş ağrısına yaklaşım: Gebelik ve laktasyon

Yılmaz E, Ünal Çevik I

KLİNİK VE DENEYSEL ÇALIŞMALAR ORIGINAL AND EXPERIMENTAL ARTICLES 165-170

Effect of lifestyle interventions on diabetic peripheral neuropathy in patients with type 2 diabetes, result of a randomized clinical trial Tip 2 diyabetli hastalarda yaşam tarzı müdahalelerinin diyabetik periferik nöropati şiddeti üzerine etkisi, randomize klinik çalışmanın sonucu Ghavamı H, Radfar M, Soheıly S, Shamsı SA, Khalkhalı HR

171-178

Ultrasound guided superficial cervical plexus block versus greater auricular nerve block for postoperative tympanomastoid surgery pain: A prospective, randomized, single blind study Ultrason eşliğinde uygulanan büyük aurikuler sinir bloğu ve yüzeyel servikal pleksus blokajının timpanomastoid cerrahisi sonrası analjezik etkinliklerinin karşılaştırılması: Prospektif, randomize, tek kör çalışma Ökmen K, Metin Ökmen B

179-182

Radiofrequency thermocoagulation combined with pulsed radiofrequency for gasserian ganglion blockage Gasser ganglion blokajında pulse radyofrekans ile termokoagülasyon radyofrekansın kombine edilmesi Arıcı T, Kurcaloğlu M, Kılıç E, Erhan E

183-188 Research on the efficacy of the rectus sheath block method

Rektus kılıf bloğu yönteminin etkinliğinin araştırılması

Karaarslan E, Topal A, Avcı O, Tuncer Uzun S 189-198 Migren hastalarında bipolar yelpaze bozukluklarının yaygınlığı

Prevalence of bipolar spectrum disorders in migraine patients

Ünsalver BÖ, Evrensel A, Mehmet Kerem Doksat MK

OLGU SUNUMLARI CASE REPORTS 199-201 A probable case of movement disorder (Tardive dyskinesia) due to duloxetine treatment

Duloksetin tedavisine bağlı beklenmedik bir hareket bozukluğu olgusu (Tardif diskinezi)

Yılmaz R, Üstün D, Tuncer Uzun S, Reisli R, Türk Ş 202-205 Migraine-like visual aura: Can it be an early-onset symptom of astrocytoma?

Migren benzeri görsel aura: Astrositomalı hastalarda erken bir başlangıç bulgusu olabilir mi?

Evcili G, Öğün MN, Utku U 206-208 Fahr hastalığıyla izlenen ve nöropatik ağrısı olan bir olguda tanısı geciken servikal myelomalezi

Late diagnosed cervical myelomalesia in a case of Fahr disease experiencing a neuropathic pain

Alemdar M

EKİM - OCTOBER 2018

v

EDİTÖRDEN E D I T O R I A L

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Kıymetli meslektaşlarım, 2018 yılının son sayısı ile karşınızdayız. Bu sayımızda yine keyifle okuyacağınız yayınlar, günlük pratikte rahatlıkla uygulanmaya geçeceğinizi düşündüğümüz çalışmalar bulunmakta.

Vaka sunumları da aynı şekilde ağrı tedavisinde uzman meslektaşlarımızın deneyimlediği olayları gözümüzün önüne sermekte.

Uluslararası katılımlı 15. Ulusal Ağrı Kongresinin tüm hazırlıkları tamamlandı. Zengin bilimsel toplantının, farklı konuşmacıların özenle ve keyifle hazırlandığı grup oturumumları, sanat köşemiz, yanında özellikle genç meslektaşlarımıza girişimsel yöntemleri detaylı olarak uygulayabilecekleri kadavra ve ultrasonografi kurslarının da kongrenin önemli bir bölümünü oluşturmakta.

Tüm meslektaşlarımız ile Uluslararası katılımlı 15. Ulusal Ağrı Kongresinde görüşmek dileğiyle.

Prof. Dr. Gül Köknel Talu Editör

Dear Colleagues, We proudly present the last issue of the journal for 2018. This issue includes a variety of manuscripts that can be implemented in daily practice.

On behalf of the Congress committee, I am also proud to inform you that all of the social and academic preparations have been finalized for the 15th National Pain Congress with International Participation.

We hope to see you there in Antalya on November 15-18 for what we believe will be an exciting event.

Prof. Gül Köknel Talu, MD Editor

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İLGİ ALANI VE AMACI Bu dergi Türk Algoloji (Ağrı) Derneği’nin süreli yayın organıdır. Üç ayda bir yayımlanır.

Ağrının yapısı, mekanizmaları ve tedavisi ile ilgili özgün araştırmalar yayınlanır. Multidisipliner bir yaklaşım ile ağrı ile ilgili temel ve klinik bilimlerde yapılan araştırmaların geniş kitlelere yayılması için bir forum oluşturulmaya çalışılır. Dergide yayımlanan makaleler Türk Algoloji Derneği’nin resmi görüşünü temsil etmez. Yayımlanan makale ve şekiller derginin malı olur.

GENEL AÇIKLAMALAR 1. Dergi Türkçe ve İngilizce olarak yayınlanır.

2. Editoryal Kurul tarafından uygun görülen metinler yayımlanır. Editoryal Kurul, yayın kurallarına uymayan metinleri yayımlamamaya ve düzeltilmek üzere yazarına geri göndermeye yetkilidir. “Derleme” kategorisindeki yazılar, Editoryal Kurul tarafından belirlenen yazarlardan yapılan istek üzerine kabul edilmektedir. Editoryal Kurul tarafından istenmedikçe bu kategoriler için yazı gönderilmemelidir. Ancak bu konuda editöre öneride bulunulabilir. Tüm yazılarda editöryel değerlendirme ve düzeltmeye başvurulur; gerektiğinde, yazarlardan bazı soruları yanıtlanması ve eksikleri tamamlanması istenebilir. Dergide yayınlanmasına karar verilen yazılar “manuscript editing” sürecine alınır; bu aşamada tüm bilgilerin doğruluğu için ayrıntılı kontrol ve denetimden geçirilir; yayın öncesi şekline getirilerek yazarların kontrolüne ve onayına sunulur.

3. Dergi, uluslararası tıbbi dergi editörleri kurulunca hazırlanan “Biyomedikal dergilere teslim edilecek metinlerde aranan ortak özelliklerin” 3. baskısındaki (1983) kurallara uygun olarak hazırlanmamış yayın metinlerini kabul etmez. Metinler teslim edilmeden once bu kuralların yayınlandığı British Medical Journal 1988;296:401-5 veya Annuals of Internal Medicine 1988;108:258-65’e bakılmalıdır.

4. Dergiye yazı gönderilmesi sadece internet üzerinden yapılmaktadır. Bunun için resmi web sitesi olan www.agridergisi.com adresindeki ilgili basamaklar takip edilmelidir.

5. Yayınlanması istenen metnin dayandığı çalışma, daha önce başka yerde yayınlanmış veya yayınlanmak üzere teslim edilmiş veya kabul edilmiş olmamalıdır. Özet biçiminde yayınlanmış bir ön bildirinin bitmiş haline yer verilebilir.

6. Dergide yayınlanan yazılar için telif hakkı ödenmez. Bu nedenle başvuru mektubunda telif hakkının dergiye bırakılacağı açıklanmalı ve metnin tüm yazarlarca okunduğunu ve onaylandığını belirten bir ifade bulunmalıdır.

7. Yayımlanmış şekil vb. gereçlerin yerinde basılabilmesi, tanınabilecek kişilerin resimlerinin kullanılabilmesi ve katkılarından dolayı kişilerin adlarının belirtilebilmesi için alınmış izinler posta ile ulaştırılmalıdır.

8. Yazarlar teslim ettikleri her şeyin birer kopyasını saklamalıdır.

9. Teslim edilmiş bir metnin tümünün veya bir bölümünün başka bir yerde yayımlanması söz konusu olursa Editoryal Kurul’a bilgi verilmesi zorunludur.

10. Araştırmalar için, ilgili kurumun bağlı bulunduğu etik komitenin onayının alınmış olması şarttır. Bu durum “gereç ve yöntem” bölümünde belirtilmelidir.

11. Yayımlanan yazıların sorumluluğu yazarlarınındır.

12. Yazarlara tıpkıbasım gönderilmeyecektir. İSTENEN DOSYA TÜRLERİ VE MİNİMUM YAZI TESLİM GEREKLİLİKLERİ Elektronik gönderim sistemiyle yazıların tesliminden önce aşağıdaki formatlama özelliklerine göre ayrı ayrı MS Word (.doc) ve Adobe (.pdf ) dosyaları hazırlanmalıdır. Başvuru mektubu ve başlık sayfası olmayan hiçbir yazı kabul edilmeyecektir.

1. Başvuru mektubu: Her türden yazının gönderimi mutlaka bir başvuru mektubunu içermelidir. Başvuru mektubunda yazar(lar) başlık, yazının türü ve yazının gönderim kategorisi ve gönderilen çalışmanın daha önce bir bilimsel bir toplantıda sunulup sunulmadığını belirtmelidir. Bu başvuru mektubu yazı AGRI Dergisi tarafından incelenme sürecindeyken başka bir yerde yayınlanmayacağı veya yayınlanmak üzere değerlendirilmeyeceğine ilişkin bir açıklama içermelidir. Ayrıca başvuru mektubunun alt kısmında yazışmadan sorumlu yazarın tam adı, adresi, telefon numarası ve e-posta adresi dahil iletişim bilgileri verilmelidir. Başvuru mektubu yazışmadan sorumlu yazar tarafından imzalanmalı, tarayıcıdan geçirilmeli, yazının diğer dosyalarıyla birlikte jpg veya .pdf formatında sunulmalıdır. Başvuru mektubu aşağıdaki gibi düzenlenmelidir: a. Başlık, yazının türü. b. İncelenme sürecindeyken başka bir yerde yayınlanmayacağı veya yayınlanmak üzere değerlendirilmeyeceğine ilişkin bir açıklama. c. Yazışmadan sorumlu yazar(lar)ın tam adı, adresi, telefon numarası ve e-posta adresi dahil iletişim bilgileri. d. Yazışmadan sorumlu yazarın imzası.

2. Başlık sayfası: Gönderilen tüm yazı türleri başlık sayfası dosyasına dahil edilmelidir. Lütfen başlık sayfanızı aşağıdaki unsurları da içeren ayrı bir elektronik dosya şeklinde hazırlayın. a. Yazının başlığı. b. Yazar (Yazarların listesi) lütfen yazarların tam adlarını ve her bir yazar için en fazla iki akademik dereceyi belirtin. Bir kurumda üyelik gibi onursal bağlantıları bu listeye dahil etmeyin. c. Her bir yazarın çalıştığı anabilim dalı veya bölüm, kurum, şehir ve ülke gibi bağlantıları. d. Yazışmalardan sorumlu yazarın (yazarların) tam adı, adresi, telefon numarası ve e-posta adresi gibi iletişim bilgilerini kaydedin. e. Fon tedariki veya başka mali destek hakkında bilgi verilmelidir. f. Çıkar çatışması beyanı: Başlık sayfasının en alt kısmında çıkar çatışması beyanı bulunmalıdır. Lütfen, her bir yazar için ICMJE önerilerine (ICMJE Recommendations) uygun biçimde tüm potansiyel çıkar çatışmaları listesi kaydedilmelidir. Çıkar çatışması yoksa lütfen “Çıkar çatışmaları: Beyan edilmemiştir” ibaresini koyun.

3. Özetler: Özetler sayfasına yazar(lar) sırasıyla özet ve anahtar sözcükler (en az 3 sözcük) yazılmalıdır. Anahtar sözcüklerin Medical Subject Headings (MeSH) (http://www.nlm.nih.gov/mesh/MBrowser.html) standartlarına uygun ve Türkiye Bilim Terimleri’nden (http://www.bilimterimleri.com) seçilmiş olması gerekmektedir.

4. Ana Metin: Gönderilen her yazı türü için bir ana metin dosyası bulunmalıdır. Bu dosya başlık, özetler sayfası, yazınızın ana metni ve tek bir elektronik dosya haline getirilmiş kaynaklar bölümünü içermelidir. Kaynaklar bölümünden sonra tablolar da ayrı sayfalar halinde bu dosyaya konulabilir veya tercihinize göre ayrıca elektronik ortama yüklenebilir. Ana metnin yapısı yazının türüne göre farklılık gösterir. Tablolarla birlikte veya yalnız başına özetler, anahtar sözcükler, ana metin, kaynakları içeren bu birleşik dosya orijinal yazının kimliklerin gizlenmiş olduğu versiyonudur. Yazarların adları, akademik ünvanları, kurumları ve adresleri yazılmaz. Yazının değerlendirme süreci istisna olmak üzere, yazara (yazarlara) ilişkin herhangi bir bilgi içeren yazılar farkına varılır varılmaz rededilecektir.

5. Tablolar: Verileri özetleyen tablolar herhangi bir şablon kullanmaksızın net biçimde formatlandırılmalıdır. Tablolardaki veriler tümüyle metin içinde belirtilmemelidir. a. Tablolar ardışık sırayla numaralandırılmalıdır. b. Metinde her bir tabloya referans verilmiş olunmalıdır. c. Her bir tablonun numarası ve başlığı tablodan önce her sayfanın başına yazılmalıdır. d. Tablolar kaynaklar bölümünden sonra ayrı sayfalar halinde bu dosyaya konulabilir veya tercihinize göre ayrıca elektronik ortama yüklenebilir. Tablolar MS Word (.doc) formatında yüklenmeli ve elektronik dosya buna göre adlandırılmalıdır (Tablolar_xxx_vx.doc). Tablolar pdf, jpeg veya başka bir formatta yüklenmemelidir.

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6. Şekiller: Yazıda şekiller varsa, her yazı türü için her bir Şekil ayrı bir dosya halinde yüklenmelidir. Şekil/görüntülerdeki bilgiler tümüyle tekrar edilmemeli, metinde şekil/görüntüye gönderme yapılmalıdır. a. Teknik gereklilikler i. Şekil alt yazıları kaynaklar bölümünden sonra ayrı bir sayfada belirtilmelidir. ii. Yazı gönderimi sırasında şekillerin hepsi metin dosyasından ayrı bir dosyaya yüklenmeli ve buna göre adlandırılmalıdır (Şekil 1_xxx; Şekil 2_xxx). iii. Şekillerin içine herhangi bir alt yazı veya başlık dahil edilmemelidir. iv. Resimler JPEG, EPS veya TIFF formatında saklanmalıdır. v. Lütfen fotograflar ve şekilleri en azından 300 nokta/inç çözünürlükte gönderin. TIFF veya EPS formatında gönderilen şekilleri son derece kolay işlemekteyiz. b. Etik gereklilikler i. Fotoğrafın sahibi ve/veya fotografı çekilen hasta onam formunu imzamalıdır. İzin alınmadan başka kaynaklardan şekiller kopyalanmamalıdır.

7. Açıklamalar, izinler ve imzalar a. Çıkar Çatışması Formu: Esas ilgilenilen konuya (hastaların iyilik hali veya araştırmanın geçerliliği) ait mesleki bir karar ikincil bir ilgi kaynağından (örn maddi kazanç) etkilenebildiğinde çıkar çatışması söz konusudur. Finansal ilişkiler kolayca saptanabilir. Ancak kişisel ilişkiler veya rekabetler, akademik yarışmalar veya entelektüel inanışlar nedeniyle de çatışmalar oluşabilmektedir. Çatışma gerçek veya potansiyel olabilir. En güvenli süreç Editöre tam olarak beyan etmekten geçer. Çatışmaları açıklamamak bir Erratum (yazım hatası) hatta yazının geri çekilmesine yol açabilmektedir. AGRI Dergisine gönderilen yazıların hepsinde potansiyel veya halen mevcut çıkar çatışmaları olduğu düşünülen tüm ilişkilerin beyan edilmiş olması gerekir. Yazarların hepsinden çıkar çatışmalarını beyan etmeleri istenir. b. Hasta Onam Formu: Hayatta olan tanımlanabilir bir hastaya ait kişisel bilgilerin yayınlanması hasta veya hamisinin açıkça onam vermesini gerektirir.

Yazarlardan Kaynaklar menüsündeki Formlar, Şablonlar ve Örnekler sayfasında bulunan standart bir hasta onam formunu kullanmalarını bekleriz. c. Telif Hakkının Nakli Formu: Yazarların tümünden telif hakkının nakli formunu doldurmaları istenir.

YAZININ FORMATLANMASI Yazının formatı 2013 Ağustosunda güncellenmiş ICMJE Tıp dergilerinde Bilimsel Çalışmaların Yürütülmesi, Raporlanması, Yayına hazırlanması ve Yayınlanması (ICMJE-Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals) kriterlerine uyumlu olmalıdır. Derginin formatına uymayan yazılar daha fazla gözden geçirilmeden düzelti için yazara iade edilecektir. O halde zaman ve emek kaybından kaçınmak için dergi gönderim kuralları dikkatlice gözden geçirilmelidir.

Yazının çatısı WAME kılavuzlarıyla (guidelines of WAME) uyumlu olmalıdır.

Genel Format 1. Genel Yazı Stili: Yazı Microsoft WordTM formatında tek sütun halinde yazılmalıdır. Tıbbi jargonlardan kaçınmak için her çaba gösterilmelidir.

2. Tanıtıcı Bilgilerin Gizlendiği İlk Gözden Geçirme: Yazarların adları ve akademik ünvanlar, kurumlar ve adresler gibi tanımlayıcı bilgiler gizlenir. Yazara (yazarlara) ait herhangi bir bilgi içeren yazılar rededilecektir.

3. İlaçlar: İlaçların jenerik adları kullanılmalıdır. Dozlar ve uygulama yolları belirtilmelidir. Ana metinde bir ilaç, ürün, bilgisayar donanım veya yazılımından söz edildiğinde, ürünün adı, üreticisi, firmanın bulunduğu il ve ülke gibi ürün bilgileri aşağıdaki formata göre parentez içinde belirtilmelidir [“Discovery St PET/CT scanner (General Electric, Milwaukee, WI, ABD)]” 4. Kısaltmalar: En gerekli olanlar dışında kısaltma kullanılmasını teşvik etmemekteyiz. Yazar için kolaylık olabilmesine rağmen kısaltmalar genellikle okuyucunun yazıyı kolayca anlamasını engeller. Kısaltmaların tümü ilk kez kullanıldığı anda tanımlanmalı (hem özette, hem de ana metinde) ve kısaltmalar tanımlamadan sonra parentezler içinde gösterilmelidir. Yazarlar başlık ve özette kısaltmalar kullanmaktan kaçınmalı, ana metinde de kullanımları sınırlandırılmalıdır.

5. Ondalık noktalar veya virgüller: Ondalık sayılar tam sayılardan noktalarla ayrılmalıdır. Yazı boyunca ondalık sayılar için virgül kullanmayınız.

6. Kaynaklar: Kaynaklar metin içinde ilk kez yazıldığı sırayla art arda numaralandırılmalıdır (6 yazardan sonra ve ark. kullanın). Özetleri kaynak göstermekten veya kamu kaynaklarında mevcut olmayan esaslı bilgiler sağlamadıkça “kişisel konuşmadan” alıntı yapmayın. Kaynak göstermeye ilişkin örnekler aşağıda gösterilmiştir: o Makale: Süleyman Ozyalçin N, Talu GK, Camlica H, Erdine S. Efficacy of coeliac plexus and splanchnic nerve blockades in body and tail located pancreatic cancer pain. Eur J Pain 2004;8(6):539-45. o Kitap: Newton ML. Current practice of pain. 1st ed. St. Luis, MO: Mosby; 1990. o Kitaptan bölüm: Turner JA. Coping and chronic pain. In: Bond MR, Charlton JE, Woolf CJ, editors. Pain research and clinical management. Proceedings of the VIth world congress on pain. Amsterdam: Elsevier; 1991. p. 219-27. o Kurslar ve konferanslar (yayınlanmamış): Erdine S. Pain. Course lecture presented at: International Pain Congress, June 7, 2008, İstanbul.

YAZI TÜRLERİ VE SPESİFİK FORMATLAMA KILAVUZLARI Makalenin türü, formatlama ve yazının sözcük sayısı dahil kullanılması gereken kılavuzları belirlediğinden yazı gönderiminde ilk adım makalenin türünün tanımlanmasıdır.

Araştırma Makalesi: Ağrıda temel bilimler ve klinik araştırmalara ait özgün çalışmalar: Bu makaleler randomize kontrollü çalışmalar, gözleme dayalı çalışmaları (kohort, olgu-kontrollü veya kesitsel), tanısal doğruluk çalışmaları, sistematik derlemeleri ve metaanalizleri, randomize olmayan davranışsal ve halk sağlığı girişimsel çalışmaları, deneysel hayvan çalışmaları veya başka klinik ve deneysel çalışmaları içerebilir. Araştırma makaleleleri aşağıda belirtilen sayfaları, bölümleri ve yukarıda gerekli dosya türleri bölümünde tanımlanmış dosyaları içermelidir: 1. Özetler Sayfası: Hem İngilizce hem de Türkçe özetlerin olması gerekir. Özetler 250 sözcüğü geçmemeli ve aşağıdaki alt başlıklar halinde yapılandırılmalıdır: Amaçlar, Gereç ve Yöntemler (çalışma tasarımıyla birlikte), Bulgular ve Sonuç (olgu kontrollü çalışma, kesitsel çalışma, kohort çalışması, randomize kontrollü çalışma, tanısal doğruluk çalışmaları, metaanalizler, ve sistematik derleme, hayvan deneyleri, randomize olmayan davranışsal ve halk sağlığı girişimsel çalışmaları vs). İstatistiksel analize göre bulgularınızın önemini vurgulayın ideal olarak etki büyüklüğü ve başlıca sonuçlar için güven aralıklarını da bulgulara dahil edin.

2. Ana Metin: Ana metin şu alt başlıklar halinde yapılandırılmalıdır: Giriş, Gereç ve Yöntemler, Bulgular, Tartışma, Teşekkür, Kaynaklar, Tablolar ve Şekil Alt Yazıları. a. Giriş: Üç paragraflı yapı kullanılmalıdır. Çalışma konusuna ilişkin arka plan bilgileri (1. paragraf ), çalışmanın bağlamı ve çıkarımları (2. paragraf ), çalışmanın varsayımları ve hedefleri (3. paragraf ). Arka plan: Ortamı oluşturan ve sizi konuyu araştırmaya sevk eden koşullar veya tarihsel bağlamı

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tanımlayın. Bağlam: Araştırmanızın niçin önemli olduğunu, potansiyel çıkarımlarının neler olduğunu, ilk paragrafta ortaya atılan konularla ilişkisini, bu spesifik araştırmanın niçin bir sonraki mantıksal adım olduğunu, çalışmanın hedeflerini anlatın ve araştırmanın spesifik amacını veya varsayımını ve birincil sonuç ölçümünüzü açıkça belirtin. b. Gereç ve Yöntemler: Yöntem bölümü özgün araştırma makalelerinin en önemli bölümlerinden biri olup yeterince detaylandırılmalıdır. Araştırma yöntemi, çalışma örneği, uygulanmış analizler, kullanılan ticari istatistik programları, ölçüm ve değerlendirmelerin ayrıntıları (örn: biyokimyasal test cihazları ve kitlerin markası ve modeli) tümüyle açık ve net biçimde belirtilmelidir. Prospektif çalışmalar için yerel etik komite ve diğer onay veren yetkili kurumların adları da Yöntemler bölümünde verilmelidir. Yöntemler bölümü mantıksal ve ardışık alt başlıklar şeklinde düzenlenmelidir. c. Bulgular: Çalışma popülasyonunun demografik özellikleri ve hipotez testinin ana ve ikincil bulguları da kaydedilmelidir. Bu bölümde bulguları yorumlamaktan ve literatür bulgularını tartışmaktan kaçınılmalıdır. Analizlerde edinilmiş olabildiğince çok veriyi bir bütün olarak mümkünse grafikler halinde sunun. Testlerde kullanılan istatistikler temelinde bulguların önemini vurgulayın. Bunun için ideal olarak her bir sonuç için etkinin büyüklüğü ve ilişkili %95 güven aralıklarından yararlanın. d. Tartışma: Çalışmanın birincil ve ikincil sonuçları kısaca sunulmalı, literatürdeki benzer bulgularla karşılaştırılmalıdır. Bu bölümde yoğun arka plan bilgileri vermektem kaçınılmalıdır. Yalnızca sonuçlarınızın yorumlanmasıyla doğrudan ilişkili yayınlanmış makaleleri göz önünde bulundurun ve bunları çalışma bağlamına dahil edin. İstatistiksel anlamı klinik önemden fazla vurgulamayın. Bulgularınızı araştırmanızda açıkça incelemediğiniz toplumlar ve koşullara uyarlamayın. Yöntemler ve Bulgular bölümlerinde formel bir maliyet-etkililik analizi sunmadıysanız maliyet ve ekonomik yarar konularında iddialarda bulunmayın. Bir sonraki aşamanın ne olduğunu spesifik olarak belirtmeden. “Daha fazla araştırma gereklidir” önerisinde bulunmayın. İsterseniz “Geriye baktığımızda …” ile başlayan bir paragraf ilave edip içtenlikle çalışmayı tekrarlama fırsatı verilseydi neleri farklı yapmak isterdiniz konusunu tartışarak başkalarının da deneyimlerinizden bir şeyler öğrenebilmesini sağlayabilirsiniz. e. Limitasyonlar: Çalışmanın limitasyonları tartışma sonunda ayrı bir paragraf içinde “Limitasyonlar” altbaşlığı altında belirtilmelidir. Sonuçlarınızın içsel ve dışsal geçerliliğini tehdit eden etmenler de dahil olmak üzere çalışmanızın limitasyonlarını açıkça tartışın. Mümkünse her bir yanlılığın boyut ve yönünü ve sonuçların yorumlanmasını nasıl etkileyebildiğini inceleyin. f. Sonuç: Çalışmanın bulguları ışığında net bir sonuca varılmalıdır. Çalışma sonuçlarının güncel klinik uygulamalar üzerine potansiyel etkileri tek bir cümleyle belirtilmelidir. Çalışmanın sonuçlarıyla desteklenmeyen çıkarımlarda bulunmaktan kaçınılmalıdır. g. Teşekkür: h. Kaynaklar: Kaynaklar ayrı bir sayfada belirtilmelidir. i. Şekil Alt yazıları: Şekil alt yazıları ayrı bir sayfada ana metin içinde belirtilmeli ve bu sayfa ana metin dosyasının sonuna konmalıdır. j. Tablolar: Ana metin dosyasının sonuna ayrı sayfalar veya ayrı bir dosya şeklinde konmalıdır. k. Şekiller: Ana metin dosyasının içine konmamalı ve yukarıda gerekli dosya türleri bölümünde tanımlandığı gibi ayrı dosyalar halinde yüklenmelidir. l. Etik ve İnceleme Kurulunun Onayı: Yazınız orijinal araştırma ise bir kurumsal inceleme veya etik kurul tarafından onaylandığı veya muaf tutulduğunu doğrulamanız istenecektir. AĞRI Dergisi onaylanmamış veya muaf tutulmamış yazılara daha fazla dikkate almayacaktır. (Yalnızca daha önce IRB (bağımsız etik kurul) onay veya muafiyeti bulunan üçüncü tarafların anonim veri tabanlarının analizleri bu kapsamın dışındadır.)

Olgu Raporları: Ağrı pratiğinde nadiren rastlanılan ve eğitsel değeri olan klinik olgular veya komplikasyonların kısa anlatımlarıdır. Mevcut literatürde daha önce belgelenmemiş klinik durumları, klinik belirtileri veya komplikasyonları, bilinen tedavi rejimlerinin raporlanmamış yan veya advers etkileri konusunda ileri araştırmayı tetikleyebilen bilimsel bulgular göz önünde bulundurulacaktır. Olgu raporlarının özetleri 150 sözcüğü geçmemeli, ayrı bir sayfaya yazılmalı ve yapılandırılmamalıdır. Olgu serilerinin ana metni aşağıdaki alt başlıklar altında yapılandırılmalıdır: Giriş, Olgu Sunumları, Tartışma ve Kaynaklar.

Kısa Rapor: İlk elde edilen veriler, bulgular veya ileri araştırmaların gerekliliğini gösteren küçük çaplı çalışmaların orijinal raporları. Özetler 250 sözcüğü geçmemeli ve araştırma makalesi şeklinde yapılandırılmalıdır. Limitasyonları, en fazla 6 yazar, 4000 sözcük (kaynaklar, tablolar ve şekil alt yazıları dahil) 15 kaynak, 4 tablo ve/veya şekli içerir. Bu kısıtlamalardan başka, araştırma makalelerin tüm formatları, onay, etik ve yazım kılavuzları kısa raporlar için de geçerlidir.

Derleme Makalesi: Güncel ağrı uygulamasına ilişkin ulusal ve uluslararası literatürü gözden geçiren kapsamlı makalelerdir. Genellikle AĞRI Dergisi yalnızca davetli yazarların derleme makalelerini yayınlamaktadır. Diğer yazarlar derleme makalelerini göndermeden önce editörle iletişime geçmelidir. Derleme makalesi en fazla 2 yazarlı olmalı, kaynaklar, tablolar ve şekil altyazıları dahil 4000 sözcüğü geçmemelidir. Kaynakların sayısı sınırlandırılmamıştır.

Editöre Mektup: AĞRI Dergisi veya başka dergilerde yayınlanmış makalelere ilişkin düşünceler, yorumlar ve önerileri içerir. Mektuplar en fazla 1.000 sözcük içermelidir. Bu tek yazarlı yazılar için en fazla 5 kaynağın referans gösterilmesine izin verilir. Özet yazılması gerekmemektedir.

YAZAR KATKI VE İNSAN VE HAYVAN HAKLARI BİLDİRİMİ Bilimsel katkı ve sorumluluklar, ilgili herhangi bir finansal ya da çıkar çatışması varsa belirtilmelidir. Sorumlu yazar, çalışmanın ve yayının hazırlanmasına katkıda bulunan yazarların adlarını içeren formu imzaladıktan sonra yayıncıya göndermelidir. İnsan deneyleri rapor edilirken, yazarlar prosedürlerin 1975 Helsinki Deklerasyonu-2000, 2008 yılında revize edilen- uyarınca insan deneylerinden (kurumsal ve ulusal) sorumlu etik standartlara uygun olarak olup olmadığı belirtmelidir. Hayvanlar üzerindeki deneyler rapor edilirken, yazarlar laboratuvar hayvanlarının bakımı ve kullanımı için kurumsal ve ulusal rehberi uygulayıp uygulamadığını belirtmelidir. Lütfen makale ile ilgili detayları doldurduğunuz formun (Yazar Katkı ile İnsan ve Hayvan Hakları Bildirimi Formu) çıktısını alın ve formu imzaladıktan sonra faks veya elektronik olarak yayıncıya gönderin.

BİLGİLENDİRİLMİŞ ONAM BİLDİRİMİ Bilimsel amaç için gerekli olmadığı sürece, yazılı açıklamalarda, fotoğraflarda ve soy ağacında hastaların isimleri, baş harfleri veya hastane numaralarını içeren tanıtıcı bilgiler yayınlanmamalıdır ve hasta (ailesi ya da vasisi) yayınlanması için yazılı bilgilendirilmiş onam vermelidir. Bu amaç için bilgilendirilmiş onam, tanımlanabilir bir hastaya yayınlanacak makalenin gösterilmesini gerektirir. Yazarlar, yazıma destek sağlayan kişileri belirtmeli ve bu destek için fon kaynağını açıklamalıdır. Tanıtıcı detaylar eğer gerekli değil ise göz ardı edilmelidir. Lütfen makale ile ilgili detayları doldurduğunuz ve hasta veya yakınına formu imzalamalarını rica ettiğiniz formun (Bilgilendirilmiş Onam Bildirimi Formu) çıktısını alın, faks ile veya elektronik olarak yayıncıya gönderin.

TELİF HAKLARI VE ÇIKAR ÇATIŞMASI BİLDİRİMİ Yazarlar makalede bahsedilen materyal ile ilgili herhangi bir finansal kuruluş ile herhangi bir çıkar çatışması olmadığını belirtmelidir. Kabul edilen makaleler için, tüm yazarlar tarafından imzalanmış telif hakkı formu gönderilmelidir. Lütfen makale ile ilgili detayları doldurduğunuz formun (Telif Hakkı Devir Formu ve Çıkar Çatışması) çıktısını alın ve formu imzaladıktan sonra faks veya elektronik olarak yayıncıya gönderin.

YAYIN ÜCRETİ AĞRI erişme açık bir dergidir. Online olarak derginin web sayfasından yazılara ücretsiz olarak ulaşılmaktadır. Yayınlanan sunumlar için yazarlardan herhangi bir ücret talep edilmez.

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SCOPE AND PURPOSE This journal, which is published quarterly, is the official publicalion of Turkish Society of Algology, Reviews, details of interentional techniques, original researehes and case reports on the nature, mechanisms and treatment of pain are published. The journal provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest. Opinions presented in published articles by no means represent the official endorsement of the Turkish Society of Algology. Articles and illustrations become the property of the Journal after publication.

INSTRUCTIONS FOR AUTHORS 1. The journal is published in Turkish and in English.

2. Manuscripts which are accepted by Editorial Board can be published. The Editorial Board have the right ro reject or to send the manuscript for review and revise. All manuscripts are subject to editing and, if necessary, will be returned to the authors for responses to outstanding questions or for addition of any missing information. For accuracy and clarity, a detailed manuscript editing is undertaken for all manuscripts accepted for publication.

Final galley proofs are sent to the authors for approval.

3. Articles not written according ro the 3rd editian (1983) of “common properties which are wanted in the articles that will be submitted to the Biomedical Journals” which was deternıined by the International Medical Journal Editorial Board, will not be accepted. Before submission it is adviced to look for these guidelines whieh are published in British Medical Journal 1988;296:401-5 or in Annals of Internal Medicine 1988;108:258-65.

4. All paper types are accepted via internet based manuscript processing system (www.journalagent.com/agri).

5. A paper which has not previously been published or being considered for publication elsewhere are accepted for publication. Papers which were published elsewhere previously as an abstract form may be published.

6. No payment for copyright of the article will be done. Therefore the letter accompanying the manuseript should include a statement that copyright of the article is transferred to the Turkish Society of Algology. The final manuscript should have been read and approved by the responsible authors.

7. If illustrations or other small parts of articles or books aIready published elsewhere are used in papers submitted to journal, the written permission of author and publisher corcerned must be included with the manuscript.

8. Authors should keep a copy of their manuscripts.

9. If a part or whole of a submitted manuscript will be published elsewhere, editor of the journal should be informed.

10. For researches, approvement of the institutional local ethics committee or its equivalent should be submitted.

11. All the responsibilities belong to authors.

12. No reprints will be sent to the author.

REQUIRED FILETYPES AND MINIMUM SUBMISSION REQUIREMENTS Before submission via electronic submission system, a number of separate MS Word (.doc) and Adobe (.pdf ) files should be prepared with the following formatting properties. No submissions will be accepted without a Cover Letter and a Title Page.

1. Cover Letter: A cover letter file should be included in all types of manuscript submissions. On the cover letter, the author(s) should present the title, manuscript type and manuscript category of the submission, and whether the submitted work had previously been presented in a scientific meeting.

The cover letter should contain a statement that the manuscript will not be published or evaluated for publication elsewhere while under consideration by AGRI Journal. In addition, the full name of the corresponding author and his/her contact information including the address, phone number and e-mail address should be provided at the bottom of the cover letter. The cover letter should be signed by corresponding author, scanned and submitted in .jpg or .pdf format with other manuscript files. The order of a cover letter should be as follows: a. Title, manuscript type. b. Statement that the manuscript will not be published or evaluated for publication elsewhere while under consideration. c. Corresponding author(s) full name, contact information including address, phone, and e-mail address. d. Signature of the corresponding author.

2. Title Page: A title page file should be included in all types of manuscript submissions. Please prepare your title page as a separate electronic file, including the following elements: a. Title of the manuscript b. Author(s) list, please list their full names and up to 2 academic degrees per author; do not include honorary affiliations, such as fellow status in an organization. c. Affiliation(s) of each author, including department or division, institution, city, country. d. Corresponding author(s) full name, contact information including address, phone, and e-mail address. e. Funding or other financial support should be acknowledged. f. Conflict of interest statement: A conflict of interest statement should be provided in bottom of the title page. Please list of all potential conflicts of interest for each author, in accordance with ICMJE recommendations. In case of no conflicts of interests, please provide a statement such as: “Conflicts of Interest: None declared”.

3. Abstracts: On the abstracts page, the author(s) should present abstract and keywords (at least three) in this order. Turkish and English keywords should be chosen from Medical Subject Headings (MeSH) (http://www.nlm.nih.gov/mesh/MBrowser.html) and Türkiye Bilimler Terimleri (http://www. bilimterimleri.com).

4. Main Text: A main text file should be included in all types of manuscript submissions. This file should include title, abstracts page, main text of your manuscript, and the references section combined into a single electronic file. Tables can be included in this file as separate pages after References section, or may be uploaded separately as you prefer. Structure of the main text differs between manuscripts types. a. This combined file with the sections of abstracts, keywords, main text, references with/without tables should be a blinded version of the original manuscript. The names of the authors’, and any identifying information including the academic titles, institutions and addresses must be omitted. Apart from the stage of the manuscript evaluation process, manuscripts submitted with any information pertaining to the author(s) will be rejected as soon as it is noticed.

5. Tables: Tables summarizing the data should be clearly formatted without using any templates. Data presented in the tables should not be included in its entirety in the text. a. Tables must be numbered consecutively. b. Each table must be referred to in the text. c. Number and title of each table should be written at the top of each page before the table. d. Tables can be included in main text file as separate pages after references section, or may be uploaded separately as you prefer. If you prefer a separate file, tables should be uploaded in MS Word (.doc) format and the electronic file should be named accordingly (Tables_xxx_vx.doc). Tables should not be uploaded as pdf, jpeg or else.

6. Figures: If the manuscript includes figures then each figure should be uploaded as a separate file in all types of manuscript submissions. The information contained in the figure/image should not be repeated in its entirety, however reference to the figure/image must be referred in the text.

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a. i. ii. iii. iv. v.

Technical requirements Figure legends should appear on a separate page after the references section.

During submission, all figures must be uploaded in a separate file from the text file and should be named accordingly (Figure1_xxx; Figure2_xxx).

No legends or titles should be included in the figures.

Pictures should be saved in JPEG, EPS or TIFF format.

Please submit photographs and figures with a resolution of at least 300 dots per inch. Figures are easiest for us to process if submitted in TIFF or EPS format. b. Ethical requirements i. The owner and/or subject of the photograph must sign the patient consent form. ii. Figures should not be reproduced from other sources without permission 7. Statements, permissions, and signatures: a. Conflict of Interest Form: A conflict of interest exists when professional judgment concerning a primary interest (such as patients’ welfare or validity of research) may be influenced by a secondary interest (such as financial gain). Financial relationships are easily identifiable, but conflicts can also occur because of personal relationships or rivalries, academic competition, or intellectual beliefs. A conflict can be actual or potential, and full disclosure to The Editor is the safest course. Failure to disclose conflicts might lead to publication of an Erratum or even to retraction. All submissions to AGRI must include disclosure of all relationships that could be viewed as presenting a potential or actual conflict of interest. All authors are required to provide a conflict of interest statement and should complete a standard form. b. Patient Consent Form: Publication of any personal information about an identifiable living patient requires the explicit consent of the patient or guardian. We expect authors to use a standard patient consent form. c. Copyright Transfer Form: All authors are required to provide a copyright transfer from with complete a standard form.

MANUSCRIPT FORMATTING Manuscript format must be in accordance with the ICMJE-Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals(updated in August 2013). Papers that do not comply with the format of the Journal will be returned to the author for correction without further review. Therefore, to avoid loss of time and work, authors must carefully review the submission rules.

Manuscript structure should be complient with the guidelines of WAME. General Format 1. General Style: o The manuscript should be typed in a Microsoft Word™ file, single-column format, Every effort should be made to avoid medical jargon.

2. For the Blind Initial Review: The names of the authors’, and any identifying information including the academic titles, institutions and addresses must be omitted. Manuscripts submitted with any information pertaining to the author(s) will be rejected.

3. Drugs: Generic names for drugs should be used. Doses and routes for the drugs should be stated. When a drug, product, hardware, or software mentioned within the main text product information, including the name of the product, producer of the product, city of the company and the country of the company should be provided in parenthesis in the following format: “Discovery St PET/CT scanner (General Electric, Milwaukee, WI, USA)” 4. Abbreviations: We discourage the use of any but the most necessary of abbreviations. They may be a convenience for an author but are generally an impediment to easy comprehension for the reader. All abbreviations in the text must be defined the first time they are used (both in the abstract and the main text), and the abbreviations should be displayed in parentheses after the definition. Authors should avoid abbreviations in the title and abstract and limit their use in the main text.

5. Decimal points or commas: Decimal numbers should be separated from the integers with points. Commas should not be used in decimals throughout the manuscript.

6. References: References should be numbered consecutively in the order in which they are first mentioned in the text (6 authors then “et al”). Avoid referencing abstracts, or citing a “personal communication” unless it provides essential information not available from a public source. Examples of Referencing are as follows: o Article: Süleyman Ozyalçin N, Talu GK, Camlica H, Erdine S. Efficacy of coeliac plexus and splanchnic nerve blockades in body and tail located pancreatic cancer pain. Eur J Pain 2004;8:539-45. o Book: Newton ML. Current practice of pain. 1st ed. St. Luis, MO: Mosby; 1990. o Book Chapter: Turner JA. Coping and chronic pain. In: Bond MR, Charlton JE, Woolf CJ, editors. Pain research and clinical management. Proceedings of the VIth world congress on pain. Amsterdam: Elsevier; 1991. p. 219-27. o Courses and Lectures (unpublished): Erdine S. Pain. Course lecture presented at: International Pain Congress, June 7, 2008, İstanbul.

MANUSCRIPT TYPES AND SPECIFIC FORMATTING GUIDELINES Identification of article type is the first step of manuscript submission because article type dictates the guidelines that should be used, including formatting and word limits of the manuscript. The main categories are outlined below: Research Article: Original studies of basic or clinical investigations in algology. These articles can include randomized controlled trials, observational (cohort, case-control or cross-sectional) studies, destructive studies, diagnostic accuracy studies, systematic reviews and meta-analyses, nonrandomized behavioral and public health intervention trials, experimental animal trials, or any other clinical or experimental studies. Submission of research articles should include below mentioned pages, sections and files as defined above in required filetypes section: 1. Abstracts Page: Both English and Turkish (if relevant) abstracts are required. Abstracts should not exceed 250 words and should be structured with the following subheadings: Objectives, Material and Methods (with design), Results, and Conclusion (case control study, cross sectional study, cohort study, randomized controlled trial, diagnostic accuracy study, meta-analysis and systemic review, animal experimentation, non-randomized study in behavioral sciences and public health, etc.). In your results emphasize the magnitude of findings over test statistics, ideally including the size of effect and its confidence intervals for the principal outcomes.

2. Main Text: The main text should be structured with the following subheadings: Introduction, Material and Methods, Results, Discussion, Acknowledgments, References, Tables, and Figure Legends. a. Introduction: A three-paragraph structure should be used. Background information on study subject (1st paragraph), context and the implications of the study (2nd paragraph) and the hypotheses and the goals of the study (3rd paragraph). Background: Describe the circumstances or historical context that set the stage and led you to investigate the issue. Context: Describe why your investigation is consequential. What are its potential implications? How does it relate to issues raised in the first paragraph? Why is this specific investigation the next logical step? Goals of the study: Clearly state the specific research objective or hypothesis and your primary outcome measure. b. Material and Methods: The method section, is one of the most important sections in original research articles, and should contain sufficient detail. The

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investigation method, study sample, analyses performed, commercial statistical programs used, details of measurement and evaluation (e.g.: make and model of biochemical test devices and kits) should all be clearly stated. The names of local ethics committee or other approving bodies should be provided in Methods section for prospective studies. The Methods section should be organized with logical and sequential subheadings. c. Results: The demographic properties of the study population, the main and secondary results of the hypothesis testing must be provided. Commenting on the results and discussing the literature findings should be avoided in this section. Present as much data as possible at the level of the unit of analysis, graphically if possible. Emphasize the magnitude of findings over test statistics, ideally using size of effect and associated confidence intervals for each outcome. d. Discussion: The main and secondary results of the study should briefly presented and compared with similar findings in the literature. Providing intensive background information should be avoided in this section. Consider only those published articles directly relevant to interpreting your results and placing them in context. Do not stress statistical significance over clinical importance. Avoid extrapolation to populations or conditions that you have not explicitly studied in your investigation. Avoid claims about cost or economic benefit unless a formal cost-effectiveness analysis was presented in the Methods and Results sections. Do not suggest “more research is needed” without stating what the specific next step is. Optionally, you may include a paragraph “In retrospect, . . .” to candidly discuss what you would do differently if given the opportunity to repeat the study, so others can learn from your experience. e. Limitations: The limitations of the study should be mentioned in a separate paragraph subtitled as the “Limitations” in the end of the discussion. Explicitly discuss the limitations of your study, including threats to the internal and external validity of your results. When possible, examine the magnitude and direction of each bias and how it might affect the interpretation of results. f. Conclusion: A clear conclusion should be made in the light of the results of the study. The potential effects of the results of the study on the current clinical applications should be stated in a single sentence. Inferences that are not supported by the study results should be avoided. g. Acknowledgments: h. References: References section should be in a separate page. i. Figure Legends: Figure legends should be included in the main text in a separate page and this page should be the at the end of the main text file. j. Tables: At the end of the main text file as separate pages or as a separate file. k. Figures: Should not be included in the main text file and should be uploaded as separate files as with the properties describes above in required filetypes section: l. Ethics or Review Board Approval: If your manuscript involves original research, you will be asked to verify approval or exemption by an institutional review or ethics board. AGRI Journal will be unable to further consider manuscripts without approval or formal exemption. (The only exceptions are for analyses of third party anonymized databases which already have pre-existing IRB approval or exemption.)

Case Reports: Brief descriptions of clinical cases or the complications that are seldom encountered in algology practice and have an educational value.

Consideration will be given to articles presenting clinical conditions, clinical manifestations or complications previously undocumented in the existing literature and unreported side of adverse effects of the known treatment regimens or scientific findings that may trigger further research on the topic. Abstracts of case reports should mainly include information about the case, should not exceed 150 words, must be on a separate page and should be unstructured. The main text of Case Series should be structured with the following subheadings: Introduction, Case Presentations, Discussion and References.

Brief Report: Original reports of preliminary data and findings or studies with small numbers demonstrating the need for further investigation. Abstracts should not exceed 250 words and structured as research articles. Limitations include: maximum 6 authors, 4000 words (including references, tables, and figure legends), 15 references, 4 tables and/or figures. Besides these constraints, all the formatting, approval, ethics and writing guidelines of research articles also applies to brief reports.

Review Article: Comprehensive articles reviewing national and international literature related to current algology practice. Generally AGRI Journal publishes only invited review articles. Other authors should contact the editor prior to submission of review articles. Maximum 2 authors, 4000 words (including references, tables, and figure legends). There is no limit to the number of references.

Letter to the Editor: Opinions, comments and suggestions made concerning articles published in AGRI Journal or other journals. Letters should contain a maximum of 1,000 words and 5 references are allowed for these single author submissions. No abstract is required.

AUTHOR CONTRIBUTION & STATEMENT OF HUMAN AND ANIMAL RIGHTS Scientific contribution and responsibilities, any financial or other conflict of interest should be mentioned. Corresponding author should include the names of the authors who contributed to the preparation of the study and the manuscript and send to publisher after signing the form. When reporting experiments on human subjects, authors should indicate whether the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. When reporting experiments on animals, authors should be asked to indicate whether the institutional and national guide for the care and use of laboratory animals was followed. Please print out the form (Author Contribution & Statement of Human and Animal Rights Form) fill in the details about the article and sent to publisher by fax or electronic submitting system after signing the form.

STATEMENT OF INFORMED CONSENT Patients have a right to privacy that should not be infringed without informed consent. Identifying information, including patients’ names, initials, or hospital numbers, should not be published in written descriptions, photographs, and pedigrees unless the information is essential for scientific purposes and the patient (or parent or guardian) gives written informed consent for publication. Informed consent for this purpose requires that a patient who is identifiable be shown the manuscript to be published. Authors should identify Individuals who provide writing assistance and disclose the funding source for this assistance. Identifying details should be omitted if they are not essential. Please print out the form (Statement of Informed Consent Form), fill in the details about the article, ask the patient or next of kin to sign the form, and sent to publisher by fax or electronic submitting system after signing the form.

COPYRIGHT & STATEMENT OF CONFLICT OF INTEREST Authors should also state that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Transfer of copyright form which is signed by all authors must be sent for accepted manuscripts. Please print out the form (Conflict of Interest & Transfer of copyright form), fill in the details about the article and sent to publisher by fax or electronic submitting system after signing the form.

PUBLISHING FEE AGRI is an open access journal. Manuscripts can be reached from the web page of journal without any fees. No additional fee is required from the authors for accepted manuscripts.

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Agri 2018;30(4):153-164

doi: 10.5505/agri.2018.85688

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REVIEW

Headache in challenging and special circumstances: Pregnancy and lactation Zorlu ve özel koşullarda baş ağrısına yaklaşım: Gebelik ve laktasyon Ezgi YILMAZ,1

Işın ÜNAL ÇEVIK2

Summary Headache has special importance during pregnancy and postpartum period. The health-care professionals and patients report headache management as challenging during pregnancy and lactation period. Cautions are recommended in preganancy and lactation due to maternal and fetal/newborn risks. Most headaches in the first trimester are due primary headaches.

Nevertheless, the incidence of secondary headaches increase in the last trimester and post-partum period. Red flags prompt early evaluation in a patient with headache. Assessment of headache patient requires a detailed history of the headache characteristics and performing appropriate examinations. Approach to headache and strategies to promote best practice in preganancy and lactation will be reviewed.

Keywords: Diagnosis; migraine; primary headaches; red flags; secondary headaches; treatment.

Özet Gebelik ve doğum sonrası dönemdeki baş ağrıları özel bir önem taşımaktadır. Bu dönemdeki baş ağrısı yönetimi sağlık çalışanları ve hastalar tarafından zorlayıcı olarak bildirilmektedir. Başağrısına doğru yaklaşım hem anne hem de fetal/yenidoğan risklerinin önlenmesi açısından önemlidir. İlk trimesterdeki baş ağrılarının büyük çoğunluğu primer baş ağrıları grubundadır.

Gebeliğin son trimesteri ve doğum sonrası dönemlerde, sekonder baş ağrılarının sıklığı ise artmaktadır. Baş ağrısı hastalarında kırmızı bayrak belirti ve bulgularına dikkat edilmelidir. Baş ağrısı hastasının değerlendirilmesinde detaylı anamnez alınması; doğru ve eksiksiz olarak fizik ve nörolojik muayene yapılması yanında gerekirse ileri tetiklerin yapılması da önemlidir. Bu derlemede gebelik ve laktasyon dönemindeki baş ağrılarına yaklaşım ve en iyi medikal uygulama stratejileri gözden geçirilmektedir.

Anahtar sözcükler: Tanı; migren; primer baş ağrıları; kırmızı bayrak bulguları; sekonder baş ağrıları; tedavi.

Headache is the most common disease of admissions to the neurology outpatient clinics and the seventh highest cause of disability worldwide.[1] Pregnancy and lactation are unique conditions in which certain diseases are seen either in a specific manner or with increased frequency. Headache has special importance during pregnancy and postpartum period due to the negative impact on both to the mother and the baby. The International Classification of Headache Disorders classifies headaches as 1) primary headaches, 2) secondary headaches and 3) painful cranial neuropathies, other facial pains and other headaches.[2] Although most headaches in pregnancy are primary and benign, pregnant women may present

with a secondary headache due to pregnancy- related conditions (e.g. role of clotting factors, vascular endothelium, hemodynamic functions, immunity etc.). Increased risk of certain secondary headaches during pregnancy seek for attentive evaluation and management.[3] Assessment of a headache patient requires a detailed history of the headache characteristics and performing appropriate examinations. Headache history is mandatory and must include location of pain, severity of pain, quality of pain, duration of pain, headache attack characteristics, accompanying features, factors that precipitate/increase or al-

Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey Department of Neurology, Pain Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey

1 2

Submitted: 09.08.2018 Accepted after revision: 11.09.2018 Available online date: 28.10.2018

Correspondence: Dr. Işın Ünal Çevik. Hacettepe Üniversitesi Tıp Fakültesi, Nöroloji Anabilim Dalı, Ağrı Ünitesi, Sıhhiye 06100, Ankara, Turkey.

Phone: +90 - 312 - 305 25 85 e-mail: isin.unalcevik@gmail.com © 2018 Turkish Society of Algology

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A RI PAIN leviate pain, etc.), medical history, and family history (genetic predisposition to headache etc.) should be obtained.[4] Red flags prompt early evaluation in a patient with headache. The sudden onset of worst headache ever experienced, headache that peaks in severity very quickly, new onset headache, change in previous headache characteristics or worsening of headache, headaches awakening a woman at night, headaches associated with blurred vision or pulsatile tinnitus, headaches precipated by valsalva, headache severity change with posture, headaches with prolonged auras or complicated features such as aphasia, weakness, or numbness, prolonged neurological symptoms, chronic persistent unilateral headaches, changes in the frequency and character of the headache, recent trauma, thrombophilia and headaches in anyone who are on anticoagulation therapy or history of malignancy, immune deficiency, HIV, pituitary tumour, hypertension prompt early evaluation.[5] Most headaches in the first trimester are due primary headaches (most commonly due to migraine, tension-type and rarely cluster headache). Nevertheless, the incidence of secondary headaches increase in the last trimester and post-partum period.[6] A complete neurologic examination is crucial. In primary headache disorders, the general and neurological examination should be normal. Positive findings on fundoscopy (e.g.papiledema or hemorrhages), neck stiffness, fever, visual disturbances, altered consciousness, unsteadiness, weakness, sensory deficits, or any focal neurological deficit must be excluded.

Headache is one of the most common cause for brain imaging during pregnancy.[7] If any red flag is present, neuroimaging and further additional studies (such as imaging of the vessels of the head and neck and lumbar puncture) may be offered to the severe headache patients.[6] Magnetic resonance imaging (MRI) is the preferred imaging modality during pregnancy. Gadolinium has a risk of passage through the placenta and may impair fetal renal function.[8] Although amount of radiation exposure to the fetus from a non-contrast maternal head computerized axial tomography (CT) is less than the amount of radiation that may cause fetal loss,[9] growth retardation or fetal anomalies are still considered as risk of a stochastic effect.[10] Thus, MRI is preferred over CT in pregnancy.

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1. Approach to primary headaches in preganancy and lactation a) Migraine Migraine is more common in women and the prevalance peaks at reproductive years.[3] Fluctuations in estrogen levels influence migraine attacks.[11] Migraine is one of the commonest headache in pregnancy. The risk of prematurity, intrauterine growth restriction and fetal malformations are of concern in pregnant migraineurs.[3] In a review of 401 women with migraine, 71.6% confirmed that they searched informations about safetiness of usage of their previous antimigraine medications during their pregnancy and lactation. Nearly half of women who consulted through multiple sources reported that they experienced conflicting informations. More than third admitted to the study reported that they had stopped taking their drugs. These women clearly signified the demand of follow-up visits and easy accesibility to their healthcare professionals during their pregnancy and breastfeeding periods.[12] Menstrually triggered migraine is reported to be more frequent in patients with migraine without aura.[11] Due to sex hormonal changes, pregnancy is in general reported to decrease the migraine attack frequency and this effect is reported to be more profound in patients with migraine without aura.[13] However, migraine may even worsen, particularly in the first trimester[3] when human chorionic gonadotropin levels are decreased.[11] Unfortunately, the frequent migraine attacks at the first trimester and usage of antimigraine treatments may represent a vulnerable time for fetal drug toxicity.[14] Strategies of migraine treatment in pregnancy and lactation General strategy is to start with behavioural/nonmedical treatments.[15] The most frequently reported triggers for migraine are stress (mental or physical), irregular or inappropriate meals, high intake or withdrawal of coffee and other caffeine-containing drinks, dehydration, sleep disorders (too much or too little sleep), and reduced or excessive physical exercise.[16] Pregnant women with migraine should be encouraged to avoid skipping meals, take regular exercise, drink plenty of fluids, and maintain a regular sleep pattern. Alcohol and smoking are potentially harmful to the fetus and should be avoided durOCTOBER 2018

Pregnancy and lactation

ing pregnancy. Nonpharmacological therapies such as relaxation, biofeedback, and physical therapy are safe and may be effective in pregnancy.[17] Acute migraine attack treatment options Acetaminophen Acetaminophen remains the first- line and safe treatment option for pain and fever in pregnancy. A large cohort study showed that acetaminophen, was used by 39.7% of women during the first 5 months of pregnancy.[18] Nevertless, reports from three independent studies[19] showed adverse neurodevelopmental effects[20] in children after long-term exposure (>28 days) in utero.[21] However, the European Medicines Agency (EMA) concluded that current evidence is still insufficient to support the association between paracetamol exposure in pregnancy and neurodevelopmental risks.[22] Acetaminophen is excreted in breast milk in low concentrations and the metabolic capacity of paracetamol is about the same in neonates as in adults.[23] Acetaminophen is considered safe during breastfeeding.[24] Nonsteroidal anti-inflammatory drugs (NSAIDs) NSAIDs are frequently used for acute attack treatment.[25] In fetus, prostaglandins mediate relaxation of smooth muscle cells of the ductus arteriosus,[26] renal blood vessels and the systemic vasculature.

[27] Adverse pregnancy outcomes following NSAIDs differ according to the trimester of the drug exposure.[28] NSAID usage in early pregnancy has been associated with miscarriages[29] and congenital malformations.[28] Use of NSAIDs at late pregnancy has been associated with premature closure of the ductus arteriosus,[30] neonatal intraventricular haemorrhage,[31] impaired renal function,[32] persistent pulmonary hypertension of the newborn[33] necrotising enterocolitis[30] and cerebral palsy.[31] As a conclusion, due to the increased risk of miscarriage and congenital malformations, NSAIDs should preferably be avoided in the first trimester. In the second trimester and the early part of third trimester, the use of single doses of NSAIDs for treating acute migraine attacks is justified when both nonpharmacological therapy and paracetamol are proven to be insufficient. Usage of NSAIDs closer to term should be avoided due to the increased risk of adverse fetal outcomes.[22] OCTOBER 2018

In general, NSAIDs are considered compatible with breastfeeding. Particularly ibuprofen being the drug of choice owing to its short elimination half-life (about 2 hours), lack of active metabolites, and low excretion in milk.[34] As children exposed to salicylates have a theoretical risk of Reye syndrome, regular use of salicylates during breastfeeding should be avoided.[15] Triptans Triptans act as serotonin 5-HT1B/1D/1F receptor agonists. Triptans pass through placenta and 5-HT1B/1D receptors are reported to be present in the umbilical cord artery[35] and fetal brain.[36] Although accumulated data suggest that sporadic use of sumatriptan is probably safe during pregnancy, concern has been raised regarding the possibility that the vasoconstrictive effects of triptans could cause malformations related to vascular effects. For triptans other than sumatriptan, safety documentation remains limited. It is suggested that sumatriptan might be the first choice if triptans are considered necessary during pregnancy.[22] The Summary of Product Characteristics for sumatriptan advises that breastfeeding should be avoided for 12 h after treatment. This precaution may be regarded as very conservative, given the drug’s short elimination half-life of about 2 hours and its low oral bioavailability.[22] Eletriptan is suggested to be even safer than sumatriptan because its high plasma protein binding and lower concentrations in breast milk compared to sumatriptan.[37] Thus, eletriptan may be an option for the breastfeeding refractory migraineurs.

Antiemetics Metoclopramide and domperidone have been widely used in acute migraine treatment. In pregnancy, metoclopramide is commonly used in the treatment of hyperemesis gravidarum, and no association with congenital malformations or other harmful fetal effects has been established.[38] Safety data for domperidone in pregnancy is lacking. However, electrocardiographic QT-prolongation in newborns and infants has been reported following paediatric use of domperidone.[39] Thus, domperidon should be avoided in pregnant women.[22] No adverse effects with metoclopramide have been reported in breastfed infants.[40] Metoclopramide in 155

A RI PAIN single dose may not cause harm in the infant, if necessary may be considered compatible with breastfeeding.[22] Migraine preventive treatment options Medications commonly used for migraine prophylaxis in the healthy adults include β-blockers, antiepileptic drugs, tricyclic antidepressants, angiotensinconverting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers and botulinum toxin type A (BTX-A).[22] During pregnancy, prophylaxis may only be advised in pregnant who have frequent (>3–4 attacks per month) and prolonged severe attacks, especially for those who do not respond to symptomatic treatment, or experience complications such as dehydration, anorexia and fetal stress.[34] Caution should always be taken according to the stage (trimester) of the preganancy. β-blockers If prophylaxis is considered necessary during pregnancy, the lowest effective doses of propranolol or metoprolol are the drugs of choice.[15] The metabolism of metoprolol is markedly enhanced during pregnancy[25] which could impair its clinical effect.

The usage of β-blockers in the third trimester can induce fetal bradycardia, and newborns exposed to β-blockers close to delivery should be monitored for pharmacological effects such as bradycardia, hypotension and hypoglycaemia.[34] β-blockers are suggested as first-choice medications during lactation if migraine prophylaxis is considered.[41] Propranolol is excreted into breast milk, but the amounts are considerably lower. Although symptoms caused by β-blockade (such as bradycardia and hypoglycaemia) have not previously been reported following exposure to propranolol or metoprolol via milk, some authors nevertheless recommend that exposed infants should be closely observed for these signs.[42] Antiepileptics Antiepileptic drugs are not recommended in pregnancy. In healthy adults, (except pregnants) valproate and topiramate are the two antiepileptic drugs with good efficacy in migraine prophylaxis.[42] Risk of fetal anomalies such as oral clefts are increased after exposure to topiramate in pregnancy.[43] Sodium 156

valproate is associated with a high risk of fetal abnormalities such as neural tube defects, cardiovascular abnormalities and is contraindicated during pregnancy in the absence of refractory epilepsy.[44] Valproate binds highly to plasma proteins, thereby limiting its passage into breast milk.[45] Although infant plasma levels after exposure via breast milk are considerably low, it has been argued that valproate is best avoided owing to its teratogenic potential once the lactating mother become pregnant again.[46] Antidepressants Antidepressants are not usually recommended in pregnancy. Among the tricyclic antidepressants used in the prevention of migraine, amitriptyline has the best-documented effect.[34] Low-dose amitriptyline 10 mg/d to 25 mg/d may be an option. While data are conflicting regarding limb deformities associated with use of high doses of amitriptyline during pregnancy, no association has been reported with low doses between 10 and 50 mg/d which are recommended doses for pain management.[15] Exposure to antidepressants in late pregnancy may cause neonatal adverse effects such as drowsiness, jitteriness, hyperexcitability, and suckling problems.[37] Amitriptyline has been suggested as a second-line choice (after β-blockers) as preventive therapy in pregnant women.[41] Milk levels of amitriptyline and its active metabolite nortriptyline are low.[47] Adverse effects have not been reported in breastfed infants, and infant plasma levels have been reported to be very low. However accumulation cannot be excluded in premature and newborn babies.[34] ACE inhibitors, ARBs and calcium channel blockers ACE inhibitors, ARBs and Calcium Channel Blockers are not recommended in pregnancy. Intrauterine exposure to ACE inhibitors and ARBs are associated with increased risk of adverse outcomes in the fetus, including miscarriage, oligohydramnios, renal failure and death.[48] ACE inhibitors and ARBs are considered to be contraindicated at any stage of pregnancy.[49] The calcium channel blocker flunarizine should not be used during pregnancy owing to its insufficient safety data.[22] Botulinum toxin type A Data is not sufficient to recommend Botulinum toxin A in pregnancy. Botulinum toxin type A is adminisOCTOBER 2018

Pregnancy and lactation

tered as intramuscular injections in the neck and head. Because of its high molecular weight, BTX-A is not expected to cross the placenta.[50] BTX-A may only be considered as an option in treatment-refractory cases. Botulinum toxin type A would consequently not be excreted into breast milk.[22] It should also be kept in mind that a black box warning information of “DISTANT SPREAD OF TOXIN EFFECT” is present in botulinum toxin products. We also do not recommend this toxin to our pregnant patients.

Magnesium and riboflavin Magnesium may be used during pregnancy for migraine, constipation and pre-eclampsia.[51] One gram intravenous magnesium sulfate given over 15 minutes is an efficient, safe, and well-tolerated drug in the treatment of migraine attacks.[52] There are no indications of any untoward maternal or fetal effects after intrauterine exposure.

Riboflavin is a safe and well-tolerated alternative in migraine prophylaxis.[53] Magnesium is normally found in breast milk. There is no reason to believe that surplus magnesium in breast milk would cause any substantial effects in the infant.[54] Neverthless, fewer data are available for riboflavin, this drug is also considered compatible with breastfeeding.[22] Peripheral nerve blocks Peripheral nerve blocks are practiced widely by headache specialists.[55] Common injection sites are upper cervical nerve branches (greater occipital nerve, lesser occipital nerve) and trigeminal nerve branches (auriculotemporal nerve, supraorbital nerve, supratrochlear nerve).[56] Lidocaine and bupivacaine which are well studied in pregnancy are commonly used in dentistry and obstetric anesthesia.[57] According to retrospective, uncontrolled case series none of the patients experienced any major maternal or fetal adverse effects related to these drugs. Peripheral nerve blocks are used for both short-term migraine prophylaxis as well as the treatment of status migrainosus.[58] Non-pharmacological interventions Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a noninOCTOBER 2018

vasive method by which weak electrical currents are induced in the brain by a rapidly changing magnetic field. When TMS is applied to the head, the magnetic field passes through the skull, inducing mild electric currents in the brain, which excite and depolarize neurons in the brain.[59] TMS is considered as a low risk technique with promise in the diagnosis, monitoring, and treatment of different types of neurological and psychiatric diseases in adults.[60] Several clinical studies have shown that single-pulse TMS (sTMS) is an effective and well tolerated treatment for migraine with or without aura, thus suggesting that sTMS may offer a nonpharmacologic, nonbehavioral therapeutic approach to the currently prescribed drugs for patients who suffer from migraine.[61] No adverse events were reported associated with repetitive transcranial magnetic stimulation application during pregnancy.[61] The Committee on the Possible Effects of Electromagnetic Fields on Biologic Systems, a committee of the National Research Council, reviewed exposures to electric and magnetic fields and concluded that reproduction and development in animals, particularly mammals, have not been shown to be affected by exposure to extremely low frequency electric or magnetic fields.[62] Acupuncture The Cochrane Collaboration review of 22 randomised controlled trials concluded that acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be considered as a treatment option for patients willing to undergo this treatment.[63] The efficacy of prophylaxis thus demonstrated in nonpregnant women can probably be reached during pregnancy, with the added benefit that this treatment may not cause any harm to the fetus.[64] Mind-body treatment options The systematic review of 10 randomized clinical trials concluded that yoga has the potential for alleviating pain.[65] Prenatal yoga with a certified instructor may improve not only headache but also the overall health quality in pregnancy[66] and decrease comorbid conditions including depression, anxiety, and sleep disorders.[67,68] b) Tension-type headache Headaches that lack associated symptoms are likely 157

A RI PAIN to be tension-type headaches. In most women, tension type headache will improve during pregnancy.

[15] Symptomatic treatment with simple analgesics is appropriate for episodic attacks (fewer than 2 days per week).[69] Prophylactic medications are indicated when headaches regularly occur more than 2 to 3 days a week. Amitriptyline is the drug of first choice for prophylaxis of tension-type headache during pregnancy and lactation.[15]

amide and diuretics are usually avoided due to safety concerns. Although the complete safety of acetazolamide during pregnancy is not known, studies have shown favorable outcomes without fetal anomalies.

[73] If vision is threatened, in conjunction and close monitorization with ophtalmology doctors, interventions such as serial lumbar punctures can safely be applied by specialist to control worsening of the symptoms.[76]

c) Cluster headache Cluster headaches are a series of relatively short but extremely painful headaches every day for weeks or months at a time. It is much more common in men than in women. It has stereotypical symptoms of strictly unilateral headache and autonomic symptoms lasting up to 2 hours in clusters typically lasting 6 to 8 weeks.[15] Acute treatment includes 100% nasal mask oxygen 7 L/min for 10 to 15 minutes at the onset or subcutaneous/intranasal sumatriptan.[70] Preferred preventive treatments during pregnancy and lactation are verapamil or prednisone/prednisolone.

Verapamil can cause cardiac conduction problems.

ECGs to assess PR interval prolongation should be undertaken at baseline, before each dose increment, and every 6 months during long-term treatment.[15]

b) Pre-eclampsia and eclampsia Pre-eclempsia and eclampsia are part of pregnancy specific dangerous conditions which remain significant risk of maternal/fetal morbidity and mortality.

Preeclampsia occurs in about 2–8% of pregnancies, usually after 20 weeks’ gestation time period and typically improves following delivery of the placenta.[77] However pre-eclampsia/eclampsia can occur in the postpartum period. Pre-eclampsia diagnosis requires arterial hypertension (>140/90 mm Hg) documented by two blood pressure readings at least four hours apart, or a rise in diastolic pressure of ≥15 mm Hg or systolic pressure of ≥30 mm Hg, coupled with urinary protein excretion >0.3 g/24 hours.[78] In addition, tissue edema, thrombocytopenia and abnormalities in liver function can occur. Eclampsia is defined by the onset of seizures in a woman with pre-eclempsia.[2] The neurological manifestations of pre-eclampsia/eclampsia reflect the areas of the brain affected. Seizures (in over 70%), hypertension (in 60%), confusion, headache and visual disturbances are common initial presentations.[79] Vision disturbances are common due to occipital and parietal lobe involvement including: cortical blindness, homonymous hemianopia, flashing lights, blurred vision, visual neglect or visual hallucinations.[80]

2. Approach to secondary headaches in preganancy and lactation a) Idiopathic intracranial hypertension (IIH) Incidence of IHH is increasing, in parallel with the epidemic of obesity.[71] The common onset of IIH is in the first half of the pregnancy. Reccurrence of preexisting IHH in pregnancy tends to ocur 20 weeks of pregnancy, reflecting the period of maximal weight gain.[72] Transient visual obscurations or dim outs and pulsatil tinnitus are predominant symptoms.

Papilledema is important finding for the diagnosis.

[73] Visual loss develops in 10%–20% of patients. Visual outcome is similar to non-pregnant state.[74] In suspected IIH patients, non-contrast Brain MRI and brain MR venography should be performed to exclude mimics, including mass lesions and cerebral venous thrombosis.[75] The next step is a lumbar puncture to check the opening pressure. After diagnosis of IIH, a referral to a neuro-ophthalmologist is warranted for close visual field monitoring. In pregnancy, controlled weight gain rather than weight loss is recommended. Medications such as acetazol158

In the brain, the posterior circulation has less ability to autoregulate and is preferentially affected. Typically, brain imaging demonstrates posterior reversible encephalopathy syndrome, with bilateral white matter abnormalities, suggesting edema in the posterior regions of the cerebral hemispheres, but the changes may involve other cerebral areas including the brainstem or the cerebellum.[81] The diagnostic criteria for preeclampsia/eclampsia are listed by ICHD-III.[2] The management of pre-eclampsia/eclampsia includes: delivery of the baby, rapid control of blood pressure and seizure control. Hypertension OCTOBER 2018

Pregnancy and lactation

is usually managed with intravenous labetalol (beta blocker) or an intravenous calcium channel blocker such as nicardipine.[82] Seizures are safely treated by intravenous magnesium. In refractory cases or in status epilepticus, additional antiepileptic medications should be introduced. Fortunately, epilepsy is a rare consequence of pre-eclampsia/eclampsia, and longterm antiepileptic medications are generally not necessary.[83] c) Cerebral venous thrombosis Cerebral venous thrombosis is an uncommon cause of stroke, accounting for only 0.5%–1% of all strokes.

[84] However pregnancy is a hypercoagulable state.

This is a normal physiological adaptation to decrease the risk of blood loss at the time of delivery. There are increased levels of multiple procoagulant factors including factors II, VII, VIII, IX, X, XII and XIII, and a decrease in the anticoagulant proteins antithrombin III and protein S, as well as an acquired resistance to activated protein C. This prothrombotic state lasts up to 6 weeks post partum.[85] Two per cent of pregnancy-related strokes are attributed to cerebral venous thrombosis. The last trimester through the postpartum period has an increased risk. Additional risk factors include dehydration, caesarean section and older age.[86] Headache is the most common presentation of cerebral venous thrombosis. The headache may be of a thunderclap onset or more commonly may mimic IIH with gradual onset and features concerning for elevated intracranial pressure—worse on awakening with associated visual obscurations, papilloedema and sixth nerve palsy. Focal neurological signs or seizures may result from venous infarction or haemorrhage. Clues to the diagnosis of cerebral venous thrombosis include bilateral hemispheric involvement, haemorrhage in unusual locations and progressive symptoms.[87] Patients who have haemorrhage, stroke and involvement of the deep venous sinuses have the worst prognosis.[88] On MRI, venous sinus thrombosis can be seen directly as thrombus with signal characteristics appropriate to the time since onset (T1-isodense and T2-hypodense when acute, with T1 becoming hyperintense followed by T2 becoming hyperintense so that the thrombus is bright on both T1- and T2-weighted images at the late subacute phase). MR venography can also show the thrombosis as a filling defect, which does not require a contrast imaging.[89] After the diagnosis of OCTOBER 2018

cerebral venous thrombosis has been confirmed, other causes of a hypercoagulable states also needs to be excluded. Laboratory studies should include, full blood count, chemistry panel, prothrombin time and activated partial thromboplastin time. Testing for prothrombotic conditions, including protein C, protein S, antithrombin deficiency, antiphospholipid syndrome, prothrombin G20210A mutation, and factor V Leiden, are needed for the decision of longterm management. Testing for protein C, protein S and antithrombin deficiency is generally indicated 2–4 weeks following completion of anticoagulation.

[87] Treatment is characterized by full heparin anticoagulation during the acute phase of cerebral venous thrombosis whether hemorrhage is present or not, and then a period of approximately 3 to 6 months of ambulatory anticoagulation.[89] Vitamin K antagonists, such as warfarin, are associated with fetal embryopathy and bleeding in the fetus; therefore, they are contraindicated in pregnancy. During pregnancy, low molecular weight heparin is the anticoagulant of choice. Postpartum low molecular weight heparin or a vitamin K antagonist can be used with a target international normalised ratio (INR) of 2.0–3.0.[90] d) Reversible cerebral vasoconstriction syndrome (RCVS) Reversible cerebral vasoconstriction syndrome (RCVS) is recently described combinations of clinical and radiological features: sudden, severe (“thunderclap”) headache; transient, multifocal, segmental vasoconstriction of cerebral arteries lasting several weeks to months; and focal neurological symptoms, sometimes with stroke.[91] RCVS is commonly reported in post-partum period, usually within a week after delivery.[92] The exact pathophysiological process resulting in RCVS is unknown.[93] Brain MRI or CT angiography, may be normal in the first days of the process.[92] There is no consessus on the optimal treatment of RVCS.[93] Symptomatic pain relief and eliminating precipitating factors are recommended. Calcium channel blockers are often used to treat RCVS. The use of steroids are not recomended by most authorities.[94] e) Pituitary apoplexy Pituitary apoplexy is a rare but potentially life-threatening condition. It is due to haemorrhagic infarction of the pituitary gland and is more common with an 159

A RI PAIN underlying pituitary adenoma. Acute changes in blood pressure, and stimulation of the gland by increased estrogen levels such as in pregnancy and coagulopathy are associated with pituitary apoplexy.

[95] Headache is the most common presentation and may be severe, thunderclap in nature. The headache is often referred retro-orbitally due to irritation of the first division of the trigeminal nerve. Other features of pituitary apoplexy include changes in visual acuity and visual fields, change in mental status from a mild encephalopathy to coma, cranial nerve III, IV, and V involvements.[6] Pituitary apoplexy is a neuroendocrine emergency due to hormonal insufficiency. There are often multiple hormonal deficiencies including: adrenocorticotropic hormone, growth hormone, thyroid hormone and hypogonadotropic deficiency.[95] The most urgent issue is to assess for fluid and serum electrolyte imbalance and to replace corticosteroids. The role for surgery is controversial and generally restricted to patients with significant neurological impairment.[6] f) Subarachnoid hemorrhage (SAH) Subarachnoid hemorrhage (SAH) refers to extravasation of blood into the subarachnoid space between the piamater and arachnoid membranes. Subarachnoid hemorrhage without a preceding trauma is caused by the rupture of an intracranial aneurysm in 80% of cases; other causes include vascular malformations and vasculitis.[96] The etiologies of SAH in pregnancy are diverse and include ruptured saccular and mycotic aneurysms, ruptured arteriovenous malformations, intracranial venous thrombosis, pregnancy-induced hypertension leading to pial vessel rupture, intracranial vertebral artery dissection, Moyamoya disease, posterior reversible encephalopathy syndrome, and postpartum angiopathy, which is a form of the reversible cerebral vasoconstriction syndrome.[97] Mostly, pregnancyrelated SAH are caused by aneurysmal rupture or bleeding from a vascular malformation.[98] Due to the increased vascular stress from expanded circulating blood volume and increased cardiac output, aneurysmal SAH is most commonly reported in the third trimester, and up to 6 weeks postpartum period.[99] Treatment include airway evaluation, blood pressure reduction, control of seizures and definitive treatment of the aneurysm once demonstrated.[100]

160

g) Postdural puncture headache (PDPH) Parturients have approximately a 1.5% risk of an accidental dural puncture with epidural anaesthesia.

Of these, about half will result in postdural puncture headache.[101] Headache occurrs within 5 days of a lumbar puncture, related with cerebrospinal fluid (CSF) leakage through the dural puncture. It is usually but not invariably orthostatic. Headache that significantly worsens soon after sitting upright or standing and/or improves after lying horizontally, accompanied by neck stiffness and/or subjective hearing symptoms.[2] Evidence of CSF leakage on contrats enhanced Brain MRI confirms the diagnosis.

Independent risk factors post-dural puncture headache have recently been demonstrated: female gender, age between 31 and 50 years, a previous history of post-dural puncture headache and orientation of the needle bevel perpendicular to the long axis of the spinal column at the time of the dural puncture.[6] The headache location, severity and description are not helpful diagnostic features. Exercise and Valsalva manoeuvres can aggravate postdural puncture headache. Other symptoms can include nausea (73%) and dizziness (60%), horizontal diplopia, altered hearing and tinnitus, neck pain/stiffness and uncommonly visual field deficits.[102] Most women with PDPH improve spontaneously with bed rest, fluid intake, simple analgesics and caffeine.

[103] Some may require parenteral treatment. In refractory cases, single epidural blood patch is highly effective with up to 90% response rate. Fever, infection on the back, coagulopathy and patient refusal are contraindications for epidural blood patch[6] In these cases, regional anesthetics (eg, occipital nerve block, sphenopalatine ganglion [SPG] nerve block) or alternative treatments (eg, acupuncture) may be offered.[104] Dural strech induced by low CSF volume may activate the trigemnal nucleus caudalis (TNC) causing increased activity in the trigeminal and greater occipital nerves. Greater occipital nerve block (GONB) results in interruption of pain transmission via occipital nerves to the TNC. The temporary reduction in afferent input to the TNC may cause a ‘winding down’ of the central sensitization, which provokes the headache.[105,106] The transnasal sphenopalatine ganglion block (SPGB) is a low-risk, noninvasive technique that is easily performed and could potentially be beneficial in the treatment of PDPH.[107] SPGB blocks the parasympathetic flow OCTOBER 2018

Pregnancy and lactation

to the cerebral vasculature through the sphenopalatine ganglion, allowing the cerebral vessels to return to normal diameter and thus relieving the headache.[108] Conflict-of-interest issues regarding the authorship or article: None declared.

Peer-rewiew: Externally peer-reviewed.

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Agri 2018;30(4):165-170

doi: 10.5505/agri.2018.45477

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ORIGINAL ARTICLE

Effect of lifestyle interventions on diabetic peripheral neuropathy in patients with type 2 diabetes, result of a randomized clinical trial Tip 2 diyabetli hastalarda yaşam tarzı müdahalelerinin diyabetik periferik nöropati şiddeti üzerine etkisi, randomize klinik çalışmanın sonucu Haleh GHAVAMI,

Moloud RADFAR,

Soraya SOHEILY,

Shams Aldin SHAMSI,

Hamid Reza KHALKHALI

Summary Objectives: Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of diabetes leading to great morbidity and resulting in a huge economic burden for diabetes care. Over half of people with diabetes develop neuropathy. Also, DPN is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. The aim of this study was evaluating the effects of lifestyle interventions on diabetic neuropathy severity in diabetes type 2 outpatients.

Methods: This clinical trial conducted on 74 patients with DPN that divided with random allocation into intervention or control group. The lifestyle interventions applied in the intervention group beginning four educational sessions on lifestyle that emphasize strategies for lowering blood sugar, increasing physical activity, promoting weight loss, prudent diet, and foot caring. Each session was lasted for1.5 hour. Then patients followed for 12 weeks. During this period, they received counseling on mentioned lifestyle interventions. DPN severity in both groups measured using modified Toronto Clinical Neuropathy Score (mTCNS) at the beginning of study and at the end of counseling for 12 weeks.

Results: Comparing differences of mean of DNP severity before and after lifestyle intervention between two groups of study, there was a significant difference (p<0.001). DNP severity in control group had not any change or it increased in some participants, but DNP decreased in intervention group, after applying lifestyle intervention.

Conclusion: Lifestyle interventions can contribute to reducing DPN severity, and consequently decreasing neuropathic pain.

Keywords: DPN severity; lifestyle interventions; modified Toronto Clinical Neuropathy Score (mTCNS).

Özet Amaç: Diyabetik periferik nöropati (DPN) diyabetin en sık karşılaştığı ve sıkıntılı bir komplikasyondur ve büyük bir morbiditeye yol açar ve diyabet bakımı için büyük bir ekonomik yük oluşturur. Nöropati diyabetli kişilerin yarısından fazlasında gelişir.

Ayrıca, ağrı, duyusal kayıp, yürüme instabilitesi, düşme ile ilişkili yaralanma, ayak ülseri ve amputasyon nedeniyle, DPN yaşam kalitesinin azalmasının temel nedenidir. Bu çalışmanın amacı, ayakta tedavi edilen diyabet tip 2 hastalarda; yaşam tarzı müdahalelerinin diyabetik nöropati şiddeti üzerine etkilerini değerlendirmekti.

Gereç ve Yöntem: Bu klinik çalışma, DPN’si olan ve rastgele yöntemi ile; müdahale ya da kontrol grubuna ayrılanan, 74 hasta üzerinde gerçekleştirildi.Kan şekerini düşürmek, fiziksel aktiviteyi arttırmak, kilo kaybını teşvik etmek, ihtiyatlı beslenme ve ayak bakımı için stratejileri vurgulayan yaşam tarzı üzerine dört eğitim oturumu ile başlanan yaşam tarzı müdahaleleri müdahale grubunda uygulanmaya başladı. Her eğitim seansi 1.5 saat sürdü. Daha sonra hastalar 12 hafta boyunca takip edildiler ve bu dönemde yaşam tarzı müdahaleleri konusunda danışmanlık aldılar. Her iki grupta da DPN`nin şiddeti, çalışmanın başlangıcında, ve 12 haftalık danışmanlık sonunda modifiye Toronto Clinical Neuropathy Score (mTCNS) kullanılarak ölçüldü.

Bulgular: Çalışma gruplarının DNP şiddeti, yaşam tarzı müdahaleleri öncesi ve sonrası, ortalamaları arasındaki farklılıkların karşılaştırıldığında anlamlı bir fark bulundu (p<0.001).Yaşam tarzı müdahaleleri uygulandıktan sonar kontrol grubunun DNP şiddeti herhangi bir değişiklik göstermemiştir ya da bazı katılımcılarda DNP şiddeti artmıştır, ancak yaşam tarzı müdahaleleri uygulandıktan sonra müdahale grubunda DNP azalmıştır.

Sonuç: Yaşam tarzı müdahaleleri, DPN şiddetinin azaltılmasında ve sonuç olarak nöropatik ağrının azaltılmasında katkıda bulunabilir.

Anahtar sözcükler: DPN şiddeti; yaşam tarzı müdahaleleri; modifiye Toronto Klinik Nöropati Skoru (mTCNS).

Urmia University of Medical Sciences Faculty of Nursing and Midwifery, Urmia, Iran Submitted (Başvuru tarihi) 22.06.2018 Accepted after revision (Düzeltme sonrası kabul tarihi) 20.09.2018 Available online date (Online yayımlanma tarihi) 24.10.2018

Correspondence: Dr. Shams Aldin Shamsi. Nursing and Midwifery Faculty of Urmia University of Medical Sciences, Pardis Nazlou, 11 km of Nazlou Road Urmia, Iran.

Phone: +989143416092 e-mail: ghavami.h@umsu.ac.ir © 2018 Turkish Society of Algology

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Introduction Diabetes mellitus (DM) is one of the largest global public health emergencies of the 21st century. Approximately 415 million adults have DM and by 2040 this number will rise to 642 million.[1] Diabetic neuropathies are a heterogeneous group of disorders of varying etiology and clinical presentation. Diabetic neuropathy with a prevalence of approximately 60% is the most common form of neuropathy in developed countries and may affect about half of all patients with diabetes mellitus, contributing to substantial morbidity and mortality and resulting in a huge economic burden. The most common form is symmetrical diabetic peripheral neuropathy (DPN), which mainly affects the lower extremities and is a major cause of morbidity because of its effects on risk for subsequent ulcers, amputation and disability.[1–3] Diabetic neuropathy (DN) severely decreases patients’ quality of life and the quality of diabetes self-management and, in consequence, is worsening the prognosis of other diabetes complications.

[1] Diabetic peripheral neuropathy (DPN) was defined by the presence of at least two of the following three characteristics: (a) pain, paresthesia, or numbness; (b) absence of tendon reflexes; (c) abnormal malleoli vibration perception threshold.[4] Studies show that improved glycemic control improves nerve function in diabetic patients.[5–9] In addition, there is good evidence that intensive glycemic control reduces the risk of developing diabetic neuropathy in patients with type 1diabetes and may reduce the risk in patients with type 2 diabetes.[9–11] Unhealthy behaviors (such as comfort eating, poor diet choices, smoking, and inactivity) implicated in up to 40% of premature deaths in the U.S. and contribute to persistent disparities in health. On the other hand, healthy lifestyles are broad and potentially unobservable orientations that organize patterns of behaviors that derive from knowledge and norms about what constitutes healthy, stress relieving, or pleasurable behaviors.[12] The aim of this study was to determine the effect of lifestyle interventions (based on; lowering blood sugar, increasing physical activity, lowering weight, and proper caring of feet) on the severity of diabetic peripheral neuropathy in patients with type 2 diabetes. We hypothesized that this lifestyle interven166

tions program would reduce the severity of diabetic peripheral neuropathy progression in the intervention group.

Material and methods Design This study is a randomized clinical trial with a pre– post-test design. This study obtained the approval from the Research Ethics Committee of Urmia University of Medical Sciences (Reference No. IR.UMSU. REC.1393.11). Patients who met the eligibility criteria invited to participate. Eligible participants were systematically randomized by computer into the control or lifestyle intervention group. Then, participants received the introductory instructional guide and all participants signed an informed-consent form (Fig. 1).

Participant recruitment and eligibility criteria Over a 12 months period study participants were recruited using face-to-face strategy. Eligibility criteria included; Adults (≥18 years and older) with diabetic neuropathy, without any ulcer on their foot, and living in Urmia. Patients were excluded if they had known non-diabetic causes of neuropathy (for example, vitamin deficiencies, uremia, thyroid disease, lumbar or cervical radiculopathy, inflammatory neuropathy or presence of alcoholism). The sample size goal of 80 (half in each treatment group) was derived a priori with G*Power software version 3.1.9.2 (Universitat Kiel, Germany) for analysis of covariance with an effect size of 0.25, p≤0.05, and 95% power.

During the study three participants from each group discontinued their participation.

Instruments Demographic information questionnaire, and the modified Toronto Clinical Neuropathy Score (mTCNS) used for data collection. For measuring the severity of neuropathy, participants were allowed a 10-minute acclimatization period in constant room temperature (24±1°C) after they had removed their socks and shoes.

The Toronto Clinical Neuropathy Score (TCNS) is a sensitive scoring system used to diagnose diabetic neuropathy, and to measure changes in such early diabetic sensorimotor polyneuropathy (DSP) pathophysiology. TCNS can be used as an inexpensive bedside screening tool.[13,14] The TCNS was modified (into OCTOBER 2018

Effect of lifestyle interventions on diabetic peripheral neuropathy

Table 1. Comparison the severity of DPN between two groups of study before and after lifestyle intervention Neuropathy score Control group Intervention group

Results of independent T test

Mean SD Mean SD

Before intervention After intervention Difference of before- after

9.51 2.7 11.9 3 10.41 2.6 6.81 2.2 0.89 0.73 -5.1 1.2

p<0.001 p<0.001 p<0.001

SD: Standard deviation.

the mTCNS) to better capture a categorical scale of simple sensory tests, which are better representative of the early dysfunction in DSP, and to eliminate reflex testing, which represent the late-stage pathophysiology of DSP, are highly variable between raters, age dependent and heavily weighted in the TCNS. The mTCNS, a clinical score with higher face validity for tracking mild to moderate DSP, has sufficient reliability and validity relative to its precursor TCNS for use in clinical research.[13] mTCNS consists of graded symptoms (foot pain, numbness, tingling, weakness, ataxia and upper limb symptoms) and a sensory test (pinprick, temperature, light touch, vibration and position sense) score associated with DPN in the judgment of the examiner. The scale varies from 0 (no signs or symptoms) to 33 (maximal symptoms and signs).[15] Intervention The lifestyle interventions applied in the intervention group beginning 4 educational sessions on lifestyle that emphasize strategies for; lowering blood sugar, increasing physical activity, promoting weight loss, and feet caring. Each session was lasted for1.5 hour. Then patients followed for 12 weeks. During this period, they received individualized counseling on mentioned lifestyle interventions. All participants of intervention group received individualized counseling with goals of reducing weight by 7%, increasing weekly exercise to 150 min, and proper daily feet caring. They received dietary counseling based on their preferences individually, too. Participants in the control group received their routine care and education, without any more education or consulting on lifestyle. Diabetic neuropathy symptom severity in both groups measured using Modified Toronto Clinical Neuropathy Score (mTCNS) at the beginning of study and at the end of counseling for 12 weeks.

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Results Demographic variables of participants In the present study, results showed that 81.1% of participants in the control group, and 70.3% of intervention group were female. 29.7% of participants in control group, and 35.1% in intervention group were illiterate. In the control group, the mean and standard deviation of age were (47.3±10.8) and in the intervention group, the mean of age were (49.38±7.9) and there was no significant difference in age of participants between the two groups of study (p=0.29). In the control group, the mean and standard deviation of diabetes duration is (16.89± 5.4) and in the intervention group, the mean and standard deviation of diabetes duration is (19±4.6) and there was no significant difference in duration of diabetes between the two groups of study (p=0.07). A higher proportion of participants in both groups of study were married.

Intervention impact measurement Based on the results of independent t-test, the mean of DPN severity was statistically significant before intervention between two groups of study, but considering before and after differences of the mean of DPN severity, there was significantly decrease in DPN severity of intervention group after the lifestyle intervention (p<0.001) (Table 1).

Before and after differences of the mean of DPN severity in the intervention group is bigger than it in the control group (Table 1).

In the intervention group, the severity of neuropathy decreased from; severe to moderate, and from moderate to mild/ without neuropathy symptom, but in the control group, the severity of neuropathy did not change or progressed to a higher levels (Tables 2, 3).

Comparing the severity of DPN in the intervention 167

A RI PAIN Table 2. Comparison the severity of DPN in the intervention group before and after lifestyle intervention

After inter.

Before inter.

Mild neuropathy Moderate neuropathy Severe neuropathy Total

Absence of neuropathy symptoms

Mild neuropathy

Moderate neuropathy

n

n

n

%

%

%

Severe neuropathy n

%

Total

n

%

6 100 0 0 0 0 0 0 6 100 5 38.5 8 61.5 0 0 0 0 13 100 0 0 10 55.6 8 4.44 0 0 18 100 11 29.7 18 48.6 8 2.6 0 0 37 100

DPN: Diabetic peripheral neuropathy; Inter.: Intervention.

Table 3. Comparison the severity of DPN in the control group before and after lifestyle intervention

After inter.

Before inter.

Mild neuropathy Moderate neuropathy Severe neuropathy Total

Absence of neuropathy symptoms

Mild neuropathy

Moderate neuropathy

n

n

n

%

%

%

Severe neuropathy n

%

Total

n

%

0 0 7 46.7 8 53.3 0 0 15 100 0 0 0 0 17 100 0 0 17 100 0 0 0 0 0 0 5 100 5 100 0 0 7 18.9 25 67.6 5 13.5 37 100

DPN: Diabetic peripheral neuropathy; Inter.: Intervention.

group, before and after lifestyle intervention presented in the Table 2; the severity of neuropathy decreased; from the severe to moderate, and from moderate level to mild or to absence of neuropathy symptom level.

For example, before the intervention, there were 13 participants with moderate neuropathy, that 5 patients had not any neuropathy symptom (absent of neuropathy) and 8 of them had mild neuropathy, after the end of lifestyle intervention (Table 2).

Comparing the severity of DPN in the control group, before and after lifestyle intervention presented in the Table 3; the severity of neuropathy had not any change or it increased to a higher level of severity after the end of lifestyle intervention. For example, before the intervention, there were 15 participants with mild neuropathy, that DPN severity in 8 of them reached to moderate level and DPN severity in the rest of 7 patients had not any change after the end of lifestyle intervention (Table 3).

Discussion Poor lifestyle choices, such as smoking, poor diet, lack 168

of physical activity and inadequate relief of chronic stress are key contributors in the development and progression of preventable chronic diseases, including type 2 diabetes mellitus. Even though physicians encourage healthy lifestyle to help prevent or manage many chronic medical conditions, many patients are inadequately prepared to either start or maintain these appropriate, healthy changes.

This randomized controlled trial study was designed to clarify the effectiveness of Lifestyle Interventions on the severity of diabetic peripheral neuropathy in patients with type 2 diabetes. Our study findings support our priori hypothesis that lifestyle interventions with emphasize strategies for lowering blood sugar, increasing physical activity, promoting weight loss, prudent diet, and foot caring, would contribute to reducing DPN severity.

Our results are consistent with the study findings of Smit et al.[4] on lifestyle intervention for pre-diabetic neuropathy in 2006, indicated; diet and exercise counseling for patients with impaired glucose tolerance results in cutaneous re-innervation and imOCTOBER 2018

Effect of lifestyle interventions on diabetic peripheral neuropathy

Enrollment patients

Assessed for eligibility (n=100)

Excluded (n=20) â&#x20AC;˘ Not meeting inclusion criteria (n=18) â&#x20AC;˘ Refused to participate (n=2)

Allocation patients

Allocated to intervention (n=40) Received allocated intervention (n=40) Did not receive allocated intervention (give reasons) (n=0)

Allocated to control (n=40) Received Routine care (n=40) Did not receive allocated intervention (give reasons) (n=0)

Allocation care providers

Care providers (n=1), teams (n=1), centers (n=1) performing the intervention Number of patients treated by each care provider, team and center (median=40)

Care providers (n=1), teams (n=1), centers (n=1) performing the intervention Number of patients treated by each care provider, team and center (median=40)

Follow-up patients

Lost to follow-up (n=2) Reason: Moving to another city Discontinued intervention (n=1) Reason: Participant died

Lost to follow-up (n=1) Reason: moving to another city Discontinued intervention (n=2) Reason: the reluctance of their families to continue to participate in research

Analysis patients

Randomized (n=80)

Analysed (n=37) Excluded from analysis (give reasons) (n=0)

Analysed (n=37) Excluded from analysis (give reasons) (n=0)

Figure 1. Consort flow diagram.

proved pain. Also, Juster-Switlyk and Smit in 2016 suggested that; weight loss and exercise are helpful strategies for patients with neuropathy in the setting of both diabetes and pre-diabetes.[16] Also, our results is consistent with other studies which improvement in health status after lifestyle interventions have seen in their results such as; A) Study of Khanji et al.[17] on lifestyle advice and interventions for cardiovascular risk reduction, B) Study of Howells et al.[18] on the clinical impact of lifestyle interventions for the prevention of diabetes, C) Study of Kolb and Martin on Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes.[19] Limitations: This study had some limitations: 1) participants were enrolled only from one hospital; 2) relatively short intervention time. It is suggested that other multi centers studies with longer intervention time be conducted.

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Conclusion Findings of this study showed that, despite the high levels of neuropathic disorders among diabetic patients, using low cost and safe methods such as lifestyle interventions, can contribute in reducing severity of diabetic peripheral neuropathy, and enhancing comfort among these patients. Traditionally, neuropathic pain prompts physicians to prescribe drugs (usually gabapentin and pregabalin) for DPN pain[20] that may be associated with adverse effects, such as drug resistance, dependence and addiction. In this study, it demonstrated that lifestyle intervention would successfully contribute in reduction of DPN severity in patients with diabetic peripheral neuropathy.

Our findings have implications for clinical and policy decisions, as well as for the design for future studies with larger sample sizes and long period of time. In particular, our findings underscore the importance 169

A RI PAIN of healthy lifestyle in the management of diabetic patients with or at risk of diabetic peripheral neuropathy. Reduction in the severity of DPN following lifestyle intervention in this study can contribute in enhancing quality of life regarding DPN is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation.

Acknowledgments This article extracted from a master’s thesis. The researchers would like to express their thanks to the study participants.

Conflict-of-interest issues regarding the authorship or article: None declared.

Peer-reiew: Externally peer-reviewed.

References 1. Timar B, Timar R, Gaiță L, Oancea C, Levai C, Lungeanu D. The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study. PLoS One 2016;11(4):e0154654.

2. Vinik A, Casellini C, Nevoret ML. Diabetic Neuropathies.

Endotext - NCBI Bookshelf – NIH. Last Update: February 5, 2018. Available at: https://www.ncbi.nlm.nih.gov/books/ NBK279175/. Accessed Jun 11, 2018.

3. Look AHEAD Research Group. Effects of a long-term lifestyle modification programme on peripheral neuropathy in overweight or obese adults with type 2diabetes: the Look AHEAD study. Diabetologia 2017;60(6):980–8.

4. Smith AG, Russell J, Feldman EL, Goldstein J, Peltier A, Smith S, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care 2006;29(6):1294–9.

5. Graf RJ, Halter JB, Pfeifer MA, Halar E, Brozovich F, Porte D Jr. Glycemic control and nerve conduction abnormalities in non-insulin-dependent diabetic subjects. Ann Intern Med 1981;94(3):307–11.

6. Holman RR, Dornan TL, Mayon-White V, Howard-Williams J, Orde-Peckar C, Jenkins L, et al. Prevention of deterioration of renal and sensory-nerve function by more intensive management of insulin-dependent diabetic patients. A two-year randomised prospective study. Lancet

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1983;1(8318):204–8.

7. Pietri A, Ehle AL, Raskin P. Changes in nerve conduction velocity after six weeks of glucoregulation with portable insulin infusion pumps. Diabetes 1980;29(8):668–71.

8. Kuwabara S, Ogawara K, Harrori T, Suzuki Y, Hashimoto N. The acute effects of glycemic control on axonal excitability in humandiabetic nerves. Intern Med 2002;41(5):360–5.

9. Feldman EL. Pathogenesis and prevention of diabetic polyneuropathy. Available at: https://www.uptodate. com/contents/pathogenesis-and-prevention-of-diabeticpolyneuropathy Accessed: Oct 30, 2018.

10. Callaghan BC, Hur J, Feldman EL. Diabetic neuropathy: one disease or two? Curr Opin Neurol 2012;25(5):536–41.

11. Peltier A, Goutman SA, Callaghan BC. Painful diabetic neuropathy. BMJ 2014;348:g1799.

12. Saint Onge JM, Krueger PM. Health Lifestyle Behaviors among U.S. Adults. SSM Popul Health 2017;3:89–98.

13. Bril V, Tomioka S, Buchanan RA, Perkins BA, mTCNS Study Group. Reliability and validity of the modified Toronto Clinical NeuropathyScore in diabetic sensorimotor polyneuropathy. Diabet Med 2009;26(3):240–6.

14. Udayashankar D, Premraj SS, Mayilananthi K, Naragon V. Applicability of Toronto Clinical Neuropathy Scoring and its Correlation with Diabetic Peripheral Neuropathy: A Prospective Cross-sectional Study. J Clin Diagn Res 2017;11(12):OC10–3.

15. Yoshioka K, Okada H. Useful application of the Neuropad test for assessment of diabetic polyneuropathy. Intern Med 2012;51(23):3241–5.

16. Juster-Switlyk K, Smith AG. Updates in diabetic peripheral neuropathy. F1000Res 2016;5. pii: F1000 Faculty Rev-738.

17. Khanji MY, van Waardhuizen CN, Bicalho VVS, Ferket BS, Hunink MGM, Petersen SE. Lifestyle advice and interventions for cardiovascular risk reduction: A systematic review of guidelines. Int J Cardiol 2018;263:142–51.

18. Howells L, Musaddaq B, McKay AJ, Majeed A. Clinical impact of lifestyle interventions for the prevention of diabetes: an overview of systematic reviews. BMJ Open 2016;6(12):e013806.

19. Kolb H, Martin S. Environmental/lifestyle factors in the pathogenesis and preventionof type 2 diabetes. BMC Med 2017;15(1):131.

20. Goodman CW, Brett AS. Gabapentin and Pregabalin for Pain - Is Increased Prescribing a Cause for Concern? N Engl J Med 2017 377(5):411–4.

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Agri 2018;30(4):171-178

doi: 10.5505/agri.2018.60251

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ORIGINAL ARTICLE

Ultrasound guided superficial cervical plexus block versus greater auricular nerve block for postoperative tympanomastoid surgery pain: A prospective, randomized, single blind study Ultrason eşliğinde uygulanan büyük aurikuler sinir bloğu ve yüzeyel servikal pleksus blokajının timpanomastoid cerrahisi sonrası analjezik etkinliklerinin karşılaştırılması: Prospektif, randomize, tek kör çalışma Korgün ÖKMEN,1

Burcu METIN ÖKMEN2

Summary Objectives: The aim of the study was to investigate the effect of ultrasound guided superficial cervical plexus (SCP) block versus greater auricular nerve (GAN) block for on postoperative tympanomastoid surgery analgesia.

Methods: In this prospective, randomized, single-blind study, a total of 50 patients aged between 25 and 70 years, those who were in the American Society of Anesthesiologists I-II class and underwent tympanomastoid surgery were included in the study. Patients were randomized to either Group Y: intravenous patient-controlled analgesia tramadol (IV PCA) + SCP block; n=25 and Group G: IV PCA + GAN block; n=25. Postoperative pain was evaluated at the 2nd, 6th, 12nd, and 24th hours using the Visual Analogue Scale (VAS) and postoperative 6th, 12nd, and 24th hour follow-up results were evaluated to identify the quantity of tramadol use.

Results: The VAS scores at all measures time were found to be no statistically significant difference between groups (p>0.05).

The amounts of PCA tramadol consumption at all measures time were significantly lower in Group Y than in Group G (p<0.05).

Conclusion: The results of this study have indicated that SCP and GAN blocks can be used for pain control after tympanomastoid surgery. We believe that the only disadvantage of SCP block application with lower amounts of tramadol use is that the complications that can occur are more serious than those that can occur in GAN application.

Keywords: Great auricular nerve; nerve block; superficial cervical plexus; tympanomastoid surgery; ultrasonography.

Özet Amaç: Bu çalışmanın amacı, postoperatif timpanomastoid cerrahisi analjezisi için ultrasonografi (US) eşliğinde yüzeyel servikal pleksus (YSP) blok ile büyük auriküler sinir (BAS) bloğunun etkinliklerini karşılaştırmaktı.

Gereç ve Yöntem: Prospektif, randomize, tek kör çalışmada, Amerikan Anestezistler Derneği (ASA) I-II sınıfında olan ve timpanomastoid cerrahisi yapılan, 25-70 yaş arasındaki toplam 50 hasta çalışmaya dahil edildi. Hastalar Grup Y (n=25): intravenöz hasta kontrollü analjezik tramadol (IV PCA) + YSP bloğu ve Grup G (n=25): IV PCA + BAS bloğu olacak şekilde randomize edildi.

Ameliyat sonrası ağrı 2., 6., 12. ve 24. saatlerde Vizüel Analog Skala (VAS) ile ve postoperatif 6., 12. ve 24. saat izlem sonuçları, tramadol kullanımının miktarını belirlemek için değerlendirildi.

Bulgular: Bütün ölçüm zamanlarındaki VAS skorlarında gruplar arasında istatistiksel olarak anlamlı bir fark olmadığı bulundu (p>0.05). Tüm ölçüm zamanlarındaki PCA tramadol tüketim miktarları, Grup Y’de Grup G’ye göre anlamlı olarak daha düşüktü (p<0.05).

Sonuç: Bu çalışmanın sonuçları, timpanomastoid cerrahiden sonra ağrı kontrolü için YSP ve BAS bloklarının kullanılabileceğini göstermiştir. Daha düşük tramadol kullanılan YSP blokajının tek dezavantajının, oluşabilecek komplikasyonların BAS uygulamasında oluşabileceklerden daha ciddi olacağına inanıyoruz.

Anahtar sözcükler: Büyük aurikular sinir; sinir bloğu; yüzeyel servikal pleksus; timpanomastoid cerrahi; ultrasonografi.

Department of Anesthesiology and Reanimation, University of Health Sciences, Bursa Yüksekİhtisas Training and Research Hospital, Bursa, Turkey Department of Physical Medicine and Rehabilitation, University of Health Sciences, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey

1 2

Submitted (Başvuru tarihi) 05.02.2018 Accepted after revision (Düzeltme sonrası kabul tarihi) 20.09.2018 Available online date (Online yayımlanma tarihi) 25.10.2018

Correspondence: Dr. Korgün Ökmen. Sağlık Bilimleri Üniversitesi, Bursa Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Mimar Sinan Mah., Emniyet Cad., Yıldırım 16130, Bursa, Turkey Phone: +90 - 505 - 708 10 21 e-mail: korgunokmen@gmail.com © 2018 Turkish Society of Algology

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Introduction Tympanomastoid surgery is applied to remove the pathology that blocks the connection between the tympan (middle ear) and mastoid cells to heal the eradication of chronic otitis media infection and hearing function.[1,2] The surgical approach may include endoaural or transmeic, retroauricular (Wilde) and suprameatal (Lempert) methods.[2-4] NSAIDs, opioids and regional anesthesia techniques (Great auricular nerve (GAN) block, infiltration, Auriculo temporal nerve blockage) are often used for pain after postoperative tympanomastoid surgery. Regional anesthesia methods are commonly used in conjunction with general anesthesia for many surgical procedures. Regional anesthesia methods provide analgesia without sedation and longer postoperative analgesia.[5] In the postoperative pain, opioids can be used alone as analgesics. However, unwanted side effects such as nausea, vomiting, sedation and respiratory depression can be experienced.[6] They can increase the incidence of post-operative nausea and vomiting, commonly experienced by patients undergoing middle ear surgery, and this is further complicated by the use of intravenous (IV) opioids.[7,8] Peripheral nerve blocks can be combined with general anesthesia as an alternative to IV analgesics. Nerve blocks that can be applied pre-operatively and postoperatively can be used to reduce the need for opioids and for analgesia. GAN blockage from regional anesthesia methods has been used for auriculotemporal nerve (ATN) block and local anesthetic infiltration in tympanomastoid surgery.[9–12] The anatomical skin sensation of the ear area is provided by GAN, ATN and Lesser Occipital nerve. The superficial cervical plexus (SCP) arises from the anterior rami of the C1-C4 spinal nerves and the GAN composed of C2 and C3 nerve roots is its biggest branch. It provides sensory innervation of the anterior and posterior parts of the ear.[13,14] Lesser occipital nerve consisting of C2-C3 roots, such as GAN, also carries senses along the superior posterior neck, skin, and auricle.

[13,14] GAN block, which can be applied ultrasoundassisted or blindly, was used for tympanoplasty and pain palliation after tympanomastoidectomy.[9–11,15] Lesser occipital nerve block, another branch of SCP, was used blindly by infiltration method in addition to GAN for ear surgery.[12] However, we have not been able to find a study carried out with SCP block in the literature for ear surgery. In this work, we aimed to 172

determine the impact of GAN and SCP blockage we applied along with ultrasonography (USG) on the pain levels and analgesic consumption after tympanomastoid surgery applied posteriorly.

Material and Methods After the local ethics committee’s approval was obtained (Ethical number: 2011-KAEK-25 2016/21-02), 56 patients to be applied tympanomastoid surgery who accepted to participate in the study and whose written approvals were received were evaluated for eligibility in this prospective, randomized, singleblind study.

Patient selection Patients aged between 25 and 70 years, those who were in the American Society of Anesthesiologists (ASA) I-II class and underwent tympanomastoid and tympanoplasty surgery were included in the study.

Exclusion criteria were as follows: previous history of opioid use preoperatively, allergy to local anesthetics, uncontrolled arterial hypertension, uncontrolled Diabetes Mellitus, mental retardation, antidepressant use, metabolic disorders, the presence of any systemic infection.

Fifty patients who were eligible for the study were randomized using a random number table as Group Y (n=25) applied 10 ml of bupivacaine at 0.25% concentration with SCP Block in addition to IV tramadol infusion with patient controlled analgesia (PCA) and Group G (n=25) applied 5 ml of bupivacaine at 0.25% concentration with GAN Block in addition to IV tramadol infusion with PCA (Fig. 1).

Anesthetic management Patients undergoing hemodynamic monitoring (non-invasive blood pressure, ECG, SpO2) were applied NaCI infusion of 0.9% through IV before induction and preoxygenated with 100% Oxygen (O2).

Propofol (2-2.5 mg/kg) and rocuronium bromide (0.6 mg/kg) were used in through IV route in anesthesia management. Following the intubation with the appropriate size endotracheal tube, a mechanical ventilation was performed with 30–35 mmHg of end-tidal CO2 (ETCO2). During the anesthesia, 3 L/ min flow was applied into the mixture of Sevoflurane (1-2, 5%), 50% O2 and 50% air. Analgesic-requiring patient was treated with 1mcg / kg fentanyl.

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SCP versus GAN block in tympanomastoid surgery

Enrollment

Assessed for eligibility (n=56) Excluded (n=6) • Not meeting inclusion criteria (n=3) • Declined to participate (n=2) • Opioid use preoperatively (n=1) Randomized (n=50)

Allocation Grup Y IV PCA+SCP Block (%0.25 10 ml bupivacaine) • Allocated to intervention (n=25) • Received allocated intervention (n=25)

Follow-up (n=25) postoperative 2nd, 4th, 6th, 12nd, and 24th hours

Analysed (n=25)

Grup G IV PCA+GAN Block (%0.25 5 ml bupivacaine) • Allocated to intervention (n=25) • Received allocated intervention (n=25)

Follow-up

Analysis

Follow-up (n=25) postoperative 2nd, 4th, 6th, 12nd, and 24th hours

Analysed (n=25)

Figure 1. Consort diagram.

Before the operation is over and before the anesthesia has ended, tramadol infusion was initiated with IV PCA and SCP blocks and GAN blocks were applied with USG. After the operation was over, the recurarized patients were extirpated and then taken to the recovery room. Patients who were monitored for 30 minutes in the postoperative recovery unit were transferred to their services when their Ramsey sedation score (RSS) 2 and hemodynamic parameters were stable.

Analgesic treatment Group Y and Group G were applied tramadol with IV PCA. 4 mg/mL tramadol solution was added into the 100 mL of normal saline (a total of 400 mg tramadol).

PCA settings: 5 ml mid-bolus dose and 20 min fixed period. The maximum daily dose was adjusted to be 400 mg.

Block applications For both block applications, injection technique and 22 gauge sonovisible peripheral nerve block needle were used. At the end of the block applications operation, the skin incision was closed and in the supine position, the patient’s head was turned to the opposite side of the block to be applied and it was applied in this position. The area was disinfected (povidone iodine). It was then placed in a transverse position with an 18-Hz Linear USG probe (Esaote MyLab 30 OCTOBER 2018

Gevova-Italia) at the level of thyroid cartilage in the neck lateral wall and at the midpoint of the sternocloidomastoid muscle (SCM).

For SCP block, the probe was shifted posteriorly and the prevertebral fascia and SCP (in the form of small hypoechoic nodules) were imaged under the SCM muscle.[16] Negative aspiration followed by injection of 1 mL bupivacaine to confirm the area was applied.

Then in 10 mL of bupivacaine (0.25% concentration) was injected under the prevertebral fascia (Fig. 2).

For GAN block, the probe was moved in superior and inferior directions and a small round hypoechoic nerve was detected at the lateral border of the SCM muscle. 5 ml of bupivacaine at 0.25% concentration was injected to surround the great auricular nerve (Fig. 3).

When both groups were VAS> 5, 1 g paracetamol was planned to be given at intervals of up to 8 hours, 3 times at most, for the analgesic requirement of the patients in the group.

Outcome measures Primary measures: Results related to the VAS score (postoperative, 2nd, 4th, 6th, 12nd, and 24th) and consumption of Tramadol (6th, 12nd, and 24th) were examined.

173

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(b)

Figure 2. Superficial cervical plexus block. (a) Arrows are showing superficial cervical plexus. (b) After superficial cervical plexus block.

Arrows are showing needle. SCM: sternocloidomastoid muscle. (a)

(b)

Figure 3. Great auricular nerve block. (a) White circle :Great auricular nerve. (b) After great auricular nerve block. Arrow are showing neddle. SCM: sternocloidomastoid muscle; White circle: Great auricular nerve+local anesthesic.

Secondary measures: Side effects (nausea and vomiting, hypotension), additional analgesic requirement, and Ramsey sedation scores (RSS) were recorded. Ramsey Sedation Score (RSS) ≥5 score was considered excessive sedation and the lock duration in PCA was increased to 40 minutes. Nausea and vomiting complaints were assessed by nauseavomiting score (NVS) (1. no nausea, 2. mild nausea, 3. severe nausea, 4. vomiting) and antiemetic medication was applied on NVS 3. Mean arterial pressure (MAP) below 60 mgHg was considered hypotension and treated.

Statistical analysis IBM SPSS 22.0 statistical package program was used to analyze the data. Chi-Square (χ2) test was used in the comparison of descriptive statistical methods as well as in qualitative data. Shapiro-Wilk test used for normality (it was found out that the data did not show normal distribution). The Mann-Whitney U test was used in the comparison of VAS scores and tramadol consumption between the groups. Probability (P) values smaller than α=0.05 were considered 174

significant and pointed to a difference between the groups.The main outcome measure of this study was a 30% reduction in opioid group’s VAS scores at postoperative 4 hour.[12] For a study power of 90% (α=0.05), the required sample size per group was calculated to be 23, for a total of 46 patients. We included 25 patients in each group to secure patients dropouts for any reason.

Results The present study was completed with a total of 50 patients (Group Y; n=25 and Group G; n=25) (Figure 1).There was no statistically significant difference between the groups in terms of gender, age, body mass index (BMI), operation indications and operation durations (p>0.05) (Table 1).There was no statistically significant difference between both two groups in terms of VAS scores in all postoperative times (p>0.05). Tramadol consumption levels were found to be statistically significantly higher in Group G at all measurement times (p<0.05) (Table 2). There was no statistically significant difference between OCTOBER 2018

SCP versus GAN block in tympanomastoid surgery

Table 1. Demographic characteristics of the patients (Mean±SD)

Group G (n=25)

Group Y (n=25)

p

Gender Female/Male (%) Age (year) Height (cm) Weight (kg) Indications for surgery Tympanomastoidectomy

Tympanoplasty

18/7 (72%/28%) 34.40±9.20 165.92±6.40 71.20±6.10 20 (80%) 5 (20%)

20/5 (80%/20%) 33.80±8.25 162.50±7.90 70.50±8.50 19 (76%) 6 (24%)

0.399 0.907 0.870 0.830 0.595

SD: Standard deviation; Group Y: Intravenous patient-controlled analgesia contramal (IV PCA)+ superficial cervical plexus block (SCPB) (0.25% 10 ml bupivacaine); Group G: IV PCA+ GAN (0.25% 5 ml bupivacaine).

Table 2. Comparison of VAS scores between groups (Mean±SD)

Post-operative

2nd hour

Group G (n=25) Group Y (n=25) P

3.36±0.70 3.50±1.02 0.636

6th hour

12nd hour

24th hour

2.32±0.90 2.08±1.03 0.371

2.00±0.70 1.80±0.70 0.315

47.70±11.40 36.22±9.01 0.001

62.40±16.70 45.50±15.30 0.003

VAS

3.28±0.79 3.12±0.92 0.403

2.80±0.57 2.68±0.74 0.677

Tramadol consumption (mg) Group G (n=25) Group Y (n=25) P

34.80±8.50 26.20±5.35 0.002

SD: Standard deviation; VAS: Visual Analogue Scale; Group Y: Intravenous patient-controlled analgesia contramal (IV PCA)+ superficial cervical plexus block (SCPB) (0.25% 10 ml bupivacaine); Group G: IV PCA+ GAN (0.25% 5 ml bupivacaine).

Table 3. Comparison of the side effects, additional analgesic requirement, Ramsay Sedation Scale (RSS) scores, and duration of surgery between the groups (Mean±SD)

Side effects Nausea and vomiting Hypotension Additional analgesic requirement Ramsay Sedation Scale (RSS) scores Duration of surgery (min)

Group Y (n=25)

Group G (n=25)

P

1 1 1 2.56±0.50 123.40±16.80

1 0 1 2.76±0.66 129.60±17.86

NA 0.317 NA 0.312 0.709

SD: Standard deviation; Group Y: Intravenous patient-controlled analgesia contramal (IV PCA)+ superficial cervical plexus block (SCPB) (0.25% 10 ml bupivacaine); Group G: IV PCA+ GAN (0.25% 5 ml bupivacaine).

the groups in terms of RSS, side effect profile and additional analgesic use (p>0.05) (Table 3).

Discussion We tried to determine the efficacy of SCP and GAN blocks we applied for pain palliation after tympanomastoid surgery by VAS scores and tramadol conOCTOBER 2018

sumption quantities. According to the results of our study, although there was no statistically significant difference in pain scores between the two groups at all measurement times, we found higher tramadol consumption in the group which was applied GAN block.

In the literature, there are a limited number of regional anesthesia methods for ear surgery.[9,17] GAN 175

A RI PAIN blockade and local anesthetic infiltration were used in case presentations and controlled trials.[9,17,18] SCP blockade studies were used for anesthesia and analgesia in the neck area surgeries such as carotis and thyroid.[19–21] Fewer studies reported that it can be used for ear analgesia and anesthesia.[22] There are two studies measuring the effect of GAN blockage in the ear surgery in the paediatric age group in the literature. The first of these is Suresh et al’s study conducted in 2002. In this study, 40 patients underwent GAN blockade for pain palliation after tympanomastoid surgery. They determined less postoperative morphine use and side effects in the patient group who were applied 2 ml of bupivacaine at 0.25% concentration than the placebo group.

[9] In another study they carried out in 2004, they tried to evaluate the analgesic efficacy of pre- and postoperative block application of GAN blockade. In the study results, they did not find any difference in the results of both block applications.[17] In another study using regional anesthesia techniques for pain after mastoid surgery, GAN and auriculotemporal nerve blockage were used together. The results of this study by Swain et al.[12] showed that this method is safe, tolerable and effective. Additionally, they determined that nerve blocks reduced the incidence of postoperative nausea and vomiting. On the other hand, the efficacy of local anaesthetic infiltration and GAN blockade were compared in the study that involved the children undergoing otoplasty.[11] There was no difference between the postoperative results of both applications and the researchers recommended the use of the local anaesthetic application.

As the reason for this, they reported that peripheral nerve block administration may result in vascular and phrenic nerve spread, especially in children.[11] In the literature, besides the studies applying GAN blockade using anatomical signal points, the case presentation about GAN block applied along with USG is also draws attention. In this study, the researchers applied GAN block with 4 mL of 0.5% bupivacaine in 2 different cases with outer ear helix and ear lobe and with ear lobe abscess. In both cases, the surgical procedure was completed without the need for additional analgesia during the surgical procedure.[18] In a study to determine the anesthetic spread of GAN block administration along with USG, Thallaj et al. applied 0.1 ml of mepivacain to 20 vol176

unteers. The results of this study revealed that the tail of the helix, antitragus, lobule, and mandibular angle were blocked in all patients while post-auricular region could be blocked in 18 of 20 patients. No complications were observed in any patient.[23] In our study, post-auricular block was performed in 25 patients after GAN block, and no complication was observed. We believe that higher block achievement in our study may depend on the use of more local anaesthetic (5 ml).

SCP block is now used mainly for neck surgeries such as carotid and thyroid. Bilateral blocks are, on the other hand, used for pain after thyroid and parathyroid surgery.[20–24] In their study in which Gürkan et al. applied block along with USG for pain after thyroidectomy, they found lower opioid consumption in the group who were applied blockade after the use of 10 ml of bupivacaine at 0.25% concentration and shared this in the literature.[19] Hering et al. found a decrease in post SCP block VAS scores applied to patients with clavicular injury. After the block application in which they used 0.25% 8 ml of bupivacaine, they obtained analgesia in the clavicle, ear and neck region. They reported that SCP block could be used safely in emergency services for pain in injuries such as soft tissue, ear, neck region bone injuries (clavicular fractures and acromioclavicular).[22] Although postoperative complications such as systemic toxicity and hematoma are predicted in the intensive vascular structure of the neck region after SCP block application, it is recommended as a safe method in the literature.[20,25–27] In our study, we did not encounter complications similar to those in the literature. This may be due to the relatively low number of patients and the use of blocks along with the USG. In addition, it was reported that complications such as hoarseness and numbness in ear may also be seen in studies conducted.[19,20,25–27] However, numbness in ear which was determined and regarded as a complication in other studies was a result that we wanted to achieve in our study. According to our study results, there are two reasons for the lower amount of tramadol found in the SCP block-administered group. The first of these reasons is: Lesser occipital nerve blockage, a branch of SCP and contributing to the sensation of ear posterior, may have provided better analgesia in OCTOBER 2018

SCP versus GAN block in tympanomastoid surgery

the ear region. The second reason may be that the 10 ml (or more) volume used in SCP block application may have provided a longer blockade than 5 ml volume used in GAN.[19,28] Limitation: Small sample size and there is no control group.

Conclusion The results of this study show that SCP and GAN blocks are similar in pain control after tympanomastoid surgery.

Informed consent: Informed consent: Informed consent was obtained from all individual participants included in the study.

Financial disclosure: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict-of-interest: The authors declare that they have no conflict of interest.

Peer-reiew: Externally peer-reviewed.

References 1. Chole RA, Sudhoff HH. Chronic Otitis Media, Mastoiditis and Petrositis. Otolaryngology Head and Neck Surgery, Vol. 4, Mosby year book. St. Louis; 1993. p.2823–31.

2. Nadol JB, McKenna MJ. Surgery of the Ear and Temporal Bone. 2nd ed. Lippincott Williams & Wilkins; 2004. p.196–7.

3. Gerber MJ, Mason JC, Lambert PR. Hearing results after primary cartilage tympanoplasty. Laryngoscope 2000;110(12):1994–9.

4. Dornhoffer JL. Hearing results with cartilage tympanoplasty. Laryngoscope 1997;107(8):1094–9.

5. Rawal N. Analgesia for day-case surgery. Br J Anaesth 2001;87(1):73–87.

6. Cann C, Curran J, Milner T, Ho B. Unwanted effects of morphine-6-glucoronide and morphine. Anaesthesia 2002;57(12):1200–3.

7. Singh T, Shah N, Patel C, Upadhayaya RM. A comparative study of prophylactic ondansetron versus palonosetron for post operative nausea and vomiting inmiddle ear surgeries. IJBAR 2014;5:619–22.

8. Stadler M, Bardiau F, Seidel L, Albert A, Boogaerts JG. Difference in risk factors for postoperative nausea and vomiting. Anesthesiology 2003;98(1):46–52.

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9. Suresh S, Barcelona SL, Young NM, Heffner CL, Coté CJ. Does a preemptive block of the great auricular nerve improvepostoperative analgesia in children undergoing tympanomastoidsurgery? Anesth Analg 2004;98(2):330–3.

10. Sarmento KM Jr, Tomita S. Retroauricular tympanoplasty and tympanomastoidectomy under local anesthesia and sedation. Acta Otolaryngol 2009;129(7):726–8.

11. Cregg N, Conway F, Casey W. Analgesia after otoplasty: regional nerve blockade vs local anaesthetic infiltration of the ear. Can J Anaesth 1996;43(2):141–7.

12. Swain SK, Pradhan C, Mohanty S, Sahu MC. Comparative study between selective nerve blocks and the intravenous opioids in mastoid surgery. Ejentas 2017;18(2):121–5.

13. Arbona FL, Khabiri B, Norton JA. Ultrasound-guided regional anesthesia: a practical approach to peripheral nerve blocks and perineural catheters. Cambridge University Press; 2011.

14. Gray AT. Atlas of ultrasound-guided regional anesthesia.

WB Saunders Co; 2009.

15. Ritchie MK, Wilson CA, Grose BW, Ranganathan P, Howell SM, Ellison MB. Ultrasound-Guided Greater Auricular Nerve Block as Sole Anesthetic for Ear Surgery. Clin Pract 201;6(2):856.

16. Hadzic A. Ultrasound-guided cervical plexus block. In: Hadzic’s peripheral nerve blocks and anatomy for ultrasound guided regional anesthesia. 2nd ed. New York: McGraw Hill; 2012. p.345–51.

17. Suresh S, Barcelona SL, Young NM, Seligman I, Heffner CL, Coté CJ. Postoperative pain relief in children undergoing tympanomastoidsurgery: is a regional block better than opioids? Anesth Analg 2002;94(4):859–62.

18. Flores S, Herring AA. Ultrasound-guided Greater Auricular Nerve Block for Emergency Department Ear Laceration and Ear Abscess Drainage. J Emerg Med 2016;50(4):651–5.

19. Gürkan Y, Taş Z, Toker K, Solak M. Ultrasound guided bilateral cervical plexus block reducespostoperative opioid consumption following thyroid surgery. J Clin Monit Comput 2015;29(5):579–84.

20. Pandit JJ, Satya-Krishna R, Gration P. Superficial or deep cervical plexus block for carotid endarterectomy: a systematic review of complications. Br J Anaesth 2007;99(2):159–69.

21. Chauhan S, Baronia AK, Maheshwari A, Pant KC, Kaushik S. Superficial cervical plexus block for internal jugular and subclavianvenous cannulation in awake patients. Reg Anesth 1995;20(5):459.

22. Herring AA, Stone MB, Frenkel O, Chipman A, Nagdev AD. The ultrasound-guided superficial cervical plexus block for anesthesia and analgesia in emergency care settings. Am J Emerg Med 2012;30(7):1263–7.

23. Thallaj A, Marhofer P, Moriggl B, Delvi BM, Kettner SC, Almajed M. Great auricular nerve blockade using high resolution ultrasound: a volunteer study. Anaesthesia 2010;65(8):836–40.

24. Aunac S, Carlier M, Singelyn F, De Kock M. The analgesic efficacy of bilateral combined superficial and deepcervical plexus block administered before thyroid surgery undergeneral anesthesia. Anesth Analg 2002;95(3):746–50.

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26. Wedel DJ, Horlocker TT. Nerve blocks. In: Miller RD, editor.

Miller’s Anesthesia. 7th ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p.1664–5.

27. Kale S, Aggarwal S, Shastri V, Chintamani. Evaluation of

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the Analgesic Effect of Bilateral Superficial Cervical Plexus Block for Thyroid Surgery: A Comparison of Presurgical with Postsurgical Block. Indian J Surg 2015;77(Suppl 3):1196–200.

28. Steffen T, Warschkow R, Brändle M, Tarantino I, Clerici T. Randomized controlled trial of bilateral superficial cervical plexusblock versus placebo in thyroid surgery. Br J Surg 2010;97(7):1000–6.

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Agri 2018;30(4):179-182

doi: 10.5505/agri.2018.88261

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ORIGINAL ARTICLE

Radiofrequency thermocoagulation combined with pulsed radiofrequency for gasserian ganglion blockage Gasser ganglion blokajında pulse radyofrekans ile termokoagülasyon radyofrekansın kombine edilmesi Tülin ARICI,1

Mustafa KURCALOGLU,1

Ertuğrul KILIC,2

Elvan ERHAN1

Summary Objectives: Trigeminal neuralgia (TN) has been effectively treated by radiofrequency thermocoagulation (RFT) of the gasserian ganglion. Recently, pulsed radiofrequency (PRF) is becoming an alternative therapy for patients with trigeminal neuralgia.

It is unclear whether the combination of RFT with PRF may decrease post-operative complications while maintaining longterm pain relief.

Methods: Twelve patients with idiopathic TN who had undergone combined RFT and PRF of the gasserian ganglion were evaluated. PRF (42 °C, 45V, 20 ms, 120 seconds) was administered, and then RFT (65 °C, 90 seconds) was performed to the gasserian ganglion. The post-operative pain relief and complications were evaluated at 1, 6, 12 and, 24 months after treatment.

Results: 10 patients (83.3%) reported significant pain relief (VAS 3) at 1 month following the treatment, while 8 patients (66.6%) at 6 months, 5 patients (41.6) at 12 months, and 2 patients (16.6%) at 24 months were pain-free. Two of the patients did not have pain relief (VAS ≥3), and 2 patients were still pain-free by the 24th month. The mean time of pain relief was 14 months.

One patient had numbness in the tongue for about a year, while in the other patients, no serious complications were reported.

Conclusion: A combination of RFT with PRF could help eliminate postoperative complications of trigeminal neuralgia. We sugesst that combining RFT and PRF therapy may serve to decrease the side effects but not increase the pain relief.

Keywords: Gasserian ganglion blockage; pulsed radiofrequency; radiofrequency thermocoagulation; trigeminal neuralgia.

Özet Amaç: Trigeminal nevralji (TN), gasserian ganglionun radyofrekans termokoagülasyonu (RFT) ile etkin bir şekilde tedavi edilmiştir. Son zamanlarda, pulse radyofrekans (PRF) trigeminal nevraljisi olan hastalar için alternatif bir tedavi haline gelmektedir.

RFT ile PRF kombinasyonunun postoperatif komplikasyonları azaltıp azaltmadığı ve uzun süreli ağrıların giderilip giderilmediği belirsizdir.

Gereç ve Yöntem: Gasser ganglionun kombine RFT ve PRF’si uygulanan idiopatik TN’lı 12 hasta değerlendirildi. PRF (42 °C, 45 V, 20 ms, 120 saniye) uygulandı ve daha sonra, Gasser gangliona RFT (65 °C, 90 saniye) yapıldı. Postoperatif ağrı rahatlaması ve komplikasyonları tedaviden 1, 6, 12 ve 24 ay sonra değerlendirildi. Ağrı için VAS 3 ve üzeri dikkate alındı.

Bulgular: 10 hastada (%83.3) tedaviden 1 ay sonra ağrıda belirgin azalma varken, 6. ayda 8 hasta (%66.6), 12. ayda 5 hasta (%41.6) ve 24. ayda 2 hasta (%16.6) ağrısızdı. Hastaların 2’sinde ağrı rahatlaması yoktu (NRS ≥3) ve 24. ayda 2 hasta hala ağrısızdı. Ağrı rahatlama süresi ortalama 14 aydı. Bir hastada yaklaşık bir yıldır dilde uyuşma vardı, diğer hastalarda ise ciddi komplikasyonlar bildirilmedi.

Sonuç: PRF ile RFT kombinasyonu, trigeminal nevraljinin postoperatif komplikasyonlarını ortadan kaldırabilir. RFT ve PRF tedavisini kombine etmenin yan etkilerin azaltılmasına hizmet edebileceğini ancak ağrıyı azaltmadığını belirtmek isteriz.

Anahtar sözcükler: Gasser ganglion blokajı; pulse radyofrekans; radyofrekans termokoagülasyon; trigerminal nevralji.

Introduction Trigeminal neuralgia (TN) is a pain syndrome characterised by paroxysmal severe pain originating from

the trigeminal nerve and has been effectively treated by radiofrequency thermocoagulation (RFT) of the gasserian ganglion in patients unresponsive to rou-

Department of Anaesthesiology, Reanimation and pain, Ege University Faculty of Medicine, İzmir, Turkey Department of Anaesthesiology, Reanimation and Pain, Dr. Ersin Arslan Research and Training Hospital, Gaziantep, Turkey

1 2

Submitted (Başvuru tarihi) 28.03.2018 Accepted after revision (Düzeltme sonrası kabul tarihi) 11.09.2018 Available online date (Online yayımlanma tarihi) 25.10.2018

Correspondence: Dr. Ertuğrul Kilic. Dr. Ersin Arslan Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, 27070 Gaziantep, Turkey.

Phone: +90 - 533 - 630 48 75 e-mail: drertugrulkilic@yahoo.com © 2018 Turkish Society of Algology

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179

A RI PAIN tine medication therapy.[1,2] RFT has often been used because of its effectiveness in providing long-term pain relief. However, in patients who underwent RFT therapy, some complications such as facial numbness, masseter weakness, decreased corneal reflex, dysesthesia, and anaesthesia dolorosa have been reported.[3] Recently, pulsed radiofrequency (PRF) is becoming an alternative therapy for patients with TN. Despite some controversial results, the efficacy of PRF of gasserian ganglion, its safe reputation[4,5] and was as its effectiveness[6] have been demonstrated. It is unclear whether the combination of RFT with PRF may decrease post-operative complications while maintaining long-term pain relief.

In this study, we evaluated patients with TN who had undergone combined RFT and PRF of the gasserian ganglion in terms of pain relief and complications in our clinic.

Material and Methods The study was approved by the research ethics committee and all patients gave their written consent to participate in the study. Fourteen patients with idiopathic TN who had undergone combined RFT and PRF of the gasserian ganglion in our clinic were evaluated in our study. Brain magnetic resonance imaging had revealed no secondary causes of the TN. All of the patients (5 men and 9 women, aged between 54 and 79 years, mean age 64 years) had pain on the mandibular or the maxillary branch of the trigeminal nerve or both. They had a severe pain [Numeric Rating scale (NRS) pain score ≥8] that was unresponsive to appropriate medical therapy. None of the patients had previously undergone interventional treatments including chemical ablation, balloon compression surgery, gamma knife or microvascular decompression. Seven patients had undergone RFT for the same complaint in our clinic once previously.

Electrocardiography, blood pressure, and arterial oxygen saturation were continuously monitored, and i.v. access put in place. Nasal oxygen was given to the patients during procedure. The patients were made to lie in a supine position with the head slightly extended. All procedures were performed under fluoroscopy which was adjusted to show the foramen ovale as the C-arm was rotated 15° obliquely to the ipsilateral affected side and 30°caudally to produce a 180

submental view. After disinfecting the puncture site, the skin was injected with a 2% solution of prilocaine 2 cm lateral from the angle of the mouth at the site of the TN. A 22-gauge, 10 cm RF needle with 5 mm active tip was directed towards foramen ovale using a tunnel view. Once the needle was in the foramen ovale, the C-arm was rotated laterally to ascertain the depth of penetration. The tip of the electrode was positioned appropriately in the gasserian ganglion. Electrical stimulation was administered at 50 Hz to determine the sensory threshold and at 2 Hz to determine the motor threshold. All patients reported paraesthesia at the area of the original pain and motor response was absent at voltages lower than 0.4 V. After the position of the needle was confirmed, PRF (42°C, 45V, 20 ms, 120 seconds) was administered, and then RFT (65 °C, 90 seconds) was performed to the gasserian ganglion. If the patients had more than one branch involved, the same procedure was repeated for the other affected branch with the same parameters. The patients were sedated by injection of 1 mg/kg propofol during the RF procedures.

The patients were observed and monitored in the recovery room and discharged the following day. The post-operative pain relief and complications were evaluated at 1-, 6-, 12- and, 24- months after treatment. The patients were questioned through a telephone interview and pain was assessed using the numeric rating scale (NRS) (0=no pain, 10=worst pain).

Results A total of 14 patients who underwent RFT and PRF treatment of the gasserian ganglion for TN were evaluated in this study. The baseline characteristics of the patients are shown in Table 1. Twelve patients were interviewed by telephone for long-term followTable 1. Demographic characteristics of the patients

Mean Range

Age 69.5 60–79 Female/Male 8/4 Duration of preoperative pain (month) 14 6–24 Preoperative NRS 8.3 Right/left 8/4 V2/V3/both 5/4/3 NRS: Numeric Rating Scale.

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Radiofrequency thermocoagulation combined with pulsed radiofrequency for gasserian ganglion blockage

Table 2. Numeric rating scale scores and number of patients without pain before and 1-,6-,12-, and 24- months after procedure

Pretreatment

1 month

6 months

12 months

24 months

NRS 8.33 2.16 2.83 4.33 5.75 Number of patients without pain 10/12 8/12 5/12 2/12 (NRS <3) (n) (%) (83.3%) (66.6%) (41.6) (16.6%) NRS: Numeric rating scale.

up, while 2 patients were lost during the follow-up period. Ten patients (83.3%) reported significant pain relief (NRS <3) at 1 month following the treatment, while 8 patients (66.6%) at 6 months, 5 patients (41.6) at 12 months, and 2 patients (16.6%) at 24 months were pain-free. Two of the patients did not have pain relief (VAS ≥3), and 2 patients were still pain-free by the 24th month (Table 2). The mean time of pain relief was 14 months.

One patient had numbness in the tongue for about a year, while in the other patients, no serious complications were reported.

Discussion Trigeminal neuralgia has been treated by RFT of gasserian ganglion effectively.[7] However, it has postoperative complications such as facial numbness, decreased corneal reflex, and masseter weakness.[2,3] More recently, PRF has been introduced to modulate pain perception without damaging the nerve.[8,9] Studies using PRF treatment for TN have reported disparate results. For example, while Erdine et al.[4] and Fang et al.[5] reported that PRF was not effective for the treatment of pain in trigeminal neuralgia patients, some studies showed that increasing the duration of PRF (4–6 minutes) could lead to better results.[10,11] Also, Chua et al.[10] showed that PRF application for 6 minutes at 45 V, 4 Hz, 10 ms to the gasserian ganglion provided excellent pain relief (>80% pain relief ) at 2, 6, and 12 months at 73.5%, 61.8% and, 55.9%, respectively. Satisfactory pain relief (50–80% pain relief ) at 2, 6, and 12 months were 14.7%, 17.6% and, 17.6, respectively.

In our study, the time of pain relief 6, 12, and 24 months after the procedure was 66.6%, 41.6% and, 16.6%. Our success rate might be low because inclusion of the patients who had received previous RFT and low degree (65 °C) of RFT. OCTOBER 2018

Previous studies have reported initial pain relief rates from RFT of the trigeminal ganglion between 85% and 97%.[12–15] In our study, the initial pain relief rate was 83.3%. The earlier reports observed that the time of mean pain recurrence was 24 to 68 months.[12,13,15] In our study, recurrence was seen after 3 months first-time and 2 patients were still pain-free in the 24th month.

Yoon KB et al.[14] demonstrated that the time of pain relief 1,2 and 11 years after the percutaneous RFT was 65%, 49% and 26%, respectively in 108 RFT of 81 patients with TN and they reported dysaesthesia in 20 patients, corneal numbness in 12 patients and masseter weakness in 3 patients. Mark V. Koning et al.[16] demonstrated that a lower sensory stimulation threshold during treatment was associated with better patient satisfaction, improved pain relief, and trended toward more hypesthesia. In their study, major side effects were hypesthesia (56%), dry eye (20%), and masseter muscle weakness (12%). Hence, Zhao et al.[2] suggested that RFT combined with PRF could help eliminate post-operative complications of TN such as facial numbness, masseter muscle weakness, and decreased corneal reflex. In our study, postoperative complications were seen only in one patient.

The exact mechanism of PRF is unknown and it is still being investigated.[17] Several studies have investigated the factors that have an impact on PRF. Luo et al.[18] showed that increasing intraoperative RF output voltage and electrical field intensity improves the outcome of PRF treatment. Although the mechanism of PRF remains completely unknown, studies like these may help to clarify its effects.

Conclusion A combination of RFT with PRF could help eliminate postoperative complications of trigeminal neuralgia.

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A RI PAIN We sugesst that combining RFT and PRF therapy may serve to decrease the side effects but not increase the pain relief. The same interventions with different parameters and different time of radiofrequency of the gasserian ganglion may generate better results.

Future studies will investigate this possibility.

Conflict-of-interest issues regarding the authorship or article: None declared.

Peer-reiew: Externally peer-reviewed.

References 1. Kosugi S, Shiotani M, Otsuka Y, Suzuki T, Katori N, Hashiguchi S, et al. Long-term outcomes of percutaneous radiofrequency thermocoagulation of gasserian ganglion for 2nd- and multiple-division trigeminal neuralgia. Pain Pract 2015;15(3):223–8.

2. Zhao WX, Wang Q, He MW, Yang LQ, Wu BS, Ni JX. Radiofrequency thermocoagulation combined with pulsed radiofrequency helps relieve postoperative complications of trigeminal neuralgia. Genet Mol Res 2015;14(3):7616–23.

3. Thapa D, Ahuja V, Dass C, Verma P. Management of refractory trigeminal neuralgia using extended duration pulsed radiofrequency application. Pain Physician 2015;18(3):E433–5.

4. Erdine S, Ozyalcin NS, Cimen A, Celik M, Talu GK, Disci R. Comparison of pulsed radiofrequency with conventional radiofrequency in the treatment of idiopathic trigeminal neuralgia. Eur J Pain 2007;11(3):309–13.

5. Fang L, Ying S, Tao W, Lan M, Xiaotong Y, Nan J. 3D CTguided pulsed radiofrequency treatment for trigeminal neuralgia. Pain Pract 2014;14(1):16–21.

6. Kang KN, Park IK, Suh JH, Leem JG, Shin JW. Ultrasoundguided Pulsed Radiofrequency Lesioning of the Phrenic Nerve in a Patient with Intractable Hiccup. Korean J Pain 2010;23(3):198–201.

7. Motamedi MH, Rahmat H, Bahrami E, Sadidi A, Navi F, Asadollahi M, et al. Trigeminal neuralgia and radiofrequency. J Calif Dent Assoc 2009;37(2):109–14.

8. Van Zundert J, Patijn J, Kessels A, Lamé I, van Suijlekom H,

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van Kleef M. Pulsed radiofrequency adjacent to the cervical dorsal root ganglion in chronic cervical radicular pain: a double blind sham controlled randomized clinical trial.

Pain 2007;127(1-2):173–82.

9. Rehman SU, Khan MZ, Hussain R, Jamshed A. Pulsed radiofrequency modulation for lingual neuralgia. Br J Oral Maxillofac Surg 2012;50(1):e4–5.

10. Chua NH, Halim W, Beems T, Vissers KC. Pulsed radiofrequency treatment for trigeminal neuralgia. Anesth Pain Med 2012;1(4):257–61.

11. Van Zundert J, Brabant S, Van de Kelft E, Vercruyssen A, Van Buyten JP. Pulsed radiofrequency treatment of the Gasserian ganglion in patients with idiopathic trigeminal neuralgia. Pain 2003;104(3):449–52.

12. Tatli M, Satici O, Kanpolat Y, Sindou M. Various surgical modalities for trigeminal neuralgia: literature study of respective long-term outcomes. Acta Neurochir (Wien) 2008;150(3):243–55.

13. Kanpolat Y, Savas A, Bekar A, Berk C. Percutaneous controlled radiofrequency trigeminal rhizotomy for the treatment of idiopathic trigeminal neuralgia: 25-year experience with 1,600 patients. Neurosurgery 2001;48(3):524–32.

14. Yoon KB, Wiles JR, Miles JB, Nurmikko TJ. Long-term outcome of percutaneous thermocoagulation for trigeminal neuralgia. Anaesthesia 1999;54(8):803–8.

15. Udupi BP, Chouhan RS, Dash HH, Bithal PK, Prabhakar H. Comparative evaluation of percutaneous retrogasserian glycerol rhizolysis and radiofrequency thermocoagulation techniques in the management of trigeminal neuralgia.

Neurosurgery 2012;70(2):407–12.

16. Koning MV, Koning NJ, Koning HM, van Kleef M. Relationship between Sensory Stimulation and Side Effects in Percutaneous Radiofrequency Treatment of the Trigeminal Ganglion. Pain Pract 2014;14(7):581–7.

17. Cohen SP, Peterlin BL, Fulton L, Neely ET, Kurihara C, Gupta A, et al. Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness. Pain 2015;156(12):2585–94.

18. Luo F, Meng L, Wang T, Yu X, Shen Y, Ji N. Pulsed radiofrequency treatment for idiopathic trigeminal neuralgia: a retrospective analysis of the causes for ineffective pain relief.

Eur J Pain 2013;17(8):1189–92.

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doi: 10.5505/agri.2018.86619

A RI PAIN

ORIGINAL ARTICLE

Research on the efficacy of the rectus sheath block method Rektus kılıf bloğu yönteminin etkinliğinin araştırılması Esma KARAARSLAN,1

Ahmet TOPAL,2

Onur AVCI,1

Sema TUNCER UZUN2

Summary Objectives: We aimed to retrospectively investigate the efficacy of ultrasound guided rectus sheath block (RSB) method in our study.

Methods: We scanned 235 patient files operated for abdominal pathology. Patients meeting the criteria were evaluated for intra-operative rectus sheath block and two different groups were formed. In these two groups of patients visual analogue scale (VAS) values recorded from the postoperative pain follow-up form and analgesic delivery (DEL) and analgesic demand (DEM) values recorded from patient controlled analgesia (PCA) device were compared. In addition, complaints of nausea, vomiting and constipation were evaluated.

Results: Postoperative VAS values (Postoperative 1, 12 and 24 hours p<0.001), DEM values (Postoperative 1, 12 and 24 hours p<0.001) and total amount of morphine consumed (Postoperative 1, 12 and 24 hours p<0.001) were lower in patients with RSB. Also, in patients with RSB nausea (p=0.014) and vomiting was less seen postoperatively (p=0.007). In the first 24 hours after surgery, constipation was seen in 8 patients with RSB and constipation was seen in 30 patients without RSB (p=0.00).

Conclusion: Ultrasound guided rectus sheath block is an effective method for postoperative pain control.

Keywords: Postoperative analgesia; rectus sheath block; ultrasonography.

Özet Amaç: Çalışmamızda ultrasonografi eşliğinde yapılan rektus kılıf bloğu (RKB) yönteminin etkinliğini retrospektif olarak araştırmayı amaçladık.

Gereç ve Yöntem: Abdominal patoloji nedeniyle ameliyat olmuş 235 hasta dosyasını taradık. Kriterleri karşılayan hastalar intraoperatif RKB yapılması yönünden değerlendirildi ve RKB yapılan ve yapılmayan olarak iki farklı grup oluşturuldu. Belirlenen bu iki grup hastada postoperatif ağrı takip formuna kaydedilmiş olan vizuel analog skala (VAS) değeri ve hasta kontrollü analjezi (HKA) cihazından kaydedilmiş olan analjezik sunumu (DEL) ve analjezik isteği (DEM) değerleri karşılaştırıldı. Ayrıca hastanın ifade etmiş olduğu bulantı, kusma ve kabızlık şikayetleri değerlendirildi.

Bulgular: Postoperatif VAS değerleri (postoperatif 1, 12, 24. saat p<0.001), DEM değerleri (postoperatif 1, 12 ve 24. saat p<0.001) ve tüketilen toplam morfin miktarları (postoperatif 1, 12 ve 24. saat p<0.001) RKB yapılmış hastalarda daha düşüktü.

Ayrıca, RKB yapılmış hastalarda postoperatif bulantı (p=0.014) ve postoperatif kusma daha az idi (p=0.007). Cerrahi sonrası ilk 24 saatte RKB uygulanmış 8 hastada, RKB uygulanmamış 30 hastada kabızlık görüldü (p=0.00).

Sonuç: Ultrasonografi eşliğinde yapılan RKB orta hat kesisi ile gerçekleştirilen batın ameliyatlarında postoperatif ağrı kontrolünde etkili bir yöntemdir.

Anahtar sözcükler: Postoperatif analjezi; rektus kılıf bloğu; ultrasonografi.

Introduction The importance of postoperative pain management has gradually increased due to unwanted and delaying effects of pain on wound healing.[1] The aim of postoperative pain management is to eliminate or to minimize the feeling of discomfort, to reduce or to prevent side effects, and to make the treatment

more economic in patients. However there is no ideal method available for this.[2,3] Rectus sheath block allows us to prevent postoperative somatic pain in a zone from the dermis to the parietal peritoneum. Before ultrasonography was being actively used, this block has not been applied often

Department of Anestesiology, Numune Hospital, Sivas, Turkey Department of Anestesiology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey

1 2

Submitted (Başvuru tarihi) 05.12.2017 Accepted after revision (Düzeltme sonrası kabul tarihi) 11.09.2018 Available online date (Online yayımlanma tarihi) 26.10.2018

Correspondence: Dr. Onur Avcı. Numune Hastanesi, Anesteziyoloji Kliniği, Sivas, Turkey.

Phone: +90 - 530 - 112 64 08 e-mail: dronuravci@gmail.com © 2018 Turkish Society of Algology

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A RI PAIN Table 1. Postoperative pain assessment form records used for patient follow-up Patient name surname

VAS

File no PCA-DEM

Age

PCA-DEL

1 hour 12 hours 24 hours

Nausea Yes/No Yes/No Yes/No

ASA

Vomiting Yes/No Yes/No Yes/No

Constipation Yes/No Yes/No Yes/No

VAS: Visual Analogue Scale; PCA: Patient controlled analgesia; DEM: Demand; DEL: Delivery.

or sufficient blocks could not have been achieved mostly with single injection method, due to the proximity of medicated zones and vital organs, and muscle layers being coherent and thin. Recently, this method is actively applied with ultrasonography guidance, single injection and catheter placement in the rectus sheath.

In this study, we retrospectively evaluated the efficacy of ultrasound guided rectus sheath block by comparing the amounts of needed analgesics and comparing symptoms like pain, nausea, vomiting and constipation in patients who were operated with above-below umbilicus incision in the general surgery operating room due to abdominal pathologies.

Material and Methods This study was conducted to retrospectively investigate the efficacy of rectus sheath block, after the approval of the ethics committee (2016/598). Controlled analgesia follow-up forms and patient files from the algology department were utilized in this study. We gathered data from 235 patients’ files, who were operated between July 2014 and March 2016.

From these files; ASA 1–3 patients of 18–75 years of age who were operated with above-below umbilicus median incision by the general surgery department were identified. In addition, all of these patients were required to receive the routine 2 mg/kg tramadole for postoperative analgesia and morphine PCA for the postoperative period. 93 patients were determined to meet all of these criteria and 13 of them were not included in the study due to insufficient data. 80 patients were assessed in terms of intraoperative rectus sheath block method usage, and two groups were formed with 40 patients with rectus sheath block (group RSB) and 40 patients without rectus sheath block (Group C).

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For these two groups; 1 hour, 12 hours and 24 hours postoperative VAS values recorded to algology clinic follow-up form (Table 1), DEL/DEM values recorded from PCA, as well as nausea, vomiting and constipation complaints from patients were compared.

Statistical analysis Gathered data were recorded to SPSS 16.0 computer program. Descriptive statistics were shown with mean±standard deviation and frequency tables. Normal distribution conformity analysis of the data were done. Student T-test was used for between-groups comparison. Comparison between measurements was done with Bonferroni corrected paired sample T-test. Chi-square test was used for comparing categorical data. For all analyses, p<0.05 was considered as significance level.

Results No statistically significant difference was observed when groups were compared in terms of demographic characteristics and ASA classification (p>0.05) (Table 2).

• VAS values in Group RSB at 1, 12 and 24 hours were found to be significantly low then Group C (p<0.001) (Fig. 1).

Table 2. Demographic characteristics of the groups

Age (years) Weight (kg) Height (cm) Gender F/M ASA I/ II/ III

Group C (n=40) 56.53±11.110 77.23±12.877 171.40±0.101 10/30 1/33/6

Group RSB (n=40)

p

57.20±12.623 79.32±13.234 171.85±0.097 10/30 1/34/5

0.800 0.474 0.840 1.000 0.948

RSB: Rectus sheath block F: Female; M: Male.

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Research on the efficacy of the rectus sheath block method

PCA DEM value

PCA DEM value

VAS score

VAS score 10.00 9.00 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 0.00

300 275 250 225 220 175 150 125 100 75 50 25 0

1 hour

12 hours

24 hours

1 hour

12 hours

24 hours

Group C

9.30

7.90

6.35

Group C

66.72

118.08

176.5

Group RSB

5.93

4.20

2.50

Group RSB

25.65

48.83

73.85

*p<0.05 significant difference between groups.

• PCA DEM values in Group RSB at 1, 12 and 24 hours were found to be significantly low then Group C (p<0.001) (Fig. 2).

• PCA DEL values in Group RSB at 1, 12 and 24 hours were found to be significantly low then Group C (p<0.001) (Fig. 3).

While 24 (%60) patients had shown the symptom nausea in Group C, 13 (%32.5) patients had shown nausea in Group RSB and there was a statistically significant difference between two groups (p=0.014).

While 17 (%42.5) patients had shown the symptom vomiting in Group C, 6 (%15) patients had shown vomiting in Group RSB and there was a statistically significant difference between two groups (p=0.007).

While 30 (%75) patients had shown the symptom constipation in Group C, 8 (%20) patients had shown constipation in Group RSB and there was a statistically significant difference between two groups (p=0.00).

While total morphine consumption average of patients with postoperative constipation in 24 hours was 80.08±32.607 mg, this value was 49.38±29.367 mg for patients with no constipation. There was a statistically significant difference between total morphine consumption averages of patients with and without constipation (p<0.001).

Discussion Postoperative pain is one of the most important factors effecting morbidity after surgery. Various oral, nasal, intravenous bolus, patient controlled intravenous and patient or nurse controlled intravenous OCTOBER 2018

Figure 2. PCA DEM values of the groups.

PCA DEL values Consumed morphine (mg)

Figure 1. VAS scores of the groups.

*p<0.05 significant difference between groups.

120 110 100 90 80 70 60 50 40 30 20 10 0

1 hour

12 hours

24 hours

Group C

8.43

46.63

88.03

Group RSB

5.9

22.68

39.9

*p<0.05 significant difference between groups.

Figure 3. PCA DEL values of the groups.

drugs like nonsteroid anti-inflammatory drugs, paracetamol and opioids are being used for postoperative pain in different applications.[4–6] Opioids are the most used agents in postoperative pain treatment. While usage of opioid agents date back to the beginning of modern surgery, management of opioid related side effects and pain can be insufficient.[7] In recent years, the usage of local anaesthetics alongside opioids has come up in order to increase success of postoperative pain treatment and to reduce side effects of opioid agents.[8,9] Peripheral nerve blocks are often used to prevent postoperative pain. With the use of ultrasonography, success rates of peripheral nerve blocks increase and less complications occur.[10] Recently, ultrasound guided rectus sheath block is performed after abdominal operations for pain control as a new method.[11–13] 185

A RI PAIN Dolan J. et al observed that with loss of resistance method; in 45% of patients the needle was placed correctly but superficial, in 21% of patients the needle was placed deeper and in 34% of patients rectus sheath ponction was done. They reported that in 89% of patients whose blocks were done with ultrasonography, the needle was placed correctly.[14] In their study, Marhoper P. et al reported that ultrasound guided nerve block with local anaesthesia has become a routine practice, and that it is more favorable for showing the needle placement and simultaneous local anaesthetic distribution than traditional methods like nerve stimulation and loss of resistance.[15] In our retrospective study, we included patients with ultrasound guided rectus sheath block and did not observe rectus sheath block related complications in any patient. Effective analgesia is achieved and less complications occur, as the usage and experience of ultrasonography usage increases.

It should not be forgotten, that afferent neural blockage with local anesthesia is one of the most effective analgesic methods.[16] Rectus sheath block for postoperative analgesia can be an important component of multimodal analgesia.

The purpose of postoperative pain management is to prevent pain, as well as to minimize its side effects. After years of development opioids are still in the center of pain treatment. Although their analgesic effects are strong, side effects like respiratory depression, sedation, nausea, vomiting, constipation, bradycardia, hypotension and itching can be seen related to their usage.[17,18] In their study, Elbahrawy et al.[19] investigated the effect of rectus sheath block on postoperative VAS, and reported that average VAS scores in rectus sheath block group was significantly lower than the control group. In a study by Halefoglu et al.[20] including pediatric patients with transverse incision laparotomy; they reported that rectus sheath block significantly lowers postoperative pain score (FLACC score). We observed that patients in the rectus sheath block group had significantly lower VAS scores than patients in the control group, too.

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Rectus sheath block is a nerve blocking method used as a postoperative analgesia method, which should reduce the need for analgesics after surgery, and there are many studies in the literature which support this. For example Elbahrawy et al.[19] reported that intraoperative and postoperative opioid consumption was significantly lower in patients who received rectus sheath block compared to the control group.

In a study by Halefoglu et al.,[20] morphine consumption was found to be significantly lower in patients with rectus sheath block. Similarly Ozcengiz et al.[21] reported, that total tramadole consumption was significantly lower in patients with rectus sheath block application.

Similar to many other studies, we observed in our study that postoperative total morphine consumption was significantly lower for patients with rectus sheath block. In addition to other studies, we looked at patientsâ&#x20AC;&#x2122; analgesic demands (DEM) from H.K.A devices in postoperative period from their pain follow-up form records, and found that as a more objective criteria of patient satisfaction, analgesic demands were lower in patients with rectus sheath block.

Multimodal analgesia, which includes non-opioid analgesics and ambulatory continuous peripheral nerve blocks, provides effective and adequate analgesia after surgery and reduces postoperative nausea and vomiting related to consumed opioids.[22] In studies involving rectus sheath block used as a postoperative analgesic method, the postoperative side effect difference of reduced opioid consumption has been assessed. In a study, Elbahrawy et al.[19] investigated sedation scores and nausea and vomiting incidences and reported that nausea and vomiting incidence was significantly lower in patients with rectus sheath block compared to patients with only general anaesthesia. They also observed, that most of the patients, who expressed satisfaction, had a rectus sheath block application. Similarly, in a study

by Halefoglu et al.;[20] while none of the patients with rectus sheath block had nausea or vomiting, 3 patients in the control group had nausea. In addition, sedation scores of patients with rectus sheath block OCTOBER 2018

Research on the efficacy of the rectus sheath block method

application was found to be significantly lower.

Ozcengiz et al.[21] reported, that nausea and vomiting incidence was significantly lower in patients whose surgical rectus sheath block was made with local anaesthetics, compared to patients whose surgical rectus sheath block was made with saline, and that patient satisfaction was significantly higher.

Cuneyitoglu et al.[23] reported, that in the first 24 hours after surgery, 5 patients with ultrasound guided rectus sheath block and 1 patient with surgical rectus sheath block could defecate, while none of the patients who received no other analgesic method other than IV opioids could. So, they concluded that gastrointestinal system functions in patients with ultrasound guided rectus sheath block were significantly better.

Considering studies by Breschan et al.[24] and Manassero et al.;[25] we can see, that with proper patient selection, rectus sheath block can be used alone for perioperative analgesia, or even alone as an anaesthesia method for operations without visceral pain.

In our study, the application of nerve block methods such as rectus sheath block provides effective analgesia and reduces opioid related side effects by reducing opioid consumption. It also provides all of the advantages of effective pain control such as patient satisfaction, early mobilization and reduced costs.

In our retrospective study, we concluded that ultrasound guided rectus sheath block is an effective analgesic method within the first 24 hours. We observed, that rectus sheath block reduces patients’ analgesic demands and opioid consumptions within the first 24 hours, and also lowers VAS scores.

In conclusion, with the effective usage of ultrasonography, success rates and safety of rectus sheath block also increases. With proper patient selection, it provides effective and adequate analgesia, while also reducing opioid related side effects by reducing opioid consumption. We think that rectus sheath block should often be considered in abdominal midline incisions for postoperative analgesia, and that it is a good alternative to other analgesic methods. It can be an important component of multimodal analgesia.

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Conflict-of-interest issues regarding the authorship or article: None declared.

Peer-reiew: Externally peer-reviewed.

References 1. Cousins MJ. Acute and postoperative pain. In: Wall PD, Melzack R, editors. Textbook of Pain. 3th. New York: Livingstone Inc; 1994. p. 357–85.

2. Pasero C, McCaffery M. Postoperative pain management in the elderly. Seattle: IASP Press; 1996. p. 45–68.

3. Aydınlı I. Geriatrik olgularda postoperatif ağrı tedavisi. T Klinik Anest Reanim 2003;1:47–58.

4. Engelhardt T, Steel E, Johnston G, Veitch DY. Tramadol for pain relief in children undergoing tonsillectomy: a comparison with morphine. Paediatr Anaesth 2003;13(3):249–52.

5. Howard R, Carter B, Curry J, Morton N, Rivett K, Rose M, Tyrrell J, et al.; Association of Paediatric Anaesthetists of Great Britain and Ireland. Postoperative pain. Paediatr Anaesth 2008;18 Suppl 1:36–63.

6. Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth 2013;23(6):475–95.

7. Bailey PL. Stanley TH. Intravenous opioid anesthetics. In: Miller RD edıtor. Anaesthesia. 4th. Churchill Livingstone; 1994. p. 291-388.

8. Kehlet H, Dahl JB. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg 1993;77(5):1048–56.

9. Kehlet H. Controlling acute pain-role of preemptive analgesia, peripheral treatment and balanced analgesia and effects on outcome. In: M Mitchell, editor. Pain 1999-an updated review. Seattle: IASP Pres; 1999. p. 459–62.

10. Gelfand HJ, Ouanes JP, Lesley MR, Ko PS, Murphy JD, Sumida SM, et al. Analgesic efficacy of ultrasound-guided regional anesthesia: a meta-analysis. J Clin Anesth 2011;23(2):90–6.

11. Isaac LA, McEwen J, Hayes JA, Crawford MW. A pilot study of the rectus sheath block for pain control after umbilical hernia repair. Paediatr Anaesth 2006;16(4):406–9.

12. Gurnaney HG, Maxwell LG, Kraemer FW, Goebel T, Nance ML, Ganesh A. Prospective randomized observer-blinded study comparing the analgesic efficacy of ultrasound-guided rectus sheath block and local anaesthetic infiltration for umbilical hernia repair. Br J Anaesth 2011;107(5):790–5.

13. Wada M, Kitayama M, Hashimoto H, Kudo T, Kudo M, Takada N, et al. Brief reports: plasma ropivacaine concentrations after ultrasound-guided rectus sheath block in patients undergoing lower abdominal surgery. Anesth Analg 2012;114(1):230–2.

14. Dolan J, Lucie P, Geary T, Smith M, Kenny GN. The rectus sheath block: accuracy of local anesthetic placement by trainee anesthesiologists using loss of resistance or ultrasound guidance. Reg Anesth Pain Med 2009;34(3):247–50.

15. Marhofer P, Greher M, Kapral S. Ultrasound guidance in regional anaesthesia. Br J Anaesth 2005;94(1):7–17.

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A RI PAIN 16. Kehlet H. Modification of response to surgery and anesthesia by neural blockade: clinical implications. In: Cousins MT, Bridebaugh PO, editors. Neural Blockade in Clinical Anesthesia and Management of Pain. 3rd. Philadelphia: Lippincott; 1998.

17. Ashburn MA, Love G, Pace NL. Respiratory-related critical events with intravenous patient-controlled analgesia. Clin J Pain 1994;10(1):52–6.

18. Etches RC. Respiratory depression associated with patient-controlled analgesia: a review of eight cases. Can J Anaesth 1994;41(2):125–32.

19. Elbahrawy K, El-Deeb A. Rectus sheath block for postoperative analgesia in patients with mesenteric vascular occlusion undergoing laparotomy: A randomized single-blinded study. Anesth Essays Res 2016;10:516–20.

20. Halefoğlu A, Güleç E, Hatipoğlu Z, Özcengiz D. Ultrasound-Guided Rectus Sheath Block in Gynaecological Surgery with Pfannenstiel Incision Cukurova Medical Journal 2015;40:534–41.

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21. Özcengiz D, Bayrak B T, GüLeç E, Alkan M, Günes Y. Rectus sheath block for postoperative pain relief in children undergoing major abdominal surgery. Journal of Anesthesiology and Clinical Science 2012;1:5.

22. Melton MS, Klein SM, Gan TJ. Management of postdischarge nausea and vomiting after ambulatory surgery.

Curr Opin Anaesthesiol 2011;24(6):612–9.

23. Cüneyitoğlu Ş, Türktan M, Biricik E, Özcengiz D. Ultrasound-Guided Rectus Sheath Block in Gynaecological Surgery with Pfannenstiel Incision. Turk J Anaesthesiol Reanim 2015;43(5):318–22.

24. Breschan C, Jost R, Stettner H, Feigl G, Semmelrock S, Graf G, et al. Ultrasound-guided rectus sheath block for pyloromyotomy in infants: a retrospective analysis of a case series. Paediatr Anaesth 2013;23(12):1199–204.

25. Manassero A, Bossolasco M, Meineri M, Ugues S, Liarou C, Bertolaccini L. Spread patterns and effectiveness for surgery after ultrasound-guided rectus sheath block in adult day-case patients scheduled for umbilical hernia repair. J Anaesthesiol Clin Pharmacol 2015;31(3):349–53.

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doi: 10.5505/agri.2018.02439

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KLİNİK ÇALIŞMA / ORIGINAL ARTICLE

Migren hastalarında bipolar yelpaze bozukluklarının yaygınlığı Prevalence of bipolar spectrum disorders in migraine patients Barış Önen ÜNSALVER,1

Alper EVRENSEL,1

Mehmet Kerem DOKSAT2

Özet Amaç: Migren ve duygudurum bozuklukları arasındaki komorbidite uzun zamandan beri bilinmektedir. Çoğu çalışma migren ve major depresyon arasındaki bağlantıya odaklanırken, sınırlı sayıdaki çalışma migren ve bipolar spektrum bozuklukları arasındaki özgül ilişkiye dikkat çekmiştir. Bu çalışmada, özelleşmiş bir baş ağrısı polikliniğine başvuran migren hastaları arasında bipolar bozukluk yaygınlığını araştırmak amaçlanmıştır.

Gereç ve Yöntem: Örneklem, bir tıp fakültesi baş ağrısı polikliniğine başvuran 78 ardışık migrenli hastadan oluşturulmuştur. Migren tanısı için Uluslararası Baş Ağrısı Derneği kriterleri kullanılmıştır. Duygudurum bozuklukları tanısı DSM-IV Eksen 1 bozuklukları için yapılandırılmış klinik görüşme formu (SCID-I) ile konulmuştur. Bipolar yelpaze tanımı, Akiskal’in tanımladığı duygulanım huylarını (siklotimik, hipertimik, irritable ve depresif ) içerecek şekilde genişletilmiştir.

Bulgular: Örneklemin %10.3’ünü (n=8) bipolar yelpaze içerisindeki olgular oluşturmuştur. On bir hasta (%14.1) unipolar depresyon ve 7 hasta (%9) distimik bozukluk tanısı almıştır. Olguların %41’inde (n=32) bir duygulanım huyu tespit edilmiştir. Migren tanılı bireylerde bipolar bozukluğun daha sık görüldüğüne işaret eden önceki bulguları destekler tarzda migrenli hastalar arasında bipolar bozukluk yüksek oranda görülmüştür.

Sonuç: Duygulanım huylarının genel nüfustan daha yüksek oranda görülmüş olması, duygudurum bozukluklarının eşik altı görünümlerini temsil ettiği, migren ve bipolar bozukluk için ortak bir patofizyolojik temel olabileceği yönünde değerlendirilebilir. Dolayısıyla, migren ve bipolar bozukluğun komorbid olduğu hastalar, duygudurum bozukluklarına yönelik ileri çalışmalarda daha homojen bir alt grubu temsil edebilir.

Anahtar sözcükler: Bipolar bozukluk; bipolar yelpaze; migren.

Summary Objectives: Comorbidity of migraine and mood disorders has long been recognized. Most of the studies have focused on the relationship between migraine and major depression with only few studies suggesting a special association between migraine and bipolar spectrum disorders. We aimed to evaluate the prevalence of bipolar disorder in migraine patients in a specialized headache outpatient clinic.

Methods: The sample consisted of 78 consecutive patients with migraine headache presenting to the specialized headache outpatient clinic in a Medical Faculty. Migraine diagnosis was established with the International Headache Society’s criteria for migraine. Patients were evaluated with Structured Clinical Interview for DSM-IV for mood disorders. Bipolar spectrum definition was broadened with the presence of Akiskal’s criteria for affective temperaments (cyclothymic, hyperthymic, irritable, and depressive).

Results: Patients in the bipolar spectrum comprised 10.3% (n=8) of the sample. 11 patients (14.1%) had a diagnosis of unipolar depression and 7 patients (9%) had a diagnosis of dysthymic disorder. 41% of the patients (n=32) had an affective temperament. Bipolar disorder was observed with increased frequency in this migraine sufferer population, supporting previous findings of increased prevalence of bipolar disorders in patients with migraine.

Conclusion: Increased frequency of affective temperaments might be considered in the context of a common pathophysiological background for migraine and bipolar disorders where these temperaments are sub-threshold presentations of mood disorders. Therefore, the definition of patients with comorbid migraine and bipolar disorder may serve as a more homogenic subgroup of mood disorders for further studies.

Keywords: Bipolar disorder; bipolar spectrum; migraine.

Üsküdar Üniversitesi İnsan ve Toplum Bilimleri Fakültesi, Psikoloji Bilim Dalı, İstanbul Beykent Üniversitesi, Psikoloji Bilim Dalı, İstanbul 1 Department of Psychology, Üsküdar University Faculty of Humanities and Social Sciences, Istanbul, Turkey 2 Department of Psychology, Beykent University, Istanbul, Turkey 1 2

Başvuru tarihi (Submitted) 20.01.2018 Düzeltme sonrası kabul tarihi (Accepted after revision) 11.09.2018 Online yayımlanma tarihi (Available online date) 28.10.2018

İletişim (Correspondence): Dr. Barış Önen Ünsalver. Üsküdar Üniversitesi, NP Feneryolu Tıp Merkezi, Ahmet Mithat Efendi Cad., No: 17, Kalamış 34726, İstanbul, Turkey.

Tel (Phone): +90 - 216 - 418 15 00 e-posta (e-mail): onenunsalver@gmail.com © 2018 Türk Algoloji Derneği

OCTOBER - EKİM 2018

189

A RI PAIN

Giriş Migren, toplumun önemli bir kısmını etkileyen ve ağrı sırasında işlevsellikte önemli derecede bozulmaya neden olabilen önemli bir halk sağlığı sorunudur.

Migren atağının bir parçası olarak veya prodrom döneminde gözlenen, depresyon, öfori, irritabilite, anksiyete, hiperaktivite, dikkat güçlüğü, anoreksi veya iştah artışı gibi duygudurum ve davranış değişiklikleri, her zaman için klinisyenlerin ve araştırmacıların ilgisini çekmiştir. Son 20–25 sene içerisinde biriken epidemiyolojik veriler, migren ve psikiyatrik rahatsızlıklar arasında, rastlantının ötesinde klinik bir bağlantı olduğuna dikkat çekmektedir. Migreni olmayan hastalarla karşılaştırıldığında, migrenli hastalardaki hayat boyu duygudurum bozuklukları sıklığı daha fazladır.[1,2] Doksat, migren ve bipolar bozukluk arasındaki görüngüsel farkın zamansal olduğunu, ancak, ultra hızlı döngülü bipolar bozuklukta bu farkın bile azaldığını vurgulamıştır (Tablo 1).[3] Migren[4,5] ve duygudurum bozukluklarının[6,7] etiyolojisinde, her iki durum için ortak olarak paylaşılan bir patofizyolojik düzenek ve ortak veya benzer nörokimyasal anormalliklerin varlığına yönelik varsayımlar önerilmektedir.[2,4,8] Nitekim hem migren[9] hem de duygudurum bozukluklarının[10] patogenezinde monoamin sistemlerindeki değişikliklerin yer aldığı düşünülerek migrenin önleyici tedavisinde kullanılan serotonin seçici gerialım engelleyicileri (SSGE) ve lityum gibi duygudurum dengeleyicilerin faydalı oldukları gösterilmiştir.

[11] Endicott,[12] Fasmer[1] ve Oedegaard[13] gibi araştırmacılar, bipolar 2 (BP-II) bozukluğun, bipolar 1 (BP-I) bozukluk’tan belirgin olarak daha yüksek oranda migrene eşlik ettiğine dikkat çekmişlerdir. Migren ve bipolar 2 bozukluk arasındaki ilişkinin farklı olduğu ve BP-I ile BP-II’nin farklı iki nozolojik durumu temsil ediyor

olabileceği öne sürülmüştür. Oedegaard ve Fasmer[13] migrenle komorbid unipolar depresyonun da, aslında bipolarite yelpazesi içerisinde değerlendirilebileceğini, migren ve komorbid depresyonun temeldeki aynı bozukluğun farklı fenotipik ifadeleri olabileceğini öne sürmüşlerdir. Bipolar duygulanım bozukluğu (BDB) olgularında migrenin daha sık görüldüğü ve bu olgularda duygudurum bozukluğu seyrinin daha kötü olduğuna dair birçok yayın mevcuttur.[14–16] Psikiyatrik rahatsızlıkların patofizyolojisine yönelik bilgilerin yetersizliği nedeniyle öncelikle görüngüsellik, hastalık seyri, tedaviye verilen yanıtlar ve ailevi yığılım gibi bilgiler kullanılarak bir tanı sistemi inşa edilmektedir. Psikiyatrik tanılarla ilgili araştırmalar, tanı ölçütlerinin özgüllüğünü daha da arttırmaya yönelmiştir. Tanı gruplarının daha homojen olması, tedaviyi ve bu rahatsızlıkların patofizyolojisine yönelik araştırmaları kolaylaştıracaktır. Bu bağlamda, migren ve majör depresyon veya migren ve bipolar yelpaze komorbiditesinin homojen bir tanı grubuna örnek teşkil ettiği düşünülebilir. Migren gibi toplumda sık görülen ve kolay tanınabilen bir durum, klinik araştırmalarda, migren ve duygudurum bozukluğu belirtileriyle belirlenen bir sendromun tanımlanmasında faydalı bir belirteç olabilir. Bilindiği gibi psikiyatrik hastalıkları olan olgular ilk olarak ağrı kliniklerine başvurabilirler ve bu sebeple psikiyatrik hasta popülasyona ağrı kliniklerinden ulaşılabilir.[17] Bu bilgilerden yola çıkarak, bipolar yelpaze tanısı huy özelliklerini de içerecek biçimde genişletilerek yelpazenin silik (soft) ucundaki olguların migrenle ne oranda birliktelik gösterdiklerini belirlemek amaçlanmıştır. Ülkemizde Bipolar bozukluk ve migren arasındaki ilişki az sayıda çalışmada incelenmiştir, bu sebeple araştırmamızın epidemiyolojik literatüre de katkı sağlaması amaçlanmıştır.

Tablo 1. Bipolar bozukluk ve migren arasında görüngüsel benzerlikler

Migren

Prodrom Var (irritabilite veya disfori) Aura Genellikle var

(her türlü duygudurum değişikliği) Nöbet Var Postdrom Var (depresyon, disfori, yorgunluk) Premenstrüel kötüleşme Var Süre Saatler, günler

190

Bipolar bozukluk Genellikle var (irritabilite, disfori, veya depresyon) Genellikle var (her türlü duygudurum değişikliği) Var Var (depresyon, disfori, yorgunluk) Var Günler, aylar

OCTOBER - EKİM 2018

Migren hastalarında bipolar yelpaze bozukluklarının yaygınlığı

Gereç ve Yöntem Örneklem: Bir Üniversite Hastanesi Nöroloji Kliniği Baş Ağrısı Polikliniği’ne başvuran ve Uluslarası Baş Ağrısı Derneği (International Headache Society, IHS, 2004) kriterlerine göre migren tipi baş ağrısı tanısı alan ardışık hastalardan 25–70 yaş arasındaki 78 kişi çalışma örneklemini oluşturmuştur. Çalışmaya kabul edilen bireyler çalışma ile ilgili bilgilendirilmiş ve yazılı onamları alınmıştır. Çalışma yerel etik kurul onayı almıştır ve Helsinki Bildirgesi’ne uygundur.

Sosyodemografik özellikler, migrenle ilgili özellikler, duygudurum bozukluklarıyla ilgili özellikler, tıbbi özgeçmiş, tıbbi soygeçmiş, alışkanlıklar, ailedeki psikiyatrik hastalık ve migren öyküsü sorgulanmıştır.

Uygulama: Baş Ağrısı Polikliniği sorumlu hekimi tarafından migren tanısı konulan hastalarla görüşülmüştür. Olgu rapor formu doldurulduktan sonra SCID-1 (Structured Clinical Interview for DSM-IV Axis 1 Disorders) uygulanmıştır. SCID-1, eksen 1 tanılarının konması için geliştirilen yapılandırılmış klinik görüşme formudur. Geçerlik ve güvenirliği Çorapçıoğlu ve arkadaşları tarafından yapılmış olan Türkçe çevirisi kullanılmıştır.[18] Bipolar yelpaze tanımı, duygulanım huylarını içerecek şekilde genişletilmiştir. Hipertimik, irritabl ve depresif (eşik altı distimik) huy tanısı Akiskal ve Mallya’nın[19] ölçütlerine göre, siklotimik huy tanısı ise Akiskal ve Akiskal’in[20] ölçütlerine göre konmuştur. Sayılan özelliklerden en az beşinin bulunması gerekliliği aranmıştır.

Hipertimik huy ölçütleri: Erken başlangıç (21 yaşından önce), nadiren araya giren ötimiyle birlikte aralıklı eşik altı hipomanik özellikler, az uyuma alışkanlığı (<6 saat/gün, hafta sonları da dâhil), yadsımanın çok fazla kullanılması ve Schneiderian hipomanik kişilik özellikleri (İrritabl, neşeli, aşırı iyimser veya coşkulu, saf, kendine fazla güvenen, övüngen, abartılı, gösterişli, gayretli, çok plan yapan, tedbirsiz ve bitmez tükenmez bir itkiyle koşuşturan, aşırı konuşkan) şeklinde tanımlanmıştır.[19] Depresif (Eşik Altı Distimik) huy ölçütleri: Erken başlangıç (21 yaşından önce), başka bir duruma ikincil olmayan aralıklı, düşük şiddette depresyon, çok uyuma alışkanlığı (>9 saat/gün), derin derin düşünme, anhedoni ve psikomotor enerji azlığına meyil (hepsi sabah saatlerinde daha belirgin) ve Schneiderian depresif kişilik özellikleri (ümitsiz, kötümser, OCTOBER - EKİM 2018

neşesiz veya eğlenmeyen, sessiz, pasif ve kararsız, şüpheci, aşırı eleştiren veya şikâyet eden, derin derin düşünen ve endişelenen, vicdanlı, kendi kendini disipline eden, kendini eleştiren, kendini cezalandıran, kendini küçülten, başarısızlıkları, yetersizlikleri ve olumsuz olaylar hakkında aşırı kafa yoran) şeklinde tanımlanmıştır.[19] İrritable huy ölçütleri: Erken başlangıç (21 yaşından önce), nadiren ötimik, çoğunlukla karamsar (irritabl ve çabuk kızma), derin düşüncelere dalmaya eğilim, aşırı eleştiren ve şikâyet eden, aksi şakalar yapan, istenmediği halde sokulup sıkıntı veren, disforik şekilde yerinde duramama, itkisellik (impulsivity) şeklinde tanımlanmıştır.[19] Siklotimik huy ölçütleri: Erken başlangıç (21 yaşından önce), nadiren ötiminin olduğu sık ve kısa döngüler, bir fazdan diğerine öznel (letarjiye karşın ötoni, kötümserliğe karşın iyimserlik, zihinsel konfüzyona karşılık keskinleşmiş ve yaratıcı düşünce, düşük kendine güvene karşılık aşırı kendine güven arasında değişen benlik saygısı) ve davranışsal (azalmış sözel dışavuruma karşılık çok konuşma, hipersomniye karşılık uyku ihtiyacının artması, nedensiz sulu gözlülüğe karşılık aşırı şakacılık, kendini soyutlamaya karşılık sınırsız insan arama, üretkenlikte belirgin değişkenlik) görünümler arasında ani geçişlerin olduğu iki dönemli hastalık şeklinde tanımlanmıştır.[17] İstatistiksel Yöntem Tüm veriler analiz için SPSS 11.0 (Statistical Package for the Social Sciences for Windows) paket programına yüklenmiştir. Tanımlayıcı istatistikler için frekans dağılımları hesaplanmıştır. Duygudurum bozukluğu tanıları ile huy özellikleri tanıları için olgu sayılarının azlığı nedeniyle gruplar arası karşılaştırmalı istatistiksel analiz yapılamamıştır. Duygudurum bozukluğu tanı grupları (majör depresyon, distimik bozukluk, bipolar 1 bozukluk, bipolar 2 bozukluk ve siklotimik bozukluk) birleştirilerek 26 olgunun bulunduğu tek bir duygudurum bozukluğu grubu elde edilmiştir.

Duygudurum bozukluğu saptananlar (n=26) ile saptanmayanlar (n=52) arasında istatistiksel anlamlılık aranmıştır. Niteliksel veriler arası ilişkiler ki-kare testi ile araştırılmıştır. Yanılma düzeyi olarak α=0.05 seçilmiş ve bu değere eşit ya da küçük p değerleri için ‘’istatistiksel olarak anlamlı farklılığın olduğu’’ yorumu yapılmıştır.

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A RI PAIN

Bulgular Örneklem, 66 kadın (%84.6) ve 12 erkek (%15.4) hastadan oluşmuştur. Yaş ortalaması 37.76+11.36’dır.

Hastaların 57’sinin evli (%73.1), 16’sının bekâr (%20 .5), 3’ünün boşanmış (%3.8) ve 2’sinin dul (%2.6) olduğu bulunmuştur. Olguların sosyodemografik özellikleri Tablo 2’de gösterilmiştir.

Yirmi altı kişi (%33.4) herhangi bir duygudurum bozukluğu tanısı almıştır. Duygudurum bozukluğu başlangıç yaşı ortalama 28.18+10.83 bulunmuştur. 11 hasta (%14.1) majör depresyon, 7 hasta (%9) distimik bozukluk, 2 hasta (%2.6) bipolar 1 bozukluk, 5 hasta (%6.4) bipolar 2 bozukluk ve 1 hasta (%1.3) siklotimik bozukluk tanı ölçütlerini karşılamıştır (Tablo 3).

23 kişinin (%29.5) birinci dereceden akrabalarında psikiyatrik hastalık öyküsü bulunmuştur. 11 kişinin (%14.1) geçmişte ve 7 kişinin (%9) yakın zamanda intihar fikri veya girişimleri olduğu saptanmıştır. Yakın zamanda intihar fikri veya girişimi olan 1 hasta ve geçmişte intihar fikri veya girişimi olan 5 hastanın herhangi bir duygudurum bozukluğu tanısını karşılamadığı belirlenmiştir. Majör depresyon tanısı alan 11 kişiden 8’i, distimik bozukluk tanısı alan 7 kişiden 2’si, bipolar 2 bozukluk tanısı alan 5 kişiden 4’ü ve hiçbir duygudurum bozukluğu tanısı almayan 10 kişi olmak üzere toplam 24 kişi, geçmişte depresyon tanısıyla antidepresan tedavi almıştır.

Bipolar 2 bozukluk tanısı alan 4 kişi ve bipolar 1 bozukluk tanısı alan 1 kişide ilk atağın depresyon olduğu saptanmıştır. Bipolar 1 bozukluk belirlenen hastaların ikisinde de, hastanın hatırlayabildiği en az iki depresif atak kaydedilmiştir. Bipolar 2 bozukluk grubundaki hastaların beşinde de, hastanın hatırlayabildiği en az iki depresif atak kaydedilmiştir. Bipolar 1 bozukluk ve bipolar 2 bozukluk tanısı alan birer hastada depresyon nedeniyle antidepresan tedavi almaktayken manik ve hipomanik kayma yaşandığı belirlenmiştir. Çalışmamızdaki 78 hastadan 40’ının (%51.3), en az 1 aydır antidepresan tedavi (6 kişide antidepresan dozun altında amitriptilin) almakta olduğu kaydedilmiştir. Bu 40 kişiden 14’ünün (%17.9) bir duygudurum bozukluğu tanısını karşıladığı, ancak bu 14 kişiden 4’üne psikiyatrik sebepler yerine migren tedavisi amacıyla antidepresan başlandığı belirlenmiştir. 4 kişi (%5.12) anksiyete bozukluğu nedeniyle antidep192

Tablo 2. Olguların sosyodemografik özellikleri Sosyodemografik özellik Cinsiyet Kadın Erkek Yaş aralığı 18–24 25–34 35–44 44–54 55–65 Medeni durum Bekâr Evli Boşanmış Dul İş durumu Memur İşçi Serbest Emekli Ev kadını Öğrenci İşsiz Ekonomik durum Kötü Orta İyi

Sayı

%

66 12

84.6 15.4

13 13 30 16 6

16.7 16.7 38.5 20.5 7.7

16 57 3 2

20.5 73.1 3.8 2.6

13 5 7 4 32 8 9

16.7 6.4 9.0 5.1 41.0 10.3 11.5

7 46 25

9.0 59.0 32.1

Tablo 3. Duygudurum bozukluğu tanılarının dağılımı Duygudurum bozukluğu Majör depresyon Distimik bozukluk Bipolar 1 bozukluk Bipolar 2 bozukluk Siklotimik bozukluk Toplam

Sayı

%

11 (10 kadın, 1 erkek) 7 (5 kadın, 2 erkek) 2 (2 kadın) 5 (4 kadın, 1 erkek) 1 (1 kadın) 26 (22 kadın, 4 erkek)

14.1 9 2.6 6.4 1.3 33.4

resan tedavi almaktadır. Geri kalan 14 kişinin de migren tedavisi için antidepresan tedavi almakta olduğu belirlenmiştir. 54 hasta (%69.2) duygudurumda mevsimsel bir değişiklik tariflemezken, 24 hasta (%29.8) duygudurumda mevsimsel değişiklik tarif ediyordu.

28 kişide (%35.9) nikotin, 2 kişide (%2.6) alkol kötüye kullanımı saptanmıştır.

OCTOBER - EKİM 2018

Migren hastalarında bipolar yelpaze bozukluklarının yaygınlığı

Tablo 4. Migren özelliklerine göre tanı gruplarının karşılaştırması

DDB var (26)

DDB yok (52)

p

Sayı % Sayı %

Aura durumu

Yok

Var Ağrının yerleşimi Sıklıkla sağ

Sıklıkla sol Her iki taraf Gündelik işlerini sürdürebilme

Sürdürebiliyor

Sürdüremiyor Ailede migren öyküsü

Var

Yok Ailede psikiyatrik öykü

Var

Yok

13 50 29 55 0.630 13 50 23 45 8 30 13 25 10 40 13 25 0.253 8 30 26 50 15 58 37 71 0.234 11 42 15 29 15 58 36 69 0.313 11 42 16 31 11 42 12 23 0.079 15 58 40 77

DDB: Duygudurum bozukluğu.

Tablo 5. Huy özellikleri dağılımı Huy özellikleri

Sayı

%

Hipertimik huy Siklotimik huy Depresif huy İrritabl huy Toplam

3 (2 kadın, 1 erkek) 9 (7 kadın, 2 erkek) 16 (15 kadın, 1 erkek) 4 (4 kadın) 32 (28 kadın, 4 erkek)

3.8 11.5 20.5 5.1 40.9

Duygudurum bozukluğu ile migren özelliklerinin (migrenin auralı veya aurasız olması, ağrının hemisferik yerleşimi, ağrı sırasında gündelik hayatın etkilenmesi, ailede migren öyküsü ve ailede psikiyatrik öykü) arasındaki ilişki ki-kare testiyle incelendiğinde gruplar arasında anlamlı ilişki saptanmamıştır. (Tablo 4) 3 hastada (%3.8 ) hipertimik, 9 hastada (%11.5) siklotimik, 16 hastada (%21.8) depresif ve 4 hastada (%5.1) irritabl huy ölçütleriyle uyumlu huy özellikleri saptanmıştır. 45 kişide herhangi bir huy özelliği belirlenmemiştir. Huy özelliklerinin sayısal dağılımı Tablo 5’te gösterilmiştir. Huy tanılarının migren özelliklerine göre sayısal dağılımı Tablo 6’da gösterilmiştir.

OCTOBER - EKİM 2018

Gerek duygudurum bozukluğu alt gruplarındaki olgu sayısının, gerekse de her bir duygulanım huyu için ölçütleri karşılayan olgu sayılarının düşüklüğü, migreni olan bireylerde duygudurum bozukluğu tanıları ve duygulanım huyları arasındaki ilişkinin istatistiksel sorgulanmasına engel olmuştur.

Tartışma Bir Üniversite Hastanesi Nöroloji Kliniği Baş Ağrısı Polikliniği’ne başvuran migren tanılı hastalarda Bipolar yelpaze bozuklukları yaygınlığının araştırıldığı bu çalışmada varsayımımıza uygun olarak migren olgularında Bipolar yelpaze bozuklukları tanı oranı genel nüfustakinden daha yüksek bulunmuştur. Örneklemimizdeki, kadın/erkek oranı=5.5/1’dir (%84.6 kadın). Bu oran Türkiye’de yürütülmüş olan migren sıklığına dair önceki iki çalışmadaki cinsiyet oranlarına (sırasıyla %86,2 ve %78.4) yakın durmaktadır.[21,22] Benbir ver arkadaşları Iğdır Devlet Hastanesi Nöroloji Kliniği’ne 1 yıl boyunca başvuran 4951 baş ağrı yakınması olan hastanın baş ağrısı özellikleri ve alt tiplerini belirlemişlerdir. Önceki çalışmalardan farklı olarak bu araştırmadaki yetişkin yaş grubundaki katılımcıların %10.50’si aurasız migren tanılı erkek ve %6.8’i aurasız migren tanılı kadından oluşmuştur.[23] Kadın193

A RI PAIN Tablo 6. Migren özellikleri ile huy özelliklerinin dağılımı İrritable

huy (4) Migren başlangıç yaşı (ortalama yıl) Auralı migren Aurasız migren Migren lokalizasyonu Sağ Sol Her iki taraf Sıklık >1/hafta <1/hafta, >1/ay <1/ay Ağrı sırasında gündelik hayatın etkilenmesi Rahatlıkla sürdürüyor Güçlükle de olsa sürdürüyor Sürdüremiyor Ailede migren öyküsü Ailede psikiyatrik hastalık öyküsü Akraba evliliği Yakın zamanda intihar girişimi/fikri Geçmişte intihar girişimi/fikri

24.8 2 2

Siklotimik huy (9)

Depresif huy (16)

Huy yok (45)

35.0 1 2

18.0 1 8

30.88 9 7

23.56 18 29

0 1 3

1 0 3

2 3 4

6 6 4

12 13 30

1 1 2

1 2 0

4 4 1

7 8 1

10 24 11

1 1 2 4 2 1 0 0

0 2 1 2 1 2 1 0

3 1 5 7 4 2 0 2

4 8 4 12 4 3 1 1

14 18 14 26 12 3 5 8

larda en yüksek migren sıklığı 20–30 yaş aralığında, erkeklerde ise 40–30 yaş aralığında bulunmuştur.

Türkiye’de klinik ortamda yürütülmüş diğer çalışmalardaki yaş ortalamaları sırasıyla 35+9.8, 32.4+10.2 ve 37.76+11.36 olarak bulunmuştur.[21,22,24] Çalışmamızda, bipolar 1, bipolar 2 ve siklotimik bozukluk tanılı olgular, önceki çalışmalardaki bipolar oranlarına yakın biçimde tüm örneklemin %10.3’ünü oluşturmuştur. Merikangas ve arkadaşlarının[25] saha çalışmasında, migrenlilerdeki 1 yıllık bipolar yelpaze sıklığı %8.8, Breslau ve arkadaşlarının[8] benzer bir saha çalışmasında migrenlilerdeki hayat boyu manik epizod sıklığı %4.7 ve bipolar 2 bozukluk sıklığı %3.9, Robbins ve Ludmer’in[26] klinik çalışmasında hayat boyu bipolar yelpaze sıklığı %8.6 bulunmuştur. Kıvılcım ver arkadaşlarının yakın tarihli çalışmasında ise 120 migren olgusundan %19.2’si (n=23) BAB tanısı almıştır.[27] Olgu sayısının yetersizliğine rağmen, önceki çalışmalara yakın bir oran bulunmuş olması, elde ettiğimiz bu sonucun anlamlı olduğunu düşündürmektedir.

194

Hipertimik huy (3)

Dünya Sağlık Örgütü’nün 2011 tarihli Bipolar yelpazenin 12 aylık prevalans çalışmasında BP-I %0.4, BP-II %0.3, Eşik altı BP %0.8 ve Bipolar spektrum bozuklukları %1.5 sıklıkta bulunmuştur.[28] Dolayısıyla, bu üç çalışma ve bizim çalışmamızın sonuçları, migrenlilerde, genel nüfustan daha yüksek oranda bipolar bozukluk görüldüğüne işaret etmektedir.

Türkiye’de yapılan bir çalışmada 12 aylık depresyon ve distimik bozukluk sıklığı sırasıyla %4 ve %1.6 bulunurken[29] Erzurum’da üniversite öğrencileri üzerinde yapılan bir tarama çalışmasında ise, depresyon ve distimik bozukluğun hayat boyu sıklığı sırasıyla %8 ve %4 bulunmuştur.[29] Ülkemizde Bipolar yelpaze bozukluklarının sıklığına dair Binbay ve arkadaşlarının yaptığı çalışmada, İzmir kent merkezinde DSM-IV tanı kriterlerine göre psikotik özellikli depresyon ve BP-I yaygınlığı %0.92 olarak bildirilmiştir.[30] Bu veriler, çalışmamızda bulunan majör depresyon (%14.1) ve distimik bozukluk (%9) oranlarının, Türk toplumunun genelinden yüksek olduğunu düşündürmektedir. Bu bulgu migrenli olgularda duygudurum bozuklukların toplumun genelinden daha sık görüldüğü bilgiOCTOBER - EKİM 2018

Migren hastalarında bipolar yelpaze bozukluklarının yaygınlığı

sini desteklemektedir. Klinik ortamlarda yürütülmüş, 40 ile 500 olgu arasında değişen büyüklükteki çalışmalardan elde edilen sonuçlar, migrenli hastalarda depresyonun nokta sıklığının %11.9–57 ve hayat boyu sıklığının ise %3.8–54.3 arasında değiştiğini göstermiştir.[11] Migrenlilerde hayat boyu depresyon oranları iki saha çalışmasında sırasıyla %26.6 ve %40.7 bulunmuştur.[8,31] Zürih kohortunda ise 1 yıllık depresyon oranı %14.7 bulunmuştur.[25] Türk toplumunda migrenlilerde hayat boyu depresyon oranı %32.51 olarak saptanmıştır.[32] Atasoy ve arkadaşları süreğen migren ağrılı 55 hastanın %10,9’unda depresyon ve %20’sinde distimi saptamıştır.[33] Semiz ve arkadaşlarının çalışmasında ise Sivas Üniversitesi öğrencileri arasında migren tanısı alan 221 olguda depresyon sıklığı %10.1 bulunmuştur.[34] Çalışmamızdaki %14.1 depresyon sıklığı, bu klinik çalışmalarla uyumludur. Çalışmada örneklemin neredeyse yarıya yakınında (%41.0) bir duygulanım huyu saptanmıştır. En yüksek oranda depresif huy (16 hasta, %20.5) ve siklotimik huy (9 hasta, %11.5) gözlenmiştir. Depresif huyun genel toplumda görülme oranları %3.6 ve %3.1 arasında değişmektedir.[35,36] Depresyon hastaları arasında depresif huya normal nüfustan daha yüksek oranlarda rastlandığı ve depresif huyun depresyonla ilintili olduğu ve ayrıca hipertimik huyun birincil olarak maniyle ilişkili olduğu gösterilmiştir.[37] BP-I bozukluk tanılı hastalar ve akrabaları huy özellikleri yönünden değerlendirildiklerinde, siklotimik huy oranları düşük çıkarken, hipertimik huy, diğer duygulanım huylarından daha yüksek oranlarda bulunmuştur.[36] Öte yandan, Akiskal, siklotimik huyun bipolarite ile en bağlantılı duygulanım huyu olduğunu bildirmiştir.[38] Siklotimik huy ise iki farklı çalışmada genel nüfusta %6.3 ve %1.7 oranlarında bulunmuştur.[35,36] Çalışmamızdaki siklotimik huy oranının, bu iki değerin belirgin olarak üstünde bulunmuş olması, siklotiminin bipolariteyle (özellikle BP-II) yakın ilişkisinin bir yansıması olabilir. Duygulanım huylarının bipolar yelpazesi ile süreklilik gösterdiği, dolayısıyla duygudurumdaki oynaklığı yansıttığı söylenebilir.[39] Fornaro ve ark. çalışmasında bu bulgu desteklenecek biçimde migrenli olgularda siklotimik huy sıklığı %45 bulunmuştur.[16] Çalışmamızda bipolar gruplara benzer biçimde duygulanım huylarının yüksek oranda görülmüş olması, OCTOBER - EKİM 2018

duygudurumda oynaklık ve baş ağrıları gibi dönemsel durumlar olarak görülen migren ve duygudurum bozukluklarının ortak bir etiyopatogenetik temeli paylaşıyor olabileceğini düşündürmüştür. Migrenle duygulanım huylarının bağlantısından bahseden önceki çalışmalarda, bir duygudurum bozukluğu tanısı almış olan hasta grupları arasında duygulanım huylarına bakılmıştır ve bu nedenle duygulanım huylarının bu hastalara eşlik etmesi beklenebilir bir bulgudur. Robbins ve Ludmer, migrenli hastalarda hipertimik ve siklotimik duygulanım huylarına bakmış olmakla birlikte, sadece başka türlü adlandırılamayan bipolar grubuna giren olguların oranını vermiştir.[26] Oysa bizim çalışmamızın farklılığı, birincil olarak migren tanısı alan bir grupta dört duygulanım huyuna bakılmış olmasıdır.

Duygulanım huylarının duygudurum bozukluklarının gelişimine zemin hazırlayıp hazırlamadıkları, duygudurum atağının seyrini etkileyip etkilemedikleri, duygudurum atağının ataklar arası veya tortu duygudurum belirtileri olup olmadıkları araştırılmaktadır. Oedegaard ve Fasmer’in araştırmasında unipolar duygudurum bozukluğu ve migrenin komorbid olduğu grupta, 63 hastanın 12’sinde depresif huy ve 13’ünde siklotimik huy tesbit edilirken, migrenin eşlik etmediği unipolar grupta depresif ve siklotimik huy özelliği bulunan hastaların sayısı belirgin düşük olacak şekilde sırasıyla 3 ve 4’dür.[13] Yani, migrenle komorbid duygudurum bozukluklarında duygulanım huyları da daha sık görülüyor gibi durmaktadır.

Bu bulgu bir yandan, duygulanım huylarının bipolar spektrumu içerisindeki konumlarıyla ilişkili olabilir.

Duygulanım huylarının daha sık görülüyor olması, migren ve duygulanım huylarının paylaştıkları ortak bir etyopatogenetik etmenin var olabileceğine işaret edebilir. Belli bir duygulanım huyu, migren gelişimine zemin hazırlıyor olabilir. Nitekim Cloninger’ın tarif ettiği psikobiyolojik karakter boyutları ve migren arasında bir bağlantı olduğunu gösteren çalışmalar da mevcuttur.[40] Cloninger’ın tarif ettiği kişiliğin psikobiyolojik modelinde karakter boyutlarının (yenilik arayışı, zarardan kaçınma ve ödül bağımlılığı) her biri farklı nörotransmitter sistemleriyle (sırasıyla; dopaminerjik, serotonerjik ve noradrenerjik) ilgilidir ve psikoz ve duygudurum bozukluklarının eşik altı sendrom biçimleri veya bu durumlara yatkınlık yaratabildikleri önerilmiştir. Başka bir deyişle, bu karakter boyutlarından birinin varlığı, migren gelişiminin 195

A RI PAIN zeminini hazırlıyor olabilir. İleri bir çalışmada, duygulanım huyları, karakter özellikleri ve migrenle psikiyatrik komorbidite birlikte ele alınarak, altta yatan psikobiyolojik düzenek daha iyi anlaşılabilir.[41] Duygudurum bozukluğu tanısının migrenin tuttuğu tarafla ilişkili olduğu öne sürülmektedir. Bipolar bozukluk sol hemisferle, unipolar depresyon ise sağ hemisfer işlev bozukluğuyla ilişkilidir. Migrenle komorbid bipolar 2 bozukluk hastalarında migren ağrılarının anlamlı olarak daha yüksek oranda sağ tarafı, migrenle komorbid unipolar bozukluk hastalarında ise migren ağrılarının anlamlı olarak daha yüksek oranda sol tarafı tuttuğu gösterilmiştir.

[13] Bizim çalışmamızda ise, ağrının tuttuğu taraf ve duygudurum bozukluğu tanısı arasında bir bağlantı bulunmamıştır.

Birinci dereceden akrabalarda migren öyküsü, psikiyatrik öykü ve akraba evliliği sorgulanarak, duygudurum bozukluğu bulunan hastalar için ayırt edici ailevi bir bulgunun varlığını araştırmak hedeflenmiştir. Önceki çalışmalarda da, migren ve duygudurum bozukluğu komorbiditesinin altında genetik bir etmenin yatmadığını ima eden sonuçlar elde edilmiştir.[4,25] Oedegaard ve Fasmer duygudurum bozukluğuyla komorbid migreni olan hastalar ve migreni olmayan hastaları karşılaştırdıklarında, ailede psikiyatrik hastalık öyküsü oranları açısından gruplar arasındaki farkın anlamlı olmadığını bulmuşlardır.[13] Bizim çalışmamızda da önceki çalışmalarla uyumlu olacak şekilde, duygudurum bozukluğunun komorbid olduğu ve olmadığı grupları ailede psikiyatrik öykü oranları açısından karşılaştırdığımızda gruplar arasındaki fark istatistiksel olarak anlamlı bulunmamıştır (p=0.079).

Ancak, ailede psikiyatrik öykü bulunan 23 kişiden 11’inde (%47.82), yani neredeyse yarıya yakınında bir duygudurum bozukluğu tanısı bulunmuştur. Buradan yola çıkarak, ailede psikiyatrik hastalık hikâyesinin migrenli hastalarda duygudurum bozukluğu ihtimalini arttırıyor olduğu öne sürülebilir. Örneklemimizdeki duygudurum bozukluğu ve duygudurum huyu saptanan olguların azlığının ileri istatistiksel analizler yapmaya olanak vermemiş olması çalışmamızın kısıtlılıklarındandır. Sonuçların, istatistiksel anlam taşımaması, olgu sayısının düşüklüğüyle bağlantılıdır. Çalışmanın klinik ortamda yürütülmüş olması, sonuçların topluma genelleştirilmesini en196

gellemiştir. Özelleşmiş baş ağrısı kliniklerine başvuran hastalar toplumu yansıtamaz, çünkü baş ağrısı yakınması olan çoğu kişi, tedavi arayışına girmemektedir. Dolayısıyla, burada elde ettiğimiz verilerin bir kısmı, tedavi arama davranışının altında yatan sebeplerle de ilintili olabilir. Çalışmamızın kesitsel özelliği ve doğrudan hastadan alınan bilgiye dayanması nedeniyle, bu araştırmanın bulgularıyla duygulanım huyları ve migren arasında bir bağlantı olduğu söylenemez. Ancak, migren kliniğinin seyri, duygulanım huyları ve duygudurum dönemlerinin seyrinin birlikte takip edildiği ileri yönelik çalışmalarla bu ilişkiler incelenebilir. Çalışmamızda duygulanım huylarının tespitinde Türkçe geçerlilik güvenilirliği yapılmış olan TEMPS-A ölçeğinin kullanılmamış olması ve bunun yerine birebir tüm kriterlerin 1. araştırmacı tarafından yüzyüze görüşmede sorulmuş olması bir yanlılık oluşturmuş olabilir. Örneklemin migren tedavisinde sıklıkla tercih edilen farmakolojik müdahalelerden olan şimdiki ve geçmişteki antidepresan ve duygudurum düzenleyici ilaç kullanımlarının sorgulanmamış olması ilaçların duygudurum ataklarını tetikleyici ya da önleyici etkisini yorumlamayı engellemiştir.

Zira, antidepresanlar BAB’da duygudurum ataklarını tetiklerken, duygudurum düzenleyiciler ataklardan koruyucudur.

Sonuç Migren tanılı bireylerde bipolar bozukluğun daha sık görüldüğüne işaret eden önceki bulguları destekler tarzda migrenli hastalar arasında bipolar bozukluk yüksek oranda görülmüştür. Duygulanım huylarının genel nüfustan daha yüksek oranda görülmüş olması, duygudurum bozukluklarının eşik altı görünümlerini temsil ettiği, migren ve bipolar bozukluk için ortak bir patofizyolojik temel olabileceği yönünde değerlendirilebilir. Dolayısıyla, migren ve bipolar bozukluğun komorbid olduğu hastalar, duygudurum bozukluklarına yönelik ileri çalışmalarda daha homojen bir alt grubu temsil edebilir.

Gelecek çalışmalarda, migren ve bipolar bozukluğun birlikte görüldüğü örneklemler içerisinde migren ataklarıyla bağlantılı psikiyatrik kötüleşmeler, her iki hastalığı hedefleyen özgül ilaçların kullanımında tedaviye yanıt ve prognoz, paylaşılan patofizyolojinin altında yatan düzenekleri izah etmek için aile ve genetik çalışmalar ile biyolojik tedavi hedefleri araştırılmalıdır.

OCTOBER - EKİM 2018

Migren hastalarında bipolar yelpaze bozukluklarının yaygınlığı

Yazar(lar) ya da yazı ile ilgili bildirilen herhangi bir ilgi çakışması (conflict of interest) yoktur.

Hakem değerlendirmesi: Dış bağımsız.

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30. Binbay T, Alptekin K, Elbi H, Zağlı N, Drukker M, Aksu Tanık F, et al. Lifetime prevalence and correlates of schizophrenia and disorders with psychotic symptoms in the general population of Izmir, Turkey [Article in Turkish]. Turk Psikiyatri Derg 2012;23(3):149–60.

31. Breslau N, Schultz LR, Stewart WF, Lipton RB, Lucia VC, Welch KM. Headache and major depression: is the association specific to migraine? Neurology 2000;54(2):308–13.

32. Kececi H, Dener S, Analan E. Co-morbidity of migraine and major depression in the Turkish population. Cephalalgia 2003;23(4):271–5.

33. Atasoy N, Atasoy HT, Ünal A, Konuk N, Atik L. Süregen günlük baş ağrısında psikiyatrik komorbidite. Klinik Psikiyatri 2004;7:26–31.

34. Semiz M, Şentürk IA, Balaban H, Yağız AK, Kavakçı Ö. Pre-

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35. Placidi GF, Signoretta S, Liguori A, Gervasi R, Maremmani I, Akiskal HS. The semi-structured affective temperament interview (TEMPS-I). Reliability and psychometric properties in 1010 14-26-year old students. J Affect Disord 1998;47(13):1–10.

36. Vahip S, Kesebir S, Alkan M, Yazici O, Akiskal KK, Akiskal HS. Affective temperaments in clinically-well subjects in Turkey: initial psychometric data on the TEMPS-A. J Affect Disord 2005;85(1-2):113–25.

37. Akdeniz F, Kesebir S, Vahip S, Gönül AS. Is there a relationship between mood disorders and affective temperaments?

[Article in Turkish] Turk Psikiyatri Derg 2004;15(3):183–90.

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38. Akiskal HS. Validating ‘hard’ and ‘soft’ phenotypes within the bipolar spectrum: continuity or discontinuity? J Affect Disord 2003;73(1-2):1–5.

39. Akiskal HS, Bourgeois ML, Angst J, Post R, Möller H, Hirschfeld R. Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000;59 Suppl 1:5–30.

40. Boz C, Velioglu S, Ozmenoglu M, Sayar K, Alioglu Z, Yalman B, et al. Temperament and character profiles of patients with tension-type headache and migraine. Psychiatry Clin Neurosci 2004;58(5):536–43.

41. Sayin A, Aslan S. The relationship between mood disorders and temperament, character and personality [Article in Turkish]. Turk Psikiyatri Derg 2005;16(4):276–83.

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CASE REPORT

A probable case of movement disorder (Tardive dyskinesia) due to duloxetine treatment Duloksetin tedavisine bağlı beklenmedik bir hareket bozukluğu olgusu (Tardif diskinezi) Resul YILMAZ,1

Damlanur ÜSTÜN,2

Sema TUNCER UZUN,3

Ruhiye REISLI,3

Şeyda TÜRK4

Summary Tardive dyskinesia and tardive dystonia are caused by dopamine receptor blocking agents, mostly antipsychotics and sometimes antidepressants or calcium channel blockers. Duloxetine is a serotonin-noradrenaline reuptake inhibitor used in the treatment of diabetic neuropathic pain and fibromyalgia, as well as major depression. In this case, we aimed to discuss the tardive dyskinesia-like appearance of a patient using duloxetine due to fibromyalgia.

Keywords: Duloxetine; fibromyalgia; tardive dyskinesia.

Özet Tardif diskineziye ve tardif distoniye, çoğunlukla dopamin reseptör bloke edici ajanlar, bazen de antidepresanlar veya kalsiyum kanal blokerleri neden olur. Duloksetin, diyabetik nöropatik ağrı ve fibromiyaljinin yanı sıra majör depresyon tedavisinde kullanılan bir serotonin-noradrenalin geri alım inhibitörüdür. Bu olguda fibromiyaljiye bağlı duloksetin kullanan bir hastanın tardif diskinezi benzeri görünümünü tartışmayı amaçladık.

Anahtar sözcükler: Duloksetin; fibromyalji; tardif diskinezi.

Introduction Duloxetine is a serotonin-noradrenaline reuptake inhibitor used in the treatment of diabetic neuropathic pain and fibromyalgia, as well as major depression.[1] The mechanisms of action of drugs are also responsible for their side effects. The most frequent side effects are nausea, dry mouth, dizziness, decreased appetite, constipation and insomnia.[1] In this case report, we aimed to discuss the presentation of involuntary contraction following duloxetine use and possible tardive side effects.

Case Report A 60-year-old male presented with occasionally exacerbated headache and sleep disturbance, for 30

years. According to the knowledge obtained from the patient’s story, thepain was in his shoulders, neck and the back of his head, which spread to the top of the head. He stated that his pain gradually increased over time and for the last three months his pain continued constantly and that he had a sleep problem.

He described his pain as throbbing and like a lighting strike. The patient also stated that his pain decreases slightly with massage and rest, but increases with movement, light and loud noise.

He had previously been examined in neurology and ear-nose-throat clinics, said he tried various treatments for pain, used analgesics and antibiotics, but none of themreduced the pain. The patient had no known systemic illness, he was found to have had acute rheumatic fever in his childhood, but had no residual effecton his follow-up. Physical examina-

Department of Anesthesiology and Reanimation, Zile State Hospital, Tokat, Turkey Department of Anesthesiology and Reanimation, Turhal State Hospital, Tokat, Turkey 3 Department of Anesthesiology and Reanimation, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey 4 Department of Anesthesiology and Reanimation, Beyhekim State Hospital, Konya, Turkey 1 2

Submitted: 19.11.2017 Accepted after revision: 02.01.2018 Available online date: 25.10.2018

Correspondence: Dr. Resul Yılmaz. Zile Devlet Hastanesi, Anesteziyoloji ve Reanimasyon Bölümü, Zile, Tokat, Turkey.

Phone: +90 - 544 - 900 55 80 e-mail: dr.r.yilmaz@gmail.com © 2018 Turkish Society of Algology

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The patient was diagnosed with fibromyalgia and his pain was evaluated as neuropathic pain. Duloxetine (30 mg/day)and dexketoprofen (25 mg, to be used when the pain intensified) was prescribed. We suggested to keep apain diary and come to a follow-up after 10 days.

When the patient arrived 10 days later, he stated that his pain decreased significantly. However, he described spazm in the temporamandibular joint and muscles, that began 3–4 days ago. He stated that this spazm starts approximately 5 hours after taking his medication and it lasts for about 4 hours. The physical examination didn’t show any pathologic findings.

But it should be kept in mind that he didn’t have any symptoms at the time of the examination. Based on the patient’s expressions, these complaints were thought to be related to tardive dyskinesia. Termination of the treatment was suggested but despite this side effect, the patient didn’t want to discontinue his medication and he didn’t accept any other treatment. The treatment was continued by recommending caution against movement disorders.

ity and upregulation of these receptors. As a result, there is an increased availability of postsynaptic D2 receptors to interact with endogenous dopamine and this leads to a hyperkinetic motor condition known as tardive dyskinesia.[3] Serotonergic and noradrenergic modulation of cholinergic pathways has also been suggested to play a role in the formation of tardive dystonia.[4] In another theory, while D2 receptor blockade is present, repeated stimulation of D1 receptor by endogenous dopamine causes D1-mediated striatal pathway sensitization and dystonia.[5] Neurophysiological and electrical studies have shown that serotonin released by the raphe nucleus inhibits striatal neurons.[6] Thus, the inhibition of neuronal serotonin reuptake by increasing the presence of serotonin may produce a similar therapeutic effect to dopamine blocking agents. This hypothesis potentially explains the movement disorders that may result from antidepressants. Preclinical researches have shown that duloxetine inhibits neuronal serotonin and norepinephrine reuptake. Increased serotonin transit may also result in inhibition of dopaminergic neurotransmission, which may contribute to tardive dyskinesia and tardive dystonia.[6]

The patient didn’t come for a follow-up after that.

About a month later we contacted him by phone and he informed us that he used the medication for 10–15 days butdid not continue to do so after the headache was fully relieved, and that his jaw contractions disappeared completely.

Tricyclic antidepressants, fluoxetine, paroxetine, venlafaxine, trazodone, valbenazine, antipsychotics, can cause tardive dyskinesia.[7–13] There are a few case reports of duloxetine-related dystonia reported, and the symptom in one of these patients is mandibular muscle contraction.[14,15]

Discussion Tardive dyskinesia and tardive dystonia are caused by dopamine receptor blocking agents, mostly antipsychotics and sometimes antidepressants or calcium channel blockers.[2] Duloxetine-associated tardive syndrome is rarely reported in the literature.

In our patient, the facts that the symptoms first began within 3–4 days after the initiation of duloxetine treatment and that they start approximately 5 hours after taking his medication suggest dystonia.

Because of this, termination of the treatment was planned.

While pathophysiological basis of tardive dystonia is still uncertain, the current model is the hypersensitivity of postsynaptic dopamine-2 (D2) receptors in the nigrostriatal dopamine pathway resulting from prolonged inhibition of receptors. According to this theory, the long-term administration of dopamine receptor blocker causes denervation supersensitiv-

While there is no definitive treatment for tardive dyskinesia, tetrabenazine is the most effective choice.

Vitamin B6, vitamin E, donepezil, levetiracetam and botulinum toxin are other treatment options. In more serious cases, surgical intervention and deep brain stimulation may be the treatment option, but further research is needed.[16]

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Conclusion Tardive dyskinesia and tardive dystonia are caused by dopamine receptor blocking agents, mostly antipsychotics and sometimes antidepressants or calcium channel blockers. To our knowledge, there is only two report of tardive dyskinesia and tardive dystonia during treatment with duloxetine. Although these medications have a lower risk of causing tardive syndrome, clinicians should be cautious for involuntary movement during duloxetine treatment.

Informed Consent: Written informed consent was obtained from the patient who participated in this study.

Conflict-of-interest issues regarding the authorship or article: None declared.

Peer-rewiew: Externally peer-reviewed.

References 1. Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ. Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol 2008;23(3):161–9.

2. Jankovic J. Tardive syndromes and other drug-induced movement disorders. Clin Neuropharmacol 1995;18(3):197–214.

3. Çavuşoğlu H. Bazal ganglionlar-Motor fonksiyonları. In: Guyton AC, Hall JE, editors. Tıbbi Fizyoloji. 9th ed. İstanbul: Alemdar; 1996. p. 728.

4. Remington GJ. The Pisa syndrome: possible role for se-

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rotonin and noradrenaline. J Clin Psychopharmacol 1988;8(3):228–9.

5. Trugman JM, Leadbetter R, Zalis ME, Burgdorf RO, Wooten GF. Treatment of severe axial tardive dystonia with clozapine: case report and hypothesis. Mov Disord 1994;9(4):441–6.

6. Leo RJ. Movement disorders associated with the serotonin selective reuptake inhibitors. J Clin Psychiatry 1996;57(10):449–54.

7. Yassa R, Camille Y, Belzile L. Tardive dyskinesia in the course of antidepressant therapy: a prevalence study and review of the literature. J Clin Psychopharmacol 1987;7(4):243–6.

8. Clayton AH. Antidepressant-induced tardive dyskinesia: review and case report. Psychopharmacol Bull 1995;31(2):259–64.

9. Dubovsky SL, Thomas M. Tardive dyskinesia associated with fluoxetine. Psychiatr Serv 1996;47(9):991–3.

10. Boffa E, Lofchy J. Paroxetine and tardive akathisia. Can J Psychiatry 2000;45(2):196.

11. Botsaris SD, Sypek JM. Paroxetine and tardive dyskinesia. J Clin Psychopharmacol 1996;16(3):258–9.

12. Lee Y, Yeh WC, Chong MY, Lin PY, Chang YY. Venlafaxine and tardive blepharospasm: a case report. Prog Neuropsychopharmacol Biol Psychiatry 2007;31(5):1139–40.

13. L Lin CC, Lin PY, Lee Y, Chang YY, Chen CH. Tardive dystonia and tardive sensory syndrome related to trazodone: a case report. Prog Neuropsychopharmacol Biol Psychiatry 2008;32(6):1609–10.

14. Deuschle M, Mase E, Zink M. Dyskinesia during treatment with duloxetine. Pharmacopsychiatry 2006;39(6):237–8.

15. Chen PY, Lin PY, Tien SC, Chang YY, Lee Y. Duloxetine-related tardive dystonia and tardive dyskinesia: a case report.

Gen Hosp Psychiatry 2010;32(6):646.e9–11 16. Kenney C, Hunter C, Davidson A, Joseph J. Metoclopramide, an increasingly recognized cause of tardive dyskinesia. J Clin Pharmacol 2008;48(3):379–84.

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CASE REPORT

Migraine-like visual aura: Can it be an early-onset symptom of astrocytoma?

Migren benzeri görsel aura: Astrositomalı hastalarda erken bir başlangıç bulgusu olabilir mi?

Gökhan EVCILI,

Muhammed Nur ÖĞÜN,

Uygar UTKU

Summary Photopsia, fortification spectra, and the slow propagation of a scintillating scotoma across the visual field are typical diagnostic features of the visual aura of migraine. In the vast majority of cases, the diagnosis can be made without the need for further investigations. Herein, we report three consecutive cases with an astrocytoma and discuss clinical features of migraine-like visual aura.

Keywords: Astrocytoma; migraine like visual aura.

Özet Görme alanında fotopsi, fortifikasyon spektrumu ve parlama skotomu, görsel auralı migrenin karakteristik tanısal özellikleridir.

Olguların büyük bir çoğunluğunda tanı ileri tetkiklere gerek kalmaksızın yapılabilmektedir. Bu makalede, astrositomlu üç ardışık olgu sunuldu ve migren benzeri görsel auranın klinik özellikleri tartışıldı.

Anahtar sözcükler: Astrositoma; migren benzeri görsel aura.

Introduction Photopsia, fortification spectra, and the slow propagation of a scintillating scotoma across the visual field are typical diagnostic features of the visual aura of migraine. In the vast majority of cases, the diagnosis can be made without the need for further investigations.[1] Typical migraine-like visual aura due to a structural lesion with the absence of other neurological signs or symptoms is rare.[2,3] Herein, we report three consecutive cases with an astrocytoma and discuss clinical features of migraine-like visual aura in the light of the literature data.

Case Reports Case–1: A 32-year-old male was admitted with a two-year history of migraine headache-associated with visual aura. He suffered from gradually increasing in frequency of headache and changing in the characteristics of visual aura for two months. The patient described the visual aura as repetitive flashes of

light every five seconds and lasting approximately two minutes in the right visual field. He experienced five to 15 episodes in this period and several minutes later by a moderate to severe right-sided throbbing headache. There were no identifiable triggers for these attacks. There was also associated nausea, vomiting, phonophobia or photophobia. He had no other neurological or ophthalmological symptoms.

His physical, neurological, and fundoscopic examination findings, including blood pressure and meningeal signs, were normal. Complete blood count and routine biochemistry results, including liver and renal function tests and erythrocyte sedimentation rate, were normal. Electroencephalography (EEG) revealed normal findings. Cranial magnetic resonance imaging (MRI) revealed a lesion without any contrast enhancement within the right frontal lobe, consistent with a low-grade astrocytoma (Fig. 1). Stereotactic biopsy was, then, performed. The biopsy result was consistent with a low-grade astrocytoma.

Department of Neurology, Kocaeli Derince Training and Research Hospital, Kocaeli, Turkey Submitted (Başvuru tarihi) 03.12.2016 Accepted after revision (Düzeltme sonrası kabul tarihi) 03.06.2017 Available online date (Online yayımlanma tarihi) 25.10.2018

Correspondence: Dr. Uygar Utku. Kocaeli Derince Eğitim ve Araştırma Hastanesi, 41900 Kocaeli, Turkey.

Phone: +90 - 262 - 317 80 00 e-mail: uygarutku@yahoo.com © 2018 Turkish Society of Algology

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Migraine-like visual aura

Figure 1. T2-weighted, axial, and fluid-attenuated inversion recovery coronal magnetic resonance imaging scans showing a well-defined focal mass lesion in the right frontal lobe.

Figure 2. T2-weighted, axial, and fluid-attenuated inversion recovery coronal magnetic resonance imaging scans showing a well-defined focal mass lesion in the right occipital lobe.

Caseâ&#x20AC;&#x201C;2: A 33-year-old female was admitted with a new-onset of episodic migraine-like visual aura for six months. The aura consisted of fortification spectra (expanding zigzag pattern) and transient flashing white lights always recurring in the left visual field followed by a moderate to severe left-sided throbbing headache several minutes later, although it did not always occur (acephalgic migraine with visual aura). Episodes of aura lasted minutes and were associated with nausea, vomiting, photophobia, and headache lasting several hours; relieved by sleep and oral analgesia. She had a positive family history, but no personal history of migraine. Her physical, neurological, and fundoscopic examination findings, including blood pressure and meningeal signs, were normal. Complete blood count and routine OCTOBER 2018

biochemistry results, including liver and renal function tests and erythrocyte sedimentation rate, were normal. Electroencephalography revealed normal findings. Cranial MRI revealed a large lesion with a mild contrast enhancement within the right occipital lobe, consistent with an astrocytoma (Fig. 2).

Caseâ&#x20AC;&#x201C;3: A 23-year-old female was admitted with an increased frequency of headaches with visual aura for six months. The aura began as a star-shaped transient flashing white lights always recurring in the right visual field and, then, triangular zigzag lines followed by a moderate to severe left-sided throbbing headache several minutes later. Episodes of aura lasted minutes and were associated with nausea, photophobia, and headache lasting several hours; 203

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Figure 3. T2-weighted, axial, and fluid-attenuated inversion recovery coronal magnetic resonance imaging scans of a focal mass lesion in the right occipital lobe.

relieved by sleep and oral analgesia. There was no family or personal history of migraine. Her physical, neurological and fundoscopic examination findings, including blood pressure and meningeal signs, were normal. Complete blood count and routine biochemistry results, including liver and renal function tests and erythrocyte sedimentation rate, were normal. Electroencephalography revealed normal findings. Cranial MRI revealed a lesion without any contrast enhancement within the left occipital lobe, consistent with a low-grade astrocytoma (Fig. 3).

Discussion A careful history and physical examination still remain the mainstays of headache assessment. Although a very low number of patients with headaches have brain tumors, recognition of tumor-associated headaches is of utmost importance. In a study including 85 patients with a brain tumor, Schankin et al.[4] examined the characteristics of brain tumor-associated headache. The authors found that headache was the sole symptom in only 2%. In another study, Forsyth et al.[5] reported that headaches were similar to tension-type in 77%, migraine-type in 9%, and other types in 14% of 111 patients with a brain tumor. Our cases presented with only migraine-type headache with migraine-like visual aura due to an astrocytoma.

Furthermore, to critically examine the true nature of visual aura secondary to structural lesions and compare them to those of migraine, we examined three cases presenting with migraine-like visual aura 204

caused by focal cerebral lesions. Neuronal hyperexcitability or cortical spreading depression can explain the comorbidity of disorders, such as migraine, epilepsy and acquired brain lesions, the overlap in clinical features, particularly visual aura.[2,6] This mechanism may explain the discorelation between the localization of structural lesion and visual aura.

Diagnostic criteria for typical migraine visual aura are shown in Table 1.[7] Our cases experienced visual aura fulfilling the diagnostic criteria for migraine.

Considering the common features of these three cases (Table 2); one of them was increased frequency or new-onset of visual aura. All cases had typical visual aura with varying disease duration. Brief visual aura for seconds or less than five minutes was seen.

The diagnostic criteria for migraine with aura stipulate that the aura symptoms develop gradually over 5 or more minutes and last no more than 60 minutes.

[7] Our experience however suggests that visual aura caused by cerebral lesions cannot be reliably differentiated from migraine on the basis of the duration of the aura. The other was changing in the characteristics of visual aura; such as repetitive flashes or transient flashing white lights with fortification spectra.

The last one was the visual aura without headache.

Based on the literature review on migraine-like visual aura due to focal cerebral lesions, the red-flag warning features of the visual aura include stereotypical visual aura, increasing frequency of visual aura, altered patterns or characteristics of chronic visual aura, any unexplained visual field defects, and negaOCTOBER 2018

Migraine-like visual aura

Table 1. Diagnostic criteria for typical migraine visual aura I. At least two attacks fulfilling criteria II-IV II. Aura consisting of at least one of the following, but no motor weakness A. Fully reversible visual symptoms including positive features (e.g., flickering lights, spots, or lines) and/or negative features (i.e., loss of vision) B. Fully reversible sensory symptoms including positive features (i.e., pins and needles) and/or negative features (i.e., numbness) C. Fully reversible dysphasic speech disturbance III. At least two of the following A. Homonymous visual symptoms and/or unilateral sensory symptoms B. At least one aura symptom develops gradually over ≥5 minutes and/or different aura symptoms occur in succession over ≥5 minutes C. Each symptom lasts ≥5 and ≤60 minutes IV. Headache begins during the aura or follows aura within 60 minutes V. Not attributed to another disorder *International Classification of Headache Disorders (ICHD).

Table 2. Characteristics of three patients with an astrocytoma and the astrocytoma case reported initially

Case 1

Age (years) 32 New onset or old aura Old Duration of aura (minutes) 2 Change in frequency of aura Increase Location of visual aura in visual field Right Location of headache Right Location of lesion Right frontal Headache associated with aura Yes

History of seizure No

tive visual phenomena or subjective persistence of a scotoma following a typical visual aura.[2] In conclusion, these cases highlight the importance of being aware that migraine-like visual aura may lead to the diagnosis of a brain structural lesion.

The study has complied with the principles of the Declaration of Helsinki.

Conflict-of-interest issues regarding the authorship or article: None declared.

Peer-rewiew: Externally peer-reviewed.

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Case 2

Case 3

Case from the literature3

33 New 15 Increase Left Left Right occipital Yes (Not always) No

23 Old 15 Increase Right Left Left occipital Yes

31 New 15 Increase Bilateral Left sided Left temporal Yes

No

No

References 1. Russell MB, Olesen J. A nosographic analysis of the migraine aura in a general population. Brain 1996;119(Pt 2):355–61.

2. Shams PN, Plant GT. Migraine-like visual aura due to focal cerebral lesions: case series and review. Surv Ophthalmol 2011;56(6):135–61.

3. Magrotti E, Frascaroli G, Mariani G. Left temporal glioma presenting as migraine with typical aura. Ital J Neurol Sci 1992;13(5):444.

4. Schankin CJ, Ferrari U, Reinisch VM, Birnbaum T, Goldbrunner R, Straube A. Characteristics of brain tumour-associated headache. Cephalalgia 2007;27(8):904–11.

5. Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology 1993;43(9):1678–83.

6. Vincent MB. Vision and migraine. Headache 2015;55(4):595–9.

7. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd. Cephalalgia 2004;24:1–160.

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OLGU SUNUMU / CASE REPORT

Fahr hastalığıyla izlenen ve nöropatik ağrısı olan bir olguda tanısı geciken servikal myelomalezi Late diagnosed cervical myelomalesia in a case of Fahr disease experiencing a neuropathic pain Murat ALEMDAR Özet Fahr hastalığı bazal ganglionlar, serebellum ve subkortikal beyin dokularında kalsiyum ve diğer bazı minerallerin birikmesiyle giden idyopatik bir hastalıktır. Son 6 aydır olan her iki kolda ağrı, uyuşma, karıncalanma ve güçsüzlük yakınması olan elli bir yaşındaki kadın hasta karpal tünel sendromu şüphesiyle elektromiyografi labaratuvarımıza refere edildi. On yıl önce geçirdiği konvülsiyonlar sonrası yapılan incelemeler neticesinde Fahr hastalığı tanısı almıştı. Ayrıca, yaygın anksiyete bozukluğu mevcuttu. Nörolojik muayenesinde; her iki tarafta ön kol fleksiyonu ve ekstansiyonunda, ve el bileği ekstansiyonunda hafif düzeyde kas gücü kaybı mevcuttu. Bilateral 6. ve 7. servikal (C6 ve C7) dermatomlarında dizestezi tarifliyordu. Beyin BT’sinde bilateral serebellar hemisferde ve bazal ganglialarda simetrik kalsifikasyonlar mevcuttu. Her iki median ve ulnar sinir ileti çalışmaları normaldi. Konsantrik iğne elektromiyografi çalışması her iki C6 ve C7 myotomuna uyan kaslardan kaydedilen motor ünit potansiyellerinin morfolojisinde kronik nörojenik değişimler gözlendi. Servikal manyetik rezonans görüntülemesi; C4-5, C5-6 ve C6-7 seviyelerinde, myelomaleziye neden olan, diskopatiler saptandı. Fahr hastalığında ekstremitelerde nöropatik ağrı, uyuşma ve güç kaybı gibi bulgular çok enderdir. Sunulan olgu, mevcut belirtilerinin Fahr hastalığıyla ilişkili olduğu zannedildiğinden dolayı, servikal diskopati tanısını geç almıştır. Bu nedenle, klinisyenler bu hastalığın seyri esnasında sıkça karşılaşılan bulguların farkında olmalı ve atipik nörolojik defisitler tespit edildiğinde olası diğer eşlik eden patolojileri araştırmalıdırlar.

Anahtar sözcükler: Elektromiyografi; Fahr hastalığı; servikal diskopati.

Summary Fahr disease is an idiopathic disorder characterized with deposition of calcium and a few other minerals in basal ganglia, cerebellum and subcortical brain area. A 51 years old female with the complaints of pain, numbness, tingling and weakness in both upper extremities for six months was referred to our electromyography laboratory with a suspicion of carpal tunnel syndrome. She got the diagnosis of Fahr disease upon the investigations for the convulsions that she experienced ten years ago. Beside, she had a generalized anxiety disoder. Neurological examination revealed mild to moderate weakness in flexion and extension of forearm, and extension of hand on both sides. She described dysesthesia on C6 & C7 dermatomes, bilaterally. Symmetric calsifications on both cerebellar hemispheres and basala ganglia were present on cranial CT. Median and ulnar nerve conduction studies were normal on both sides. Concentric needle electromyography revealed chronic neurogenic changes on the morphology of motor unit potentials recorded from the muscles of C6 & C7, bilaterally. Cervical magnetic resonance imaging revealed discopathies on C4-5, C5-6 and C6-7 levels causing myelomalacia. Neuropathic pain, paresthesia or muscle weakness on upper extremities are rare in Fahr disease. Presented case got the diagnosis of cervical discopathies in late as those findings were supposed to be related with Fahr disease. Therefore, clinicians should be aware of common findings occured during the course of this disease, and consider the possible coincidental pathologies when the atypical neurological deficits are observed in these patients.

Keywords: Electromyography; Fahr disease; cervical discopathy.

Giriş Fahr hastalığı; bazal ganglionlar, serebellum ve subkortikal beyin dokularında kalsiyum ve diğer mine-

rallerin (aliminyum, magnezyum, çinko, bakır, demir vb) birikmesiyle giden idyopatik bir hastalıktır. İntraserebral kalsifikasyonlar; paratiroid bozukluklar,

Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi, Nöroloji Kliniği, Sakarya Department of Neurology, Sakarya University Training and Reserach Hospital, Sakarya, Turkey Başvuru tarihi (Submitted) 07.03.2017 Düzeltme sonrası kabul tarihi (Accepted after revision) 03.06.2017 Online yayımlanma tarihi (Available online date) 25.10.2018

İletişim (Correspondence): Dr. Murat Alemdar. Sakarya Üniversitesi Eğitim ve Araştırma Hastanesi, Nöroloji Kliniği, Adnan Menderes Caddesi, Sağlık Sokak, No: 195, Adapazarı, Sakarya, Turkey.

Tel (Phone): +90 - 264 - 888 40 00 e-posta (e-mail): drmuratalemdar@yahoo.com © 2018 Türk Algoloji Derneği

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EKİM - OCTOBER 2018

Fahr hastalığıyla izlenen ve nöropatik ağrısı olan bir olguda tanısı geciken servikal myelomalezi

hipotroidi, tüberoz skleroz, TORCH enfeksiyonları ve granülamatöz hastalıklar gibi nedenlere ikincil olarak da gözlenebilir.[1–3] Fahr hastalığına bağlı serebral hasarın oluşumunda non-vasküler mineralizasyonun yanı sıra, minerallerin kapiller duvarda ve perivasküler alanlarda birikmesine bağlı mikrovasküler oklüzyon, perivasküler nöron dejenerasyonu ve gliozis de rol oynar.[4] Fahr hastalığı; yavaş seyreden ilerleyici bir bozukluk olup, genelde 4–6. dekadlar arasında semptomatik hale gelir. Fahr hastalığının başlıca beliritileri; ilerleyici mental hasar, hareket bozuklukları, psikiyatrik bozukluklardır. Bu olgu sunumunda servikal myelomaleziye ikincil her iki üst ekstremitede ağrı, uyuşma ve güç kaybı yaşayan, ancak bulguları Fahr hastalığına bağlı olduğu düşünüldüğünden dolayı geç tanı alan bir olgu rapor edilmiştir.

Şekil 1. Beyin BT’de bilateral serebellar hemisferlerde ve bazal ganglialarda izlenen yaygın ve simetrik kalsifikasyonlar.

Sağ biceps brachii

Olgu Sunumu Elli bir yaşında kadın hasta son 6 aydır olan her iki elde ağrı, uyuşma ve güçsüzlük yakınması nedeniyle dış bir merkezden karpal tünel sendromu ön tanısıyla elektromiyografi (EMG) labaratuvarımıza refere edildi. On yıl önce geçirdiği konvülsiyonlar sonrası yapılan incelemeler neticesinde Fahr hastalığı tanısı alan hasta, o dönemden bu yana sodyum valproat tedavisi almaktaydı. Nöbetleri; önce ağız çevresinde uyuşma ve konuşmada peltekleşme, sonrasında da tüm vücutta kasılma ve bilinç bozulması şeklindeydi. Ayrıca, yaygın anksiyete bozukluğu nedeniyle venlafaksin ve alprozolam tedavisi kullanmaktaydı.

Herhangi bir bilişsel belirti tariflemeyen hasta, dengesizlik nedeniyle sıkça düştüğünden yakınıyordu.

Nörolojik muayenesinde; bilinci açık, koopere ve oryante olan hastanın kraniyel sinirlerinin muayeneleri intakttı. Yapılan kas gücü muayenesinde her iki ön kol fleksiyonu ve ekstansiyonu, ve el bileği ekstansiyonunda 3/5 kas gücü mevcuttu. Diğer kas gücü muayenelerinde defisit izlenmedi. Her iki C6 ve C7 dermatomlarında dizestezi tarifliyordu. Serebellar muayenesinde: her iki üst ekstremitede dismetri ve disdiadokokinezisi, trunkal ataksisi mevcuttu. Derin tendon refleksleri ise her iki üst ve alt ekstremitede canlıydı. Taban derisi refleksi bilateral lakayttı.

Düşme atakları ve ellerdeki kuvvet kaybı nedeniyle başvurduğu nöroloji uzmanı tarafından yaptırılan beyin bilgisayarlı tomografisinde bilateral serebellar hemisferde ve bazal ganglialarda yaygın ve simetrik EKİM - OCTOBER 2018

Sol biceps brachii Şekil 2. Maksimum kası esnasında biceps brachii kaslarından kaydedilen ve kronik nörojenik değişimler gözlen motor ünit potansiyelleri.

kalsifikasyonlar mevcuttu (Şekil 1). Kan sayımı, biyokimya ve hormon tetkikleri normal sınırlardaydı. Hastaya EMG işleminin olası risk ve faydaları anlatıldıktan sonra hastadan aydınlatılmış onam formu alındı. Ardından yapılan her iki median ve ulnar sinirin motor ve duyusal ileti çalışmaları normal sınırlardaydı. Mevcut kas gücü kaybı nedeniyle konsantrik iğne elektrot ile kas çalışmaları yapıldı. İstirahat halindeyken spontan denervasyon bulgusu izlenmezken, maksimum kası esnasında her iki C6 ve C7 myotomuna uyan kaslardan kaydedilen motor ünit potansiyellerinde kronik nörojenik değişimler gözlendi (Şekil 2).

Bu bulgular nedeniyle, servikal manyetik rezonans görüntülemesi (MRG) yapıldı. MRG’sinde C4-5, C5-6 ve C6-7 disk aralıklarında, spinal kordda myelomalezi ile uyumlu sinyal artışına neden olan, diskopatiler saptandı (Şekil 3). Hasta operasyon için değerlendirilmek üzere beyin cerrahisi bölümüne refere edildi.

Tartışma Fahr hastalığı; genellikle herhangi bir nörolojik anormalliğin olmadığı olgularda başka nedenlerle (travma, başağrısı vb.) istenilen beyin görüntülemelerinde tesadüfen tanı alan bir tablodur. Klinik özelikleri kalsifikasyon alanlarının bulunduğu beyin 207

A RI PAIN nulan olguda olduğu gibi gerçek nedeni tespit etme süresinin uzaması, hastaların daha uzun süre ağrılı bir süreç geçirmesine ve nörolojik hasarın giderek ilerlemesine neden olmaktadır. Tedavinin gecikmesi ise defisitlerin kalıcı olmasına sebebiyet verebilir.

Şekil 3. Servikal MRG’de C4-5, C5-6 ve C6-7 disk aralıklarında, spinal kordda myelomalezi ile uyumlu sinyal artışına neden olan diskopatiler.

bölgelerinin disfonksiyonu şeklindedir. Erkeklerde iki kat daha sık görülen hastalığın tanısında en duyarlı görüntüleme yöntemi bilgisayarlı tomografidir.[1–3] Bazen başvuru bulgusu olarak bazen de hastalığın klinik seyri esnasında; ilerleyici mental hasar, hareket bozuklukları ve psikiyatrik bozukluklar gözlenebilir.[5] Hareket bozuklukları; genelde koreatetoz, parkinsonizm, distoni gibi ekstrapiramidal sistem bozuklukları şeklinde ortaya çıkar. Epileptik nöbetler, demans ve duygudurum bozuklukları daha az sıklıktadır.[6] Sunulan olgunun öyküsünde de konvülsiyonlar ve yaygın anksiyete bozukluğu mevcuttu.

Genellikle simetrik kalsifikasyonlara neden oluşu Fahr hastalığının seyrinde gözlenen belirtilerin genellikler her iki tarafta da az ya da çok mevcut olmasına neden olur. Olasılıkla, bizim olgumuzdaki nöropatik ağrı yakınmalarının ve nörolojik defisitin her iki üst ekstremitede simetrik olarak varoluşu, mevcut yakınmaların Fahr hastalığına bağlanmasında rol oynamış olabilir. Ancak, ekstremitelerde ağrı, uyuşma ve güç kaybı gibi belirtilerin Fahr hastalığında çok ender olması nedeniyle, bu hastalarda nöropatik ağrı veya kas kuvveti kayıpları tespit edildiğinde, eşlik edebilecek olası diğer nörolojik patolojiler akla gelmelidir. Su-

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Nöropatik ağrı ile başvuran hastaların ayrıntılı nörolojik muayenelerinin yapılması, uygun tetkiklerin planmasına ve uygun tedavinin zaman kaybı olmadan uygulanabilmesine olanak sağlar. EMG labaratuvarlarımıza nöropatik ağrının altında yatabilecek olası bir tuzak nöropatinin tespiti için refere edilen, ancak eşlik eden yeni nörolojik defisiti olan hastalarda, sinir ileti çalışmaları mevcut klinik bulguları açıklamıyorsa, iğne EMG ile kas çalışmalarının yapılması doğru olur. Sunulan olgunun öyküsü, kuvvet kaybı olan nöropatik ağrılı olguların etiyolojisinin tespitinde, iğne EMG ile yapılacak kas çalışmaların etkinliğini açıkça göstermektedir.

Yazar(lar) ya da yazı ile ilgili bildirilen herhangi bir ilgi çakışması (conflict of interest) yoktur.

Hakem değerlendirmesi: Dış bağımsız.

Kaynaklar 1. Kıroğlu Y, Callı C, Karabulut N, Oncel C. Intracranial calcifications on CT. Diagn Interv Radiol 2010;16(4):263–9.

2. Manyam BV. What is and what is not ‘Fahr’s disease’. Parkinsonism Relat Disord 2005;11(2):73–80.

3. Uslu Fİ, Hanağası HA. Hypoparathyroidism and Bilateral Striopallidodentate Calcinosis [Article in Trkish]. Nöropsikiyatri Arşivi 2006;43(1-4):31–6.

4. Bouras C, Giannakopoulos P, Good PF, Hsu A, Hof PR, Perl DP. A laser microprobe mass analysis of trace elements in brain mineralizations and capillaries in Fahr’s disease. Acta Neuropathol 1996;92(4):351–7.

5. Mufaddel AA, Al-Hassani GA. Familial idiopathic basal ganglia calcification (Fahr`s disease). Neurosciences (Riyadh) 2014;19(3):171–7.

6. Benke T, Karner E, Seppi K, Delazer M, Marksteiner J, Donnemiller E. Subacute dementia and imaging correlates in a case of Fahr’s disease. J Neurol Neurosurg Psychiatry 2004;75(8):1163–5.

EKİM - OCTOBER 2018