Rutin sinir iletim calismlarinin sinirlari Hatice TANKISI by Klinik Norofizyoloji EEG EMG Dernegi Antalya

Rutin sinir iletim çalıșmalarının sınırları Hatice Tankiși, Associate professor, MD, Phd Nörofizyoloji Departmanı, Aarhus Üniversite Hastanesi VII. Korkut Yaltkaya Neurofizyoloji Sempozyumu, 21-23 Aralık, 2012, Antalya, Türkiye

Rutin sinir iletim çalıșmaları  Çok eski bir teknik fakat hala en sık kullanılanı

PC-BASE EMG SİSTEMLERI

1950, DISA A/S (Denmark)

Keypoint® G4 Workstation

Rutin sinir iletim çalıșmaları      

Süre/sinir iletim hızı Amplitüd Geç yanıtlar (F-dalgası, H-refleksi) Temporal dispersion İletim bloğu Aksiyon potansiyellerinin süre ve formu

Rutin sinir iletim çalıșmaları  Supramaksimal uyarı kullanılır  Kalın miyelinli lif fonksiyonunu gösterir  Maksimal yanıtın amplitüd ve süresinin ölçümü ile akson sayısı ve saltatory iletim hakkında bilgi verir

Rutin sinir iletim çalıșmaları Demiyelinizasyon

Aksonal kayıp

Aksonal ve demiyelinizan PNP lerde amplitüd düșüklüğü SNAP Amplitude

CMAP Amplitude

-1

Mean decrease in CMAP amp. in SDs

Mean decrease in SNAP amp. in SDs

-2

-3

-4

-5

-6

-7

-8

* 53 aksonal PNP

* -2

45 demyelinizan PNP 112 duyu ve 132 motor sinir

-3

● Demyelin □ Axonal

-4

*p<0.05,

-5

Median dig I

Median dig III

Ulnar

Sural

144 duyu ve 145 motor sinir

Median

Ulnar

Tankisi et al, Clin Neurophsiol 2007

Peroneal

Tibialis

İletim hızı ve amplitüd arasındaki ilișki

Tankisi et al. Clin Neurophysiol, 2007

BKAP süresi ve amplitüdü arasındaki ilișki

Tankisi et al. Clin Neurophysiol, 2012

BKAP s端resi

Tankisi et al. Clin Neurophysiol, 2012

Near nerve tekniği ile duyu sinir iletim çalıșmaları Demyelination

Axonal loss

Rutin sinir iletim çalıșmalarının sınırları Rutin sinir iletim çalıșmalarının bilgi vermediği konular:  Denervasyon ve reinnervasyon, nöromuskuler transmisyon ve kas hastalıkları  Motor birim sayısı  Miyelinize olmayan C-lifleri ve ince miyelinize Aδ-lifleri (ısı ve ağrı)  Aksonların uyarılabilirliği, membran potansiyelleri ve iyon kanal fonksiyonu

Elekromiyografi  Spontan aktivite  MÜP analizi (niceliksel ve niteliksel)  Tam kası analizi (niceliksel ve niteliksel), turns amplitüd analizi gibi  Tek lif EMG’si  Makro EMG

Elekromiyografi ď Ż Denervasyon

ď Ż Reinnervasyon

MUNE (Motor unit number estimation) Motor birim sayısı bir kası innerve eden ön boynuz hücreleri veya aksonlarin sayısını gösterir Direk olarak motor unit sayısını ölçebilecek bir elektrofizyolojik teknik bulunmamaktadır O yüzden MUNE metodları kullanılmaktadır

Daube, 2005

MUNE (Motor unit number estimation)  MUNE, alt motor nöron kaybi derecesi ve zamansal gelișimini gösteren en uygun elektrofizyolojik testtir  MUNE, hastalıkların teșhisi, takibi ve prognozunun belirlenmesinde ve ilaç tedavilerine yanıtı değerlendirmede faydalıdır  MUNE, ortalama yüzeysel kaydedilmiș motor unit potansiyelinin (SMUP) maksimal birlesik kas aksiyon potansiyeline (CMAP) bölünmesi temeline dayanır

Değișik MUNE Metodları  MUNE metodları yüzeysel MUP (SMUP) nasıl elde edildiğine göre değișir  Inkremental stimulation  Multiple point stimulation (MPS) “Hep ya da hiç” yanıtı  Adapted MPS (AMPS)  Statistiksel metod - submaksimal BKAP deki değișimler ölçülür  Spike triggered averaging –yüzeyel elektrodlarla kaydedilmiș ve iğne EMG si ile tetiklenmiș ortalama MUP  MUNIX (Motor unit number index)  Stimulus yanıt eğrileri/CMAP scan

Aarhus’da MUNE deneyimi  ALS’de incremental stimulation MUNE ve MUNIX (Furtula et al, 2012)  Polio’da MPS-MUNE ve MUNIX (veriler değerlendiriliyor, Jan Nielsen)  ALS’de MPS-MUNE, MUNIX ve CMAP Scan (PhD projesi, Barıș İsak)  GBS ve CIDP’de MPS-MUNE, MUNIX ve CMAP Scan (Arastırma yılı projesi, Sansuthan Paramanathan)  Üst motor neuron hastalıklarında MPS-MUNE, MUNIX ve CMAP Scan (Ece Ünlü)

GBS’de CMAP Scan (Median sinir) Demyelinizan GBS

CMAP-scan Hø. APB Sağlıklı kontrol 9 8 7

MPS = 64 Munix = 39

4 3 2

MPS = 256 MPS Munix==256 131 Munix = 131

1 0 0

1,3 1,2

SI (mA)

Maksimum BKAP nin %5, %50 ve %95’ini olușturan Sis (S5, S50 ve S95) Absolut SI aralıkları (S95–S5) Rölatif SI aralıkları (S95–S5)/S5) Step yüzdeleri (Blok et al., 2010)

Aksonal GBS CMAP-scan: Højre APB

1,1 CMAP amplitude (mV)

Amp (mV)

1 0,9 0,8 0,7 0,6 0,5 0,4

MPS = 48 MUNIX = 21

0,3 0,2 0,1 0 4

7 8 9 Stimulation intensiten (mA)

ALS’de CMAP Scan (Median sinir) ALS Çok etkilenmiș taraf

Sağlıklı kontrol CMAP-scan Hø. APB

9 8 7

Amp (mV)

6 5 4 3 2

MPS = 256 Munix = 131

1 0 0

Az etkilenmiș taraf

SI (mA)

MPS = 188,46 Munix = 150

Küçük lif fonksiyonunun belirlenmesi  Büyük boyutlu nociceptiv olmayan afferentlerin elektriksel eșiği küçük boyutlu nociceptive afferenlere göre cok daha düșüktür  Özel teknikler (deneysel bloklar gibi) ya da özel organ uyarımları (kornea, dis eti, glans gibi) kullanılmadıkça, elektriksel uyarım nociceptive sinyalleri engelleyerek büyük affarent lifleri uyarır

Lazer uyarılmıș potansiyeller (LEPs)  Nociceptive yolların fonksiyonunu inceleyen en güvenilir ve kolay elektrofizyolojik yöntem  Radiant-ısı dalgaları seçici olarak yüzeyel derideki serbest sinir uçlarını (Aδ ve C) uyarır (Cruccu and Truini, 2010)  Ana sınırlaması sadece cok az merkezde uygulanıyor olması

neodymium:yttrium–aluminum– perovskite laser (Nd:YAP)

Lazer uyarılmıș potansiyeller (LEPs)  



(Cruccu et al, Clin Neurophysiol 2008)

   

N2-P2 (vertikal kompleks) Cingulate girusun orta parcası (MCC) Insular ve/vaya frontal operkulum

N1 Sekonder somatosensoriyel alan (SII) Posterior insula Pr. SSA (SI) (küçük bileşke) Dikkat ve algılamadan N2-P2 ye göre daha az etkilenir Bipolar montajla daha büyük potansiyeller elde edilir

Lazer uyarılmıș potansiyeller (LEPs) 

Erken küçük lif nöropatilerinin teșhisi zor olabilir



Yaklașık ½-1 saat sürebilir Habituasyon problem



Multisinaptik yollar hakkında bilgi verir PNS afferent Uzun spino- talamik yollar Talamo-kortikal yollar

Healthy subject

Patient 1

Patient 2

Contact heat-evoked potansiyeller (CHEPs)  Hâlâ klinik geçerliliği gerekmekte olan yeni bir yöntem  Lazere göre daha büyük bir alan uyarılıyor

Iannetti et al, Physiol 2006

İğne deri biopsisi  Aδ ve C sinir lifleri sayısal olarak belirlenir ve intraepidermal sinir lifleri (IENF) yoğunluğu ölçülür  Santral ağrıda ve demyelinizan nöropatilerde kullanılamaz  Sadece çok az sayıdaki merkezde uygulanabilir

Casanova-Molla et al, Pain 2011

Kvantitativ duyu testleri ve mikronöronografi Kvantitativ duyu testi:  Kontrollü dıș uyarımlara karșı algılamayı test eder  Nöropatik olmayan ağrı durumlarında da değișiklikler gösterir  Zaman alıcı bir yöntem

Mikronöronografi:  Miyelinize olmayan afferent ve efferent nöronal trafiği incelemede önemli bir yöntem

Periferal sinirlerin elektriksel uyarimlarla test edilmesi (Bostock) Sinir eksitabilite çalıșmaları:  Submaksimal uyarı kullanılır  Özel uyarı yanıtlarını ölçerek: → Aksonların uyarılabilirliği → Membran potansiyelleri → İyon kanal fonksiyonu

Sinir iletim çalıșmaları:  Supramaksimal uyarı kullanılır  Maksimal yanıta karșı amplitüd ve süre ölçümü ile: → Akson sayısı → İletim hızı

Sabrınız ve ilginiz için teșekkürler

Stimulus Response Curve/CMAP Scan

Blok et al., 2010 The Sis that elicited 5%, 50%, and 95% of the maximum CMAP (S5, S50, and S95) The absolute SI range (S95–S5), The relative SI range (S95–S5)/S5) Step percentage (sum of the step sizes of all steps relative to the maximum CMAP amplitude)

Microneurography ď Ż Particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers ď Ż Recordings of efferent discharges provide direct information about neural control of autonomic effector organs including blood vessels and sweat glands ď Ż Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control

Microneurography ď Ż

ď Ż

Particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers Recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control

Microneurography 

  



Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion. Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain. Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch. No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans

Microneurography  Microneurography provides useful peripheral neural information concerning autonomic, motor and sensory functions in humans.  This method is a particularly important tool to analyze directly neural mechanisms underlying autonomic functions under normal and abnormal conditions.  Sympathetic microneurography has achieved an stable position in human autonomic testing.  By using this method, the detailed neural mechanisms underlying autonomic dysfunctions often encountered in neurological diseases such as orthostatic hypotension, sleep apnea, and sweat disturbances have been elucidated in detail as well as in cardio- and renovascular impairment.

Microneurography  Microneurography also provides valuable information concerning peripheral afferent mechanisms of motor control.  This technique provides an invaluable approach to the peripheral mechanisms involved in sensory functions of various modalities by identifying objective signals traveling in sensory afferent nerves.  In the future this method may be more and more employed in combination with other parameters of clinically neurophysiological, psychological/psychophysical, and neuroradiological methods, including functional magnetic resonance imaging and positron emission tomography, as a key approach to the central mechanisms of information processing of peripheral neural signals.

Nicolet Viking Microprocessor controlled EMG System, 1985

In 1950, DISA A/S (Denmark) introduced a three channel EMG system capable of displaying and recording waveforms from each channel.

DISA 1500, Digital EMG System 1976

PC-BASE EMG SYSTEMS: 1993

  

MICROPROCESSOR-CONTROLLED EMG SYSTEMS: 1982-1993 PC-BASE EMG SYSTEMS: 1993–2001 HANDHELD & WIRELESS EMG SYSTEMS: 2001-PRESENT DAY

Nicolet Viking EMG System, 1985

Routine nerve conduction studies  Use supramaximal stimuli  Measure large myelinated fibre function  Show functional changes in conduction velocity which may not persist with time  Measure amplitude and latency/conduction velocity of maximal response  Assess number of axons and saltatory conduction

Correlation between SNAP amplitude and sensory CV Median (digit I)

Median (digit III)

* *

○ Demyelin. ● Axonal

i es aer ce D

Sural

* *

Ulnar

Decrease in CV (SD) Tankisi et al. Clin Neurophysiol, 2007

❃ Correlation

(p<0.05)

MUNE (Motor unit number estimation) Motor unit number refers to the number of anterior horn cells or axons innervating and controlling a single muscle. Motor unit number is a critical measure in any disease involving injury or death of motor neurons or motor axons. There is no electrophysiologic technique that allows for simple direct measurement of motor unit number. By providing an accurate estimate of motor unit number, MUNE provides insight into the underlying disorder, its distribution and severity.

MUNIX and IS MUNE in control subjects and ALS patients  48 control subjects and 14 ALS patients  Retest on 14 control subjects and follow-up on 6 ALS patients

Sensitivity: MUNIX: 0.77 IS MUNE: 0,31

(Furtula et al, 2012 in press)

MUNIX and IS MUNE in controls subjects and ALS patients ď Ż CMAP amplitude and MUNIX decreased in follow-up but IS MUNE did not decrease significantly

Validity of MUNIX and IS MUNE in ALS patients

Individual values of CMAP, MUNIX and IS of 6 patients at inclusion and during follow-up.

(Furtula et al, 2012 in press)

MUNIX and IS MUNE in controls subjects and ALS patients Conclusion:  MUNIX is a useful MUNE indicator to assess progression of LMN affection  MUNIX has lower intrasubject variability than IS  MUNIX has a better sensitivity than IS

MPS and MUNIX in control subjects and polio patients MPSMUN:

1,00 mps

MPSMUN:

400



500

400 300

300 200

MUNIX



8 controls and 8 patients with history of polio MPS MUNE and MUNIX MUAP duration, peak ratio analysis and force measurement

MPS MUNE



2,00 munix

200

100

0 0,0

0 1,0

2,0

patient control

3,0

0,0

1,0 patient

2,0 control

3,0

MPS and MUNIX in control subjects and polio patients 120

100

MPS MUNE

p=0,779

100

0 0

0,0

MUAP Duration 160

1,0

Peak-ratio (nr/sec.pr.uV) 160

p=0,056

140

120

100

MUNIX

ď Ż No significant correlation was found between QEMG changes and MPS MUNE and MUNIX in m. APB

120

p=0,101

p=0,111

0 0

MUAP Duration

0,0

Peak-ratio (nr/sec pr. uV)

1,0

MPS and MUNIX in control subjects and polio patients Conclusion:  MPS MUNE and MUNIX are not well correlated with QEMG methods probably due to they measure different parameters  MUNE can be a supplement for QEMG

Assesment of small-fiber function  Large-size, non-nociceptive afferents (i.e., those that do not carry pain) have a lower electrical threshold than small-size, nociceptive afferents.  Unless special techniques are used, i.e., experimental blocks or stimulation of special organs (cornea, tooth pulp, glans), electrical stimuli unavoidably also excite large afferents, thus hindering nociceptive signals.  Hence standard neurophysiological responses to electrical stimuli, such as nerve conduction studies and somatosensory- evoked potentials (SEPs), can identify, locate, and quantify damage along the peripheral or central sensorypathways, but they do not assess nociceptive pathway function.  For many years researchers have tried numerous techniques for selectively activating pain afferents.

Laser evoked potentials (LEPs) ď Ż

ď Ż

The most reliable and widely accepted diagnostic tools for assessing nociceptive pathway function are laser evoked potentials (LEPs) and skin biopsy The currently preferred approach uses laser stimulators to deliver radiant-heat pulses that selectively excite the free nerve endings (Ad and C) in the superficial skin layers. Consensus from over 200 studies now confirms that late laserevoked potentials (Ad-LEPs) are nociceptive responses.

Laser evoked potentials (LEPs) 



LEPs are the easiest and most reliable neurophysiological tools for assessing nociceptive pathway function and are diagnostically useful in peripheral and central neuropathic pain. In clinical practice, their main limitation is that they are currently available in too few centres. Ultralate LEPs (related to Cfibre activation) are technically more difficult to record, and few studies have assessed their usefulness.

Contact heat-evoked potentials (CHEPs)  A recent development that still need clinical validation  The thermode for contact heat stimulation activates a larger surface area than the laser stimulation  CHEPs may be considered a robust technique for the evaluation of patients with sensory

Iannetti et al, Physiol 2006

Quantitative sensory testing   



Analyses perception in response to external stimuli of controlled intensity Detection and pain thresholds are determined by applying stimuli to the skin in an ascending and descending order of magnitude. Mechanical sensitivity for tactile stimuli is measured with plastic filaments that produce graded pressures, such as the von Frey hairs, pinprick sensation with weighted needles, and vibration sensitivity with an electronic vibrameter. Thermal perception and thermal pain are measured using a thermode, or other device that operates on the thermoelectric effect. QST has been used for the early diagnosis and follow-up of small-fibre neuropathy that cannot be assessed by standard NCS, and has proved useful in the early diagnosis of diabetic neuropathy. QST is also especially suitable for quantifying mechanical and thermal allodynia and hyperalgesia in painful neuropathic syndromes, and has been used in pharmacological trials to assess treatment efficacy on provoked pains [2]. QST abnormalities, however, cannot provide conclusive evidence of neuropathic pain, because QST shows changes also in non-neuropathic pain states, such as rheumatoid arthritis and inflammatory arthromyalgias. QST is time-consuming and thus difficult to use in clinical practice [2].

Microneurography  

 

  

Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task.

Correlation between CV and CMAP amplitude Median

* *

Peroneal

* *

○ Demyelin. ● Axonal Ulnar

Tibial

i es aer ce D

Decrease in CV (SD) Tankisi et al. Clin Neurophysiol, 2007

❃Correlation

(p<0.05)

Cutaneous silent period (CSP)

CSP Electric stimulation

CSP Laser stimulation