ξανα για τα φαρματα του παιδιου 2014 by CONSTANTINOS KALLIMACHOS

ΥΠΟΜΝΗΜΑ του Κωνσταντίνου και της Αντιγόνης Καλλιμάχου., Δ.Τ.: 697927 Για τη 12χρονη βαριά άρρωστη κόρη μας Μαρία-Φωτεινή Καλλιμάχου (αρ. Φακ. 1098/04) Διεύθυνση: Επιδαύρου 8, Πλατύ, 2114 Λευκωσία - Τηλ.: 22462252, 99.694461

Εντιμότατο Υπουργό Υγείας της Κυπριακής Δημοκρατίας, κο Φίλιππο Κ. Πατσαλή 8 Απριλίου 2014

Αιτούμεθα: α) όπως μας επιστραφούν οι 13 χιλιάδες δολάρια που δώσαμε το 2013 για την προμήθεια φαρμάκων τής κόρης μας (από τις ΗΠΑ) β) όπως επίσης επιδοτηθούν τα εν λόγω φάρμακα και για το 2014, κάτι που ανέκαθεν συνέβαινε από το 2005 έως και το 2012 γ) και τέλος, όπως καθιερωθεί με υπουργική απόφαση η ακώλυτη επιδότηση των εν λόγω φαρμάκων από τις ΗΠΑ μέχρις ότου (πάλι με υπουργική απόφαση) διαταχθούν οι Φαρμακευτικές Υπηρεσίες να τα εξασφαλίζουν αδιαλείπτως στην κόρη μας, καθώς εκκρεμεί αίτημα του θεράποντος ιατρού από το 2010.

Α. Γιατί δεν πρέπει να αλλάξουν τα φάρμακα της 12χρονης κόρης μας Εντιμότατε Υπουργέ Υγείας της Κυπριακής Δημοκρατίας, Η 12χρονη κόρη μας Μαρία-Φωτεινή (αρ. φακ. 1098/04) αν και πάσχει από βαρύτατη φαρμακοανθεκτική επιληψία (ποσοστό θνησιμότητας 20 έως και 25 τοις εκατό) και μέχρι τριών ετών είχε εκατοντάδες επιληπτικά επεισόδια (παρά την εν τω μεταξύ διακομιδή της σε νοσοκομεία της Ελλάδας, της Βρετανίας και της Γαλλίας), εντούτοις από το 2005, δηλαδή μετά τη διακομιδή τού παιδιού στις ΗΠΑ (με πρωτοβουλία του Μακαρείου Παιδιατρικού Νοσοκομείου) σταδιακά άρχισε να έχει έλεγχο των κρίσεων. Μάλιστα, τα τελευταία χρόνια, δεν έχει πλέον επιληπτικά επεισόδια και αυτό οφείλεται τόσο στην επιτυχημένη και πολυσύνθετη φαρμακευτική αγωγή που επί εννέα χρόνια επιμελείται η θεραπευτική ομάδα τής Μέιγιο Κλινικ όσο και σε συγκεκριμένα φάρμακα που προμηθευόμαστε από τις ΗΠΑ (όταν κάθε χρόνο πηγαίνουμε εκεί για επανεξέταση και θεραπεία). Αυτά τα «εισαγόμενα» φάρμακα, σύμφωνα με τους θεράποντες ιατρούς, όπως θα δείτε πιο κάτω (αλλά και ευρύτερα σύμφωνα με την τρέχουσα επιστημονική βιβλιογραφία1) δεν πρέπει να αντικατασταθούν ή να υποκατασταθούν με άλλα αντιγραφικά ή παρεμφερή, επειδή μια αλλαγή των φαρμακευτικών σκευασμάτων (λόγω τής ποικίλης βιοδιαθεσιμότητάς που παρουσιάζουν μεταξύ τους ακόμη και τα παρεμφερή σκευάσματα) ενδέχεται να θέσει σε κίνδυνο την υφιστάμενη ισορροπία που έχει πλέον επιτευχθεί με πολύ κόπο και τεράστια έξοδα, απειλώντας ακόμη και τη ζωή του παιδιού μας.

1 [Σελίδα 4] The epilepsies: the diagnosis and management of the epilepsies in adults and children . in primary and secondary care., NICE clinical guideline 137

Β. ΑΙΤΗΜΑΤΑ για επιδότηση των εισαγομένων φαρμάκων τής κόρης μας - Αιτούμεθα την επιστροφή χρημάτων που δώσαμε πέρσι το 2013 προκειμένου να αγοράσουμε από τις ΗΠΑ τα ετήσια φάρμακα τής βαριά άρρωστης 12χρονης κόρης μας (τα οποία ανέκαθεν επιδοτούσε η Πολιτεία μέσω του Τμήματος Επιδοτουμένων Ασθενών) - Αιτούμεθα, επίσης, και την επιδότηση των φετινών (του 2014) φαρμάκων του παιδιού. (Η μητέρα του παιδιού έχει προγραμματίσει ταξίδι στις ΗΠΑ προς τα μέσα τρέχοντος Μαΐου του 2014, μόνο και μόνο για να αγοράσει τα εν λόγω φάρμακα από τη Μέιγιο, βάσει της συνταγής του εκεί θεράποντος ιατρού. - Και τέλος, αιτούμεθα όπως, με υπουργική απόφαση, εισάγονται κάθε χρόνο τα εν λόγω φάρμακα της κόρης μας από τις ΗΠΑ και της παρέχονται μέσω τού Μακαρείου. Μέχρις ότου υλοποιηθεί αυτό το πάγιο αίτημα των θεραπόντων ιατρών (που εκκρεμεί από το 2010), παρακαλούμε όπως με υπουργική απόφαση καθιερωθεί η κρατική επιδότηση των εν λόγω ετησίων φαρμάκων: εμείς θα τα αγοράζουμε από τις ΗΠΑ και η Πολιτεία θα μας επιστρέφει τα χρήματα (μέσω του Τμήματος Επιδοτουμένων Ασθενών, όπως έγινε και το 2012).

Γ. ΛΕΠΤΟΜΕΡΕΙΕΣ ΚΑΙ ΤΕΚΜΗΡΙΩΣΗ Εντιμότατε Υπουργέ, Το αίτημά μας υποστηρίζεται επιστημονικά με «ιατρικό σημείωμα» τόσο από τον Κύπριο θεράποντα ιατρό της 12χρονης κόρης μας2 στο Μακάρειο, όσο και από τον Αμερικανό συνάδελφό του3 ο οποίος εδώ και χρόνια συντονίζει την εξαιρετικά πολύπλοκη, αλλά πάνω απ΄ όλα αποτελεσματικότατη αντιεπιληπτική θεραπεία της. Γι΄ αυτό, αιτούμεθα την κάλυψη των «εισαγομένων» φαρμάκων4 από τις ΗΠΑ (αξίας δεκατριών χιλιάδων δολαρίων5) που αγοράστηκαν το 2013 στις ΗΠΑ6 υπέρ τής χρονίως και βαρέως ασθενούσας 12χρονης κόρης μας, Μαρίας-Φωτεινής Καλλιμάχου (Αρ. Φακ. 1098/04) η οποία τώρα έχει έλεγχο των κρίσεων. Σημειωτέον ότι η κόρη μου που είναι λήπτης δημοσίου βοηθήματος7 (άρα και δικαιούχος δωρεάν ιατροφαρμακευτικής περίθαλψης) παρακολουθείται από το 2005 στο Μακάρειο. (Γιατρός της τώρα είναι ο εκλεκτός παιδονευρολόγος Δρ. Ιωάννης Ιωάννου ο οποίος άλλωστε υπογράφει και το προαναφερθέν «Ιατρικό σημείωμα».)

[Σελίδα 7] Δείτε το συνημμένο «Ιατρικό σημείωμα» (Φεβρ. 3., 2014) του Κυπρίου θεράποντος παιδιάτρου-παιδονευρολόγου στο «Μακάρειο», Δρα Ιωάννη Ιωάννου.

[Σελίδα 10] Δείτε το συνημμένο έγγραφο του θεράποντος ιατρού τής Μαρίας-Φωτεινής από την Mayo Clinic (Jul 7., 2013) που πιστοποιεί ότι τα υφιστάμενα «εισαγόμενα» φάρμακά της είναι συμβατά με την Κετογενική της Δίαιτα και γι΄ αυτό με κανένα τρόπο δεν πρέπει να υποκατασταθούν άλλως πως.

[Σελίδα 11] Δείτε τις συνημμένες επίσημες συνταγές του 2013 (της Μέιγιο Κλίνικ) για τα εν λόγω «εισαγόμενα» φάρμακα.

[Σελίδα 55] Επισυνάπτονται οι αποδείξεις πληρωμής για τα του 2013 «εισαγόμενα» φάρμακα από τις ΗΠΑ, κατά την εκεί ετήσια πολύμηνη outpatient επανεξέταση τής κόρης μας. (Τα φάρμακα αυτά μάς φτάνουν μέχρι και τον Απρίλη τού 2014.)

[Σελίδα 59] Δείτε τα συνημμένα ιατρικά αρχεία τής Μαρίας-Φωτεινής από τη Mayo Clinic για το τετράμηνο Μαΐου-Αυγούστου 2013 απ΄ όπου προκύπτουν οι προαναφερθείσες συνταγές.

[Σελίδα 93] Επισυνάπτεται βεβαίωση (28/2/2013) από το Επαρχιακό Γραφείο Ευημερίας ότι η 12χρονη Μαρία-Φωτεινή είναι λήπτης δημοσίου βοηθήματος.

Γι΄ αυτό, επίσης, αιτούμεθα όπως υλοποιηθεί το επανειλημμένο αίτημα τού παιδονευρολόγου τής κόρης μας8, δρα Ιωάννη Ιωάννου για εισαγωγή των φαρμάκων τού παιδιού από τις ΗΠΑ και παροχή των μέσω του Φαρμακείου τού Μακαρείου. Υπενθυμίζουμε ότι αμφότεροι οι θεράποντες ιατροί του παιδιού μας δηλώνουν ρητά ότι τα εν λόγω «αμερικάνικα» φάρμακα δεν πρέπει ούτε να αντικατασταθούν με άλλα, ούτε και να υποκατασταθούν από άλλα, διότι μια οποιαδήποτε αλλαγή ενδέχεται να αλλοιώσει την αποτελεσματικότητα τής υφισταμένης θεραπευτικής αγωγής και να επαναρχίσουν τα επιληπτικά επεισόδια που ίσως θέσουν σε κίνδυνο τη ζωή τού παιδιού μας – δείτε τις παραπομπές 1 & 2. Παρεμπιπτόντως, σημειώνουμε ότι ανάλογο αίτημα προς τις Φαρμακευτικές Υπηρεσίες είχε υποβάλει από το 2010 και ο τότε θεράπων ιατρός της κόρης μας, ο αείμνηστος παιδονευρολόγος και επιληπτιολόγος Σταύρου Χατζηλοϊζου9. Πάντως, Εντιμότατε Υπουργέ, παρά το γεγονός ότι ανέκαθεν οι Φαρμακευτικές Υπηρεσίες ομολογούσαν την αδυναμία τους να μας προμηθεύσουν τα ζητούμενα φάρμακα10, ωστόσο, επί χρόνια η Πολιτεία (από το 2005 έως το 2012) τα επιδοτούσε μέσω του Τμήματος Επιδοτουμένων Ασθενών11. Σχετικά με την όλη κατάσταση του παιδιού και το ιστορικό του, και προς επίρρωσιν των ισχυρισμών μας, πέραν των προσφάτων συνημμένων εγγράφων, επισυνάπτουμε και τις κυριότερες ιατρικές βεβαιώσεις12 της περιόδου 2012-2005 απ΄ όπου τεκμαίρεται η σοβαρότητα της βαριάς φαρμακοανθεκτικής επιληψίας από την οποία πάσχει η κόρη μας Μαρία-Φωτεινή Καλλιμάχου και κυρίως το γεγονός ότι παλαιότερα το παιδί είχε πάμπολλα και παρατεταμένα επιληπτικά επεισόδια ενώ τώρα είναι ελεύθερο κρίσεων (χάρη στην υφιστάμενη θεραπευτική αγωγή που δεν πρέπει να αλλάξει).

Εντιμότατε Υπουργέ, αισιοδοξούμε, ότι το αίσθημα δικαίου που σας συνέχει, η επιστημοσύνη σας και η ανθρωπιά σας δεν θα αφήσουν το παιδί μας στο έλεος του Θεού.

Μετά Τιμής - Οι γονείς:

Αντιγόνη και Κωνσταντίνος Καλλίμαχος

[Σελίδα 94] Επισυνάπτουμε συναφή επιστολή/αίτημα τού θεράποντος ιατρού τής ΜαρίαςΦωτεινής στο Μακάρειο, παιδονευρολόγου δρος Ιωάννη Ιωάννου, προς τη Διεύθυνση Φαρμακευτικών Υπηρεσιών (από τις 2 Απριλίου του 2013) ότι επείγει «προμήθεια τής ασθενούς Μαρίας-Φωτεινής Καλλιμάχου με φαρμακευτικά σκευάσματα» τα οποία είναι απολύτως συμβατά με την επιτυχή αντιεπιληπτική Κετογόνο Δίαιτα στη οποία το παιδί βρίσκεται από το 2005.

[Σελίδα 96] Δείτε το συνημμένο αντίστοιχο αίτημα του αειμνήστου παιδονευρολόγου και επιληπτιολόγου Σταύρου Χατζηλοίζου με ημερομηνία 03/03/2010.

[Σελίδα 98] Επισυνάπτουμε βεβαίωση (Απρ. 2012) των Φαρμακευτικών Υπηρεσιών ότι τα εν λόγω σκευάσματα δεν είναι διαθέσιμα, ως εκ τούτου δεν δύνανται να ανταποκριθούν στο αίτημα του θεράποντος ιατρού της κόρης μου. Παρά ταύτα, και το 2012 εγκρίθηκε η επιδότηση των φαρμάκων, με παρέμβαση τού τότε Υπουργού Υγείας προς το Τμήμα Επιδοτουμένων Ασθενών.

[Σελίδα 100] Δείτε τα συνημμένα έγγραφα τού Υπουργείου Υγείας (με ημερομηνία 8 Απριλίου 2013) που πιστοποιούν ότι από το 2005 έως το 2012 η Μαρία-Φωτεινή κάθε χρόνο νοσηλεύεται στις ΗΠΑ ως outpatient και πως ανέκαθεν τα «εισαγόμενα» φάρμακά της (τα οποία, λόγου χάρη και το 2011 κόστισαν περί τις 13 χιλιάδες δολάρια) καλύπτονταν από το Τμήμα Επιδοτουμένων Ασθενών.

[Σελίδα 103] Ιατρικές βεβαιώσεις της περιόδου 2012-2005.

The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care

NICE clinical guideline 137

1.9.1.4 Consistent supply to the child, young person or adult with epilepsy of a particular manufacturer's AED preparation is recommended, unless the prescriber, in consultation with the child, young person, adult and their family and/or carers as appropriate, considers that this is not a concern. Different preparations of some AEDs may vary in bioavailability or pharmacokinetic profiles and care needs to be taken to avoid reduced effect or excessive side effects. Consult the summary of product characteristics (SPC) and 'British national formulary' (BNF; available at http://bnf.org) on the bioavailability and pharmacokinetic profiles of individual AEDs, but note that these do not give information on comparing bioavailability of different generic preparations[ ],[ ]. [New 2012] 11

1.9.1.5 It is recommended that children, young people and adults should be treated with a single AED (monotherapy) wherever possible. If the initial treatment is unsuccessful, then monotherapy using another drug can be tried. Caution is needed during the changeover period. [2004] 1.9.1.6 If an AED has failed because of adverse effects or continued seizures, a second drug should be started (which may be an alternative first-line or second-line drug) and built up to an adequate or maximum tolerated dose and then the first drug should be tapered off slowly. [2004] 1.9.1.7 If the second drug is unhelpful, either the first or second drug may be tapered, depending on relative efficacy, side effects and how well the drugs are tolerated before starting another drug. [2004] 1.9.1.8 It is recommended that combination therapy (adjunctive or 'add-on' therapy) should only be considered when attempts at monotherapy with AEDs have not resulted in seizure freedom. If trials of combination therapy do not bring about worthwhile benefits, treatment should revert to the regimen (monotherapy or combination therapy) that has proved most acceptable to the child, young person or adult, in terms of providing the best balance between effectiveness in reducing seizure frequency and tolerability of side effects. [2004] 1.9.1.9 If using carbamazepine, offer controlled-release carbamazepine preparations. [new 2012]

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The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care Issued: January 2012 last modified: December 2013 NICE clinical guideline 137 guidance.nice.org.uk/cg137

NICE has accredited the process used by the Centre for Clinical Practice at NICE to produce guidelines. Accreditation is valid for 5 years from September 2009 and applies to guidelines produced since April 2007 using the processes described in NICE's 'The guidelines manual' (2007, updated 2009). More information on accreditation can be viewed at www.nice.org.uk/accreditation ÂŠ NICE 2012

The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care

NICE clinical guideline 137

Contents Introduction.................................................................................................................................

Person-centred care ...................................................................................................................

Key priorities for implementation ................................................................................................ 10 Diagnosis............................................................................................................................................... 10 Management ......................................................................................................................................... 10 Prolonged or repeated seizures and convulsive status epilepticus....................................................... 10 Special considerations for women and girls of childbearing potential ................................................... 11 Review and referral ............................................................................................................................... 11

1 Guidance ................................................................................................................................. 12 1.1 Principle of decision making............................................................................................................ 12 1.2 Coping with epilepsy ....................................................................................................................... 12 1.3 Information ...................................................................................................................................... 13 1.4 Following a first seizure................................................................................................................... 16 1.5 Diagnosis......................................................................................................................................... 17 1.6 Investigations .................................................................................................................................. 18 1.7 Classification ................................................................................................................................... 22 1.8 Management ................................................................................................................................... 22 1.9 Pharmacological treatment ............................................................................................................. 23 1.10 Referral for complex or refractory epilepsy ................................................................................... 39 1.11 Psychological interventions ........................................................................................................... 41 1.12 Ketogenic diet ............................................................................................................................... 41 1.13 Vagus nerve stimulation (VNS) .................................................................................................... 42 1.14 Prolonged or repeated seizures and convulsive status epilepticus .............................................. 42 1.15 Women and girls with epilepsy...................................................................................................... 45 1.16 Children, young people and adults with learning disabilities (see also sections 1.15 and 1.17)... 50 1.17 Young people with epilepsy (see also section 1.15)...................................................................... 52

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2013- MARIA-FOTINI- Clinical Notes and Hospital Summaries documents per screen from Document Type:

05/01/2013

Clinical Notes

09/15/2013

Hospital Summaries

Date

Title

Result Type

Provider

05/17/2013

Neurology Subsequent Visit

Clinical Note

Kotagal, Suresh, MD

05/21/2013

Physical Medicine & Rehabilitation Con

Clinical Note

Shubert, Terry Ann, PT

05/21/2013

Physical Medicine & Rehabilitation SV

Clinical Note

Nash, David Lowell, MD

05/24/2013

Gastroenterology Consult

Clinical Note

Ibrahim, Samar Houssein, MBChB

05/29/2013

Gastroenterology Subsequent Visit

Clinical Note

Ibrahim, Samar Houssein, MBChB

06/12/2013

Neurology Subsequent Visit

Clinical Note

Kotagal, Suresh, MD

06/13/2013

Orthodontic Limited Evaluation

Clinical Note

Chew, Li-Ping, DMD

07/05/2013

Neurology Subsequent Visit

Clinical Note

Kenney, Daniel Lewis, MD

07/05/2013

Neurology Miscellaneous

Clinical Note

Kenney, Daniel Lewis, MD

07/05/2013

Neurology Supervisory

Clinical Note

Kotagal, Suresh, MD

07/23/2013

Neurology Miscellaneous

Clinical Note

Kotagal, Suresh, MD

08/15/2013

Neurology Subsequent Visit

Clinical Note

Kotagal, Suresh, MD

08/16/2013

Neurology Miscellaneous

Clinical Note

Klingsporn, Patricia a, RN

Showing documents 1 to 13 (of 13 )

Patient Copy Child & Adolescent Neurology 6-252-122 17-May-2013 13:51 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:30

Subsequent Visit Page 1 of 3

DEMOGRAPHIC INFORMATION Clinic Number: 6-252-122 Patient Name: Maria Foteini Kallimachou Age: 11 Y Birthdate: 25-Apr-2002 Sex: F Address: 8 Epidavrou Str., Platy City: Nicosia, CY 2114 Service Date/Time: 17-May-2013 13:51 Provider: Suresh Kotagal, MD Pager: 5-3652 Service: PDN Type/Desc: SV Status: Fnl Revision #: 4 CHIEF COMPLAINT/PURPOSE OF VISIT Followup for intractable epilepsy. HISTORY OF PRESENT ILLNESS Maria is an 11-year-old child with Dravet syndrome with associated intractable epilepsy characterized by generalized tonic-clonic seizures and myoclonic absence seizures. She was reevaluated today, accompanied by her mother. The patient's last tonic-clonic seizure was in August 2012. With regard to her myoclonic absence seizures, she is experiencing between 5 to 20 such events per day. These are especially likely to happen when she is very hot. Exposure to high temperatures also leads to her becoming red over the face, as she is unable to sweat. For her seizures, Maria is on a 4:1 ketogenic diet which she is taking on a regular basis. She is also receiving Depakote and clobazam for seizure control. Diastat is available as a rescue medicine. CURRENT MEDICATIONS Bicitra 500-334 mg/5 mL solution by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Take 2.5 mL twice a day after meals Bicitra 500-334 mg/5 mL solution by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: International patient, Dx epilepsy: Take 2.5 mL twice a day after meals Calci-Mix capsule 500 mg calcium (1,250 mg) by mouth one time daily. Indication, Site, and Additional Prescription Instructions: Constipation 1 capsule twice a day with food Children's Multi Vitamins chewable tablet one-half tablet by mouth one time daily. Children's Silapap 160 mg/5 ml* (Free Text Entry) as directed by prescriber. Indication, Site, and Additional Prescription Instructions: 10 ml prn for fever > 101 degrees Children''s Silapap Liquid 160 mg/5 mL 10 mL by mouth three times a day as needed. Indication, Site, and Additional Prescription Instructions: Fever 10 ml three times a day when needed International patient

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Patient Copy Child & Adolescent Neurology 6-252-122 17-May-2013 13:51 Maria Foteini Kallimachou

Subsequent Visit

Generated: 15-Sep-2013 04:30

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clobazam [ONFI] 5 mg tablet 1 TABLET by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab three times a day Depakote 250 mg tablet enteric coated by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure 1.5 tabs in a.m., 1 tab at 2:00 p.m., 1.5 tab at 8:00 p.m. Diastat AcuDial 5-7.5-10 mg kit 10 mg rectally as directed as needed. Indication, Site, and Additional Prescription Instructions: seizure activity 10 mg rectally for tonic-clonic seizure more than 1 minute Ketogenic Diet* (Free Text Entry). Klonopin 0.25 mg tablet Rapid Dissolve by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab twice a day lacosamide [VIMPAT] 50 mg tablet by mouth as directed by prescriber #1 MONTHS SUPPLY. Indication, Site, and Additional Prescription Instructions: Seizure one and one half tabs twice a day International patient levocarnitine [CARNITOR] 330 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: one tab three times a day International patient melatonin 3 mg tablet by mouth every bedtime as needed. Indication, Site, and Additional Prescription Instructions: sleep 3 mg at bed onset, 3 mg in the night upon awakening International patient MiraLAX 17 gram/dose Powder 1 packet by mouth one time daily as needed. Indication, Site, and Additional Prescription Instructions: constipation International patient selenium 100 mcg tablet one-half tablet by mouth every morning. Indication, Site, and Additional Prescription Instructions: International patient Topamax 25 mg tablet 1 TABLET by mouth two times a day. Indication, Site, and Additional Prescription Instructions:

This printout was generated through Patient Online Services and was the most current version as of the date and time generated.

Patient Copy Child & Adolescent Neurology 6-252-122 17-May-2013 13:51 Maria Foteini Kallimachou

Subsequent Visit

Generated: 15-Sep-2013 04:30

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half tab in a.m., one tab in p.m. International patient Topamax 50 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure one tab in a.m., 2 tabs at night These are the patient's medications as of Friday, 17-May-2013 at 14:29. SYSTEMS REVIEW The mother is concerned that since February of this year the patient has had intermittent diarrhea. On some days her bowel movements are normal, whereas on other days she may experience five to six loose stools which are watery, foul-smelling, and yellowish. She has developed hemorrhoids as a complication, and these are quite painful to her. VITAL SIGNS Height: 136.8 cm. Weight: 28.4 kg. BSA(G): 1.05 M2. BMI: 15.18 KG/M2. (17-May-2013 13:51) PHYSICAL EXAMINATION Neuro: The patient is quiet, quite intently playing with an electronic tablet. She can communicate in simple sentences in both English and Greek. Extraocular movements are normal. She has a slightly broad-based gait. There is no salivary drooling. IMPRESSION/REPORT/PLAN The seizure control is suboptimal. We may have to make some adjustments in the dose of her various medications or the ketogenic diet. I have recommended checking of a CBC, serum beta hydroxybutyrate level, serum valproic acid level, serum carnitine level, and a 24-hour urinary calcium-to-creatinine ratio. For her chronic diarrhea, I am requesting a pediatric GI consultation. The diarrhea could be related to a parasitic infestation or the carnitine supplementation. #1 Dravet syndrome #2 Intractable epilepsy related to above, with developmental delay #3 Chronic diarrhea of undetermined etiology DIAGNOSES #1 Dravet syndrome #2 Intractable epilepsy related to above, with developmental delay #3 Chronic diarrhea of undetermined etiology Original: SK:hlt by sk Electronically Signed: 22-May-2013 15:55 by S.. Kotagal, MD

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Patient Copy Physical Medicine & Rehabilitation 6-252-122 21-May-2013 16:47 Maria Foteini Kallimachou

Consult

Generated: 15-Sep-2013 04:53

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DEMOGRAPHIC INFORMATION Clinic Number: 6-252-122 Patient Name: Maria Foteini Kallimachou Age: 11 Y Birthdate: 25-Apr-2002 Sex: F Address: 8 Epidavrou Str., Platy City: Nicosia, CY 2114 Service Date/Time: 21-May-2013 16:47 Provider: Terry A. Shubert, PT Pager: 127-00864 Service: PMR Type/Desc: CON Status: Fnl Revision #: 1 REFERRAL Dr. Nash 4-7928 CHIEF COMPLAINT/PURPOSE OF VISIT Dravet syndrome with global developmental delay. HISTORY OF PRESENT ILLNESS Please refer to Dr. Nash's note dated 5/21/2013. PHYSICAL EXAMINATION Musculoskeletal: Tests and Measures: Gait, Locomotion, and Balance: Maria Foteini ambulates with short steps and a shuffling style gait with initial contact a flat foot and a very slight crouched gait. She tends stand with slight hi flexion. Muscle Performance (Including Strength, Power, and Endurance): Maria will not participate with manual muscle test, but she can squat and rise. She has difficulty maintaining half-kneeling and descending stairs especially leading with the right. Posture: Rounded shoulder posture. Range of Motions (Including Muscle Length): Within normal limits, except tight hip flexors. Special tests: Positive Thomas test for hip flexor tightness, however, Marie Foteini was quite wiggly at the time so it was difficult to be certain if she was not fully relaxing. IMPRESSION/REPORT/PLAN Medical diagnosis (impression): #1 Dravet syndrome with intractable myoclonic generalized tonic clonic and atypical absence seizures #2 Head drops, some representing cataplexy Impairment-based treatment diagnosis (impression): hypotonia, hip group weakness, trunk weakness Functional limitations: Maria-Fotini cannot maintain half-kneeling and has increased lumbar lordosis, she often tried to use her arms on a support surface when rising from a low seat. PLAN OF CARE Goals/outcomes: Patient's mother will be instructed in a home program, demonstrate understanding, and state the ability to continue independently. Frequency: 2-4 times per month. Duration: Until the end of August. Today's interventions: Reviewed activities to improve balance and strength. Practice various single leg stance activities including modified single leg stance, stepping over things (such as a swimming noodle), Dancing with one foot in the air (Maria loves to dance), kicking activities. Also practiced balance on a Bosu ball.

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Patient Copy Physical Medicine & Rehabilitation 6-252-122 21-May-2013 16:47 Maria Foteini Kallimachou

Consult

Generated: 15-Sep-2013 04:53

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Reviewed hip flexor stretching in a Thomas test position, emphasizing that she needs to maintain a protected/flat back position. Completed a trial of the Rifton Rager tricycle which Maria Foteini and she was able to pedal and steer around the W16 loop. Made adjustments for growth to the footplate of her Convaid stroller. Printed the following previous activity list for Maria Foteini's mother. PHYSICAL THERAPY RECOMMENDATIONS FOR HOME STRENGTHENING AND BALANCE ACTIVITIES: Quadriceps strengthening (front thigh muscles): - Practice squatting and retuning to stand. - Practice sitting on a low stool and then standing up without using her hands to help her. - Practice jumping - Wall slides - "Monster" walks Hip strengthening: - Position into half-kneeling and "noodle fight" -Take side-ways steps along a wall with toes pointing straight ahead. - Kick sideways to kick over a bolster or similar item. - Complete "clam shell" exercises (have Maria-Foteini lie on one side with knees bent and rotate her top leg up - goal 10 reps) - "Monster" walks sideways Gluteal Muscles: - Have Maria Foteini lie on the floor with her knees bent and lift her bottom up off the floor (Bridges) - "Donkey kicks" on hands and knees. - Moving from a heel-siting position to kneeling - Walk on her knees backward Abdominal strengthening: - Have Maria-Foteini lie in supine and hold a ball between her feet, she can then take it with her hands and shoot a basket - Sit-ups (on or off an exercise ball)

Back strengthening: - Have Maria-Foteini lie over an exercise ball (or on the floor) and lift her body up (Superman flies)

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Patient Copy Physical Medicine & Rehabilitation 6-252-122 21-May-2013 16:47 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:53

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- sitting on a ball and throwing overhead - Position into a crawl position and lift arm/leg.

Weight-shifting activities: - Have Maria-Foteini stand on an unstable surface (pillow) while completing an activity (e.g. throwing a ball) - Have Maria-Foteini kick a cone (we placed a cone on top of a balance disc) - Have Maria-Foteini stand on a stool or a ball while standing. Also completed gentle balance activities on the swing in quadruped and standing. Plan: Patient was given my business card to contact me if they should have further questions or concerns. will prepare a justification letter for the adaptive tricycle. Original: TAS Electronically Signed: 24-May-2013 09:17 by T.A. Shubert, PT

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Patient Copy Physical Medicine & Rehabilitation 6-252-122 21-May-2013 13:59 Maria Foteini Kallimachou

Subsequent Visit

Generated: 15-Sep-2013 04:31

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DEMOGRAPHIC INFORMATION Clinic Number: 6-252-122 Patient Name: Maria Foteini Kallimachou Age: 11 Y Birthdate: 25-Apr-2002 Sex: F Address: 8 Epidavrou Str., Platy City: Nicosia, CY 2114 Service Date/Time: 21-May-2013 13:59 Provider: David L. Nash, MD Pager: 4-7928 Service: PMR Type/Desc: SV Status: Fnl Revision #: 3 CHIEF COMPLAINT/PURPOSE OF VISIT Followup Dravet syndrome with global developmental delay. HISTORY OF PRESENT ILLNESS Maria is an 11-year-old girl with global developmental delay and a diagnosis of Dravet syndrome which is also referred to as severe myoclonic epilepsy of infancy (SMEI). I last saw Maria on May 23, 2012. She generally comes with her mother from Cyprus every year for several months. Maria no longer has a nanny that she had in the past. She is here today with her mother and her grandmother. Maria's mother speaks Greek and English well. Maria is bilingual. Concerns: Maria's mother has no specific new concerns today. She does note that earlier this year Maria would occasionally complain of some pain in her legs and indicated both thigh areas but really did not localize it well, and it never affected her activity or mobility. Maria has had no significant deterioration over the last four years since I began seeing her. She has made some slight qualitative gains in various areas. Mobility: Maria remains an independent ambulator. She needs to be supervised on the stairs. She will go for walks outside. They have a stroller that they obtained in 2008 that she still uses for being passively pushed for longer distances. Fine motor: Maria is left-handed for feeding herself and right-handed for scribbling and drawing. Activities of daily living: Maria continues to wear diapers at night. She needs assistance with feeding, dressing, undressing, and toileting. Her diet is primarily a ketogenic diet. Communication: Maria is able to communicate in both Greek and English. Her mother notes that in the past year her Greek has improved with noticeable increase in the length and complexity of phrases in Greek. She also notes that it is clear that her receptive language is better than her expressive language. She continues to be able to count to 20 and recognize some letters of the Greek alphabet and a few words. She knows basic colors and shapes. She is unable to print her name. Services: Maria continues to be cared for at home with some attempts of home schooling by her mother who is a teacher by training. She has no ongoing therapy services. She did have an adaptive tricycle at home that she enjoyed using but has outgrown now. PHYSICAL EXAMINATION General: Maria is a generally nonverbal girl. She does follow many simple commands on exam. Musculoskeletal: Deep tendon reflexes are normal to hyporeflexic. She has some limited ability to squeeze my fingers and push my hands away with her hands and feet, although not with full force. She can not follow other commands for muscle testing. Straight leg raising is 45/45. There is a slight tightness in the posterior knee capsule,

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Patient Copy Physical Medicine & Rehabilitation 6-252-122 21-May-2013 13:59 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:31

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but the knees can be stretched into full extension. Ankles dorsiflex to 30/30 with the knees flexed and 20/20 with the knees in extension which is unchanged. Gait: Maria has a fairly symmetric gait with a foot flat to heel strike. She tends to take short little steps and weight shift to and fro laterally to the right and left. IMPRESSION/REPORT/PLAN #1 Global developmental delay #2 History of severe myoclonic epilepsy of infancy #3 Dravet syndrome COMMENTS AND RECOMMENDATIONS Maria has not been approved for therapies yet for this summer. I think it would be most helpful to have some sessions of occupational therapy to continue to try to advance self-care skills to a level of increased independence. I will have physical therapy also evaluate for a larger size adaptive tricycle which may be a helpful form of exercise for Maria to utilize. I will follow up in one year and on an as-needed basis. DIAGNOSES #1 Global developmental delay #2 History of severe myoclonic epilepsy of infancy #3 Dravet syndrome Original: DLN:lla by dln Electronically Signed: 29-May-2013 06:17 by D.L. Nash, MD

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Patient Copy Pediatric Gastroenterology 6-252-122 24-May-2013 09:52 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:32

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DEMOGRAPHIC INFORMATION Clinic Number: 6-252-122 Patient Name: Maria Foteini Kallimachou Age: 11 Y Birthdate: 25-Apr-2002 Sex: F Address: 8 Epidavrou Str., Platy City: Nicosia, CY 2114 Service Date/Time: 24-May-2013 09:52 Provider: Samar H. Ibrahim, MBChB Pager: 3-5843 Service: PDGI Type/Desc: CON Status: Fnl Revision #: 3 CHIEF COMPLAINT/PURPOSE OF VISIT Abnormal bowel habits HISTORY OF PRESENT ILLNESS Maria is an 11-year-old female patient with Dravet syndrome. She has been followed by Dr. Kotagal and was last seen by him on May 17. She has intractable epilepsy. She is on multiple antiepileptic medications. The reason for referral to the Pediatric GI Clinic is because of an abnormal bowel pattern. This started in February. The patient has been maintained on one dose of MiraLAX before that with one bowel movement a day. Mother reports that when they came to the U.S. from Cypress she had five days without any bowel movement, and then she had five to six bowel movement per day that are loose. Then the frequency dropped to five times, then three times a day for two days, and then today she has not had any bowel movement so far, no blood in the stool. No associated fever with that and no vomiting. Mother is concerned that in the past she had issues with constipation and sometimes straining might trigger her seizures. CURRENT MEDICATIONS Bicitra 500-334 mg/5 mL solution by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Take 2.5 mL twice a day after meals Bicitra 500-334 mg/5 mL solution by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: International patient, Dx epilepsy: Take 2.5 mL twice a day after meals Calci-Mix capsule 500 mg calcium (1,250 mg) by mouth one time daily. Indication, Site, and Additional Prescription Instructions: Constipation 1 capsule twice a day with food International patient Children's Multi Vitamins chewable tablet one-half tablet by mouth one time daily. Children's Silapap 160 mg/5 ml* (Free Text Entry) as directed by prescriber. Indication, Site, and Additional Prescription Instructions: 10 ml prn for fever > 101 degrees Children''s Silapap Liquid 160 mg/5 mL 10 mL by mouth three times a day as needed. Indication, Site, and Additional Prescription Instructions: Fever

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Patient Copy Pediatric Gastroenterology 6-252-122 24-May-2013 09:52 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:32

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10 ml three times a day when needed International patient clobazam [ONFI] 5 mg tablet 1 TABLET by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab three times a day Depakote 250 mg tablet enteric coated by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure 1.5 tabs in a.m, 1 tab at 2:00 p.m., 1.5 tab at 8:00 p.m International patient Diastat AcuDial 12.5-15-17.5-20 mg kit 10 mg rectally as directed as needed. Indication, Site, and Additional Prescription Instructions: seizure activity 12.5 mg rectally for tonic-clonic seizure more than 1 minute Ketogenic Diet* (Free Text Entry). Klonopin 0.25 mg tablet Rapid Dissolve by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab twice a day lacosamide [VIMPAT] 50 mg tablet by mouth as directed by prescriber #1 MONTHS SUPPLY. Indication, Site, and Additional Prescription Instructions: Seizure one and one half tabs twice a day International patient

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Patient Copy Pediatric Gastroenterology 6-252-122 24-May-2013 09:52 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:32

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selenium 100 mcg tablet one-half tablet by mouth every morning. Indication, Site, and Additional Prescription Instructions: International patient Topamax 25 mg tablet 1 TABLET by mouth two times a day. Indication, Site, and Additional Prescription Instructions: half tab in a.m., one tab in p.m. International patient Topamax 50 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure one tab in a.m, 2 tabs at night These are the patient's medications as of Tuesday, 28-May-2013 at 21:36. ALLERGIES/ADVERSE REACTIONS Food : (FREE TEXT) ANIMAL HAIR - associated with eczema Other : RABBITS - associated with eczema Allergies above current as of Tuesday, 28-May-2013 at 13:21. SYSTEMS REVIEW As per the History of Present Illness. PAST MEDICAL/SURGICAL HISTORY As outlined in the HPI. SOCIAL HISTORY She is an only child. Father is a Greek history teacher at a university, and mom is a primary care teacher in a school in Cypress. FAMILY HISTORY History of irritable bowel versus nonspecific GI symptoms in Mother and Father and hemorrhoid. PHYSICAL EXAMINATION General: General appearance, not in acute distress. Heart: Regular rhythm. No murmur. Abdomen: Soft, nontender. Tympanic node on percussion. No organomegaly on palpation. No palpable mass of stool. Rectum: The patient had an anterior skin tag but no visible hemorrhoid on physical exam of the perineal area. Extremities: Extremities are warm and perfused. IMPRESSION/REPORT/PLAN #1 Abnormal bowel habits #2 Dravet syndrome with intractable epilepsy The patient's abnormal bowel habit might be secondary to an acute infectious process that was going on during the last few days. It also might be secondary to constipation with fecal mass and overflow diarrhea , we will check some stool studies to rule out an infectious etiology, do an abdominal x-ray to rule out a fecal mass, and we will do some blood work to rule out celiac disease because of the family

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Patient Copy Pediatric Gastroenterology 6-252-122 24-May-2013 09:52 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:32

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history of a GI disorder without any specific diagnosis. I will meet back with the family once we have the result. DIAGNOSES #1 Abnormal bowel habits #2 Dravet syndrome with intractable epilepsy Original: SHI:jep by shi Electronically Signed: 28-May-2013 21:40 by S.H. Ibrahim, MBChB

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Patient Copy Pediatric Gastroenterology 6-252-122 29-May-2013 15:34 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:33

Subsequent Visit Page 1 of 1

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Patient Copy Child & Adolescent Neurology 6-252-122 12-Jun-2013 15:33 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:34

Subsequent Visit Page 1 of 3

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Patient Copy Child & Adolescent Neurology 6-252-122 12-Jun-2013 15:33 Maria Foteini Kallimachou

Subsequent Visit

Generated: 15-Sep-2013 04:34

Page 2 of 3

levocarnitine [CARNITOR] 330 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: one tab three times a day International patient melatonin 3 mg tablet by mouth every bedtime as needed. Indication, Site, and Additional Prescription Instructions: sleep 3 mg at bed onset, 3 mg in the night upon awakening International patient MiraLAX 17 gram/dose Powder 1 packet by mouth one time daily as needed. Indication, Site, and Additional Prescription Instructions: constipation International patient selenium 100 mcg tablet one-half tablet by mouth every morning. Indication, Site, and Additional Prescription Instructions: International patient

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Patient Copy Child & Adolescent Neurology 6-252-122 12-Jun-2013 15:33 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:34

Subsequent Visit Page 3 of 3

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Patient Copy Orthodontics 6-252-122 13-Jun-2013 09:50 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:35

Limited Exam Page 1 of 4

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Patient Copy Orthodontics 6-252-122 13-Jun-2013 09:50 Maria Foteini Kallimachou

Limited Exam

Generated: 15-Sep-2013 04:35

Page 2 of 4

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Patient Copy Orthodontics 6-252-122 13-Jun-2013 09:50 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:35

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Topamax 50 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure one tab in a.m, 2 tabs at night These are the patient's medications as of Monday, 17-Jun-2013 at 08:26. ALLERGIES/ADVERSE REACTIONS Food : (FREE TEXT) ANIMAL HAIR - associated with eczema Other : RABBITS - associated with eczema Allergies above current as of Monday, 17-Jun-2013 at 08:26. PHYSICAL EXAMINATION Masticatory System: Maria appeared to be mildly defiant during this visit. After speaking to her mother for a brief period of time I was able to examine intraorally. The teeth which are present in Maria include upper and lower maxillary incisors, upper Es, and the upper left 6. On the mandibular arch the patient only has lower Ds and Es. The patient was seen by Dr. Keller previously for the extraction of teeth letters C, H, M, and R, did not appear that any of those teeth had begun to erupt. Upon examination there is some slight redness to her anterior gingiva. In comparison to her previous initial orthodontic records her gums appear to be in better health than last year. Mother is very integrated into Maria's dental health and brushes her teeth after every meal. There appears to be severe protrusion as well as severe deep overbite. Because of this Maria is not able to close her lips and must resort to mouth breathing. IMPRESSION/REPORT/PLAN The mother's concern regarding the inflamed gingiva appears to be predominantly due to the open mouth breathing as well as Maria's extensive list of medications which may result in xerostomia. As a result of this I informed the mother that it would be important for her to continue her oral health regimen as well as have Maria drink water to keep her mouth hydrated. Mother also stated that she was concerned that Maria was unable to chew. Maria is on a ketogenic diet which is primarily a liquid-based diet. In her mother's attempts to give her a cookie she did not chew it; however, given the dentition that is present in Maria there are sufficient teeth in order to masticate the food. It is possible that Maria still needs to get used to the texture of solid foods, and I encouraged the mother to continue to try to expose Maria to these solid foods. Maria is severely dentally delayed. A panoramic radiograph was last taken in August of 2011. It appears that most of the teeth are present although the upper left segment of the panoramic radiograph is not diagnostic. Under the advice of Dr. Regennitter we will continue to monitor the eruption of Maria's permanent dentition and reconsider extracting primary teeth to help facilitate the permanent teeth to erupt. With regards to the protrusion and deep overbite I showed the mother an Invisalign type retainer as well as a Hawley retainer to help to retract the anterior teeth. I stated that braces may not be the most suitable option for Maria, as it may not be well tolerated. In describing the retainers I also stated that it would not fully correct the protrusion but simply be a means to close the anterior spaces. Mother stated that she did not have much concern regarding aesthetics but more for functionality and allowing Maria to bring her lips over her teeth. She was concerned that both the Hawley retainer and Essix retainer would not be well tolerated by Maria.

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Patient Copy Orthodontics 6-252-122 13-Jun-2013 09:50 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:35

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The patient does not have a general dentist at this time. The nearest dentist is approximately an hour and 40 minutes away from their location in Cyprus. I stated that I would e-mail the American Cleft Palate Association e-mail group to see if there was a dentist or orthodontist who would be willing to care for Maria and provide her with orthodontic care. We will wait and see Maria back in one year to note the development of her permanent dentition and determine whether orthodontic care can be provided as a means to help reduce protrusion and close the anterior spacing. A panoramic radiograph should be taken to monitor the eruption of her permanent dentition. The mother appeared to be satisfied with this. At this appointment I received her e-mail address to contact her and give her information regarding any possible dentists closer in her area. DIAGNOSES #1 Class II malocclusion in the transitional dentition #2 Severe delayed dental eruption #3 Mandibular retrognathia #4 Excessive dental alveolar protrusion as well as severe deep bite Original: LC:ati by lc Electronically Signed: 17-Jun-2013 08:31 by L.. Chew, DMD

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Patient Copy Child & Adolescent Neurology 6-252-122 05-Jul-2013 16:28 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:36

Subsequent Visit Page 1 of 4

DEMOGRAPHIC INFORMATION Clinic Number: 6-252-122 Patient Name: Maria Foteini Kallimachou Age: 11 Y Birthdate: 25-Apr-2002 Sex: F Address: 8 Epidavrou Str., Platy City: Nicosia, CY 2114 Service Date/Time: 05-Jul-2013 16:28 Provider: Daniel L. Kenney, MD Pager: 127-10535 Service: PDN Type/Desc: SV Status: Fnl Revision #: 2 CHIEF COMPLAINT/PURPOSE OF VISIT Supervised by: Dr. Suresh Kotagal (5-3652). Followup for Dravet syndrome. HISTORY OF PRESENT ILLNESS Maria is an 11-year-old child who is followed by Dr. Suresh Kotagal in clinic for intractable epilepsy secondary to Dravet syndrome. At her previous visit, her mother had reported worsening mood symptoms, specifically depressive-type symptoms. At that time, the decision was taken to drop her topiramate by 25 mg per day. Her mother has seen some improvement and feels that the dropping of the Topamax was useful. Maria does continue to have significant mood concerns. She has daily "crises" three to four times per day where she will get upset and essentially throw tantrums. These have not changed, but her mood in between has improved somewhat. She has not had any increase in her seizure frequency. She has not had a generalized motor seizure for three years, but she continues to have daily head drops and absences which have not been affected by the drop in topiramate. Her urine ketones continue to be in the large range. She had a recent increase in her calories by 5%. Her mother, due to insurance concerns and the possibility of returning back home to Cyprus soon, does not believe she will be able to keep the psychiatry appointment in September; however, her mother will be receiving advice from a psychologist on August 2 for guidance on management of Maria's challenging behavioral issues. As far as Maria's sleep is concerned, it has been quite good. In fact, her mother feels that it is better than it has ever been. She goes to bed at about 9 p.m. and wakes up at about 6:30. She does move around a lot and occasionally has some vocalizations. She has become a little bit more oppositional with respect to bathroom behavior, and she has ceased to communicate about when she has to go to the bathroom. This has been somewhat challenging for her mother, but it seems to be an inconstant feature. She continues to eat well and is able to feed herself. She recently learned to drink from a cup. CURRENT MEDICATIONS Bicitra 500-334 mg/5 mL solution by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: International patient, Dx epilepsy: Take 2.5 mL twice a day after meals Bicitra 500-334 mg/5 mL solution by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Take 5 mL twice a day after meals

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Patient Copy Child & Adolescent Neurology 6-252-122 05-Jul-2013 16:28 Maria Foteini Kallimachou

Subsequent Visit

Generated: 15-Sep-2013 04:36

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Calci-Mix capsule 500 mg calcium (1,250 mg) by mouth one time daily. Indication, Site, and Additional Prescription Instructions: Constipation 1 capsule twice a day with food International patient Children's Multi Vitamins chewable tablet one-half tablet by mouth one time daily. Children's Silapap 160 mg/5 ml* (Free Text Entry) as directed by prescriber. Indication, Site, and Additional Prescription Instructions: 10 ml prn for fever > 101 degrees Children''s Silapap Liquid 160 mg/5 mL 10 mL by mouth three times a day as needed. Indication, Site, and Additional Prescription Instructions: Fever 10 ml three times a day when needed International patient clobazam [ONFI] 5 mg tablet 1 TABLET by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab three times a day Depakote 250 mg tablet enteric coated by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure 1.5 tabs in a.m, 1 tab at 2:00 p.m., 1.5 tab at 8:00 p.m International patient Diastat AcuDial 12.5-15-17.5-20 mg kit 10 mg rectally as directed as needed. Indication, Site, and Additional Prescription Instructions: seizure activity 12.5 mg rectally for tonic-clonic seizure more than 1 minute Ketogenic Diet* (Free Text Entry). Klonopin 0.25 mg tablet Rapid Dissolve by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab twice a day lacosamide [VIMPAT] 50 mg tablet by mouth as directed by prescriber #1 MONTHS SUPPLY. Indication, Site, and Additional Prescription Instructions: Seizure one and one half tabs twice a day International patient

levocarnitine [CARNITOR] 330 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions:

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Patient Copy Child & Adolescent Neurology 6-252-122 05-Jul-2013 16:28 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:36

Subsequent Visit Page 3 of 4

one tab three times a day International patient melatonin 3 mg tablet by mouth every bedtime as needed. Indication, Site, and Additional Prescription Instructions: sleep 2 tabs at bed time International patient MiraLAX 17 gram/dose Powder 1 packet by mouth one time daily as needed. Indication, Site, and Additional Prescription Instructions: constipation International patient selenium 100 mcg tablet one-half tablet by mouth every morning. Indication, Site, and Additional Prescription Instructions: International patient Topamax 50 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure one tab in a.m, 1.5 tabs at night These are the patient's medications as of Friday, 05-Jul-2013 at 16:32. ALLERGIES/ADVERSE REACTIONS Food : (FREE TEXT) ANIMAL HAIR - associated with eczema Other : RABBITS - associated with eczema Allergies above current as of Friday, 05-Jul-2013 at 16:32. SYSTEMS REVIEW Please refer to HPI. All other systems reviewed and negative. PHYSICAL EXAMINATION General: Physical exam is as per Dr. Suresh Kotagal's note. IMPRESSION/REPORT/PLAN #1 Dravet syndrome #2 Global developmental delay #3 Medically intractable seizure disorder, secondary to No. 1 Maria is an 11-year-old child suffering from Dravet syndrome with concomitant developmental delay, behavioral issues, and very intractable seizure disorder. Her seizures are actually reasonably controlled at this point, at least as far as the generalized motor seizures on a combination of antiepileptic drugs and the ketogenic diet. The decision has been taken given the response to the dropping of her topiramate to drop it further to 50 mg in the morning and 75 mg at night.

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Patient Copy Child & Adolescent Neurology 6-252-122 05-Jul-2013 16:28 Maria Foteini Kallimachou

Subsequent Visit

Generated: 15-Sep-2013 04:36

Page 4 of 4

Her urinary calcium-to-creatinine ratio was somewhat elevated. In response to this, the decision was taken to increase her Bicitra to 5 mL twice daily from 2.5 mL twice daily. There is concern around Maria's imminent return to Cyprus that changing her seizure medications will have a deleterious effect on her seizure control. This is quite justified as the pharmacokinetics and the nondrug components of medications can change radically from formulation to formulation even when the drug is the same. In the past, we have had patients run into problems when they change from a brand name drug to a generic (or for that matter, from a generic to a brand name). It is very likely that Maria could suffer a decompensation if her drug formulations are changed, and so for that reason, we have written a letter in support of Maria's remaining on the formulations (all of which are brand name) of the medication that she is currently on. If she is changed to other formulations (either other brands or generic formulations), she does indeed run an increased risk of losing seizure control. DIAGNOSES #1 Dravet syndrome #2 Global developmental delay #3 Medically intractable seizure disorder, secondary to No. 1 Original: DLK by ejq Electronically Signed: 31-Jul-2013 16:01 by D.L. Kenney, MD

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Patient Copy Child & Adolescent Neurology 6-252-122 05-Jul-2013 14:20 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:37

Supervisory Page 1 of 3

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Patient Copy Child & Adolescent Neurology 6-252-122 05-Jul-2013 14:20 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:37

Supervisory Page 2 of 3

Seizure 1.5 tabs in a.m, 1 tab at 2:00 p.m., 1.5 tab at 8:00 p.m International patient Diastat AcuDial 12.5-15-17.5-20 mg kit 10 mg rectally as directed as needed. Indication, Site, and Additional Prescription Instructions: seizure activity 12.5 mg rectally for tonic-clonic seizure more than 1 minute Ketogenic Diet* (Free Text Entry). Klonopin 0.25 mg tablet Rapid Dissolve by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab twice a day lacosamide [VIMPAT] 50 mg tablet by mouth as directed by prescriber #1 MONTHS SUPPLY. Indication, Site, and Additional Prescription Instructions: Seizure one and one half tabs twice a day International patient

levocarnitine [CARNITOR] 330 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: one tab three times a day International patient melatonin 3 mg tablet by mouth every bedtime as needed. Indication, Site, and Additional Prescription Instructions: sleep 2 tabs at bed time International patient MiraLAX 17 gram/dose Powder 1 packet by mouth one time daily as needed. Indication, Site, and Additional Prescription Instructions: constipation International patient selenium 100 mcg tablet one-half tablet by mouth every morning. Indication, Site, and Additional Prescription Instructions: International patient Topamax 50 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure one tab in a.m, 1.5 tabs at night These are the patient's medications as of Friday, 05-Jul-2013 at 15:13.

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Patient Copy 86 Child & Adolescent Neurology 6-252-122 05-Jul-2013 14:20 Maria Foteini Kallimachou

Supervisory

Generated: 15-Sep-2013 04:37

Page 3 of 3

ALLERGIES/ADVERSE REACTIONS Food : (FREE TEXT) ANIMAL HAIR - associated with eczema Other : RABBITS - associated with eczema Allergies above current as of Friday, 05-Jul-2013 at 14:20. VITAL SIGNS Height: 137.2 cm. Weight: 29.2 kg. BSA(G): 1.07 M2. BMI: 15.51 KG/M2. (05-Jul-2013 14:20) IMPRESSION/REPORT/PLAN I have reviewed the history and findings of Dr. Daniel Kenney and concur with them. I spoke with Mrs. Kallimachou and briefly examined Maria. The patient is 11 years old and has Dravet syndrome with intractable generalized tonic-clonic, myoclonic, and atypical absence seizures. Seizure control is reasonably stable, though she continues to persist with frequent myoclonic jerks during the day. She is ambulatory. The patient is on a combination of antiepileptic medications and ketogenic diet. She has adequate levels of serum beta-hydroxybutyrate, and her urine ketones are also adequate. The major problem with Maria Foteini has been her aggressive and at times oppositional behavior. There was a concern that this might in part be related to one of her medications, i.e., topiramate. Consequently, the dose of the topiramate had been lowered slightly by 50 mg over the past few weeks. Mother does indeed note some improvement in the child's behavior, and despite reduction in the dose of the topiramate, her seizure control has remained stable. Present dose of topiramate is 50 mg in the morning and 100 mg at night. I, therefore, recommended a slight additional decrease in the topiramate dose to 50 mg in the morning and 75 mg at night while maintaining all her other antiseizure medications unchanged. Another issue of concern is the increased urinary excretion of calcium relative to creatinine. Present dose of Bicitra is 2.5 mL b.i.d. Once again, this was altered to 5 mL b.i.d., and we plan to repeat her urinary calcium to creatinine ratio in a couple weeks. At that point, we may also obtain additional serum investigations. The family will be going back shortly to Cypress. The family is concerned that there may be some changes in her brands of antiepileptic medication. Given her brittle seizure control, it would be safer to maintain the patient on her current regimen of medications and not switch to generic formulations. We have written a letter in support of this recommendation which we will be forwarding to the family. I plan to reevaluate the patient in a few weeks, so that we can repeat the urine calcium ratio and obtain any additional tests. Also, while I suspect that the oppositional behavior may be related to topiramate, another consideration might be that of adding a low dose of fluoxetine in case she has ongoing symptoms of depression. DIAGNOSES #1 Dravet syndrome #2 Intractable epilepsy related to above #3 Daytime behavioral problems #4 Increased urinary calcium excretion Original: SK:rab by skr Electronically Signed: 07-Jul-2013 21:47 by S.. Kotagal, MD

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Patient Copy Child & Adolescent Neurology 6-252-122 05-Jul-2013 15:11 Maria Foteini Kallimachou

Miscellaneous

Generated: 15-Sep-2013 04:36

Page 1 of 1

July 7, 2013 To whom it may concern: Maria Kallimachou (date of birth 25-April-2002) is an 11 year old child with a severe form of epileptic encephalopathy (Dravet syndrome). Part of this disorder involves seizures, which are very difficult to control. Her seizures are controlled by means of a special medical diet (the ketogenic diet) as well as by anticonvulsant medications. She takes the following medications for seizure control: valproic acid (brand name: Depakote), clobazam (brand name: Onfi), clonazepam (brand name: Klonopin), lacosamide (brand name: Vimpat) and topiramate (brand name: Topamax). Her medical diet involves very strict monitoring of the amount of carbohydrates and other nutrients that she consumes, and it can be disrupted by very slight changes in her foods and medications. For this reason, we strongly recommend that she NOT change brands of medication right now. Because of regional differences in binders used in the formulations of these medications, it will be best for this patient's seizure control that she stay on the brand of medication that she is currently stable on. Using other forms of the medication could be disruptive to her medical diet, and for this reason as well as differences in pharmacokinetics could result in a loss of her current seizure control. Thank you, Suresh Kotagal, M.D. Consultant in Child and Adolescent Neurology Daniel Kenney, M.D. Senior resident in Child and Adolescent Neurology Original: DLK Electronically Signed: 05-Jul-2013 15:12 by D.L. Kenney, MD

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Patient Copy Child & Adolescent Neurology 6-252-122 23-Jul-2013 16:25 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:37

Miscellaneous Page 1 of 1

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Patient Copy Child & Adolescent Neurology 6-252-122 15-Aug-2013 17:17 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:38

Subsequent Visit Page 1 of 1

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Patient Copy Child & Adolescent Neurology 6-252-122 16-Aug-2013 10:51 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:38

Miscellaneous Page 1 of 3

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Patient Copy Child & Adolescent Neurology 6-252-122 16-Aug-2013 10:51 Maria Foteini Kallimachou

Miscellaneous

Generated: 15-Sep-2013 04:38

Page 2 of 3

Indication, Site, and Additional Prescription Instructions: seizure activity 12.5 mg rectally for tonic-clonic seizure more than 1 minute Ketogenic Diet* (Free Text Entry). Klonopin 0.25 mg tablet Rapid Dissolve by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: One tab twice a day Klonopin 0.5 mg tablet Rapid Dissolve by mouth every bedtime. Indication, Site, and Additional Prescription Instructions: 1/2 tab twice a day lacosamide [VIMPAT] 50 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure 1 tab in a.m., 1.5 tabs in p.m. International patient levocarnitine [CARNITOR] 330 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: one tab three times a day International patient melatonin 3 mg tablet by mouth every bedtime as needed. Indication, Site, and Additional Prescription Instructions: sleep 2 tabs at bed time International patient MiraLAX 17 gram/dose Powder 1 packet by mouth one time daily as needed. Indication, Site, and Additional Prescription Instructions: constipation International patient Polycitra-K Crystals [CYTRA K] 3,300-1,002 mg Pack 1 packet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: 1/3 pack once a day selenium 100 mcg tablet one-half tablet by mouth every morning. Indication, Site, and Additional Prescription Instructions: International patient Topamax 50 mg tablet by mouth as directed by prescriber. Indication, Site, and Additional Prescription Instructions: Seizure one tab in a.m., 1.5 tabs at night These are the patient's medications as of Friday, 16-Aug-2013 at 10:52.

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Patient Copy Child & Adolescent Neurology 6-252-122 16-Aug-2013 10:51 Maria Foteini Kallimachou Generated: 15-Sep-2013 04:38

Miscellaneous Page 3 of 3

IMPRESSION/REPORT/PLAN "Please provide the prescription refills for the Silapap." Per Mayo Nursing Protocol 1156-951 Prescription refills faxed to Mayo Subway Pharmacy. I called Mother (locally) and informed her of this. Original: PAK Electronically Signed: 16-Aug-2013 10:53 by P.A. Klingsporn, RN

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MAYO CLINIC

9@ 200 First Street SW

Rochester, Minnesota 55905 507-284-257"r

February 7,2012

Administrative Health Cyprus

Suresh Kotagal, M.D. Division of Child & Adolescent Neurology

RE: Maria F. Kallimachou MC#: 6-252-122

DOB

2002-4-25

To Whom It May Concern: This is

to.

certify that the above.menrioned 9 year-old child with intractable epireps'

oe]av is under my care. r Lave ueen ia.irs'i;;h.; foiiir."i"ri" ::j^9:,"..!ry:'!{ several years as an outpatient. The patient has a rare neurololicat oisoraei iirilia Dravet s1'ndrome. This reads to.a

severe form of epilepsy thai is oirni"riio coni.or despite using a variely o.f firsr line anriep.irepti. uglntrl fr'.r. ,r. .w"-rr.i.iv'ooo cases reported worldwide. I am not sure ho'i man'y cases ororaveiJyndi;;;;il";;'"r. il;iy".r, in C.yprus b-ut I anticipate thar it is relativeiy the patient staved in Rochester for a period of about eight four montfis. make a varietv of chanees in her riedication and diii. she receives the ketogenic diet which is a sp6cialized itet ror.eizure "" monitoring of various biochemical parameters.

*;. Du.re,i;.*;;i;iliil;iJil#. ."iii.L'ir,iii'lr";[;;;;;; i;;;;;?:;'"

Despite the above manasement, the patient still suffers from tremor and perhaps some degree.of cognitive difficulty. t-at"ry, seiru."s-ir;;;6;;o-. more difficult to control, thus additional investigations are necessary.

I have recornmended that the family bring Maria Foteini back to Mayo clinic for medical re-evaluation this summer. The a"ttendance oia medical ooii- ouiing^;he trip would also be appropriate and medicaly indicated. Ai thi; p"i; " appointments scheduled at our institution commencing . pliase let -i-t"o* #i .un provide any additional information.

th;il;ilffir*"

Sincerely,

sKjlk

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