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Научная статья "Протокол предхирургической диагностики для пациентов с фармакорезистентной формой эпилепсии" из журнала "Астана медициналык журналы", специальный выпуск №4/2015

 Научная статья "Протокол предхирургической диагностики для пациентов с фармакорезистентной формой эпилепсии" на английском языке из журнала "Астана медициналық журналы", специальный выпуск №4/2015 






Z.Utebekov 2, I.Bondareva 2, N.Djainakbaev 1, S.Savinov 2, I.Akchurina 1, R.Abedimova 1, I.Sitnikov 2, N.Mikhailova 2, G. Esimova 2

1 Kazakh-Russian Medical University, Almaty

2 SVS Laboratory of epilepsy, convulsive diseases research and family monitoring named after V.M. Savinov, Almaty



Over recent years epileptology has made a huge breakthrough in Kazakhstan. Based on the Kazakh-Russian Medical University the Faculty of Functional Diagnostics with the course of neurophysiology was opened that has until today trained more than 400 EEG and epileptology specialists. Practically in every city there is equipment for long-term EEG monitoring. Since 2010 the National Center for Neurosurgery has held operations for surgical treatment of epilepsy. An important role in attaining a positive result of operative treatment of epilepsy is played by correct presurgical diagnostics.

Identification and confirmation of drugresistent, performance of long-term ictal EEG monitoring, comparison of neurophysiological data with the results of MRI, CT, MEG, PET and other neuroimaging methods form the basis of presurgical examination.

Thereafter a patient is reviewed by a multidisciplinary council of physicians where a decision is taken concerning one or another method of treatment or surgical intervention.

Since 2010 the Faculty of Functional Diagnostics with the course of neurophysiology and SVS Laboratory of epilepsy, convulsive diseases research and family monitoring named after V.M. Savinov have conducted a presurgical study of epilepsy patients. This paper has summarized the experience and presents developed evaluation protocols for patients with epilepsy who are candidates for surgical treatment.

Key words: pharmacoresistence epilepsy, drugresistent epilepsy, EEG, MRI, surgical treatment, epileptology.


Over 11 years the SVS Laboratory of epilepsy, convulsive diseases research and family monitoring named after V.M. Savinov and Faculty of Functional Diagnostics with the course of neurophysiology have been consistently developed epileptology jointly with other faculties and clinics. As a result, detectability of epilepsy patients at early stages has increased in tens of times. Accordingly, a percentage of achieving remission and recovery has also reached almost a worldwide level. After the Department of Surgical Treatment of Epilepsy was opened in the National Center for Neurosurgery in Astana, it made possible to combat severe, drugresistent forms. But, unfortunately, many doctors and patients have no full and clear understanding of indications for surgical treatment of epilepsy. As a consequence, district neurologists and epileptologists send patients to neurosurgeons without a prior specialized in-depth examination under a presurgical evaluation protocol. And even patients themselves without a referral try to seek for an operative treatment without being aware of whether they need it or not.

Therefore, doctors of the National Center for Neurosurgery lose time and tertiary care bed-days for patients many of whom either have no indications for surgical treatment at all, or have been chosen improper therapy.

In order to optimize patients flows and develop clear criteria for surgical treatment of epilepsy, we have analyzed the international experience, attracted specialists from Kazakhstan, Russia, Greece, Turkey, Italy in the area of expert examination for surgical treatment of epilepsy, and developed an evaluation protocol.

Such protocol for examination of candidates for surgical treatment of epilepsy is critical in order to organize a correct stage-by-stage approach in providing surgical services in epileptology.


- analyze the international experience in preparing epilepsy patients for operative treatment;

- work out a methodology of long-term ictal video EEG monitoring;

- develop schemes of drug dosage reduction to provoke seizures during EEG monitoring;

- develop a presurgical evaluation protocol for patients with epilepsy in order to select candidates for surgical treatment.


Presurgical examination was received by 1,200 patients who were admitted to the SVS Laboratory from various clinics and cities of Kazakhstan with a provisional

diagnosis of pharmacoresistent epilepsy. Presurgical examination includes as follows:

- evaluation of a neurological status and consultation by a neurologist-epileptologist;

- determination of a level of antiepileptic drugs (AED) to exclude an inadequate dosage, as well as general blood tests;

- analysis of EEG available and performance of daily video EEG monitoring;

- consultation with a psychologist and geneticist;

- high-resolution brain MRI under a protocol of search for an epidemiological block with subsequent consultations by leading specialists;

- where necessary, performance of brain CT, SPECT and PET;

- for patients with the established true pharmacoresistence – conducting long-term video EEG monitoring with recording acute EEG – no less than 3 seizures (from 3 to 7 days);

- holding a multidisciplinary council of physicians upon the results of examination with participation of neurosurgeons-epileptologists, neurologists-epileptologists,

neurophysiologists-epileptologists, psycholo-gists, MRI and CT specialists followed by decision making concerning further tactics.


Based on the international experience patients undergo the following stages of examination:

Stage 1 – there was established a correct diagnosis: pharmacoresistence – absence of effect when using two tolerant, adequately selected and used AEDs of the first line (either in monotherapy, or in their combination) depending upon an epileptic syndrome. In adults a period of use is at least 2 years [1-7]. At this stage 72% of patients were filtered out. The reasons were as follows: incorrect selection of an AED, inadequate dosage, low adherence.

Stage 2 – long-term video EEG monitoring with mandatory recording of seizures; if all seizures are the same, then of at least two seizures, if they are different, then of three seizures [1,3-12]. At this stage 6% of patients were filtered out due to a non-epileptological reason of seizures.

Stage 3 – MRI with a magnetic field induction of 1.5-3 Tesla with the use of anepileptological protocol [2,5,6,7,13-15]. Taking into consideration that a hippocampus change is often an epileptogenic substrate, it is necessary to use an additional protocol of study of mediobasal divisions of temporal lobes, including the performance of Flair-oblique Cor and Ax: RealIR-obliqueCor. These images produced in skew axial and skew coronal planes demonstrate very well the structures of mediobasal divisions of temporal lobes[2,15]. At the initial stage in 20 patients out of those being examined there were no MRI changes. It is explained by the fact that radiation therapists are often insufficientlyqualified and do not use an epileptological protocol, and also low-resolution MRI (1.0 Tesla and less) is used with the section thickness of more than 2.0mm. After repeated performance of MRI with the resolution of 1.5-3.0 Tesla (under an epileptological protocol) in increments of 1.0 and 2.0mm, in 10 patients there was detected an epileptic substrate - FCD, mesial temporal sclerosis, heterotopions. At this stage no deviances on MRI shots were found in 18% of patients.

Stage 4 – in the absence of congruence of focuses on MRI and EEG such additional methods of examination as PET and SPECT are to be held [1,5-7,11,13,]

Stage 5 – neuropsychological study to identify a cognitive and linguistic deficit prior to operation [1,5-7,13,14].

Stage 6 – multidisciplinary council of physicians to make a decision on further tactics of patient management.

Upon the results of presurgical diagnostics, only in 47 patients (4% of all those examined) a diagnosis of true drugresistence was established.

Of them:

- 3 patients (6%) were recommended a ketogenic diet;

- 11 patients (23%) were recommended surgical treatment (4 patients (8%) were operated, 7 patients (17%) are prepared for being operated);

- 11 patients (23%) were recommended a vagus nerve stimulation (4 patients (8%) were operated, 7 patients (17%) are prepared for being operated);

- the rest 22 patients (47%) were recommended additional methods of examination to localize an epileptogenic focus.


Long-term video EEG monitoring was held by means of device Nicolet one (made in USA) – 44-channel, and neuron-spectrum (made in Russia) – 21-channel with the use of modified Jasper scheme in a specialized ward where there are special medicines for the first aid treatment and an oxygen cushion.

Before EEG monitoring a preliminary talk with a patient and parents is held and the following issues are discussed:

- voluntary consent to the procedure;

- goal of the examination;

- expected outcome;

- difficulties that may be encountered;

- complications (post-acute psychotic disorder, epileptic status, muscle and extremities joints damage);

- predictable (insufficiency of one seizure) and unpredictable (technical errors) circumstances;

- keeping a seizure diary.

A seizure diary filled in by a patient and thorough analysis of seizures help to determine a cyclicity of a seizure, a post-seizure behavior of a patient, thereby

minimizing the period of stay in VEEG monitoring and expenses, accordingly. If it is impossible to determine a circadian nature of seizures, then stage-by-stage induction of seizures is used: Three days before EEG monitoring AED is reduced by 50% (if monotherapy), on the day of examination AED is completely cancelled. If there is no seizure, on the next day - partial sleep deprivation (night sleep deprivation). On the third day - partial deprivation and hyperventilation within 5-6 minutes up to 4 times a day at a 2-hour interval.

If a patient has polytherapy, then the first AED is also reduced by 50% three days before, on the day of examination the rest (2 or 3) AEDs are reduced by 10% with partial sleep deprivation. On the second day - frequent hyperventilation with the duration of 5-6 minutes. On the third day - full cancellation of one of the drugs.

The results of distribution by gender, localization of seizure onset, by form of epilepsy and changes on MRT are shown in Tables No. 1,2,3,4.



Table 1 - Patient Distribution by Gender and Age.


Table 2 - Localization of Epileptic Discharge Onset.

Тable 3 - Distribution by Epilepsy Form.

Тable 4 - MRT Changes upon the Results of Studies.

1. Our study shows that out of 1,200 patients who were initially diagnosed a pharmacoresistent form of epilepsy only 47 (4%) patients have true pharmacoresistence. According to the international data, a percentage of pharmacoresistent forms varies from 10 to 30% [5,6], accordingly, patient management and diagnosing should be made more thoroughly.
2. An important role in attaining a positive result of operative treatment is played by timely and correct presurgical evaluation of patients with hard-curable convulsions. The data of world surveys, our activities experience and outcomes of the joint work with neurosurgeons allowed creating a protocol of presurgical diagnostics of patients with pharmacoresistent forms of epilepsy. This response protocol contributes to minimizing time and means, thus helping to reduce irreversible changes in a person related to long-term disease progression and frequent convulsive seizures.
3. Only interdisciplinary councils of physicians should participate in final decision making on operative treatment of epilepsy patients, such councils will include neurologists-epileptologists, neurosurgeons, radiation therapists, psychologists.
4. Due to a possibility of complications during ictal long-term EEG monitoring there emerges a need in creating specialized wards to register epileptic and non-epileptic paroxysmal states.
1.Healthcare utilization and costs in adults with stable and uncontrolled epilepsy/ Cramer J.A., Wang Z.J., Chang E. et al. //EpilepsyBehav. – 2014. – V. 31. – P. 356-362.
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4. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies/ Kwan P., Arzimanoglou A., Berg A.T. et al.// Epilepsia. – 2010. – V. 51. – P. 1069-1077.
5. Panayiotopoulos C.P. A Clinical Guide to Epileptic Syndromes and their Treatment//Secondedition, 2010. - P. 222-224.
6. Rosenow F., Lüders H. Presurgical evaluation of epilepsy// Brain. – 2001. – V. 124. – P. 1683-1700.
7. RyvlinP., Rheims S. Epilepsy surgery: eligibility criteria and presurgical evaluation//DialoguesinClinicalNeuroscience. – 2008. – Vol. 10 (1). – P. 91-103.
8. Ictal clinical and scalp-EEG findings differentiating temporal lobe epilepsies from temporal ’plus’ epilepsies/ Barba C., Barbati G., Minotti L. et al.//Brain. – 2007. – V. 130. – P. 1957-1967.
9. Loddenkemper T., Kotagal P. Lateralizing signs during seizures in focal epilepsy//EpilepsyBehav. – 2005. – V. 7. – P. 1-17.
10. On the prognostic value of ictal EEG patterns in temporal lobe epilepsy surgery: A cohort study/ Monnerat B.Z., Velasco T.R., AssiratiJr J.A. et al.// Seizure. – 2013. – V.22. – P. 287-291.
11. Radhakrishanan K. Cost-effective utilization of single photon emission computed tomography (SPECT) in decision making for epilepsy surgery/Rathore C., Kesavadas C., Ajith J. et al.// Seizure. – 2011. – V. 20. – P. 107-114.
12. Serles W., Pataraia E., Bacher J. Clinical seizure lateralization in mesial temporal lobe epilepsy: Differences between patients with unitemporal and bitemporalinterictal spikes//Neurology. – 1998. – V. 50. – P. 742-747.
13. Asano E., Brown E.C., Juhász C. How to establish causality in epilepsy surgery//BrainDev. – 2013. – V. 35. – P. 706-720.
14.Tellez-Zenteno J.F., Dhar R., Wiebe S. Long-term seizure outcomes following epilepsy surgery: A systematic review and meta-analysis//Brain. – 2005. – V. 128. – P. 1188-1198.
15. Yezhova R.V., Shmelyova L.M. et al. Application of voxel morphometry for diagnostics of limbic structures affection in temporal lobe epilepsy with affective disorders//Review of Psychiatry and Medical Psychology. – 2013. - No. 2.
Утебеков Ж.Е. 2, Бондарева И.В. 2, Джайнакбаев Н.Т. 1 , Савинов С.В. 2 , Абедимова Р.А. 1 , Акчурина Я.Е. 1 , Ситников И.Ю. 2 , Михайлова Н.В. 2 , Есимова Г.Н. 2, Т.Н. Синицина 2
1 Қазақ-Ресей Медицина Университеті, Алматы 2 В.М. Савинов атындағы эпилепсия және тырыспалы мемлекеттердін лабораториясы, Алматы ЭПИЛЕПСИЯНЫҢ ЕМГЕ ТӨЗІМДІ ТҮРІМЕН АУРЫРАТЫН НАУҚАСТАРДЫ ОТАҒА ДЕЙІНГІ ТЕКСЕРУЛЕРДІ ЖҮРГІЗУ ХАТТАМАСЫ
Бұл жұмыста жалпыланған тәжірибелер және хирургиялық емге үміткер эпилепсиямен ауыратын науқастарды тексерістер жүргізу хаттамасы ұсынылған. Науқастарды отаға дейінгі тексерулерді жүргізу хаттамасының қорытындысы бойынша тек 4% (n=47) науқастарға ғана емге төзімді түрі қойылған. Дайындалған алгоритм іс-жарасы диагноздың дұрыстыңын және емдеу тәсілдерін, эпилепсияның нағыз емге төзімді тұрін дәлелдеуге және бағалауға мүмкіндік берді. Сонымен қатар, ұзақ уақыт эпилепсиямен ауыратын науқастардың әлеуметтік және медициналық бейімделуіне, өмір сүру салтының жақсаруына, неврологиялық бұзылыстарды болдырмауға көмектесті.
Утебеков Ж.Е. 2 , Бондарева И.В. 2 , Джайнакбаев Н.Т. 1 , Савинов С.В. 2 , Абедимова Р.А. 1 , Акчурина Я.Е. 1 , Ситников И.Ю. 2 , Михайлова Н.В. 2 , Есимова Г.Н., Синицина Т.Н. 2 1 Казахстанско- Российский Медицинский Университет, Алматы 2 SVS Лаборатория изучения эпилепсии, судорожных состояний и семейного мониторинга им. Савинова В.М., Алматы
В данной работе обобщен опыт и представлены разработанные протоколы обследований пациентов с эпилепсией - кандидатов на хирургическое лечение. По результатам проведенной предхирургической диагностики только у 4% (n=47) пациентов был выставлен диагноз фармакорезистентность. Разработанный алгоритм действия позволяет оценить правильность диагноза и тактики лечения, определить истинные фармакорезистентные формы эпилепсии, тем самым помогает пациентам, длительно страдающим от эпилепсии, минимизировать неврологические нарушения, адаптироваться в социальном и медицинском плане, улучшая качество жизни.
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