Padaczka po udarze niedokrwiennym. Czy warto stosować leki przeciwpadaczkowe już po pierwszym napadzie?

Mykhailo M. Oros 1, Volodymyr I. Smolanka1, Nina V. Sofilkanich1, Olesya I. Borovik1, Vitaliy V. Luts2, Pavlo G. Andrukh3

1 DEPARTMENT OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY, MEDICAL FACULTY, UZHHOROD NATIONAL UNIVERSITY, UZHHOROD, UKRAINE

2 MUKACHEVO CENTRAL DISTRICT HOSPITAL, MUKACHEVO, UKRAINE

3 KHARKIV MEDICAL ACADEMY OF POSTGRADUATE EDUCATION, KHARKIV, UKRAINE

ABSTRACT

Introduction: Epileptic attacks frequency in patients after stroke ranges widely from 3 % up to 60 %. Today many aspects of this problem in post-stroke epilepsy haven’t been completely studied, regarding the problem of the time for administering antiepileptic drugs (AEDs).

The aim of this study was to define the prognosis of symptomatic epilepsy development after stroke depending on the patients taking AEDs after the first epileptic attack.

Materials and methods: We perform a complex examination of 1012 patients (562 males and 450 females) aged from 49 up to 90 who had suffered from ischemic stroke during 2011-2014. Neurologic examinations were carried out according to the conventional methods scaling score NIHSS (National Institute of Health Scale of Stroke Severity, USA).

Results: It was revealed that within 6 months after the ischemic stroke at least one epileptic attack was observed in 151 patients. According to the type of attacks focal attacks (80.9%, p<0.001) prevailed, and only in 11.1% initially generalized epileptic attacks were diagnosed. In the first patients group who took anticonvulsants during one year repeated epileptic attacks were revealed in 27.1% of patients while in the other group where there was no treatment with anticonvulsants during a year repeated attacks were observed in 53.75% patients.

Conclusions: Obtained results are the basis for further investigations and possible recommended administration of AEDs just after the first epileptic attack in the patients after stroke.

 

Wiad Lek 2018, 71, 2 cz. I, -272

 

INTRODUCTION

Epilepsy is one of the most widespread nervous system diseases. It is considered to be the third neurological problem in frequency after dementia and strokes among old-aged people [1]. The firstly revealed epilepsy in adults is often symptomatic which requires a more precise definition of its risk factors and development [2]. Recent research results demonstrated that one of the main risk factors of epilepsy development in old-aged patients is cerebral blood circulation impairment [3]. About 30% of the firstly diagnosed epileptic attacks in patients over 60 are considered to appear after the stroke [4]. The frequency of epileptic attacks in the patients after stroke, according to different authors data, ranges widely from 3% to over 60% [3, 5-7]. Such significant data intervals can be explained by the different measurements methods, absence of exact definitions, not uniform groups as well as the different time length of the observation of the stroke patients under investigation.

In spite of the great amount of the investigations dedicated to the “vascular” epilepsy problems (first of all post-stroke epilepsy), many aspects of this problem remain not fully studied. One should mention that epileptic attacks based on acute cerebral blood circulation impairment are often neglected and not taken into consideration during the treatment. Modern instrumental diagnostic methods are the basis for getting exact information about structural changes in the central nervous system, functional cerebral state and cerebral hemodynamics in patients with epileptic attacks.

A very important aspect is therapy features of epilepsy which are developed after cerebral ischemia. As a rule, patients with cerebral ischemia represent groups of old-aged patients who have some concomitant diseases for which they take several therapeutic remedies. That’s why antiseizure drug selection depends on the epilepsy form and possible therapeutic interactions. Today among the traditional antiseizure drugs are carbamazepin and valproatic acid preparations. Considering the similarity of pathogenic mechanisms of ischemishe stroke and epilepsy development while choosing AEDs for the treatment of epilepsy there is a growing interest in antiepileptic drugs which have neuroprotective features (such as lamotrigin, topiramate, levetiratsetam).

Nowadays in spite of the diverse results of different investigations there is a predominant opinion that early attacks don’t require immediate antiepileptic treatment [7, 8]. It’s necessary to keep the patient under thorough dynamic observation. Antiseizure treatment should be started after repeated unprovoked seizure. The question of prevention among the patients after the stroke is disputable. According to the American Stroke Association recommendations of their preventive treatment is indicated to the patients with lobar and subarachnoid hemorrhage during acute period [9]. At the same time preventive antiepileptic treatment among the patients after ischemic stroke is not recommended, though possible [10].

THE AIM

Thus, our research is aimed to reveal the prognosis of symptomatic epilepsy development after the stroke depending on the patients antiseizure therapy after the first epileptic seizure.

MATERIALS AND METHODS

The complex examination of 1012 patients (562 males and 450 females) of age from 49 till 90 years with ischemic stroke in the period of 2011-2014 was performed. The examination was carried out at the in-patient department of Mukachevo Central District Hospital (Mukachevo, Ukraine). Instrumental investigations were performed during the period without attacks. Neurologic examination were carried out according to the conventional methods scaling score NIHSS (Scale of Stroke Severity, National Institute of Health, USA). Cerebral structures visualization was carried out with magnetic-resonance tomography (MRT) on the equipment with 0.25 tension Tesla at T1, T2, FLAIR regimes with MR angiography application. The functional state of big hemispheres was evaluated according to electroencephalogram (EEG). During transcranial doplerography carotid arteries and vertebro-basilar pool (VBP) were investigated with determining medium linear blood stream speed (LBS), reactivity during dilatators (Kp+) and constrictor (Kp) responses. Besides, duplex extracranial and transcranial cerebral vascular examination was made with evaluation of the level and degree of stenosis and cerebrovascular reactivity (CVR).

Numerical material was mathematically analyzed by means of Microsoft Excel, Statistica programs (v 6.0). Frequencies in control and basic groups were compared by two by means of χ2 criterion. Kraskel-Wallis criterion was used to evaluate the importance of quantitative features having different distribution from normal. Normal distribution of quantitative features was checked by means of Kholmogorov-Smirnov criterion.

RESULTS AND DISCUSSION

It shoud be noted that in 1012 patients under investigation in the period of 6 months after the stroke the one epileptic seizure at least was noticed in 151 patients (Fig. 1). It is shown (Fig. 1) that the quantity of epileptic seizure in the patients of the investigated group was 16%, besides 86 of them were males and 75 were females. Epileptic attacks didn’t depend on the gender. According to the types of attacks there were more focal attacks (89.9%, p<0.001), and only in 11.1% initially-generalized epileptic attacks were diagnosed. In 2.4% of patients with ischemic stroke in its debut or during the first 7 days was developing epileptic status. In this case patients with ischemic stroke showed that among early post-stroke attacks simple partial attacks were more often diagnosed (55.4%, p<0.01). Similar results were obtained by other researchers. In Ref. [11] the simple partial attacks made up 50-90% of early post-stroke epileptic seizures. A.B. Gekht et al in Ref. [12] noticed the prevalence of partial over secondary generalized attacks among patients with early seizures. At the same time S.A. Siddiqi et al in Ref. [13] observed a much higher frequency (74%) of initially generalized tonico-clonical attacks development in the early stroke period.

Epileptic seizures can appear during different periods of the stroke which depends on the period of their development, with respect to the stroke we distinguish predictable seizures, early seizures and late seizures. Nowadays there is no uniform commonly accepted opinion about the terms of these attacks development, they differ in many studies. Similarly to many other neurologists who deal with the problem of post-stroke epilepsy, for our research we accept G.S. Barolin and E. Sherzer classification proposed in 1962 [14], according to which:

(1) predictable seizures occur before the development of the stroke (we distinguished 10% of predictable seizures among the patients studied after the ischemic stroke and with epileptic seizures);

(2) early seizures develop during the first 7 days after stroke (according to our investigation 41% of patients had early attacks);

(3) late seizures appear after 7 days after stroke (according to our data 49% of patients had late attacks).

According to our observations early attacks appeared more often in patients with ischemic stroke in the left carotid pool (40.5%, p<0.05) compared with the patients with the stroke in the right carotid pool (42.9%) and in the vertebro-basilar pool (16.6%), while patients with late attacks had practically the same quantity of seizures as in patients with left (45.9%) and right (44.7%) carotid pool seizures. Late attacks during strokes in vertebro-basilar pool developed in 11.4% of observations.

One part of the patients at least with one epileptic attack was divided into two groups: in the first group there were 81 patients among them 43 males and 38 females, the second group included 80 patients, among them 43 males and 37 females. The average age of the first group was 65 1.2) years while the average age of the other group was 64 1.3) years.

In the first group AEDs were administered immediately after the first epileptic attack in accordance with the type of the attack, we used carbamazepin (from 400 to 1000 mg per day) with gradual dose titration, valproates (in the dose from 600 to 1500 mg per day) and lamotrigin (200 mg a day with gradual titration), all patients were correctly treated by means of monitoring the level of antiepileptic preparations in the blood plasma with further correction of their dose.

In the second group of patients after the first epileptic attack we did not use any of antiepileptic drugs, we only observed the patients state and dynamics of both their main disease and secondary epileptic attack emergence.

In the patients with epileptic seizures lesion pathologic activity was observed on the encephalogram in 39.5% of observations prevailing in the temporal lobe region (87.3%, p<0.001) compared with all other registered localizations. Leftside localization of regional activity prevailed (59.6% compared with 40.4% in the right hemisphere), both in patients with ischemic stroke (57.7%) and in patients with chronic cerebral ischemia without clinical stroke manifestation (63.6%).

One should emphasize the importance of electroencephalographie among the patients with cerebral ischemia when paroxysmal clinical states develop, as well of those stroke patients with impaired conscience, even without seizure syndrome clinic in order to early diagnose non-seizure epileptic status and timely correction therapy.

Considering the above mentioned we took similar groups of the first one (81 patients) and the second one (80 patients) for comparison. The patients condition was evaluated one year after the first epileptic attack. The evaluation criteria were: (1) the presence of the second and more epileptic attacks (i.e. the diagnosed symptomatic post-stroke epilepsy), or (2) the total absence of epileptic attacks.

In the first group of patients where we used antiepileptic drugs the second attack was observed in 22 patients out of 81, while in the second group in which we didn’t use antiepileptic drugs for prevention, the second and more epileptic attacks were fixed in 43 out of 80 patients (for comparison one can see Fig. 2).

According to the obtained results in the first group who took antiseizure therapy during one year 22 patients had repeated epileptic attacks which makes 27.1%, while in the second group where AEDs were not used for the treatment during one year 43 patients had repeated epileptic attacks that made up 53.8%.

CONCLUSIONS

Post-stroke epilepsy is a concomitant pathology that complicates the patients rehabilitation after the stroke. According to the results of our investigation 16% of patients who had a stroke during 6 months had at least one epileptic attack. The second epileptic attack appeared in 27.1% of the patients who took AEDs, while in the group without AEDs repeated attacks were revealed in 53.8% of patients. These results can be used as the basis for further studies and possible recommendations for administering AEDs just after the first epileptic seizure in the patients who had stroke.

REFERENCES

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2. Geht AB. Modern standards of epileptic patients’ management and general principles of their treatment. Consilium Medicum. 2000;2(2):2–11.

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4. Forsgren L, Bucht G, Eriksson S et al. Incidence and clinical characterization of unprovoked seizures in adults: a prospective population based study. Epilepsia. 1996;7:224-229.

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11. Lami C, Domigo V, Semah F et al. Early and late sizures after cryptogenic ischemic stroke in young adults. Neurology. 2003;60:400–404.

12. Geht AB, Lebedeva AV, Ruleva ZS et al. Epilepsy in Stroke Patients. Russian Medical Journal. 2000;2:14–17.

13. Siddiqi SA, Hashmi M, Khan F et al. Clinical spectrum of post-stroke seizures. J. Coll. Physicians Sung. Pak. 2011;21(4):214–218.

14. Barolin GS, Sherzer E. Epileptische. Anfalle bei Apoplektikern. Wein Nervenh. 1962;20: 35–4714.

Research were carried out under the scientific project “Genetical and clinical electrophysiological criteria of efficiency prognosis for epileptical pharmacotherapy”.

ADDRESS FOR CORRESPONDENCE

Mykhailo M. Oros

Narodna Sq.3

88000, Uzhhorod, Ukraine

tel.: +380672746300

e-mail: mihoros@meta.ua

Received: 20.02.2018

Accepted: 10.04.2018

Figure 1. The quantity of patients who had an epileptic attack during six months after the stroke.

Figure 2. Comparison of the quantity of patients with epileptic attacks one year after the first epileptic attack depending on the presence or absence of antiepileptic treatment (p<0.01).