Epilepsy and paroxysmal conditions

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Vol 10, No 2 (2018)
View or download the full issue PDF (Russian)




6-18 989

ASL (Arterial Spin Labeling) – a novel modality of MR angiography – is based on radio-frequency labeling of aqueous protons in the arterial blood; the method is used to monitor blood supply to  organs, including the brain. So far there has been little information on the use of ASL in children with focal epilepsy, especially in the pre-surgery period.

Aim: to evaluate the perfusion patterns in seizure-free children with drug resistant focal epilepsy (FE) using the ASL mode of MRI.

Materials and methods. We studied the ASL data of 54 (23-boys/31 girls) patients with FE  treated in the Dpt. of Neurology at the Russian State Children Hospital from 2015 to 2018. The  patients’ age varied from 4 months to 17 years. All images were produced with a 3T GE Discovery  750W system.

Results. We found several brain perfusion patterns in children with FE; among other factors, those patterns depended on the clinical status of the patient, i. e. the interictal period or the early post- seizure period. The main pattern of the interictal period was characterized by a focal decrease in  perfusion located around a structural focus identified on MRI scans. In the early post-seizure  period, there was an increase in the arterial perfusion in the area of a structural epileptogenic lesion.

Conclusion. ASL-MRI is an effective diagnostic method providing more information on children  with FE during their pre-surgery phase. The ASL modality needs further research to rationalize its wider use as a preferred diagnostic tool or as a combination with the more complex PET and SPECT.

19-25 584

Aim: to study the sexuality aspects of the “Ego-function” in male and female patients with epilepsy.

Material and methods. A group of 102 respondents (52 patients diagnosed with epilepsy and 50  apparently healthy subjects) aged 19 to 45 years were examined with the help of a clinical interview and the Ammon’s Ego-Structure Test.

Results. We found significant differences between men and women with epilepsy when the  patients were tested for “destructive anxiety”, “constructive outer ego-demarcation”, “deficient  outer ego-demarcation”, “constructive sexuality”, and “deficient sexuality”. Also, significant  differences were found between women in the “healthy” and “epilepsy” groups when they were  scored for “destructive anxiety”, “deficit outer ego-demarcation”, and “deficient sexuality”.  Likewise, significant  differences were noted between men in these two groups when scored for  “deficient aggression”, “constructive outer ego-demarcation”, and “deficient sexuality”.

Conclusion. Formation and maintenance of normal sexuality in patients with epilepsy is impaired by the disabled central Ego-functions.

26-34 592

Aim: to study the bioelectric activity of the brain in relation to changes in the tone of the autonomic nervous system as assessed by heart rate variability (HRV) and evoked skin  sympathetic potentials (ESSP) in patients with migraine and epilepsy.

Materials and methods. We studied patients with epileptic foci in the left (group 1) or right (group 2) hemisphere with migraine attacks followed by epileptic seizures. We used EEG recording  and EEG mapping programs and also determined HRV and ESSP.

Results. We found that the subjects in group 1 had the normothymic and parasympathetic types  of heart rate control, and the subjects in group 2 tended toward the sympathetic type of heart rate  regulation. The spectral correlation EEG data indicated that the epileptiform activity in group  1 was more generalized than in group 2, which pointed to a more pronounced epileptogenesis in  group 1. In this group, all pain scores were higher than those in group 2. In group 2 though, depression, anxiety, and emotional disorders were more pronounced than in group 1.

Conclusion. The findings can be explained by a closer connection between the right hemisphere and the limbic system. This, in our view, underlies the more pronounced changes in the tone of the  autonomic nervous system as assessed by the HRV and ESSP in patients with the right hemisphere epileptic activity and migraine attacks.

35-42 1744

Aim: to adapt the HPLC-MS/MS technique to determining valproic acid and its metabolites in blood plasma for drug therapy monitoring.

Materials and Methods: The chromatographic assay was run using an Agilent 1260 Infinity II chromatograph with a Phenomenex synergi Fusion analytical column 4 μm-C18 2×50 mm. The mobile phase consisted of 0.1% ammonium acetate in distilled water and 0.1% ammonium acetate in methanol (10:90 v/v, 0.5 ml/min). The multiple ions monitoring (MIM) mode was used for mass- spectrometric detection of valproic acid at m/z = 143.1, with the negative ion mode. The method  was found applicable over the range from 1 mcg/ml to 200 mcg/ml of valproic acid. For the mass  spectroscopy detection of valproic acid metabolites, the multiple reaction monitoring (MRM mode)  was used. MS identifications of 2-propyl-4-pentanoil-β-О-glucuronide; 2-propyl-4-pentenoic acid,  3-hydroxy-2- propylpentanoic acid, 4-hydroxy-2-propylpentanoic acid, 2-propylglutaric acid and 3- oxo-2-propylpentanoic acid in the negative ion mode were carried out at m/z 319.2→143.2; m/z  140.1→140.1; m/z 159.1→101; m/z 159.1→123.1; m/z 173→129.1 and m/z 157.05→11,  respectively. The method was sensitive over the range from 10 ng/ml to 500 ng/ml of the tested  compounds.

Results: The developed technique allows for determining valproic acid and its metabolites in a single sample; thus, the preliminary stage of separate sample preparation can be omitted, which increases the informative value of the assay without increasing its cost.

Conclusion: This innovative methodology for the quantification of valproic acid and its metabolites in the blood plasma is expected to facilitate the individual approach to the treatment of patients with epilepsy, thereby increasing the efficacy and safety of the pharmacotherapy.

43-50 1898

Aim: confirm the connection between hyperandrogenism and side effects of antiepileptic drugs in women. Materials and

Methods. Body weight, the menstrual cycle periodicity and the blood concentration of dihydrotestosterone were monitored in 278 women taking various antiepileptic drugs (valproic  acid, carbamazepine, lamotrigine, topiramate, and levetiracetam). The measurements were made at 3, 6, and 12 month after the treatment began.

Results. Among women taking valproic acid for 12 months, the average weight gain was 14.4%,  and in the group of carbamazepine – 5.4%. In women taking lamotrigine and levetiracetam, the  weight gain did not exceed 1.2%. With topiramate, a decrease in the body weight by 1.4% was  found. Among women taking valproic acid, the occurrence rate of menstrual cycle disorders increased by 64.9% after 12 months of treatment. In women taking carbamazepine the  increase was 22.6%. In the other groups, this increase did not exceed 3.7%. The occurrence of  menstrual cycle disorders correlated with an increase in the level of dihydrotestosterone. In women taking valproic acid, an increase in the concentration of blood dihydrotestosterone from 256.8  pg/ml to 526.32 pg/ml was found at the time-point of 12 months. In the group taking carbamazepine, an increase in the concentration of dihydrotestosterone from 268.4 pg/ml to 354.4 pg/ml was noted. In the other groups, fluctuations in the concentration of dihydrotestosterone were insignificant.

Conclusion. The body weight gain and the menstrual cycle disorders during anticonvulsant therapy are associated with hyperandrogenism.

51-58 879

Recently, the International League Against Epilepsy (ILAE) defined epileptic spasms as a separate type of seizures. According to the international recommendations, the treatment of infantile  spasms (IS) begins with hormones or vigabatrin (in the cases of tuberous sclerosis complex –  TSC). However, in the Russian Federation, other antiepileptic drugs (AEDs) are often used as the first line medications.

Aim: to analyze the current practice of prescribing AEDs for the treatment of epileptic spasms.

Materials and Methods. We studied the medical records of 175 patients with IS (59 of them with TSC) hospitalized for the treatment with hormonal therapy.

Results. Valproic acid was the most commonly prescribed antiepileptic drug in patients with IS  (more than in 80% of cases), both in children with TCS (49/59) and without TCS (102/116). As  expected, the clinical effect (cessation of IS and suppression of hypsarrhythmia) of valproic acid  was insufficient: it was observed in 9/49 (18.4%) children with TSC and in 12/102 (11.2%)  children without TSC. Although ethosuximide, oxcarbazepine, and carbamazepine were known to  be ineffective in IS, they were prescribed by medical doctors and taken by IS patients with no  clinical improvement at all. Taking into account the possible limitation of this analysis (not all of the children were consulted and hospitalized in our clinics), the real efficacy of AEDs might be some higher.

Conclusion. We then conclude that the treatment of IS in the Russian Federation is not in line with the international recommendations and the worldwide clinical practice. There is an urgent need in  updating the national standards for the diagnosis and treatment of IS. The work in this direction is now under way in the Russian Federation.

59-73 854

Aim – to elucidate the role of antiepileptic pharmacotherapy in pathomorphosis of focal epilepsy in adult patients.

Materials and methods. We examined 91 patients with focal epilepsy (main group, G); among them, 37 (41%) men (M) and 54 (59%) women (W). At the time of the first visit, 82 (90%) of  them [33 (89%) M and 49 (91%) W] were under antiepileptic therapy. The age of patients ranged  from 18 to 78 years (average 37.5 years). The debut of epilepsy was observed at the ages from 4  to 71 years. The duration of the disease ranged from 1 to 52 years, with the average of 16.1 years. All patients were then followed up for 1 to 2.5 years. Clinical and neurological examinations were  conducted in all patients; laboratory and instrumental diagnostic tests were used if indicated. The  medical history of patients was analyzed from the onset of epilepsy; if needed, new therapies were  prescribed or the existing therapies were modified. The therapeutic efficacy was assessed  using the data from the daily-seizures diary. The differences between the groups were tested for  their significance using the Chi-square test or the exact Fisher test if there were less than five  observations in the group. 

Results. Only 47 (52%) patients of group G [21 (57%) M and 26 (48%) W] received an antiepileptic therapy from the debut of the disease; the therapy was then adjusted in 41 (45%)  cases [19 (51%) M and 22 (41%) W (р>0.05)]. Of the 82 patients receiving therapy at the time of  examination, 37 (45%) received the basic, 20 (24%) – the updated, and 24 (29%) – a  combination of the basic and updated AED; in about 2% of cases, a combination with the 1st  generation drugs was prescribed. Monotherapy was used in 45 (55%), and polytherapy – in 37  (45%) patients. Of the 19 patients taking KBZ as the starting monotherapy, 10 (52%) received the drug in the non-prolonged form, twice a day. Relapse after long-term remission (12 months or  more) in 80% of cases was associated with changes in the AED regimen. Side effects were  observed in 43 (52%) patients under the treatment [15 (45%) M and 28 (57%) W]. Among those,  who underwent MRI examination, structural epileptogenic changes were detected in 37 (54%)  patients [21 (72%) M and 16 (40%) W (p<0.05)]. Comorbidity and the associated co-therapy were detected in 88% M and 90% W who were >50 years old.

Conclusion. Antiepileptic pharmacotherapy is a leading factor that induces evolutionary changes in the clinical and neurophysiological picture of epilepsy. With a timely and rational approach, the  use of AED allows for creating favorable development of pathomorphosis of the disease. Full  patients awareness of the AED therapeutic regimens and the associated risks may increases the  compliance, reduce the risk of decompensation and improve the prognosis of epilepsy.


74-81 1463

At present, treatment recommendations are developed considering the principles of evidence-based medicine. General practitioners (GP) are offered a choice of different medications with the known  characteristics of efficacy and tolerance. For a GP, the right choice of the optimal drug from the  proposed list may become a problem. Therefore, it is important not only to provide complete  information on all treatment options for a patient with epilepsy, but also discuss a scheme of the  proposed therapy (“key”) so to guide a GP through the treatment options and assess the possibility of  alternative treatment strategies. Contrary to the trial and error method, when the drug efficacy and  safety is assessed during the treatment, the proposed optimized approach allows for achieving a maximal therapeutic effect in patients with epilepsy.


82-94 651

There are considerable variations in the reported incidence of early and late epilepsy in children with lymphoproliferative diseases. The etiology of seizures in pediatric patients with hemoblastosis during  polychemotherapy can be diverse: dysmetabolic, infectious, toxic, ischemic, posthemorrhagic. The  treatment strategy selected by the neurologist largely depends on the causes of the paroxysmal  conditions. When choosing the anti-seizure therapy one should consider the course of hemoblastoses  and the possible effects of polychemotherapy. The article presents pediatric cases and the analysis of acute lymphoblastic leukemia with developing epileptic seizures.

95-103 849

The article reviews the use of antiepileptic drugs in various forms of epilepsy. We present a complex case of juvenile myoclonic epilepsy, the diagnostic process and antiepileptic therapy. Our own data and the results of others demonstrated a high efficacy and tolerability of valproate drugs, and a low aggravation potential in all types of epileptic seizures.

ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)