Assessing efficacy and safety of rectally vs. intravenously administered Sibazon in treatment of generalized epileptic seizures in children

Objective: to prove the therapeutic equivalence and similar safety profile of “Sibazon, rectal solution” (international nonproprietary name: diazepam) and “Sibazon, solution for intravenous and intramuscular administration” in children with primary generalized and bilateral tonic, clonic and tonic-clonic seizures.Material and methods. An open-label, randomized clinical trial on efficacy and safety was conducted in 20 patients suffering from epilepsy with generalized seizures aged 1 to 17 years. Clinical blood and urine tests, biochemical blood analysis were used for diagnostics (glucose, total protein, albumin, total bilirubin, cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, alkaline phosphatase, creatinine, urea, creatinine clearance), as well as data on electrocardiographic (ECG) and electroencephalographic (EEG) studies. The patients were divided into two groups: in Group 1 (n=8), a rectal solution was used, in Group 2 (n=12) – a solution for intravenous and intramuscular administration.Results. The number of cases in which seizures were completed within 10 minutes after using the drug without resuming within subsequent 60 minutes, in Group 1 was 7 (87.5%), and in Group 2 – 9 (75.0%) (Fisher exact test (FET): p=0.617). Repeated primary generalized or bilateral tonic/clonic/tonic-clonic seizures within 24 hours after drug administration, in Group 1 were absent in 5 (62.5%) patients, in Group 2 – in 6 (50%) (FET: p=0.670); within 48 hours after drug administration – in 5 (62.5%) and 7 (58.3%) children, respectively (FET: p=1.00). Physical examination revealed no pathology in all patients at the final visit. While comparing ECG and EEG data at the final visit, no inter-group differences were found by the number of children with deviations from the norm. The results of laboratory studies confirmed that using the studied drugs had no negative effect on the main indicators of clinical and biochemical blood tests as well as clinical urine analysis.Conclusion. The effectiveness of the rectal form of Sibazon in relieving pediatric generalized epileptic seizures is comparable to that of Sibazon for intramuscular administration. The drug rectal form, due to easy-to-use administration, is preferable for outpatient practice. “Sibazon, rectal solution” is safe and has good tolerability.

Regulatory restrictions on the use of valproate in girls and women of childbearing potential: status update

In 2019, some restrictions for use of valproic acid in women with reproductive potential by regulatory authorities and the original drug manufacturer based on the results of studies in real clinical practice were introduced. During 2019–2021, there were a further clinical data accumulation and labeling changes. The review presents a critical analysis of the changes in prescribing information and product label. There is a long lead time from the moment when safety data become known to the moment when changes are made to the medicinal product label and patient brochures. Some of the changes, including the need for high doses of folic acid to prevent neural tube defects, are debatable. Repealing the provision for mandatory archiving of informed consent forms for valproic acid use in girls and women raises legal risks. Improvements in pregnancy prevention programs and further research on the safety of valproic acid in real-world clinical settings are needed.

Mental development of children from paired mothers with epilepsy: assessing remote teratogenic effects and predictors of developmental disorders

Objective: to study teratogenic effect – the long-term pregnant mother-taken antiepileptic drugs (AEDs) related consequences on paired child mental, social and intellectual development.Material and methods. There were enrolled 80 subjects: 40 children aged 3–9 years and paired mothers suffering from epilepsy for 3 to 35 years. Thirteen and 27 patients had generalized and focal epilepsy, respectively. Seven mothers were in prolonged remission without taking AEDs, 23 were on monotherapy and 10 were on polytherapy. Child research methods: T. Achenbach's clinical CBCL (The Child Behavior Checklist) scales (for children aged under 5 and 6–18 years), a questionnaire for detecting attention deficit hyperactivity disorder and other behavioral disorders modified by N.N. Zavadenko, Wechsler Intelligence Scale for Children (WISC), Luria batteries of neuropsychological tests adapted by J.M. Glozman (for children aged 3–6 and 7–12 years).Results. Neuropsychological study and assessment of intelligence revealed problems in the development of praxis, speech, gnostic functions and memory, as well as disproportion in the development of verbal and non-verbal structures of intelligence. The most common behavioral disorders in children were impulsivity, distraction, difficulties in controlling and organizing movements. The most affected spheres were praxis (motor awkwardness, fine motor disorders of the hands) and speech.Conclusion. The proposed hypothesis that the teratogenic effect of taking AEDs may result in unevenness or delay in developing mental functions in a child was confirmed.

Treatment of epilepsy associated with primary and metastatic brain tumors

There is a number of unsolved issues in management of epilepsy associated with primary and metastatic brain tumors (BTs). In particular, no consensus approaches to treatment of patients with epilepsy associated with BTs have been proposed regarding use of current anti-epileptic drugs (AEDs). The review presents the relevant data on epidemiology, features of clinically manifested epilepsy at varying stages of BTs, aspects of drug-drug interaction between AEDs and anti-tumor agents, AED-related effects on cognitive functions as well as quality of life in patients with epilepsy associated with BTs. Levetiracetam and valproic acid comprise the first-line drugs for treating seizures in patients with BTs. It is unreasonable to use AEDs acting as hepatic microsomal enzyme inducers for therapy of epileptic seizures in BTs, because it may decrease efficacy of chemotherapy agents and glucocorticoids along with elevated rate of side effects. Perampanel acting as a selective noncompetitive AMPA receptor antagonist, may be one of the drugs of choice for the adjunctive therapy of epileptic seizures associated with BTs.

Reiterating the role of corpus callosum in generalization of interictal and ictal epileptiform discharges: a case report with post-callosotomy intracranial electroencephalography in Lennox–Gastaut syndrome

Lennox–Gastaut syndrome (LGS) is an epileptic encephalopathy characterized by delayed mental development and intractable multiple seizure types, predominantly tonic. Drop attacks are the commonest and the most disabling type of seizures. Resective surgery is often not possible in LGS as the electroencephalogram (EEG) abnormalities are usually multifocal and generalized, and magnetic resonance image is often either normal or multilesional. We report a case of LGS with bilateral parieto-occipital gliosis where EEG before and after callosotomy demonstrated synchronized bilateral interictal epileptiform discharges and ictal discharges becoming desynchronized and running down. This phenomenon emphasizes the role of the corpus callosum in secondary bilateral synchrony.

Neurophysiological features in patients with migraine at risk for epilepsy

Objective: to study the electrophysiological parameters of brain bioelectric activity and features of the autonomous nervous system assessing heart rate variability, sympathetic skin response, clinical and physiological tests depending on the lateralization of migraine pain syndrome in the right or left brain hemisphere in patients with epileptic electroencephalogram (EEG) signs and migraine.Material and methods. Thirty six patients with aura-free episodic migraine at risk of developing epilepsy and 9 age-matched healthy subjects were examined. All participants underwent EEG, clinical and physiological tests, assessment of heart rate variability and sympathetic skin response.Results. Patients with right-hemisphere migraine headache had signs of activated sympathetic nervous system at baseline level and during exercise, lower baseline EEG epileptiform activity and in provocative tests. In contrast to the subjects of this group, patients of other group featured with a more stable migraine pain syndrome in the left hemisphere tended to dominate with functional activity of the parasympathetic system such as increased trophotropic support during exercise, as well as greater magnitude of baseline epileptiform bioelectric activity and during load tests.Conclusion. Values of heart rate variability in combination with objective results of clinical and physiological assessment of the autonomous nervous system and electrophysiological parameters of brain bioelectric activity are reliable prognostic indicators for varying functional conditions in patients with episodic migraine.

Igor Dmitrievich Stulin

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Effectiveness, safety and assessing the results of drug therapy in patients with epilepsy

On June 26, 2021, a meeting of the experts of the Russian League Against Epilepsy (RLAE) was held, dedicated to the effectiveness, safety and assessing the results of drug therapy in patients with epilepsy. Having considered the history of the issue and guided by domestic and foreign experience, the participants discussed the problems associated with the use of various antiepileptic drugs for different forms of epilepsy in patients of different sex and age. Special attention was paid to psychiatric comorbidity in patients with epilepsy, increasing their compliance with treatment and quality of life. The article presents the Resolution of RLAE experts meeting adopted as a result of the discussion.

Applying the International Classification of Functioning, Disability and Health in establishing a rehabilitation diagnosis for patients with juvenile myoclonic epilepsy

The International Classification of Functioning, Disability and Health (ICF) is a globally recognized classification for health components and health-related factors, which has been recommended by the World Health Organization for use in medical rehabilitation. In the practice of a rehabilitation doctor dealing with patients suffering from juvenile myoclonic epilepsy (JME), the ICF is used to establish a rehabilitation diagnosis and formulate the goal of rehabilitation, as well as to implement its basic principles. It provides better insight into a range of difficulties patients with JME might face at the level of personal health and in everyday life.

Mozart effect in patients with epilepsy

Objective: to analyze available publications assessing efficacy of the Mozart effect in patients with epilepsy.Material and methods. A search for scientific publications has been performed in PubMed, Scopus and eLibrary databases by retrieving inquiries "Mozart effect" and "epilepsy" in paper title, resume and keywords. As a result, 18 studies matching inclusion and exclusion criteria were selected. The data obtained were systematized into four categories: 1) whether a single listening of Mozart’s Sonata for Two Pianos in D major, K.448 affect interictal epileptiform activity (IEA) immediately during an event; 2) whether a repeated (course) of listening K.448 affect IEA; 3) is there a delayed effect on IEA after a single or repeated listening of K.448; 4) how does the Mozart effect act on rate of epileptic seizures during ongoing therapy course of listening K.448 or afterwards.Results. It was found that therapy with Mozart’s sonata K.448 may lower IEA index during a single listening of this musical composition and shortly afterwards. A lowered IEA index during a course listening of K.448 lasting for some time afterwards may be observed as well. Moreover, a repeated listening of K.448 may reduce rate of epileptic seizures within entire music course.Conclusion. The analysis revealed that there are currently some reasons to consider the Mozart effect as a means of neurostimulation impacting on rate of epileptic seizures and IEA.