International Journal of Epilepsy

Background The main purpose of this study is to assess efficacy and tolerability of perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist, as an add-on treatment in adult patients with refractory focal-onset seizures.

Patients and Methods A prospective, open label, observational study was conducted in patients with refractory focal-onset seizures treated with PER at our Epilepsy Unit, from May 2015 to February 2016. Patients were followed up for 1 year. Frequency of seizure and tolerability was assessed every 3 months. Patients were under a polytherapy, and the mean number of concomitant antiepileptic drugs (AEDs) at PER initiation was 2.9.

Results We consecutively enrolled 52 patients (M/F = 18/34). Three were lost on follow-up. Mean age was 38.7 years, with a mean duration of disease of 28.1 years. After 1 year of treatment, 57.14% reported a 50% or greater reduction in seizure frequency; five (10.21%) were seizure free. Six (12.25%) patients reported a reduction lower than 50%. Mean dosage of PER was 7.57 mg. Thirty-one patients were taking enzyme-inducing AEDs (carbamazepine, oxcarbazepine, phenytoin). In this subgroup, the responder rate was 45.2%. Twenty-one patients reported side-effects, most frequently somnolence (11), vertigo/ataxia (6), and aggressiveness (5). Eleven (22.4%) patients reduced or discontinued at least one concomitant AED, while the electroencephalography improved in four (8.16%). Sixteen (32.65%) patients withdrew PER, after a mean duration of 163 days, the mean dosage being 6.4 mg (range 4–12).

Conclusions Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in almost two-thirds of patients suffering from refractory focal-onset epilepsies. It seems similarly safe and well-tolerated. Enzyme-inducing AEDs may limit the efficacy of PER.

Background and purpose Our goal was to determine fiber tract integrity in hippocampal sclerosis (HS) using diffusion tensor imaging (DTI) and to correlate white matter damage with other pathology in this disease.

Methods Twenty-six patients and eight controls were studied with DTI tractography for 8 pairs of white matter fiber tracts and 2 commissural tracts. Fractional anisotropy (FA) of the fiber tracts was compared with controls. The FA of select fiber tracts was also compared with change in T2 signal in the anterior temporal lobe (ATC), and the performance on neuropsychological tests.

Results In comparison with controls, subjects with left sided hippocampal sclerosis (L-HS) had 3 ipsilateral fiber tracts with decreased FA. The FA of fiber tracts was similar in right sided HS (R-HS) to controls. The ipsilateral inferior longitudinal fasciculus had a decrease in FA that correlated with the ATC (T2 signal change). The right superior longitudinal fasciculus had a decrease in FA proportional to lower performance on tests of memory and language.

Conclusion The subjects with L-HS had more extensive structural abnormalities involving white matter tracts, both ipsilateral and contralateral. In contrast, subjects with R-HS had limited changes in white matter integrity. Pathology of white matter appears to be involved in deficits associated with HS, including ATC and cognitive performance.

Glutaric aciduria type 1 (GA-1) is a rare inherited neurometabolic disorder due to enzymatic block in the common degradation pathway for lysine and tryptophan. We report a 16 month girl child who presented with an initial acute encephalopathic crisis followed by static encephalopathy with characteristic neuroimaging findings. Diagnosis was confirmed by demonstrating elevated urinary glutaric acid and 3-hydroxyglutaric acid levels. Early diagnosis and adequate dietetic therapy can prevent most of the neurological symptoms.

Perampanel is a non-competitive antagonist at the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) subtype of ionotropic glutamate receptor. It is approved as an adjunctive therapy in focal epilepsy with or without secondarily generalised seizures in patients aged >12 years. This in-depth review describes the structure, mechanism of action, pharmacokinetic profile, indications, dosage and efficacy, contraindications, possible drug interactions, adverse effect profile and its management with regards to Perampanel. It is one of the latest additions in the therapeutic armamentarium of an epileptologist being useful in focal as well as generalised epilepsies as an add-on. It has shown high rates of efficacy and a relatively good tolerability. Slow dose titration, patient education and bed time dosing along with downtitration of medications which may aggravate Perampanel associated adverse events improves the patients’ compliance and quality of life.

Background Many people with epilepsy suffer from cognitive deficits as a consequence of their seizure episodes. Relatively few researches have been undertaken to assess the short term impacts of seizure on cognitive function. This study aimed to evaluate changes in cognitive performance in adults with a new onset generalized seizure in the first 24 h after the onset of their attack.

Methods After having given informed consent, 40 patients with first episode of unprovoked generalized tonic-clonic seizure were investigated with a neuropsychological test battery (Wechsler Memory Scale III). Their performance was compared with 40 healthy individuals from the patients' companions.

Results Newly diagnosed patients had significantly worse performance in paired association recall which is a parameter of verbal memory; other memory parameters showed no significant changes after seizure attack.

Conclusion Our data suggested that even with a one-time seizure episode, patients are susceptible to verbal memory impairment.

Neonatal seizure is the most frequent clinical manifestation of central nervous system dysfunction in the newborn. It is defined as a paroxysmal alteration in neurologic function that include motor, behavior and/or autonomic functions occurring in the first 28 days after birth of a term neonate or before 44 weeks of gestational age in a preterm infant. Seizures in the presence of encephalopathy are the most important clinical pattern of an acute cerebral insult in the immature brain. Chronic epileptic disorders very rarely may have their onset in the neonatal period and may persist well into infancy and later childhood. Structural brain defects and metabolic disorders constitute a substantial proportion of this group. Ictal EEG recordings remain the gold standard for the accurate identification of neonatal seizures of cortical origin and for the distinction from non-epileptic paroxysmal events. This review focuses on the electroclinical patterns of neonatal seizures and epilepsies with an emphasis on the classification and terminologies. The current therapeutic options are also highlighted briefly.

In order to understand true incident burden of epilepsy in South America and Caribbean, several sources were searched in multiple languages using keywords and combinations. The results were presented as counts, proportions, means, and/or medians along with their 95% confidence intervals (CI). No information was found from Caribbean and no information was available from six South American countries. Based on 14 estimates, annual median incidence (N = 185319, 1984–2010, 7 in rural area) of epilepsy for South America was 115.2/100,000 (95% CI 61.0–133.4, range 0.0–410.0). Random-effect pooled annual epilepsy incidence was 84.8/100,000 (95% CI 65.2–104.5). The 25th and 75th percentile of annual epilepsy incidence were 62.2/100,000 and 130.9/100,000 respectively with an interquartile range (IQR) of 68.7. Between-study variance attributable to each explanatory factor was estimated to be: 38.8% from study year, 18.1% from urban-rural milieu, 15.4% from case size, and 0.6% from study size. Descriptively, on average, 445824 (between 236070 and 516258) new cases of epilepsy are possibly occurring every year in South America. In conclusion, Caribbean needs to come forward for its own epilepsy incidence data especially when risk from numerous factors such as substance abuse, mental health, etc. deems high. Epilepsy incidence in South America is likely to be slightly lower than previously reported although this varies considerably for each country. Inter-population differences are in-part (more than 50%) related to urban-rural differences and variations over time. Our work is especially important to monitor secular trends of epilepsy incidence especially when new data would emerge and countries continue to undergo transitions.

Đặc điểm kháng thuốc dẫn đến những khuyết tật nghiêm trọng, không thể phục hồi và tử vong sớm trong khoảng 30% trường hợp động kinh mặc dù đã được điều trị đầy đủ và hợp lý bằng các loại thuốc chống co giật (ASDs) có sẵn mà không có nguyên nhân tiềm ẩn. Dựa trên một khối lượng lớn chứng cứ cho thấy tác dụng chống co giật của taurine ở động vật thí nghiệm và biên độ an toàn rộng rãi ở người, việc bổ sung acid amin ức chế này vào các ASDs có sẵn dường như mang lại triển vọng điều trị động kinh kháng thuốc.

Phương pháp Chúng tôi đã khảo sát tác động chống co giật của lamotrigine (15 mg/kg), levetiracetam (40 mg/kg), carbamazepine (40 mg/kg), phenytoin (35 mg/kg) và taurine (50, 100 & 200 mg/kg) ở chuột gây động kinh bằng pentylenetetrazole đã được tiền điều trị bằng lamotrigine (LPK), đây là mô hình mô phỏng các đặc điểm chính của động kinh kháng thuốc, cả về ASDs đơn lẻ hay kết hợp, trong đó ba liều lượng khác nhau của taurine được bổ sung cùng các ASDs đã thử nghiệm.

Kết quả Cả ASDs và taurine đều không có khả năng ức chế cơn co giật toàn thể ở chuột LPK. Tuy nhiên, việc bổ sung taurine đã rõ ràng phục hồi tác dụng chống co giật của các ASDs đã thử nghiệm. Các nghiên cứu sinh hóa thần kinh tiếp theo đã chỉ ra rằng mức taurine cao hơn trong hồi hải mã và vỏ não đã phục hồi sự mất cân bằng giữa các chất dẫn truyền thần kinh kích thích chính, glutamate và GABA, chất dẫn truyền ức chế tương ứng của nó.

Kết luận Những phát hiện này nhấn mạnh rằng việc bổ sung taurine vào các ASDs có thể hữu ích trong việc điều trị động kinh kháng thuốc. Do đó, việc xác thực lâm sàng thêm là được khuyến khích.

Hypomyelinating disorders have wide spectrum of clinical and radiological manifestations. A 17-month-old girl presented with baseline global developmental delay with insidious onset global neuroregression with refractory seizures from 1 year of age. Her birth and family history were noncontributory. Salient features on examination were central hypotonia and retinal cherry red spot. MRI Brain revealed characteristic white matter and basal ganglia changes. Her serum hexosaminidase A levels were undetectable. Identification of these radiological changes is crucial in directing appropriate enzyme and mutation testing in these patients.