Brivaracetam: How Well Does It Fare as an Anti-Epileptic? A Review.

OBJECTIVES: Epilepsy is a common neurological ailment contributing to significant disability. About one-third of all epilepsy patients would be refractory to two or more medications. Brivaracetam (BRV) is one of the newer anti-seizure medications on which extensive data is available, but its efficacy as an early add-on agent (first/second adjuvant) is unclear. The principal objective of this review is to assess the efficacy of BRV as an early add-on agent in refractory Focal Onset Seizures (FOS) and its pharmacology and usage in various clinical situations associated with seizures. METHODS: We searched two databases, Medline and Cochrane Central, for papers on BRV and FOS, and selected six studies with randomized parallel control design to extract the data for a meta-analysis. We also did a comprehensive review of the available literature on its pharmacology and usage in various clinical scenarios associated with seizures. RESULTS: For the meta-analysis, we extracted 145 articles; six studies fulfilled the selection criteria that gave us data on 1938 patients who received Brivaracetam as an early add-on agent in FOS. The Risk Ratio (RR) (95% CI) for 50% responders across the trials was 1.88 (1.55-2.29). Similarly, the overall RR (95% CI) was 5.82 (2.15-15.70) for seizure freedom. CONCLUSION: Our analysis provides moderate evidence for Brivaracetam as an effective agent as an early adjuvant in FOS. Its efficacy for several other indications needs further clinical trials and evaluation.

Role of pulse methylprednisolone in epileptic encephalopathy: A retrospective observational analysis.

OBJECTIVES: To study the effect of monthly pulses of intravenous methylprednisolone (IVMP) on seizure and global outcomes in children with epileptic encephalopathy (EE). METHODS: This retrospective study was undertaken in a tertiary care epilepsy center in India. Consecutive patients with EE who had received IVMP as adjunctive therapy for a minimum of 3 months and had at least one pre-and post-steroid EEG each, were identified and a structured questionnaire was used to collect information including outcomes at 3 months post-steroid course completion and beyond, as available. RESULTS: Ninety-seven patients (M:F=71:26) fulfilling the inclusion criteria with a mean age at onset of seizures being 20.52 ± 25.69 months were included. Commonest seizure types were myoclonic (66%); Lennaux-Gastaut and West Syndromes accounted for 57 % and 24 % patients respectively. The etiology was unknown in 52 %. All children were on a combination of standard anti-seizure drugs. The duration of IVMP pulse therapy was 7.72 ± 6.25 months. One-fourth (26 %) patients experienced minor adverse events. Greater than 50 % seizure burden reduction was seen in 66 % patients at 3 months with seizure-freedom in 25 %. A total of 45 (46 %) patients became seizure-free in the cohort eventually with continuation of steroids beyond 3 months. Children with idiopathic EEs, normal neuroimaging, myoclonic jerks, and West syndrome showed the best response. The presence of burst-suppression and generalized paroxysmal fast activity (GPFA) predicted inadequate response. CONCLUSIONS: Adjunct pulse doses of IVMP are safe, well-tolerated, and effective in reducing seizures and improving global outcomes in children with idiopathic EEs, West syndrome, normal neuroimaging, and myoclonic jerks. Seizure freedom might be delayed in a subset of these patients, hence duration of therapy beyond 3 months may be warranted.

Clinical conundrum: status epilepticus culminating into acute dystonia myoclonus.

A 7-year-old child who suffered from symptomatic focal epilepsy as a sequel to perinatal hypoxia used to have frequent seizures. This time she developed prolonged status epilepticus lasting for over 5 hours. She received a treatment in the form of intravenous midazolam and reinitiation of sodium valproate and clobazam that were discontinued previously. Seizures were controlled over a couple of hours, but she remained unresponsive. Later, she developed acute onset dystonia (day 3 post-status epilepticus) and also myoclonic jerks. She presented to us after 3 weeks of onset of these complaints and we considered hypoxic encephalopathy resulting from prolonged status epilepticus or acute encephalitis or non-convulsive status epilepticus. However, acute onset dystonia and periodicity of myoclonic jerks were pointers against it, and on evaluation, she was diagnosed with atypical fulminant subacute sclerosing panencephalitis (SSPE). Knowing the atypical presentations of SSPE is important in planning management and prognostication.

Sporadic Creutzfeldt-Jakob disease (sCJD) with asymmetric findings.

We report a case of a patient with probable Creutzfeldt-Jakob disease (CJD) who had psychiatric manifestation in the form of withdrawn depressive behaviour at the onset, followed by rapidly progressive ataxia, parkinsonism, mutism and cognitive decline with generalised asynchronous multifocal myoclonic jerks. His EEG exhibited focal (lateralised) periodic triphasic sharp waves on the background of generalised delta slowing, which later on became more generalised. MRI of the brain showed hyperintensity in basal ganglia with cortical ribbon sign in bilateral frontal region. Clinical course showed progressive deterioration to an akinetic-abulic stage. He died 2 months after the onset of symptoms.

The prevalence of headache may be related with the latitude: a possible role of Vitamin D insufficiency?

According to recent observations, there is worldwide vitamin D insufficiency (VDI) in various populations. A number of observations suggest a link between low serum levels of vitamin D and higher incidence of chronic pain. A few case reports have shown a beneficial effect of vitamin D therapy in patients with headache disorders. Serum vitamin D level shows a strong correlation with the latitude. Here, we review the literature to delineate a relation of prevalence rate of headaches with the latitude. We noted a significant relation between the prevalence of both tension-type headache and migraine with the latitude. There was a tendency for headache prevalence to increase with increasing latitude. The relation was more obvious for the lifetime prevalence for both migraine and tension-type headache. One year prevalence for migraine was also higher at higher latitude. There were limited studies on the seasonal variation of headache disorders. However, available data indicate increased frequency of headache attacks in autumn-winter and least attacks in summer. This profile of headache matches with the seasonal variations of serum vitamin D levels. The presence of vitamin D receptor, 1alpha-hydroxylase and vitamin D-binding protein in the hypothalamus further suggest a role of vitamin D deficiency in the generation of head pain.