Efficacy and Safety of adjunctive Perampanel in a prospective, real-world, Phase IV study in Indian patients aged ≥12 years for Treatment of focal-onset Epilepsy: Study 508.

OBJECTIVE: ESPRITE (Study 508; NCT03836924) evaluated the real-world safety, tolerability, and efficacy of adjunctive perampanel in patients aged ≥12 years with focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), in India. METHODS: ESPRITE was a prospective, multicenter, single-arm, observational, Phase IV study with a 6-month Treatment Period. Patients were aged ≥12 years and had been prescribed perampanel for adjunctive treatment of FOS, with or without FBTCS. Assessments included incidence of treatment-emergent adverse events (TEAEs; primary endpoint), median percent reduction in seizure frequency per 28 days from baseline, 50% responder rates, and seizure-freedom rates. RESULTS: Overall, 200 patients were enrolled (199 patients in the Safety Analysis Set and 174 patients who completed all visits in the main efficacy analyses). TEAEs (all mild or moderate in severity) were reported in 18.1% (n = 36/199) of patients (the most common were dizziness [3.0%] and irritability [2.0%]). TEAEs leading to discontinuation of perampanel were reported in 2.0% of patients; no deaths or serious TEAEs occurred. At 6 months, median percent reduction in seizure frequency was 100.0%, 50% responder rate was 83.3%, and seizure-freedom rate was 49.4%. SIGNIFICANCE: Adjunctive perampanel (at a mean daily dose of 4 mg/day) was shown to be well tolerated and effective in patients aged ≥12 years with FOS, with or without FBTCS, from India. PLAIN LANGUAGE SUMMARY: Many patients do not receive adequate treatment for epilepsy and need effective seizure control medications. In this 6-month clinical study, 199 patients from India, aged 12 years or older, added perampanel to the anti-seizure medications they were already taking. At 6 months, 49% of patients experienced no seizures since starting perampanel and seizure frequency was reduced by half in 83% of patients. Side effects occurred in 18% of patients (most commonly dizziness and irritability) and caused 2% to stop perampanel; no deaths were reported. Perampanel was an effective and generally safe added medication for patients with epilepsy from India.

Efficacy and safety of adjunctive perampanel in patients with focal seizures or generalized tonic-clonic seizures: Post hoc analysis of Phase II and Phase III double-blind and open-label extension studies in India.

Objective: This post hoc analysis assessed the efficacy and safety of adjunctive perampanel in patients (aged ≥ 12 years) with focal seizures (FS), with/without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS) in India. Methods: Centers in India were identified from six double-blind, randomized, Phase II and Phase III studies of adjunctive perampanel (2-12 mg/day) and their open-label extensions (OLEx). Efficacy assessments included median percent change in seizure frequency per 28 days, 50% and 75% responder and seizure-freedom rates. Treatment-emergent adverse events (TEAEs) were monitored. Results: Overall, 128 patients (placebo, n = 39; perampanel, n = 89) were included in the double-blind Safety Analysis Set and 126 (FS, n = 113 [placebo, n = 32; perampanel, n = 81]; FBTCS, n = 35 [placebo, n = 14; perampanel, n = 21]; GTCS, n = 13 [placebo, n = 6; perampanel, n = 7]) comprised the Full Analysis Set. Median percent reductions in seizure frequency per 28 days for placebo vs perampanel for Indian patients were as follows: 34.8% vs 49.8% (FS; not significant [NS]) and 43.1% vs 60.5% (FBTCS; NS) at 4-12 mg/day, respectively, and -22.4% vs 8.2% (GTCS; NS) at 8 mg/day, respectively. Fifty-percent responder rates were 37.5% vs 55.1% (FS; NS), 42.9% vs 60.0% (FBTCS; NS), and 16.7% vs 42.9% (GTCS; NS), respectively; seizure-freedom rates were 0.0% vs 5.8%, 7.1% vs 10.0%, and 0.0% vs 14.3%, respectively (all NS). Overall, 110 patients entered OLEx studies (FS, n = 99; GTCS, n = 11). Perampanel was efficacious for up to four years for FS and FBTCS and two years for GTCS. Across double-blind and OLEx studies, TEAEs occurred in 58.4% and 83.6% of Indian perampanel-treated patients, respectively; dizziness was most common. Efficacy and safety outcomes were generally similar overall between Indian and non-Indian patients. Significance: These data suggest adjunctive perampanel (up to 12 mg/day) may be a suitable anti-seizure medication for patients (aged ≥ 12 years) with FS, with/without FBTCS, or GTCS in India.

Idiopathic Intracranial Hypertension - Challenges and Pearls.

Idiopathic intracranial hypertension (IIH) is defined as a syndrome of raised intracranial pressure with normal imaging of the brain and cerebrospinal fluid (CSF) composition. There is a rising incidence and prevalence of this disease related to the increased prevalence of obesity. It typically affects women of working age, and headache is the predominant morbidity in over 90%. The disease is also more prevalent in young males. There are many controversies and myths that surround IIH. There are currently few treatment options for IIH, management is typically medical with those experiencing progressive visual loss undergoing surgical procedures. Weight loss and venous sinus stenting are a few therapies directed at the etiology.

Intracranial Atherosclerosis is the Most Common Stroke Subtype: Ten-year Data from Hyderabad Stroke Registry (India).

AIM: Limited data regarding stroke subtypes exist from South Asian countries. The aim of the study was to determine the pattern of ischemic stroke subtypes and their associated risk factors, in a 10-year long hospital-based registry in the South Indian city of Hyderabad. MATERIALS AND METHODS: The Hyderabad stroke registry systematically collected clinical, radiological, and laboratory data of fully investigated consecutive stroke patients and studied pattern of ischemic stroke subtypes and their risk factor association. RESULTS: The cohort comprised of 2642 patients: 2072 (78.4%) were ischemic and 570 (21.6%) were hemorrhagic strokes. In the ischemic stroke cohort, the mean age was 54.1 years and 1622 (78.3%) were men. The most common ischemic stroke subtype was large artery atherosclerosis (LAA) comprising 37.6% (n = 779), followed by small vessel occlusion comprising 19.9% (n = 413) and cardioembolism 11% (n = 228). Stroke of other determined etiologies constituted 4.2% (n = 86) and stroke of undetermined etiology was observed in 27.3%. Among patients with LAA, 610 (78.3%) patients had intracranial and 169 (21.7%) had extracranial disease as the underlying mechanism. Risk factor profile demonstrated that hyperlipidemia was significantly associated with LAA and ischemic heart disease with cardioembolic strokes. CONCLUSIONS: The study reveals a distinct pattern of ischemic stroke subtypes in the Indian context that has overlapping features of registries from West and East Asian countries. Both large artery and small vessel diseases are substantially represented with a predominance of intracranial atherosclerosis. The study results have significant implications for developing preventive and management strategies for stroke care and research in India.

Anti-ganglioside antibodies profile in Guillain-Barré syndrome: Correlation with clinical features, electrophysiological pattern, and outcome.

BACKGROUND: Guillain-Barré syndrome (GBS) and its subtypes are associated with distinct anti-ganglioside antibodies. Hence, we aimed to determine the frequency of anti-ganglioside antibodies and its correlation with clinical features, electrophysiological patterns, and outcome in patients with GBS. MATERIAL AND METHODS: The data regarding clinical features, electrophysiological patterns, and outcome at 6 months were collected and analyzed from the case records of patients diagnosed with GBS during 2008-2013 at a tertiary care hospital in south India. RESULTS: A total of 204 patients with GBS were studied, and 73 patients (mean age: 37.6 ± 17.5 years) who underwent anti-ganglioside antibody testing were analyzed. Male-to-female ratio was 2.5:1. IgG anti-ganglioside antibodies were positive in 41/73 patients. The most common IgG anti-ganglioside antibody observed in the acute demyelinating variant was anti-GT1b (n = 13; 17.8%), and, those in the acute axonal variant were anti-GM1, anti-GM2, anti-GD1b, and anti-GT1b antibodies (n = 9;12.3% each). Three patients died and 5 patients were unable to walk independently at the end of 6 months. CONCLUSIONS: The frequency of anti-ganglioside antibodies in our cohort with GBS was 56%, with IgG anti-GT1b antibody being the most common. The anti-ganglioside antibodies were significantly positive in acute motor axonal neuropathy (AMAN) subtype of GBS. The presence of anti-ganglioside antibodies was not found to be of significant use in predicting the outcome. Although it was observed that the absence, and not the presence, of anti-ganglioside antibodies was associated with antecedent infection, dysautonomia, and requirement of ventilator support, the overall disease severity was not antibody dependant.