Hyperthermic seizures: an animal model for hot-water epilepsy

Freely ambulant wistar adult rats of both sexes when exposed to a hot water jet on the head (50°C–55°C) for a period of 8–10 minutes, manifested seizure activity similar to the ones noted in ‘hot-water epilepsy’ (HWE) in humans. Depth electrode recording from the hippocampus revealed seizure discharges during the ictus lasting from 34 seconds to three minutes, followed by low voltage indeterminate activity and a quiescent resting phase. Seizure initiation was noted to be critically dependent on the rectal temperature of 41.5°C and regional hippocampal temperature of 37°C. There appeared to be no clear evidence for kindling phenomenon. Intervention of hyperthermia by cooling the body after the ictus prevented subsequent occurrence of spontaneous seizures. Pathological study of the brain revealed ischaemic changes in specific topographic areas like Sommer's sector in hippocampus, layer 4 and 5 neurons of the cerebral cortex and reticular neurons in the brain stem—a pathological feature reminiscent of the human epileptic brain. Seizure initiation by hyperthermic stimulation with hot water poured over the head, the progression and the EEG recording the seizure activity in these rats appears to resemble the HWE in human subjects and could thus serve as the first animal model for this form of ‘reflex’ epilepsy. This has given new insight into the understanding of human HWE. Our preliminary observations in humans has suggested that HWE is a type of hyperthermic seizure similar to febrile convulsion but differs from it with respect to stimulus and rate of rise in temperature in a susceptible individual

Cardiac autonomic dysfunction in drug naïve hot water epilepsy

AbstractPurposeThis study aimed to characterize the role of autonomic nervous system dysfunction in hot water epilepsy (HWE). Heart rate variability (HRV) has been established as a good index of cardio-autonomic regulation.MethodologyForty-five patients with HWE (age: 24.6±10.1 years; M:F=37:8) and 45 age and gender matched controls (age: 24.17±10.37 years; M:F=37:8) were studied. Five minutes resting lead II electrocardiogram (ECG) was obtained (AD instruments) under standard conditions and analyzed for time and frequency domain HRV parameters using LabChart software.ResultPatients with hot water epilepsy showed significant increase in LF nu (Low frequency normalized unit) and LF/HF denoting an interictal increase in sympathetic activity. In addition, reductions were noted in parasympathetic function [RMSSD (root mean square successive difference of RR intervals), HF (High frequency) nu and LF/HF].ConclusionThis study has demonstrated an impaired sympatho-vagal balance characterized by increased sympathetic activity and reduced parasympathetic activity in patients with HWE. The present study supports the notion that the hypothalamus is involved in both, the pathogenesis of HWE and autonomic regulation

Phenothiazine-Based D-A-π-A Dyes for Highly Efficient Dye-Sensitized Solar Cells: Effect of Internal Acceptor and Non-Conjugated π-Spacer on Device Performance.

Three new D-A-π-A metal-free organic dyes based on phenothiazine as a donor (D) and non-conjugated π-spacer were designed and synthesized. The incorporation of different 'internal acceptors' (electron traps) such as benzothiadiazole (BTD), benzotriazole (BTA), and pyridine were shown to allow systematic tuning of the energy levels and the photophysical properties. The AI-1 dye showed lower electronic disorder compared with the other two dyes. The efficiencies achieved with AI-1, AI-2, and AI-3 dyes were 8.5 % (Jsc =15.42 mA cm-2 , Voc =0.78 V, FF=68 %), 7 % (Jsc =12.8 mA cm-2 , Voc =0.78 V, FF=68 %) and 6.7 % (Jsc =11.57 mA cm-2 , Voc =0.82 V, FF=68.26 %), respectively. The incorporation of non-conjugated phenothiazine as a π-spacer in D-A-π-A dyes showed remarkable enhancement in the photovoltaic performance of dye-sensitized solar cell (DSSC) devices. The sealed DSSC devices with iodide/tri-iodide (I- /I3 - )-based liquid electrolyte showed promising stability under ambient conditions

A REVIEW ON PHARMACO KINETIC DRUG INTERACTIONS OF STATINS

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are generally well tolerated as monotherapy. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Myopathy is most likely to occur when statins are administered with other drugs. Statins are substrates of multiple drug transporters (including OAT- -P1B1, BCRP and MDR1) and several cytochrome P450 (CYP) enzymes (including CYP3A4, CYP2C8, CYP2C19, and CYP2C9). Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway. This review aim is to summarize the most important interactions of statins

Subcortical structural abnormalities in juvenile myoclonic epilepsy (JME): MR volumetry and vertex based analysis

AbstractPurposeImaging studies in juvenile myoclonic epilepsy (JME) have shown abnormalities of the thalamus and frontal cortex. The purpose of this study was to systematically investigate the morphological changes in the deep gray matter (GM) structures using techniques of voxel based morphometry (VBM), MR volumetry and shape analysis.MethodologyThe study included 40 patients with JME (M:F=21:19; age 22.8±5.3 years) and 19 matched controls (M:F=13:6; age 24.5±4.2 years). All subjects underwent MRI using standard protocol that included T1-3D TFE (Turbo Field Echo) images with 1mm thickness. VBM analysis and MR volumetry were performed. The volumes of deep subcortical GM structures were extracted and vertex-wise shape analysis was performed using FSL-FIRST (FSL-Integrated Registration and Segmentation Toolbox) software.ResultsVBM analysis with a thalamic mask revealed focal thalamic alterations in the anteromedial aspect of the thalamus (p<0.05, false discovery rate (FDR) corrected) which remained significant after adjusting for age, gender and intracranial volume (ICV). Significant volume loss was noted in both the thalami. Vertex-wise shape analysis showed significant focal surface reductions in the thalami bilaterally in patients that were predominantly seen in the medial as well as lateral aspects of the thalamus (p<0.05, FDR corrected). The disease duration correlated with left hippocampus volume while age of onset correlated with right hippocampus volume.ConclusionsThis study confirms the presence of thalamic alterations in patients with JME. Shape analysis technique provided complementary information and disclosed the presence of focal atrophic changes in patients’ thalami. The striatum and hippocampus did not show any significant alterations

Neuropathology of HIV/AIDS with an overview of the Indian scene

Neurological manifestations of HIV infection and AIDS are being recognized with a frequency that parallels the increasing number of AIDS cases. Next to sub-Saharan Africa, India has the second largest burden of HIV related pathology, essentially caused by HIV-1 clade C in both the geographic locales, in contrast to USA and Europe. But the true prevalence of HIV related neuroinfections and pathology is not available due to inadequate medical facilities, social stigma and ignorance that lead to underdiagnosis. Neurotuberculosis, followed by cryptococcosis and toxoplasmosis in various combinations are the major neuropathologies reflecting the endemicity and manifesting clinically by reactivation of latent infection. Discordance in the clinical prevalence of various infections, when compared to pathological studies highlight similarities in clinical, radiological modalities of diagnosis and inherent problems in establishing definitive diagnosis. Viral infections appear to be relatively rare. Inspite of heavy burden of HIV/AIDS, HIV associated neoplasia is infrequent, including primary CNS lymphomas. HIV encephalitis and HIV associated dementia are considered infrequent, though systematic studies have just been initiated in various centres. Peripheral neuropathy characteristically manifests with vasculitic neuropathy while diffuse infiltrative lymphocytosis syndrome (DILS) involving nerves has not been reported from India. Spinal cord pathology including vacuolar myelopathy is rare, even in asymptomatic cases. Till now the AIDS cases in India were drug naÏve but a new cohort of cases following initiation of HAART therapy as a national policy is soon emerging, altering the biology and evolution of HIV/AIDS in India. Lacunae in the epidemiology, diagnosis and study of biology of HIV/AIDS are outlined for future research

Neurology exit examination system in India: a survey of examiners' perceptions and recommendations

Background: The traditional Neurology exit examination in India has remained unchanged over the last few decades. In developed countries, objective evaluation methods have replaced the traditional ones. A need for such methods has not been explored in India. Objective: We aimed to study the perceptions and key recommendations of Neurology examiners on the existing examination pattern. Material and Methods: We conducted an online survey of examiners perceptions and recommendations using a set of 10 multiple-choice questions and an open-ended question. Results: 46 examiners provided completed responses suitable for analysis. Nearly equal proportions (30%) of the examiners had 10 years, 10–25 years and >25 years' experience. 92% were not satisfied with current system, 95% did not find adequate time for correction of theory scripts, 90% felt that theory questions were random, and 95% had legibility issues. 84% felt that the practical exams do not test true learning, 98% felt the examination stress impairs the performance and 85% felt that there are no objective criteria to pass the candidate. 83% felt the current system-needed changes. The key suggestions provided by the examiners to improve the system included objective assessments like MCQ, OSCE, OSLER and DOPS, inclusion of larger number of short answer type questions and periodic internal assessments of the candidates. Conclusions: A vast majority of examiners favoured changes to the current examination system and provided key recommendations. A larger study is needed to extrapolate these findings to the rest of India