Intermittent clobazam prophylaxis in hot water epilepsy is safe and effective: a prospective study.

PURPOSE: To evaluate the role of intermittent prophylaxis with clobazam in the management of HWE in a long-term prospective study. MATERIAL AND METHODS: Two hundred and sixty patients [M:F - 194:66] with HWE were recruited. Patients were divided into: (a) 'HWE alone' (n=198) - received intermittent clobazam prophylaxis, 1-1½h prior to hot water head bath (group A); (b) 62 patients (20.4%) with 'HWE with spontaneous seizures were treated with continuous AEDs along with intermittent clobazam therapy (group B). RESULTS: Patients (n=198) in group A was followed for mean of 17.6 ± 10.6 months (range: 3-57). One hundred and forty seven patients (74.2%) had excellent response with complete seizure freedom with clobazam therapy while 12 (6.1%) had >75% reduction in seizure frequency. Remaining 39 (19.7%) required additional standard AED along with clobazam and 18 patients among them developed spontaneous/unprovoked seizure at follow up of 6.7 ± 4.1 months. Forty five patients in group B were seizure free while on continuous AEDs. CONCLUSIONS: Intermittent clobazam prophylaxis prior to head water bath might be a preferred mode of treatment of pure HWE. Additional AEDs are required if they have associated non-reflex unprovoked seizure.

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

PURPOSE: Imaging 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. METHODOLOGY: The 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. RESULTS: VBM 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. CONCLUSIONS: This 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.

Hot water epilepsy clinical profile and treatment--a prospective study.

PURPOSE: This study characterized the demographic, clinical, EEG and imaging profile, and therapeutic outcome among patients with hot water epilepsy (HWE). METHODOLOGY: This prospective study included 70 patients with HWE (M:F=55:15; age: 25.3±8.4 years). Details of demography, seizure characteristics and outcome, and imaging/EEG observations were recorded. RESULT: There was male dominance. Majority of the patients belonged to Mandya: 30.5%, Ramanagara: 30.0% and Mysore: 15.2% districts of Karnataka, India. Forty-five patients (M:F=37:8; age: 24.6±10.1 years) had features of 'HWE alone'. Twenty-five (M:F=18:7; age: 26.7±7.9 years) had HWE with spontaneous seizures. The age at onset of seizures was comparable in both the groups - HWE: 18.7±10.2 years vs. HWE with spontaneous seizure: 16.8±10.3 years (p=0.34). The duration of seizures were more in HWE with spontaneous seizure group: 119.5±66.9 months compared to HWE alone: 69.9±13.8 months (p=0.028). Inter-ictal EEG (n=70) showed epileptiform activities in 15 patients (21.4%). The therapeutic outcome after 3-8 months of follow up were - (a) HWE group: 6 stopped hot water head bath; 39 were on intermittent clobazam therapy - seizure free: 33; and 6 received AEDs; (b) HWE with spontaneous seizure group: all were on AEDs and seizure free. CONCLUSIONS: Three-fourth of patients belonged to 'Mandya-Mysore belt of Karnataka'. There was increased duration of seizures among those with additional spontaneous seizure. About 3/4th subjects with HWE alone were seizure free with intermittent clobazam and remaining patients on AEDs were seizure free, confirming the earlier observations from this center.

Temporal resolution deficits in patients with refractory complex partial seizures and mesial temporal sclerosis (MTS).

We studied the temporal resolution ability in patients with refractory complex partial seizures and mesial temporal sclerosis (MTS) using Gaps-In-Noise (GIN) test in a prospective cross-sectional study. Thirteen patients with right MTS (age: 31±7.67 years; M:F=8:5) and 13 patients with left MTS (age: 25.76±8.26 years; M:F=9:4) having normal hearing and mini-mental state examination (MMSE) score of >23/30 were recruited. Fifty healthy volunteers (26.3±5.17 years; M:F=28:22) formed the control group. Gaps-In-Noise test demonstrated impaired temporal resolution: 69.2% of patients with right MTS (RMTS) and 76.9% of patients with left MTS (LMTS) had abnormal scores in the right ear for gap detection threshold (GDT) measure. Similarly, 53.8% of patients in the RMTS group and 76.9% of patients in the LMTS group had abnormal scores in the left ear. In percentage of correct identification (PCI), 46.1% of patients with RMTS and 69.2% of patients with LMTS had poorer scores in the right ear, whereas 46.1% of patients with RMTS and 61.5% of patients with LMTS had poorer scores in the left ear. Both patient groups, viz., RMTS and LMTS, demonstrated bilateral temporal resolution deficits.

Modulation of cardiac autonomic balance with adjuvant yoga therapy in patients with refractory epilepsy.

The practice of yoga regulates body physiology through control of posture, breathing, and meditation. Effects of yoga on autonomic functions of patients with refractory epilepsy, as quantified by standardized autonomic function tests (AFTs), were determined. The yoga group (n=18) received supervised training in yoga, and the exercise group (n=16) practiced simple routine exercises. AFTs were repeated after 10 weeks of daily sessions. Data were compared with those of healthy volunteers (n=142). The yoga group showed significant improvement in parasympathetic parameters and a decrease in seizure frequency scores. There was no improvement in blood pressure parameters in either group. Two patients in the yoga group achieved normal autonomic functions at the end of 10 weeks of therapy, whereas there were no changes in the exercise group. The data suggest that yoga may have a role as an adjuvant therapy in the management of autonomic dysfunction in patients with refractory epilepsy.

Kindling & mossy fibre sprouting in the rat hippocampus following hot water induced hyperthermic seizures.

BACKGROUND & OBJECTIVES: Hot water epilepsy (HWE) is well recognized reflex epilepsy with possible genetic susceptibility. Rat model and human experimentation had proven that HWE is a type of hyperthermic seizure with possible kindling on repeated stimulation in animals. The present study was undertaken to investigate kindling associated with hyperthermic seizures induced by repeated hot water stimulation in the rat model and to prove hyperthermic kindling. METHODS: Epileptic seizures were induced in 36 male Wistar albino rats by means of hot water sprays at 48 h time intervals. Progression of seizure activity was investigated by studying the behaviour, severity and duration of the seizure. Threshold of rectal temperatures and timed latency for seizure induction were studied. Seizure discharges (EEG) were recorded from ventral hippocampus in six of these rats. Timm's staining was used to study the neuronal sprouting as a consequence of kindling. Studying the seizure threshold, latency, duration of seizure discharge and behavioural seizure following a stimulus-free interval of 30 days tested permanence of kindling. RESULTS: Following 8-12 episodes of hot water stimulations there was progressive epileptic activity manifested in the form of lowering of rectal temperature thresholds from 41.5 to 40.0 degrees C, drop in latency for developing seizures from 185 to 118 sec, increase in duration of hippocampal seizure discharge from 15 to 140 sec, along with progressive increase in complexity of EEG after discharges, increase in behavioural seizure severity from Grade 1 to 5 in all the rats, and neuronal sprouting observed in supragranular molecular layer and in stratum lacunosum. INTERPRETATION & CONCLUSION: Our study covered all aspects of kindling and provided a useful animal model for human hot water epilepsy. Hyperthermic seizures induced by hot water in the rat model kindle as demonstrated by Timm's staining.

Primary auditory neuropathy - an enigma.

OBJECTIVES: To report audiological and neuroradiological findings in patients with primary auditory neuropathy (PAN) from a tertiary institution in south India. MATERIAL AND METHODS: The auditory profiles in 24 patients were analyzed along with neurological and radiological findings. RESULTS: Puretone audiometry showed varied hearing acuity and configuration. The syllable recognition score (n=15) was above 80% except in three. The dichotic digit test (n=11) showed bilateral suppression except in two who showed unilateral suppression. The auditory brainstem responses and the acoustic stapedius reflex were absent with distortion product otoacoustic emission (DPOAE) present in all. The neurological and radiological studies were normal. CONCLUSION: The audiological profile is consistent with the presence of DPOAE and absence of acoustic stapedius reflex and auditory brainstem responses. In patients with adequately preserved syllable recognition in quiet conditions, there was a significantly poor performance on dichotic digit test. As these patients had no neurological deficits and absence of specific etiological factors, we propose to use the term PAN for this entity.

Visual pathway abnormalities Wilson's disease: an electrophysiological study using electroretinography and visual evoked potentials.

The pathogenesis of the pattern reversal visual evoked potential (PRVEP) abnormalities in patients with Wilson's disease (WD) has not been investigated earlier. Since electroretinography (ERG) assesses the functional integrity of the retina, it was used along with PRVEP to localize the abnormalities in PRVEP in Wilson's patients. Ten newly diagnosed Wilson's disease patients underwent PRVEP and flash ERG soon after the diagnosis was established. The PRVEP latencies were prolonged in comparison with the controls (P<0.001). Photopic and scotopic A waves and oscillatory potentials were prolonged (P<0. 02) with reduction in amplitudes of photopic A and B waves (P<0.001). Six of these patients were subjected to repeat PRVEP and flash ERG after the clinical improvement with specific therapy. Comparison of the pre and post-treatment visual electrophysiological studies revealed significant reduction in latencies of PRVEP and flash ERG A wave (P<0.05) with increase in amplitudes of P100 of PRVEP (P<0.05), A and B waves of flash ERG (P<0.01). These findings confirm the reported PRVEP changes in WD and in addition demonstrate the reversibility of the retinal dysfunction which partially contributes to the PRVEP abnormalities. To the best of our knowledge this is the first study of ERG in patients with Wilson's disease in the literature. Further, there have been no earlier reports in the literature evaluating the effect of specific treatment on the PRVEP and ERG in Wilson's disease.

Effect of antiepileptic drugs and calcium channel blocker on hyperthermic seizures in rats: animal model for hot water epilepsy.

Hyperthermic seizures were elicited in groups of freely ambulant rats with jets of hot water of 55 degrees C on the head for about 10 mins. Bipolar depth EEG from the hippocampus and the behavioural seizures following the stimulation were recorded. The rectal temperature (threshold) for seizure initiation was 41.5 degrees C. The seizures were predominantly clonic jerks accompanied by large spikes and slow waves lasting for 30-60s. After 3 stimulations (once a day), Phenobarbitone (Pb) 0.02 mg/g daily, Diphenylhydantoin (DPH) 0.001 mg/g, 0.005 mg/g and 0.04 mg/g. daily and Nifedipine (Nif) 0.005 mg/g twice daily were administered intraperitoneally in different rats. During the 10-days injection trials, Pb completely suppressed seizures whereas DPH and Nif did not have any effect. One of the rats with DPH showed increased epileptic activity. After a 10 day 'washout' period' Pb and DPH were interchanged and again the rats were tested for seizures on 10 days. On changing over to Pb from DPH there was complete suppression of seizures and electrical seizure discharges. Whereas those rats which earlier had no seizure activity with Pb started showing the same on changing over to DPH.

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 degrees C - 55 degrees 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 degrees C and regional hippocampal temperature of 37 degrees 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.