S. Sinha

Spectrum of epilepsy in Wilson's disease with electroencephalographic, MR imaging and pathological correlates

BACKGROUND Seizures are uncommon in Wilsons disease. OBJECTIVE To analyze profile of seizures in WD and to correlate with EEG and MR imaging observations. SUBJECTS AND METHODS 41/490 patients (8.3%) of WD were documented to have seizures. Autopsy observations were available in 3 cases. RESULTS The age at onset of seizures was 12.8+/-5.7years. Seizure - preceded the onset of characteristic features of WD (19.5%); occurred concurrently (46.3%); or, followed de-coppering therapy (29.2%) and occurred as terminal event (4.8%). The types of seizures were: generalized tonic-clonic - 29, simple partial - 8, complex partial - 6, partial seizures with secondary generalization - 2 and periodic myoclonus - 1. Six patients had multiple seizure types and 4 had status epilepticus. EEG abnormalities were frequent (19/24) consisting of background slowing and epileptiform discharges. MRI (n=20) revealed varying degree of atrophy and signal changes involving basal ganglia, brainstem and white matter. The duration of follow-up was 8.1+/-9.2years. The outcome of seizure was: no recurrence - 68.3%, breakthrough seizures - 17.1%, poor control - 9.7% and no follow-up - 4.9%. Two of them succumbed following cluster attacks. Autopsy revealed cavitatory lesions in white matter in frontal, temporal and parietal areas with varying involvement of cortical ribbon. Patients with seizures had more often white matter changes than those without. It was also noted that patients whose seizures were not controlled had MRI suggestive of cavitation of white matter, though the reverse was not true. CONCLUSIONS This is the largest series regarding epilepsy in WD. Seizures are not uncommon and could occur at any stage. Deafferentation of white matter tracts from cortex may contribute for seizure in WD.

Neurosyphilis: MRI features and their phenotypic correlation in a cohort of 35 patients from a tertiary care university hospital

IntroductionThe clinical and MR imaging features of neurosyphilis are highly varied. In this study, we describe the spectrum of the imaging findings in patients with neurosyphilis.MethodsThe MR imaging observations of 35 patients diagnosed to have neurosyphilis on the basis of cerebrospinal fluid reactive for the Venereal Disease Research Laboratory test were reviewed.ResultsAll the 35 patients, including four with human immunodeficiency virus coinfection, met the CDC diagnostic criteria for neurosyphilis. Patients were classified into three groups: (1) neuropsychiatric, (2) meningovascular, and (3) myelopathic, based on the dominant clinical manifestations. Fourteen patients with neuropsychiatric manifestations showed diffuse cerebral atrophy (14), parenchymal signal changes in the mesial temporal region (2) and temporal and basifrontal regions (1), infarcts (3), and nonspecific white matter changes (3). Eleven patients with meningovascular form showed infarcts (6), diffuse cerebral atrophy (3), signal changes in the mesial temporal region (3), sulcal exudates (1), progressive multifocal leukoencephalopathy (1), and a mass surrounding the carotid sheath (1). Spine imaging in ten patients with myelopathy showed long-segment signal changes (5), contrast enhancement (2), and dorsal column involvement (2). Three of these patients had normal spinal study. Six patients in the myelopathic group also underwent brain MRI that showed signal changes in the temporal region (2) and frontal region (1), multiple infarcts (1), and enhancing hypothalami (1). Three patients had normal study.ConclusionMRI abnormalities in neurosyphilis are protean and mimic of many other neurological disorders and thus require a high index of suspicion to reduce diagnostic omissions.

Management of generalised convulsive status epilepticus (SE): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam – Pilot study

OBJECTIVE This study was conducted to compare the efficacy of phenytoin, valproate and levetiracetam in patients with GCSE. METHODS This randomised controlled prospective study was conducted on 150 patients to compare the efficacy of phenytoin (n = 50), valproate (n = 50) and levetiracetam (n = 50) along with lorazepam in patients with GCSE. All recruited patients received i.v. lorazepam (0.1mg/kg) followed by one of the 3 AEDs viz. phenytoin (20 mg/kg), valproate (30 mg/kg), and levetiracetam (25 mg/kg). Those who remained uncontrolled with 1st AED, received the other two AEDs sequentially. Clinical, imaging, EEG, etiological factors were analysed. Predictors of poor seizure control and outcome at discharge and at one month follow-up were assessed. RESULTS In the phenytoin subgroup, the seizures could be controlled in 34 (68%) with lorazepam+phenytoin infusion. In the valproate subgroup (n = 50), seizures could be controlled in 34 (68%) with lorazepam+valproate infusion. In the levetiracetam subgroup (n = 50), seizures could be controlled in 39 (78%) with lorazepam+levetiracetam infusion. There was no statistically significant difference between the subgroups (p = 0.44). Overall, following lorazepam and 1st AED, 107/150 (71.3%) were controlled; with addition of 2nd AED, 130/150 (86.7%) and by adding 3rd AED, 138/150 (92%) were controlled. Fifteen out of 110 (13.6%) expired within 1 month of SE: phenytoin-6; valproate-4; and levetiracetam-5. Interestingly, 3 patients in the levetiracetam had post-ictal psychosis. SIGNIFICANCE Phenytoin, valproate, and levetiracetam are safe and equally efficacious following lorazepam in GCSE. The choice of AEDs could be individualised based on co-morbidities. SE could be controlled in 92% of patients with AEDs only and anaesthetics were not required in them.

Tumefactive demyelination: clinical, imaging and follow-up observations in thirty-nine patients

We describe the clinical, neuroimaging and pathological features and therapeutic outcome in a large cohort of 39 patients with tumefactive demyelination.

New-onset status epilepticus and cluster seizures in the elderly

We evaluated the frequency, therapeutic response and predictors of status epilepticus (SE) and cluster seizures among elderly people. Patients over 60 years old with epilepsy (n=201; age, 68.0 ± 7.5 years) were prospectively recruited. Among them, 64 patients (32%) who presented with new-onset cluster attacks and/or SE formed the study group. All underwent evaluation with electroencephalography (EEG) and CT scans. The mean duration of SE and cluster seizures at admission was 14.9 ± 53.7 hours. Cluster seizures were observed in 53 (26.4%) and SE in 34 (17%) elderly patients with seizures (n=201). The types of SE were: generalized convulsive (23 patients), epilepsia partialis continua (eight patients), non-convulsive (two patients) and myoclonic (one patient). The types of epilepsy syndrome included were: acute symptomatic (37 patients; 57.8%), cryptogenic (15 patients; 23.4%) and remote symptomatic (12 patients; 18.8%). Interictal EEG was abnormal in 79.7% of patients with critical presentation compared to 53.3% of patients without critical presentation. Epileptiform activity was observed in 46.9% of patients with SE and/or cluster seizures compared to 27.0% without SE and/or cluster seizures (p=0.001). The neuroimaging differences between the two groups were the absence of white-matter changes on CT scan in those with, compared to those without, SE and/or cluster seizures (28.1% compared to 41.6%, p=0.06). The risk factors for SE and/or cluster seizures were: acute symptomatic seizures, simple partial seizures, a higher number of seizures, lower Glasgow coma scale (GCS) score and an absence of white-matter changes on CT scan. After multivariate analysis, lower GCS score (p=0.01; odds ratio [OR]=0.82) and a higher number of seizures (p=0.03; OR=1.03) significantly predicted the occurrence of SE and/or cluster seizures. Seizures were controlled with two antiepileptic drugs in 70.6%. To conclude, SE and/or cluster seizures are common (32%) among elderly patients with epilepsy. Early and aggressive treatment is effective in the majority.

Quantitative analysis of heart rate variability in patients with absence epilepsy.

BACKGROUND There are no studies quantifying the nature of autonomic changes in absence epilepsy. Aims : We characterized the heart rate variability (HRV) during pre-interictal epileptiform discharges (IED), IED and post-IED states in absence epilepsy. MATERIAL AND METHODS Electroencephalogram (EEG) records with generalized 3-Hz spike-wave discharges in 8 patients (M: F: 3 : 5; mean age: 13.0 ± 2.5 years) with absence epilepsy were identified and corresponding electrocardiogram (ECG) time series were obtained. The time domain HRV measures were applied to pre-IED, IED and post-IED simultaneous ECG tracing. RESULTS There was slight tachycardia during the IED phase (pre-IED: 90.15 ± 3.45 bpm, IED: 94.82 ± 4.63 bpm, P = 0.09) which returned to baseline during the post-IED phase (post-IED: 89.65 ± 3.78 bpm). There was significant decrease in the standard deviation of RR interval (pre-IED: 40.0 ± 4.15 ms, IED: 30.4 ± 4.19 ms, P = 0.032) and trend in reduction of triangular index (pre-IED: 0.05 ± 0.01, IED: 0.04 ± 0.004, P = 0.08) during the IED phase when compared to pre-IED phase. The percentage of RR intervals >50 ms was lower during the IED phase and achieved significance when compared to post-IED phase (IED: 10.08 ± 4.89, post-IED: 18.74 ± 6.17, P = 0.050). While mean HR and RR interval significantly correlated with the duration of IEDs, there was no significant correlation between its duration with change in HRV parameters between the groups. There was no significant difference in HRV parameters between patients with long (>10s) and short (<10s) duration of IED. CONCLUSIONS Transient increase in heart rate during IED phase was noted in patients with absence epilepsy. Longer duration of IED seems to be linked with significant tachycardia. While most HRV parameters did not reach statistical significance, standard deviation of RR intervals and triangular index was noted to be decreased during the IED phase and returns to pre-IED levels after the episode.

Prevalence and profile of sleep disturbances in Guillain-Barre Syndrome: a prospective questionnaire-based study during 10 days of hospitalization

Sleep disturbances in Guillain‐Barre Syndrome (GBS), though common, have not received focused attention.

Progressive myoclonic epilepsy

Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. It encompasses different diagnostic entities and the common causes include Lafora body disease, neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber (MERRF) syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Recent advances in this area have clarified molecular genetic basis, biological basis, and natural history, and also provided a rational approach to the diagnosis. Most of the large studies related to PME are from south India from a single center, National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore. However, there are a few case reports and small series about Lafora body disease, neuronal ceroid lipofuscinoses and MERRF from India. We review the clinical and research experience of a cohort of PME patients evaluated at NIMHANS over the last two decades, especially the phenotypic, electrophysiologic, pathologic, and genetic aspects.

Evolution of MRI changes in Rasmussen's encephalitis.

We studied the MRI findings in 16 patients with Rasmussens encephalitis (RE), further analysed serial MRI changes in 11 of them and correlated it with clinical features.

Study of sleep microstructure in patients of migraine without aura

PurposeAlthough the relationship between sleep and migraine has been widely reported, studies on sleep microstructure are few. The aim was to study and compare microstructural polysomnographic characteristics in patients of “migraine without aura” (MOA) with controls.MethodsTwenty-five patients of MOA and 25 age- and gender-matched healthy controls were subjected to overnight polysomnography. Microstructural sleep analysis, including arousal and cyclic alternating pattern (CAP) analysis was performed. Arousals and CAP parameters were compared between the two groups using the Mann-Whitney U test (p ≤ 0.05).ResultsThe overall arousal index (p = 0.528) and that during non-rapid eye movement (NREM) sleep (p = 0.503) were comparable between the two groups. However, the arousal index was lower in migraineurs during rapid eye movement (REM) sleep (p = 0.001). The overall CAP rate (p = 0.020) as well as the number of CAP cycles and sequences (p = 0.032) was lower among migraineurs. The total phase A duration (p < 0.0001) was increased, and conversely, phase B duration (p = 0.001) was decreased in migraineurs. The phase A1 duration (p = 0.036) was higher in migraineurs. Finally, phase A1 (p = 0.357) index was comparable, and conversely, A2 (p < 0.0001) and A3 (p = 0.020) indices were decreased in migraineurs.ConclusionsThis study showed a decreased REM arousability as well as a decreased overall CAP rate and CAP cycling in patients with migraine as compared to controls. This indicates that there is probably an alteration of the arousal mechanisms in patients with migraine that may facilitate the occurrence of headache paroxysms during sleep.