Sunil Pradhan

Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis

We describe 4 patients with acute disseminated encephalomyelitis (ADEM) who were treated with intravenous immunoglobulins (IVIg) after getting no immediate response from a 3-5 day course of high dose intravenous methylprednisolone. All had clinical features to suggest poor prognosis and MRI findings to indicate extensive white matter changes in the brain. Two patients who had spinal cord involvement as well, required ventilatory support during acute phase of the illness. All the 4 patients recovered dramatically. Recovery pattern suggested that IVIg might be useful in fulminant ADEM. Further trials are needed to look for the efficacy of IVIg alone and in combination with methylprednisolone in the treatment of ADEM.

Reduction in oxidative stress and cell death explains hypothyroidism induced neuroprotection subsequent to ischemia/reperfusion insult.

Hypometabolic state following hypothermia is known to protect tissues from ischemic injury. Hypothyroidism produces a hypometabolic state. The present study was undertaken to investigate the protective effects of hypothyroidism following cerebral ischemia and to ascertain the underlying mechanism. Euthyroid (E) and hypothyroid (H) animals were exposed to a 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion (I/R). Specific enzymatic methods and flowcytometry were used to assess the quantitative changes of molecules involved in neuronal damage as well as in protection. As compared to euthyroid ischemic reperfused (E + I/R) rats, H + I/R rats had insignificant neurological deficit, and smaller area of infarct. H + I/R rats had significantly lower markers of oxidative stress, and lactate dehydrogenase (LDH) activity (a marker for necrosis). Natural antioxidant activity (particularly superoxide dismutase) and integrity of mitochondria (membrane potential) were maintained in H + I/R group but not in E + I/R group. The number of neurons undergoing apoptosis significantly lower in hypothyroid ischemic rats as compared to euthyroid ones. These results suggest that hypothyroid animals face ischemia and reperfusion much better compared to euthyroid animals. A possible explanation could be the decreased oxidative stress and maintained antioxidant activity that finally leads to a decrease in necrosis and apoptosis. These observations may suggest strategies to induce brain-specific downregulation of metabolism that may have implications in the management of strokes in human beings.

Magnetic resonance imaging in juvenile asymmetric segmental spinal muscular atrophy

Magnetic resonance imaging (MRI) of cervical spine was performed in 16 patients of juvenile asymmetric segmental spinal muscular atrophy (JASSMA) in neutral and flexed positions to look for abnormalities in the spinal cord and the surrounding structures. The study included 5 normal individuals and 5 disease-negative controls who had spinal cord atrophy due to amyotrophic lateral sclerosis. In normal and disease-negative controls, lower cervical spinal cord moved forward and got mildly flattened against the vertebral bodies during flexion. The subarachnoid space increased behind the cord with no significant forward movement of the posterior dura mater; epidural space was just visible. The patients of JASSMA showed spinal cord atrophy in a small vertical segment in front of cervical 4 to 7 vertebral bodies. In addition, 9 patients had high cord signal on T2 weighted images, mainly localized to anterior and lateral horns of the grey matter. In flexion, there was marked anterior displacement and anteroposterior flattening of lower cervical cord against the vertebral bodies; posterior dura mater also moved forward obliterating subarachnoid space in all the patients. A large posterior epidural space was visible which showed enhancement after gadolinium-DTPA administration. Twelve patients had prominent blood vessels in this epidural space. These findings suggest that MRI done in neck flexion may have diagnostic significance in JASSMA.

Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population

AIMS To evaluate sodium channel genes as candidates for epilepsy susceptibility and their role in therapeutic efficacy, we screened coding single-nucleotide polymorphism of SCN1A p. Thr 1067 Ala or c.3184 A-->G (rs2298771) and SCN2A p.Arg19Lys or c.56 G-->A (rs17183814) in north Indian epilepsy patients. METHODS The genotyping was performed in 160 control subjects and 336 patients with epilepsy, of whom 117 were drug resistant and 219 were drug responsive. Therapeutic drug monitoring for phenytoin, carbamazepine, phenobarbital and valproate was also performed in 20% of the patients to confirm compliance. RESULTS AG genotype of SCN1A 3184 A-->G polymorphism was significantly higher and associated in epilepsy patients [P= 0.005; odds ratio (OR) 1.76, 95% confidence interval (CI) 1.19, 2.61], whereas A variant of SCN2A c.56 G-->A was associated with multiple drug resistance in north Indian patients with epilepsy (P= 0.03; OR 1.62, 95% CI 1.03, 2.56). CONCLUSIONS Overall, results indicate a differential role of genetic polymorphisms of sodium channels SCN1A and SCN2A in epilepsy susceptibility and drug response.

Demonstration of scolex within calcified cysticercus cyst: its possible role in the pathogenesis of perilesional edema.

Summary:  Purpose: This study was performed to understand the relation between the scolex as demonstrated on gradient echo (GRE) imaging in a calcified cysticercus cyst and the development of perilesional edema that may be of value in understanding the pathogenesis of this entity.

Kluver Bucy syndrome in young children

For the first time, Kluver Bucy syndrome (KBS) is described in young children who had no environmental learning of sex. The syndrome has so far been noted only in adults after bilateral temporal lobe affection. A few of its components, especially the hypersexuality and hypermetamorphosis, are likely to manifest differently in very young children. Seven patients in the pre-pubertal age group, who developed KBS as a post-encephalitic sequelae, are described. The patients, 2.5-6 years old, suffered from acute herpes simplex encephalitis (HSE) at 10 months-5.5 years of age and developed KBS on regaining consciousness and ambulation. Altered emotional behaviour, changes in dietary habits, hyperorality and hypersexuality were present in all, while psychic blindness and hypermetamorphosis were noted in a few of the patients. All showed marked indifference and lack of emotional attachment towards their close relatives. Apathy and easy distractibility were rare. Bulimia and strong urge to put non-food items into the mouth were common. Hypersexuality manifested as frequent holding of genitals, intermittent pelvic thrusting movements and rubbing of genitals to the bed on lying prone. Due to lack of environmental learning of sex and also, due to emotional and physical dependence on parents, the manifestations in young children showed modification over those of adults.

Role of the ACE ID and MTHFR C677T polymorphisms in genetic susceptibility of migraine in a north Indian population

Migraine is a common debilitating neurovascular disorder. The vascular genes ACE and MTHFR are involved in alterations in vascular endothelium and are suggested to play a role in migraine susceptibility. The aim of our study was to find out the role of ACE ID (rs no. 4646994) and MTHFR C677T (rs no.1801133) polymorphisms in genetic susceptibility of migraine in north Indian population. A total of 150 migraine patients, 220 non-migraine headache patients (Disease controls) and 150 age-sex matched normotensive healthy controls were enrolled for our study. DNA was isolated from peripheral blood leucocytes, and subjected to amplification using specific primers and genotyped using PCR (in case of ACE ID) or PCR-RFLP (in case of MTHFR C677T) methods. chi(2) test was applied for the analysis of genotypic and allelic distributions. Logistic regression analysis was used to find out contribution of genetic polymorphisms to the risk of disease. ACE DD genotype showed significant association in migraine patients with aura (MA) but a marginal significance in female MA patients in comparison with healthy controls. No significant differences in genotype and allelic frequencies of MTHFR C677T polymorphism were found on comparing migraine patients with either disease controls or healthy controls. In contrast, we found synergistic role of ACE (DD)*MTHFR (CT) interaction, showing a positive association in total migraine with aura patients as well as female migraine patients with aura when compared with healthy controls.

Neurocysticercosis in patients with active epilepsy from the pig farming community of Lucknow district, north India

Epilepsy is a major health problem worldwide, and neurocysticercosis (NCC) is one of the important causes of epilepsy in the tropics. The present study was carried out in a rural pig farming community of north India to estimate the prevalence of NCC in patients with active epilepsy (AE) and to determine the associated risk factors. Based on 30-cluster sampling recommended by WHO, a total of 1640 individuals belonging to 294 families from 30 villages were enrolled in the study. Demographic and socio-economic details of all individuals and families were recorded. Individuals with AE were identified by door-to-door survey. NCC was diagnosed by clinical, immunological, neuroimaging (brain magnetic resonance imaging) and epidemiological criteria. During the survey, 95 (5.8%) patients with AE were identified and clinically confirmed; 91 agreed to further evaluation for NCC and 44 (48.3%) of them fulfilled either definitive or probable diagnostic criteria for NCC. These 44 patients belonged to 37 households. Epilepsy in the family and no separate place for keeping pigs were identified as risk factors for NCC clustering in a family. The study shows a very high prevalence of AE in the pig farming community and NCC as its major cause. Since NCC is a preventable and potentially eradicable disease, appropriate intervention strategies may help to reduce the disease burden.

Human and porcine Taenia solium infection in rural north India

72 members of a pig farming community and 50 slaughtered pigs in Uttar Pradesh, India, were examined between November 2000 and June 2001 for Taenia solium infection. 27 of the human subjects (38%) had intestinal taeniasis and 7 (9.7%) had reported seizures. All 3 of the latter who were examined had neurocysticercosis. 13 of the pigs (26%) had cysticercosis. Such high prevalences indicate the need for detailed assessment of the disease burden in this community.

Role of the oestrogen receptor (ESR1 PvuII and ESR1 325 C→G) and progesterone receptor (PROGINS) polymorphisms in genetic susceptibility to migraine in a North Indian population

We aimed to explore the single-locus, haplotype and epistasis patterns and the contribution of oestrogen receptor [ESR1 PvuII (rs2234693), ESR1 325 C→G (rs1801132)] and progesterone receptor [PROGINS (rs1042838)] polymorphisms in genetic susceptibility to migraine by analysing 613 subjects consisting of 217 migraine patients, 217 healthy controls (HC) and 179 patients with tension-type headache (TTH). Entire data were analysed by taking the Bonferroni corrected P-value into account. We found significant association of TT genotype [odds ratio (OR) 3.458, confidence interval (CI) 1.757, 6.806; P = 0.0003] and T allele (OR 1.729, CI 1.309, 2.284; P = 0.0001) of ESR1 PvuII single nucleotide polymorphism with migraine when compared with HC. Significant association was seen only in female migraine patients at both genotype (P = 0.002; OR 3.834, CI 1.625, 9.043) and allele level (P = 0.002; OR 1.721, CI 1.228, 2.413). Moreover, higher risk was limited to migraine with aura (MA) (in case of TT genotype, P = 0.002; OR 4.377, CI 1.703, 1.246; in case of T allele, P = 0.001; OR 1.888, CI 1.305, 2.735) rather than migraine without aura (MoA) (P-value of TT genotype = 0.003; OR 3.082, CI 1.465, 6.483; P-value T allele = 0.002; OR 1.630, CI 1.188, 2.236). In case of a recessive model, risk was seen with migraine patients (P = 0.0003; OR 2.514, CI 1.635, 3.867), MA (P = 0.0001; OR 3.583, CI 1.858, 6.909) and MoA patients (P = 0.002; OR 2.125, CI 1.304, 3.464) when compared with HC. No risk was observed when TTH patients were compared with HC. No significance of ESR 325 G→C polymorphism was seen in any of the models under study. Significant differences in genotypic (P = 0.0001) and allelic frequency (P = 0.0002) were seen in case of PROGINS polymorphism when migraine patients were compared with HC, showing a protective effect (for A1A2 genotype, OR 0.292, CI 0.155, 0.549; for A2 allele, OR 0.320, CI 0.174, 0.589). Moreover, significance was seen only in case of female migraine patients at genotype (P = 0.002; OR 0.344, CI 0.176, 0.684) as well as allele levels (P = 0.004; OR 0.379, CI 0.198, 0.727) in case of PROGINS polymorphism. ESR1 PvuII TT*ESR1 325 C→G CG genotype, PROGINS A1A2*ESR1 325 C→G CG genotype and ESR1 PvuII CT*PROGINS A1A2 interacted significantly, but significance was lost after Bonferroni correction. In conclusion, ESR1 PvuII polymorphism is a significant risk factor for migraine particularly in women and MA patients, but ESR 325 C→G polymorphism is not associated with migraine susceptibility. PROGINS polymorphism seems to play a protective role in genetic susceptibility to migraine in the North Indian population.