Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma.

PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach. RESULTS: Unsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment. CONCLUSIONS: We show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.

Successful treatment of primary cerebral mucormycosis: Role of microbiologist.

Fungal brain abscess is rare with a rapidly progressive disease with fulminant course and invariably fatal outcome, unless diagnosed early and treated rapidly. We report a 56-year-old woman diagnosed to have fungal abscess who recovered completely following amphotericin B treatment. She presented with weakness of the right hand, deviation of mouth to left and aphasia for 2 days. Computed tomography of the brain revealed a left frontal capsuloganglionic hypodense lesion. Stereotactic biopsy was performed, and microbiological confirmation of non-septate fungal hyphae from pus from aspirate within 2 h helped initiate timely and appropriate treatment leading to cure. Histopathology and culture later confirmed mucormycosis.

Reduced small world brain connectivity in probands with a family history of epilepsy.

BACKGROUND AND PURPOSE: The role of inheritance in ascertaining susceptibility to epilepsy is well established, although the pathogenetic mechanisms are still not very clear. Interviewing for a positive family history is a popular epidemiological tool in the understanding of this susceptibility. Our aim was to visualize and localize network abnormalities that could be associated with a positive family history in a group of patients with hot water epilepsy (HWE) using resting-state functional magnetic resonance imaging (rsfMRI). METHODS: Graph theory analysis of rsfMRI (clustering coefficient γ; path length λ; small worldness σ) in probands with a positive family history of epilepsy (FHE+, 25) were compared with probands without FHE (FHE-, 33). Whether a closer biological relationship was associated with a higher likelihood of network abnormalities was also ascertained. RESULTS: A positive family history of epilepsy had decreased γ, increased λ and decreased σ in bilateral temporofrontal regions compared to FHE- (false discovery rate corrected P ≤ 0.0062). These changes were more pronounced in probands having first degree relatives and siblings with epilepsy. Probands with multiple types of epilepsy in the family showed decreased σ in comparison to only HWE in the family. CONCLUSION: Graph theory analysis of the rsfMRI can be used to understand the neurobiology of diseases like genetic susceptibility in HWE. Reduced small worldness, proportional to the degree of relationship, is consistent with the current understanding that disease severity is higher in closer biological relations.

Monitoring peri-ictal changes in heart rate variability, oxygen saturation and blood pressure in epilepsy monitoring unit.

PURPOSE: The peri-ictal autonomic disturbances have been studied as predictors of seizure outcome and as markers of seizure onset. We studied the changes in heart rate (HR), HRV, oxygen saturation and blood pressure (BP) in the peri-ictal period in patients with drug-resistant localization-related epilepsy. METHODOLOGY: Ninety one subjects undergoing video-EEG monitoring, underwent continuous HR, SpO2, BP and Lead II ECG monitoring. The changes during the preictal, ictal and postictal periods were analyzed for 57 seizures in 42 patients with artifact-free recordings and correlated with VEEG ictal onset and MRI characteristics. RESULTS: Ictal tachycardia was noted in 15 (26.3%) seizures, of which, 60% had temporal lobe onset. HR increased by an average of 20.1% from pre-ictal to ictal phases (p=0.04). Ictal bradycardia was noted in one event with right temporal seizure onset. Heart rate variability (HRV) analysis of the preictal, ictal and postictal phases showed an increase in the sympathetic and decrease in parasympathetic activity during the ictus with relatively preserved total power. Ictal oxygen desaturation (84.1%±3.5%) was noticed in 10 (17.5%) seizures. Ictal hypertension was observed in 15 (26.3%); ictal hypotension was noted in 5 (8.7%) seizures. Both the systolic BP and diastolic BPs increased from the pre-ictal to ictal phase (p=0.01). CONCLUSIONS: Peri-ictal dysautonomia can present in variable patterns and can be measured and compared over different modalities such as BP, HR and HRV. Though degree of tachycardia and increase in BP were higher during extratemporal onset of seizures, a fall in variability was noted in seizures of temporal lobe origin. Oxygen desaturation is not an uncommon event during the peri-ictal period in localization related epilepsy.

Clinical, electrophysiological, imaging, pathological and therapeutic observations among 18 patients with Rasmussen's encephalitis.

We studied the clinical, electrophysiological, imaging and pathological features of 18 patients with Rasmussen's encephalitis (RE). This descriptive study included 18 patients (six males, 12 females) with RE who were evaluated for demographic and phenotypic details, electroencephalogram (EEG) results, MRI results, pathological features, virological markers and outcome. Radiological staging as per Bien et al. and pathological staging in accordance with Robitaille et al. were performed. Simple partial seizures were the most common initial manifestation. During the disease course, epilepsia partialis continua (EPC) developed in 15/18 (83.3%) and hemiparesis in 17/18 (94.4%) patients. EEG revealed hemispheric slowing (100%), interictal epileptiform discharges (100%) and ictal pattern (44.4%). Brain MRI revealed unihemispheric focal cortical atrophy (100%), white matter changes (88.2%), basal ganglia-ipsilateral caudate and putamen involvement (50.0%) and progression of atrophy on serial MRI (100%). Unusual presentations in this series included late onset (n=1), and isolated lingual EPC (n=1). Diagnostic biopsies in two patients revealed Robitaille stage 3 disease. The six hemispherotomy specimens showed stage 2 disease in one, stage 3 in three and stage 4 in two cases. Heterogeneity in disease stage in the different neuroanatomical regions and within the same cortical segment reflected progression of immune-mediated damage. Immunomodulation provided only temporary benefit. Patients who underwent functional hemispherotomy had reduction in seizure frequency and improved quality of life. The clinical, EEG and MRI findings are in accordance with the established literature. MRI staging was concordant with Robitaille pathological staging. Immunomodulation did result in transient reduction in seizure frequency while surgery in six produced reasonable benefit.

Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI.

BACKGROUND AND PURPOSE: The frequency of seizures is an important factor that can alter functional brain connectivity. Analysis of this factor in patients with epilepsy is complex because of disease- and medication-induced confounders. Because patients with hot-water epilepsy generally are not on long-term drug therapy, we used seed-based connectivity analysis in these patients to assess connectivity changes associated with seizure frequency without confounding from antiepileptic drugs. MATERIALS AND METHODS: Resting-state fMRI data from 36 patients with hot-water epilepsy (18 with frequent seizures [>2 per month] and 18 with infrequent seizures [≤2 per month]) and 18 healthy age- and sex-matched controls were analyzed for seed-to-voxel connectivity by using 106 seeds. Voxel wise paired t-test analysis (P < .005, corrected for false-discovery rate) was used to identify significant intergroup differences between these groups. RESULTS: Connectivity analysis revealed significant differences between the 2 groups (P < .001). Patients in the frequent-seizure group had increased connectivity within the medial temporal structures and widespread areas of poor connectivity, even involving the default mode network, in comparison with those in the infrequent-seizure group. Patients in the infrequent-seizure group had focal abnormalities with increased default mode network connectivity and decreased left entorhinal cortex connectivity. CONCLUSIONS: The results of this study suggest that seizure frequency can alter functional brain connectivity, which can be visualized by using resting-state fMRI. Imaging features such as diffuse network abnormalities, involvement of the default mode network, and recruitment of medial temporal lobe structures were seen only in patients with frequent seizures. Future studies in more common epilepsy groups, however, will be required to further establish this finding.

Repetitive transcranial magnetic stimulation induced modulations of resting state motor connectivity in writer's cramp.

BACKGROUND AND PURPOSE: Writer's cramp (WC) is a focal task-specific dystonia of the hand which is increasingly being accepted as a network disorder. Non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI). METHODS: Nineteen patients with right-sided WC and 20 matched healthy controls (HCs) were prospectively evaluated. All patients underwent a single session of rTMS and rsfMRI was acquired before (R1) and after (R2) rTMS. Seed-based functional connectivity analysis of several regions in the motor network was performed for HCs, R1 and R2 using SPM8 software. Thresholded (P < 0.05, false discovery rate corrected) group level mean correlation maps were used to derive significantly connected region of interest pairs. RESULTS: Writer's cramp showed a significant reduction in resting state functional connectivity in comparison with HCs involving the left cerebellum, thalamus, globus pallidus, putamen, bilateral supplementary motor area, right medial prefrontal lobe and right post central gyrus. After rTMS there was a significant increase in the contralateral resting state functional connectivity through the left thalamus-right globus pallidus-right thalamus-right prefrontal lobe network loop. CONCLUSIONS: It is concluded that WC is a network disorder with widespread dysfunction much larger than clinically evident and changes induced by rTMS probably act through subcortical and trans-hemispheric unaffected connections. Longitudinal studies with therapeutic rTMS will be required to ascertain whether such information could be used to select patients prior to rTMS therapy.

Dexmedetomidine anesthesia enhances spike generation during intra-operative electrocorticography: A promising adjunct for epilepsy surgery.

BACKGROUND: Anesthetic-induced suppression of cortical electrical activity is a major concern during epilepsy surgery. Dexmedetomidine (Dex) has been recently evaluated in a few small series for its effect on the electrocorticographic spikes intra-operatively. METHODS: In this prospective study, electrocorticogram (ECoG) was monitored during dexmedetomidine infusion in 34 patients (M:F=23:11, age=29.2 ± 10.9 years; duration of epilepsy=15.3 ± 8.9 years) undergoing anterior temporal lobe resection with amygdalo-hippocampectomy for drug-resistant mesial temporal lobe epilepsy (Right: 18, Left: 16). Anesthesia was induced with thiopental/propofol and maintained with oxygen-N2O-isoflurane. ECoG was recorded for 5 min after the end tidal MAC of N2O and isoflurane were decreased to zero; anesthesia was maintained with O2:Air=50:50, vecuronium and fentanyl. ECoG was recorded using a 4-contact strip electrode for: (a) 5 min prior to dexmedetomidine (PreDEX), (b) 5 min during dexmedetomidine infusion (DEX; 1 µg/kg) and (c) 5 min after stopping dexmedetomidine (PostDEX). RESULTS: The ECoG spikes were manually counted in all the channels. The mean spike rate in the 2 channels with maximum spikes (MAX CH A and MAX CH B) was normalized to a 3-min duration. RM-ANOVA and post hoc comparison of three phases were used to compare the spike rates. The mean spike rate during Dex phase was higher compared to preDEX (MAX CH B: p=0.007 and MAX CH A: p=0.079) and PostDEX (MAX CH B: p=0.17, MAX CH A: p=0.79) phases. The spike rate increased in 67.6% patients, while 11.8% patients showed ≤ 25% reduction and 20.6% patients showed >25% reduction in spike frequency. CONCLUSION: Dexmedetomidine is useful during intra-operative ECoG recording in epilepsy surgery as it enhances or does not alter spike rate in most of the cases, without any major adverse effects.

Hemodynamic effects of dexmedetomidine during intra-operative electrocorticography for epilepsy surgery.

BACKGROUND: Dexmedetomidine, a predominant alpha-2-adrenergic agonist has been used in anesthetic practice to provide good sedation. The drug is being recently used in neuroanesthesia during awake surgery for brain tumors and in functional neurosurgery. MATERIALS AND METHODS: This prospective study analyzed the hemodynamic effects of dexmedetomidine infusion during electrocorticography in patients undergoing surgery for mesial temporal sclerosis. Dexmedetomidine infusion was administered during intra-operative electrocorticography recording, 15 minutes after the end tidal MAC of N2O and isoflurane were decreased to zero. Anesthesia was maintained with O2 : air mixture = 50:50, vecuronium and fentanyl. Heart rate (HR), mean arterial pressure (MAP) and end tidal carbon dioxide (ETCO2) were recorded across at induction, 2 min prior to dexmedetomidine (PreDEX), 5 min during dexmedetomidine infusion (DEX; 1 µg/kg), 5 min after stopping dexmedetomidine and 10 minutes after stopping dexmedetomidine. RESULTS: Forty patients with mesial temporal sclerosis (M: F = 27:13, mean age = 28.15 ± 10.9 years; duration of epilepsy = 12.0 ± 7.9 years) underwent anterior temporal lobe resection with amygdalohippocampectomy for drug-resistant epilepsy. Infusion of dexmedetomidine caused a transient fall in HR in 87.5% of patients and an increase in MAP in 62.5% of patients, which showed a tendency to revert back towards PreDEX values within 10 min after stopping the infusion. Sixty-five percent of the patients showed ≤25% reduction and 10% of them showed >25% reduction in HR. 47.5% of the patients showed ≤25% increase and 15% of them showed >25% increase in MAP. These changes were over a narrow range and within physiological limits. CONCLUSION: The infusion of dexmedetomidine for a short period causes reduction of HR and increase in MAP in patients, however the variations are within acceptable range.

Clinico-pathological factors influencing surgical outcome in drug resistant epilepsy secondary to mesial temporal sclerosis.

BACKGROUND: Mesial temporal sclerosis (MTS) is the most common cause of drug resistant epilepsy amenable for surgical treatment and seizure control. METHODS: This study analyzed the outcome of patients with MTS following anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH) over 10 years and correlated the electrophysiological and radiological factors with the post operative seizure outcome. RESULTS: Eighty seven patients were included in the study. Sixty seven (77.2%) patients had an Engel Class 1 outcome, 9 (11.4%) had Class 2 outcome. Engel's class 1 outcome was achieved in 89.9% at 1 year, while it reduced slightly to 81.9% at 2 years and 76.2% at 5 year follow up. Seventy seven (88.5%) patients had evidence of hippocampal sclerosis on histopathology. Dual pathology was observed in 19 of 77 specimens with hippocampal sclerosis, but did not influence the outcome. Factors associated with an unfavorable outcome included male gender (p=0.04), and a higher frequency of pre-operative seizures (p=0.005), whereas the presence of febrile seizures (p=0.048) and loss of hippocampal neurons in CA4 region on histopathology (p=0.040) were associated with favorable outcome. The effect of CA4 loss on outcome is probably influenced by neuronal loss in other subfields as well since isolated CA4 loss was rare. Abnormal post operative EEG at the end of 1 week was found to be a significant factor predicting unfavorable outcome (p=0.005). On multivariate analysis, the pre-operative seizure frequency was the only significant factor affecting outcome. CONCLUSIONS: The present study observed excellent seizure free outcome in a carefully selected cohort of patients with MTS with refractory epilepsy. The presence of dual pathology did not influence the outcome.

Evolution of MRI changes in Rasmussen's encephalitis.

PURPOSE: We studied the MRI findings in 16 patients with Rasmussen's encephalitis (RE), further analysed serial MRI changes in 11 of them and correlated it with clinical features. METHODOLOGY: The diagnosis of RE was based on the European consensus statement (Brain, 128, 2005, 454). Details related to demographical, clinical, MRI observations were analysed. RESULTS: Forty MRIs of brain of 16 patients were reviewed. Eleven patients had undergone serial brain MRIs ranging from two to five occasions. All the patients had unihemispheric focal cortical atrophy, predominantly in the perisylvian region (n = 13). Other features were white matter signal changes (n = 14), and ipsilateral caudate (n = 6) and putamen (n = 4) atrophy. Signal alterations in putamen and caudate were noted in four each. In all the 11 patients with serial MRI, there was progression of cerebral atrophy and a trend towards increase in MRI staging. The MRI signal changes remained same in five patients, resolved in three patients, differential change in two patients and increased in one patient. Diffusion-weighted imaging showed facilitated diffusion (n = 5), and MR spectroscopy showed reduced N-acetyl-aspartate and elevated lactate (n = 2). CONCLUSIONS: Pattern recognition of MRI findings and the changes in serial MRI might serve as a surrogate marker of disease viz. unihemispheric progressive focal cortical atrophy and signal changes predominantly in the perisylvian distribution and caudate followed by putamen involvement. This might assist in understanding and monitoring of the disease progression.

Eating epilepsy: phenotype, MRI, SPECT and video-EEG observations.

BACKGROUND: Eating epilepsy is one of the rare forms of reflex epilepsy precipitated by eating. Previous studies have demonstrated lesions due to variable aetiology involving the temporolimbic and suprasylvian regions. OBJECTIVE: To study anatomical correlates of reflex eating epilepsy using multimodality investigations (MR imaging, video-EEG and SPECT). METHODOLOGY: Six patients (M:F=3:3; mean age: 20.7±4.9 years) with eating epilepsy were subjected to MRI of brain, video-EEG studies and SPECT scan. These were correlated with phenotypic presentations. RESULTS: Among the five patients with ictal recording of eating epilepsy during video-EEG, semiology was characterized by behavioural arrest followed by either flexion or extension of trunk and neck and two patients had speech arrest and four had salivation from angle of mouth. Another patient had EEG changes during "thought about eating". Four patients had perisylvian frontal lobe lesions and one had high frontal lesion on MRI. Ictal EEG (n=6) showed ictal rhythmic slowing/fast activity in parieto-temporal (n=2) or fronto-temporal (n=4) regions with subsequent secondary generalization in three. Ictal and interictal SPECT imaging showed changes in frontal lobe (n=1), anterior temporal lobe (n=1), and parieto-insular region (n=1) suggesting it to be seizure onset zone. Three of four patients with structural lesions in MRI had concordant ictal EEG and ictal SPECT changes. CONCLUSION: Lesions near the perisylvian region might play a major role in eating epilepsy.

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

INTRODUCTION: The 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. METHODS: The 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. RESULTS: All 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. CONCLUSION: MRI abnormalities in neurosyphilis are protean and mimic of many other neurological disorders and thus require a high index of suspicion to reduce diagnostic omissions.

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

PURPOSE: We describe the clinical, neuroimaging and pathological features and therapeutic outcome in a large cohort of 39 patients with tumefactive demyelination. MATERIALS AND METHODS: A retrospective audit of 39 patients with 'tumefactive demyelination' was performed. The demographic, clinical, MR imaging and pathological details were reviewed. RESULTS: The clinical course was monophasic (n = 22) or relapsing-remitting (n = 17). Common neurological manifestations at presentation included hemiparesis - 27; ataxia - 11; vomiting - 10; headache -9; ophthalmoplegia - 7; seizure - 5; impaired vision - 4; aphasia - 4; visual field defects - 3; papilloedema - 5; extrapyramidal - 5; intellectual decline - 5; behavioural disturbances - 3; altered sensorium - 5. MRI revealed fronto-parietal lesions, which were isolated in 14 (36%) patients. Moderate perilesional oedema and/or mass effect was noted in 12 (30.8%) patients. Post-contrast MR sequences revealed partial ring enhancement in 15, complete ring in seven, patchy enhancement in six, uniform enhancement in two and lack of enhancement in nine cases. Clinical and MR characteristics did not help distinguish between monophasic and relapsing-remitting subgroups. In the monophasic group, 53.8% had complete recovery, while 38.5% had partial improvement (follow-up duration, 8.31 ± 9.3 months). In the relapsing-remitting subgroup, the median time to relapse was 4 months (n = 12, follow-up, 37.8 ± 39.4 months). Patients with monophasic course or single relapse received steroids. Patients with more than one relapse received cyclophosphamide (2), mycophenolate (1), azathioprine (1) or methotrexate (1). CONCLUSIONS: A high proportion of cases of tumefactive demyelination follow a relapsing course, thus necessitating a long-term follow-up. MRI, although helpful in diagnosis, does not predict monophasic or relapsing-remitting course. Guidelines for the management of acute episodes and prevention of relapses are required.

Steroid-responsive encephalopathy in autoimmune thyroiditis: Clinical spectrum and MRI observations in three cases.

Hashimoto's encephalopathy (H.E.) is probably of autoimmune etiology, and manifests with seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, myoclonus. It is presumed to be autoimmune in origin with high serum titers of antithyroid peroxidase antibodies (anti-TPA). Thyroid function might often be normal. The diagnosis is arrived at by excluding other toxic, metabolic and infectious causes of encephalopathies, supportive clinical profile, elevated thyroid antibodies and optimum steroid response. We present the characteristic phenotypic manifestations, magnetic resonance imaging and electroechography observations and response to immunomodulation with follow-up in three cases of H.E. All the three cases manifested with subacute to chronic progressive encephalopathy, cerebellar dysfunction, seizures, behavioral abnormalities and oculomotor disturbances and had evidence of hypothyroidism, elevated titers of anti-TPA and positive thyroid anti-microsomal antibodies. Atypical and uncommon presentations are known. This report emphasizes that a high index of suspicion is often required in cases with "investigation negative encephalopathy" for early diagnosis of H.E.

Clinical, neuroimaging and pathological features of 5-nitroimidazole-induced encephalo-neuropathy in two patients: Insights into possible pathogenesis.

We report two patients manifesting with involvement of central and peripheral nervous system with brain magnetic resonance imaging (MRI) changes and pathological features of neuropathy possibly due to harmful and chronic use of various nitroimidazole group of medications for recurrent diarrheal illness. Patient 1, a 21-year-old man with obsessive-compulsive disorder, impulsive behavior and harmful use of substance (tinidazole), had developed encephalopathy and biopsy-proven neuropathy with partial remission. The MRI of brain showed involvement of bilateral caudate, lentiform and dentate nuclei, and splenium, with contrast enhancement of the caudate and putaminal lesions and restricted diffusion of the splenial lesion. Patient 2 was a 50-year-old woman with irritable bowel syndrome and was on harmful use of tinidazole and metronidazole. She manifested with encephalopathy, ataxia, and neuropathy. Her MRI of brain revealed involvement of bilateral putamen, dentate nuclei and periventricular white matter with restricted diffusion. Sural nerve biopsy revealed evidence of vasculitic neuropathy. At follow-up, there was definite, though incomplete, recovery in both the patients. The MRI alterations improved completely in patient 2 and substantially in patient 1. Increasing awareness among the physicians may enable early recognition of potentially reversible neurotoxicity and avoid unwarranted prescription of such medications.

Tuberculous meningitis presenting as isolated interhemispheric exudates.

The total number of tuberculosis cases in the world is increasing, and less common forms of tuberculous meningitis (TBM) with varying imaging manifestations are being encountered more often. We describe anterior interhemispheric variety of TBM, which has not been previously described to the best of our knowledge in the literature. Common imaging findings in these five patients include predominant involvement of the meninges in the anterior interhemispheric fissure with relatively little enhancement of the basal cisterns. Knowledge of uncommon radiological findings is vital in early diagnosis and treatment of this common disease.

Giant axonal neuropathy: a pictorial essay and review of literature.

Giant axonal neuropathy (GAN) is a neurodegenerative disorder classified within the hereditary motor and sensory neuropathies, affecting both the peripheral and central nervous systems. GAN typically presents in early childhood before the age of five years and progresses to death usually by early adulthood. Various imaging findings in giant axonal neuropathy have been described and documented in literature in the form multiple case reports. We here present a pictorial essay of all the major imaging GAN findings described in the literature. In addition, involvement of the dentate nucleus hitherto not described in the literature was noted in the present case.

Hyperemesis-gravidarum-induced Wernicke's encephalopathy: serial clinical, electrophysiological and MR imaging observations.

Wernicke's encephalopathy (W.E.), a potentially reversible condition caused by thiamine deficiency, is usually suspected in the setting of chronic alcoholism and might not be recognized when associated with other conditions. We describe a young pregnant woman who presented with rapidly evolving ataxia, diplopia and irrelevant speech following repeated vomiting. Characteristic brain MRI and rapid response to thiamine suggested that she had W.E. possibly due to hyperemesis gravidarum. A high index of suspicion is required, since delayed or lack of treatment may lead to high morbidity and mortality.