Exposure to Toxocara Canis is not Associated with New-Onset Epilepsy.

Purpose: The association between exposure to Toxocara canis and epilepsy is at the best contentious. Most of previous studies were retrospective, community-based, and contradictory to one another. As the impact of a positive association on the magnitude of epilepsy will be huge especially in developing countries where toxocariasis is common owing to poor hygienic practices, this study was carried out to determine whether exposure to T. canis predisposes to development of epilepsy. Patients and Methods: This case-controlled observational study was carried out a tertiary healthcare center in North India on 120 patients with newly diagnosed epilepsy who presented within 3 months of diagnosis. A total of 120 age- and sex-matched individuals from the same community were chosen as controls. Epilepsy was defined according to ILAE 1993 definition. Serological testing for T. canis was carried out using commercially available ELISA kits. All the positive samples were subjected to Western blot testing for confirmation. Results: The prevalence of antibodies to T. canis was similar in cases (16/120; 13.3%) and controls (16/120; 13.3%). Among the various risk factors, history of pica was significantly associated with T. canis seropositivity, while lack of hand washing was significantly associated with higher risk of epilepsy. Conclusion: Our study could not find any association between exposure to T. canis and epilepsy.

Prevalence of Patent Foramen Ovale in North Indian Cryptogenic Young Strokes.

Background: : Strokes of the undetermined cause or cryptogenic strokes (CS) account for 30-40% of ischemic strokes. Paradoxical embolism secondary to patent foramen ovale (PFO) may be associated with CS. Transcranial Doppler (TCD) with bubble contrast is a noninvasive bedside tool for diagnosis of right-to-left shunt (RLS) with high sensitivity and specificity. Data on the prevalence of PFO in CS in India are lacking. We determined the prevalence of RLS likely secondary to PFO in cryptogenic young strokes of the north Indian population using TCD with bubble contrast. Patients and Methods: : In this hospital-based prospective cross-sectional study, TCD with bubble contrast was performed in 57 young (age 15 > 45 years) CS and 50 healthy controls for the detection of RLS. The risk of paradoxical embolism (RoPE) score was calculated from various variables such as age, presence of cortical stroke on neuroimaging, and absence of vascular risk factors. Results: : 57 young CS and 50 healthy controls were recruited. TCD with bubble contrast was positive in 31% cases vs 6% in controls (P = 0.001). All patients with TCD positive for RLS had superficial cortical infarcts (P = 0.03). The median RoPE score of our patients was 9 (range: 7-10). Conclusions: : There is a high prevalence of RLS likely secondary to PFO in cryptogenic young strokes in north India. TCD with bubble contrast is an excellent bedside tool for the detection of RLS.

Presence of allele CYP3A4*16 does not have any bearing on carbamazepine-induced adverse drug reactions in North Indian people with epilepsy.

OBJECTIVES: The objectives of this study were to determine the relationship between genetic polymorphisms in gene encodings for CYP3A4 and carbamazepine (CBZ)-induced dose-related side effects in North Indian people with epilepsy. PATIENTS AND METHODS: The current prospective study included 37 patients with CBZ-induced dose-related side effects and 102 patients who did not experience side effects while on CBZ. The genotyping for CYP3A4 allele (CYP3A4*16) was done using real-time polymerase chain reaction (RT-PCR) in Applied Biosystems 7500 RT-PCR System (USA). CBZ was administered in all patients at a dose varying from 15 to 20 mg/kg daily. RESULTS: Various demographic variables were comparable between the groups except that control of seizures was far better in controls. After testing, it was found that none of our patients had the presence of CYP3A4*16 allele. CONCLUSION: CYP3A4*16 allele is not represented significantly in North Indian people with CBZ-induced dose-related side effects.

Can Cheiromancy Predict Mean Survival or Fatality of a Patient with Amyotrophic Lateral Sclerosis?

Background The past three decades have seen palmistry as an interface to human health. There have been no previously organized attempts in utilizing this knowledge to predict the state of disease. Objective Due to unavailability of any biological marker for diagnosing amyotrophic lateral sclerosis (ALS) till date, we attempt to examine whether palmistry could be used for detecting the onset and survival of patient suffering from ALS. Methods Patients suffering from ALS attending the neurology outpatient department at Postgraduate Institute of Medical Education and Research, India were selected for study. Palm photographs were obtained from all patients including controls after their consent. Patients suffering from other comorbidities such as diabetes, hypertension, migraine, as well as smokers and nonsmokers were included in the study. Twenty-six ALS patients, 30 neurological controls, and 34 healthy age matched controls were recruited in the study. Retrospective analysis of the palm pictures based on blinding method was performed by academically qualified palmists. Results The results demonstrated the need for further studies in the subject even though the observations made were independent by both the palmists. Conclusion This study opens new vistas for cheiromancy to be further explored for analysis in larger samples.

Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study.

OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). PATIENTS AND METHODS: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). RESULTS: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. CONCLUSION: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.

Transcranial Doppler and Hematoma Expansion in Acute Spontaneous Primary Intracerebral Hemorrhage.

CONTEXT: The data on the role of Transcranial Doppler (TCD) in the management of acute primary intracerebral hemorrhage (ICH) is meager. AIMS: To study TCD variables associated with hematoma expansion in acute primary ICH. SETTINGS AND DESIGN: The study was carried out in the neurosciences department of Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh from July 2010 to September 2011 employing a prospective, double blinded non randomized study design. MATERIALS AND METHODS: Acute ICH patients within 24 h of symptom onset were recruited. Baseline neuroimaging study (Computerized tomography, CT scan of brain) was performed to assess the pure hematoma volume by AXBXC/2 method. Baseline TCD parameters were obtained from both the middle cerebral arteries (MCAs; affected and unaffected hemisphere): Peak Systolic velocity, End Diastolic velocity, Mean Flow velocity, Resistance Index, and Pulsatility Index. Follow up (24 h) assessment of hematoma volume and TCD were carried out. Each of the TCD variables were compared in hematoma expansion (>33% increase in hematoma volume on the follow-up CT) and non-expansion group. STATISTICAL ANALYSIS: On univariate analysis, the Student's t-test and contingency tables with the X2 test were used. A forward stepwise multivariate logistic regression analysis with hematoma expansion at 24 h as the dependent variable and ROC analysis was carried out, using SPSS software version 16 (Chicago, IL). P value < 0.05 was considered significant. RESULTS: Twenty-five patients completed the study. Ten patients (40%) had hematoma expansion. Multivariate analysis revealed unaffected hemisphere MCA Pulsatility Index ratio [unaffected hemisphere MCA Follow up Pulsatility Index/baseline Pulsatility Index] of > 1.055 as the lone correlate of hematoma expansion (sensitivity of 90% and specificity of 60%). CONCLUSION: Frequent assessment with TCD could aid in prediction of hematoma expansion by measuring unaffected hemisphere Pulsatility Index ratios.

Prevalence of Epilepsy and its Association with Exposure to Toxocara canis: A Community Based, Case-control Study from Rural Northern India.

OBJECTIVES: Many community-based and hospital-based studies across the world have yielded contradictory results regarding association of positive Toxocara canis serology and epilepsy. The present study was planned to analyze disease burden of epilepsy in rural community of North India and its association with exposure to T. canis in this part of the world. METHODS: A door-to-door screening survey was carried out in the rural community using a validated questionnaire for epilepsy by trained field workers, which was finally confirmed by trained neurologists. The risk factors for epilepsy and for predisposing infections were also enquired. The results were compared with an equal number of age- and sex-matched healthy controls enrolled from the same community. Serologic evaluation was carried out to detect antibodies against T. canis. RESULTS: A total of 41,973 persons from the rural community in 49 villages were enrolled in the study. Two hundred and eleven persons were confirmed to be suffering from active epilepsy, resulting in a crude prevalence of 5 per 1000 population. More than 50% of people with epilepsy were in the second or third decade of life. The prevalence of antibodies to T. canis was similar in people with epilepsy (13.7%; 29 of 211 individuals) and controls (9.95%; 21 of 211 individuals). Of the 151 persons with epilepsy, who underwent CT scan, 34 people (22.3%) had evidence of inflammatory granuloma, thereby confirming high incidence of this infestation in rural Northern India. SIGNIFICANCE: Our study does not support the association between epilepsy and exposure to T. canis in rural Northern Indian population.

Prevalence of the apolipoprotein E ε4 allele in amyloid ß positive subjects across the spectrum of Alzheimer's disease.

INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid ß (Aß) pathology. METHODS: We included 3451 Aß+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. RESULTS: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aß+ cognitively normal and Aß+ mild cognitive impairment (P < .05) but not in Aß+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. DISCUSSION: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aß pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

Reliability and validity of telephonic Barthel Index: an experience from multi-centric randomized control study.

Telephonic Barthel Index (BI) assessment is less time-consuming and more feasible than a face-to-face interview. The aim of this study was to test the validity as well as reliability of the BI administered by telephone in comparison with face-to-face assessment in a multi-centric study. The study was conducted during the course of a randomized controlled trial in which 120 patients with subacute strokes from five teaching hospitals from different parts of India were recruited. Central telephonic follow-up and face-to-face assessment of BI and modified Rankin Scale (mRS) at 3 and 6 months were done by trained and certified blinded researchers. Kappa or weighted kappa (wK) was estimated. Sensitivity and specificity at various cutoff levels of telephonic BI were calculated. Concurrent validity of the telephonic BI was assessed by correlating it with the mRS and National Institutes of Health Stroke Scales (NIHSS) at 3 and 6 months. We observed high sensitivity and specificity at various cutoff levels of BI. Moderate to substantial agreement was observed between the two methods at 6 months wK 0.72 (95% CI 0.70-0.77). Item-wise and center-wise kappa also reflected substantial agreement. The study shows that telephonic assessment of activities of daily living with the BI in moderate to severely disabled stroke patients is valid and reliable compared to face-to-face assessment. Our study shows that telephonic assessment requires smaller sample size compared to face-to-face assessment of BI.

Temporal Trends in Intravenous Thrombolysis in Acute Ischemic Stroke: Experience from a Tertiary Care Center in India.

BACKGROUND: Acute ischemic stroke (AIS) is a time-dependent treatable cause of morbidity and mortality. Despite the increasing stroke incidence in developing countries, parallel increasing stroke thrombolysis rates have not been documented. AIM: This study aims to determine trends in patient characteristics and rates of recombinant tissue plasminogen activator (rtPA) use in AIS patients in a tertiary care center in northern India. METHODS: All AIS patients presenting within 8 hours of symptoms onset from January 2011 to December 2015 were enrolled and analyzed. RESULTS: A total of 867 AIS patients presented within 8 hours of symptoms onset. Out of 593 eligible patients, 189 (31.87%) underwent intravenous thrombolysis (IVT) with rtPA within 4.5 hours of the window period. Patients (undergoing) IVT had onset-to-door times of 2 hours or less (23.81%), 2-3 hours (33.86%), and 3.0-4.5 hours (42.33%). IVT rates in 2 hours or less of symptom onset increased from 22% to 25% and IVT rates in 2-3 hours increased from 38.9% to 43.8%. Door-to-computerized tomographic time (median 27 versus 11 minutes, P = .0001) and door-to-needle time (median 83 versus 67 minutes, P = .011) improved, with a significant improvement of computerized tomography imaging time within 25 minutes of arrival (from 50% to 78.4%, P = .014). Post-IVT symptomatic hemorrhage was noted in 5 patients (2.65%). The median National Institutes of Health Stroke Scale score at presentation was 11, whereas a favorable modified Rankin Scale score (0-1) at 3 months was seen in 39.68%. CONCLUSIONS: Encouraging trends in IVT over the years may be indicative of increasing community awareness of stroke and improving quality of stroke care in developing countries such as India.

Transplantation of lineage-negative stem cells in pterygopalatine artery ligation induced retinal ischemia-reperfusion injury in mice.

Retinal ischemia is a condition associated with retinal degenerative diseases such as glaucoma, diabetic retinopathy, and other optic neuropathies, leading to visual impairment and blindness worldwide. Currently, there is no therapy available for ischemic retinopathies. Therefore, the aim of this study was to test a murine model of pterygopalatine artery ligation-induced retinal injury for transplantation of mouse bone marrow-derived lineage-negative (lin-ve) stem cells. The mouse external carotid artery and pterygopalatine artery were ligated for 3.5 h followed by reperfusion. The model was validated through fundus fluorescein angiography, laser Doppler and FITC dextran perfusion in whole-mounts. Lin-ve stem cells isolated from mouse bone marrow were transplanted through tail-vein, which showed migration to retina leading to decrease in GFAP expression. The neurotrophic factors such as BDNF and FGF2 showed enhanced expression in the retina. The functional analysis with electroretinogram did not demonstrate any significant changes before or after injury or stem cell transplantation. This study shows a neuroprotective potential in lin-ve stem cells in the retinal ischemia induced by pterygopalatine artery ligation and presents a practical model for validating therapies for ischemic disorders of the retina in future.

Evaluation of practice effect on neuropsychological measures among persons with and without HIV infection in northern India.

An evaluation of the effects of HIV infection on neurocognition over time is important for understanding disease progression. Changes in cognitive function can be evaluated longitudinally by using neuropsychological testing at repeated intervals. The assessment of change over time, however, is complicated by the potentially confounding influence of learning on repeated test administrations, often referred to as practice effect. In this study, we present data on testing of persons with or without HIV infection on a battery administered at study baseline and repeated 1 year later. Results suggest that practice effects may be diminished in persons with HIV infection compared to without it. This appears to be true even among those with relatively intact immune functioning as measured by CD4 count.

Alteration of Neurotrophic Factors After Transplantation of Bone Marrow Derived Lin-ve Stem Cell in NMDA-Induced Mouse Model of Retinal Degeneration.

Retinal ganglion cell layer (RGCs) is one of the important layers of retina, depleted in Glaucoma. Loss of RGC neurons is a major cellular mechanism involved in its pathogenesis resulting in severe vision loss. Stem cell therapy has emerged as a potential strategy to arrest the apoptotic loss of RGCs and also replace the degenerative cells in damaged retina. Here, we have investigated the incorporation and survival of mouse bone marrow derived Lin-ve stem cells in N-methyl-d-aspartate (NMDA)-induced mouse model of retinal degeneration. Two days after intravitreal injection of NMDA (100 mM) showed significant decrease in ganglion cell number and increase in TUNEL positive apoptotic cells in retinal layers. The injury was further characterized by immunohistochemical expression of Brn3b, GFAP, Bcl2, pCREB, CNTF, GDNF, and BDNF in retinal layers. Lin-ve cells (100,000 dose) were intravitreally transplanted after 2 days of injury and evaluated after 7, 14, and 21 days of transplantation. Transplanted cells were found to have migrated from intravitreal space and incorporated into injured retina at 7, 14, and 21 days post-transplantation. At 21 days Brn3b, CNTF, and BDNF expression was found to be upregulated whereas GDNF was downregulated when compared to respective injury time points. Molecular data showed decrease in the expression of Brn3b, BDNF, CNTF, and GDNF post transplantation when compared with injury groups. This study reveals that Lin-ve stem cells may exert neuroprotective effect in damaged retina mediated by participation of neurotrophic factors induced by stem cell transplantation at the site of injury. J. Cell. Biochem. 118: 1699-1711, 2017. © 2016 Wiley Periodicals, Inc.

Role of Plasma Clusterin in Alzheimer's Disease-A Pilot Study in a Tertiary Hospital in Northern India.

OBJECTIVE: To evaluate the role of plasma clusterin in Alzheimer's disease (AD). BACKGROUND: Plasma clusterin is a promising biomarker as various studies have shown it to be associated with AD. But other studies have shown that plasma clusterin levels were not related to Alzheimer's disease or presymptomatic AD. Hence the diagnostic value of plasma clusterin is still not conclusive. METHODS: Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD were used for establishing the diagnosis of MCI, AD or Vascular dementia. The CSF control group included patients who were having knee or hip surgery and plasma control group included the spouses of patients. RESULTS: Forty-six patients who gave consent for CSF examination and FDG PET brain were included in the study along with 19 control samples. Alzheimer's group had 34 patients and Vascular group had 12 patients. Both had a significantly lower value of clusterin than the control samples (p<0.01). The median plasma clusterin level was 84.38 µg/ml in control group, 57.98µg/ml in Alzheimer's group and 49.93µg/ml in the vascular group. Alzheimer and Vascular group did not differ in plasma clusterin levels. Moreover there was no correlation of plasma clusterin with AD severity. The sensitivity and specificity of plasma clusterin was low for any significance for clinical use. CONCLUSION: Our pilot study shows that plasma clusterin is lower in Alzheimer's disease with respect to control population. Plasma clusterin levels and severity of Alzheimer's disease had no significant correlation. There was no difference in plasma clusterin between Alzheimer's disease and Vascular Dementia. The sensitivity and specificity of plasma clusterin is low for any use in clinical practice. More studies are required to ascertain the utility of plasma clusterin as a biomarker in Alzheimer's disease.

Report: Stem cell applications in neurological practice, an expert group consensus appraisal.

INTRODUCTION: Neurologists in their clinical practice are faced with inquiries about the suitability of stem cell approaches by patients with a variety of acute and chronic (namely neurodegenerative) disorders. The challenge is to provide these patients with accurate information about the scope of stem cell use as well as at the same time, empowering patients with the capacity to make an autonomous decision regarding the use of stem cells. METHODS: The Indian Academy of Neurology commissioned an Expert Group Meeting to formulate an advisory to practicing neurologists to counsel patients seeking information and advice about stem cell approaches. RESULTS AND CONCLUSIONS: In the course of such counselling, it should be emphasized that the information provided by many lay websites might be unsubstantiated. Besides, standard recommendations for the stem cell research, in particular, the application of several layers of oversight should be strictly adhered in order to ensure safety and ethical use of stem cells in neurological disorders.

Effect of Vitamin D and calcium supplementation on ischaemic stroke outcome: a randomised controlled open-label trial.

BACKGROUND AND AIMS: Vitamin D deficiency is a common problem in stroke survivors. Observational studies have reported an association of low vitamin D levels with greater stroke severity, poststroke mortality and functional disability. Randomised clinical trials are lacking. We sought to assess the effect of calcium and vitamin D supplementation in ischaemic stroke survivors with vitamin D deficiency/insufficiency on disability/mortality outcomes. METHODS: In this randomised controlled open-label trial, 73 patients of acute ischaemic stroke were screened for serum 25 hydroxy Vitamin D (25(OH)D) levels. A total of 53 patients with baseline 25(OH)D <75 nmol/L were randomised into two arms. One received vitamin D and calcium supplementation along with usual care (n=25) and the other received usual care alone (n=28). Primary outcome was the proportion of patients achieving a good outcome [modified Rankin Scale score 0-2] at 6 months and all cause mortality at 6 months. RESULTS: The age (mean±SD) of participants was 60.4±11.3 years, 69.8% were males. The proportion of patients achieving good outcome was higher in the intervention arm (Adjusted OR 1.9, 95% CI 0.6-6.4; P=.31). The survival probability was greater in the intervention arm (83.8%, CI 62.4-93.6) as compared with the control arm (59.5%, CI 38.8-75.2; P=.049) with adjusted Hazard ratio (HR) of 0.26 (95% CI 0.08-0.9; P=.03). CONCLUSIONS: This is the first randomised controlled study assessing the effect of vitamin D and calcium supplementation on ischaemic stroke outcomes and points towards a potential benefit. Findings need to be validated by a larger trial.

Revisiting the dilution factor as vital parameter for sensitivity of ELISA assay in CSF and Plasma.

BACKGROUND: Enzyme Linked Immunosorbent Assay (ELISA) is very sensitive assay which provides quantitative data about expression of antigens. However, its utility is based on certain parameters which vary in the experimental situations. PURPOSE: We aimed to analyse the dilution factor as an important parameter for determining the sensitivity of ELISA in human samples. METHODS: Total of n = 57 ALS patients and n = 48 normal controls were selected for the study. All the patients were recruited from, Department for Neurology and Anaesthesia, PGIMER. Blood and CSF sample was collected and ELISA run was performed in both plasma and blood sample. ELISA of OPTN and TDP-43 was employed to check the respective protein concentration in CSF and Plasma. RESULTS: There was no significant difference which was reported for Plasma as well as CSF values of TDP-43 and OPTN. Dilution test prior to actual experiment made a significant impact in deciding the actual concentration of sample and led to overshootingbeyond range of reference protein. CONCLUSION: Negative results from our study highlights the significance of determining the dilution factor as an important parameter for conduct of ELISA.

Effect of human umbilical cord blood derived lineage negative stem cells transplanted in amyloid-ß induced cognitive impaired mice.

Alzheimer's disease (AD) is pathologically characterized by extracellular deposition of insoluble amyloid-ß (Aß) plaques and intracellular tangles made up of phosphorylated tau in brain. Several therapeutic approaches are being carried out in animal AD models for testing their safety and efficacy in altering disease pathology and behavioral deficits. Very few studies have examined the effect of human umbilical cord blood (hUCB) derived stem cells in degenerative disease models despite growing number of cord blood banks worldwide. Here we have examined the therapeutic efficacy of hUCB derived lineage negative (Lin -ve) stem cells in alleviating behavioral and neuropathological deficits in a mouse model of cognitive impairment induced by bilateral intrahippocampal injection of Aß-42. Lin -ve cells were transplanted at two doses (50,000 and 100,000) at the site of injury and examined at 10 and 60 days post transplantation for rescue of memory deficits. These cells were found to ameliorate cognitive impairment in 50,000-60 days and 100,000-10 days groups whereas, 50,000-10 days and 100,000-60 days groups could not exert any significant improvement. Further, mice showing spatial memory improvement were mediated by up-regulation of BDNF, CREB and also by concomitant down regulation of Fas-L in their brain. The transplanted cells were found in the host tissue and survived up to 60 days without expressing markers of neuronal differentiation or reducing Aß burden in mouse brain. We suggest that these undifferentiated cells could exert neuroprotective effects either through inhibiting apoptosis and/or trophic effects in the brain.