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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.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.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.Our study could not find any association between exposure to T. canis and epilepsy.

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.: In this hospital-based prospective cross-sectional study, TCD with bubble contrast was performed in 57 young (age 1545 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.: 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).: 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.

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.

The predictors of poor outcome in tuberculous meningitis (TBM) remain to be delineated. We determined role of various clinical, radiological and cerebrospinal fluid (CSF) parameters in prediction of outcome in TBM.Current study was a prospective observational study including 209 patients of TBM. All patients underwent detailed evaluation including Gadolinium enhanced Magnetic resonance imaging (GdMRI) of brain as well as tests to detect evidence of tuberculosis elsewhere in body. They also underwent GdMRI at three and nine month follow up. All patients received treatment as per standard guidelines.Mean age was 30.4±13.8years. 139 (66.5%) patients had definite TBM while 70 (34.5%) had highly probable TBM. 53 (25.4%) patients died. On univariate analysis, longer duration of illness, altered sensorium, stage III TBM, hydrocephalus and exudates correlated with poor outcome. On multivariate analysis presence of hydrocephalus (p=0.003; OR=3.2; 95% CI=1.5-6.7) and stage III TBM (p0.0001; OR=8.7; 95% CI=3.7-20.2) correlated with higher risk of mortality. In addition, there was significant positive association between presence of hydrocephalus (p=0.05; OR=2.2; 95% CI=0.97-5.1), stage III TBM (p0.0001; OR=28; 95% CI=4.9-158) and presence of altered sensorium (p=0.05; OR=22; 95% CI=0.99-4.8) with either death or survival with severe disability.It is possible to prognosticate TBM using a combination of clinical and radiological. The duration of illness (65.9±92days) before diagnosis of TBM continues to be unacceptably long and this stresses on need to educate primary care physicians about TBM. Future studies where intensity and duration of treatment is guided by these cues may help in sorting out some of the most difficult questions in TBM, namely duration of antitubercular therapy as well as dose and duration of steroid therapy etc.

SummaryBackground 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

Introduction: Apolipoprotein E (APOE) epsilon 4 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 beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P

Accurate identification of neurocognitive impairment associated with HIV infection (and other CNS-involved conditions) is dependent upon utilization of appropriate normative neuropsychological test performance data from healthy individuals with a similar background, culture, and characteristics of the target individual or group to be tested. In India, regional differences in language, culture, and availability of resources can significantly affect performance on neuropsychological testing. This study developed age- and education-adjusted normative data for commonly used neuropsychological test scores for use in northern India.

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.

Background and Purpose— Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. Methods— This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of 18 fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days. Results— Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P =0.92), modified Rankin scale shift analysis ( P =0.53) or score >3 (47.5% versus 49.2%; P =0.85), NIHSS score (6.3 versus 7.0; P =0.53), change in infarct volume (−11.1 versus −7.36; P =0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of 18 fluorodeoxyglucose uptake. Conclusions— With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome. Clinical Trial Registration— URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov . Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.

Smoking has been suggested as one of the risk factor for amyotrophic lateral sclerosis (ALS) development. In order to investigate whether adverse effects of cigarette smoke in ALS have any association with increase in oxidative stress, disease severity, lipid hydroperoxides (LPO) and superoxide dismutase-1 (SOD1) levels were measured in biofluids of smoker and never smoker ALS patients and clinically correlated. Serum and CSF from sporadic ALS patients (n=50) diagnosed with El Escorial criteria were collected in the study. Serum (n=50) and CSF (n=42) were also collected from normal healthy controls. The LPO levels were estimated using commercially available kits. Enzyme-linked immunosorbent assays (ELISAs) were used to quantitate SOD1. Their levels were further analyzed among smoker and never smoker subjects. Significantly elevated LPO in sera and CSF of ALS patients were observed (p0.05). There was considerably increased LPO in sera and CSF of smoker ALS subjects matched with disease severity as compared to never smoker ALS (p0.05). ALS group did not show any alteration in SOD1 when compared to controls (p0.05). In addition, no change has been observed in SOD1 levels in ALS subjects who smoke (p0.05). Increased LPO and unaltered SOD1 in ALS patients may suggest the neuro-pathological association of LPO with ALS disease independent of SOD1. With current findings, it may be proposed that LPO levels might constitute as probable biomarker for smoker ALS patients, however, it cannot be concluded without larger gender matched studies. Additional investigations are needed to determine whether LPO upregulation is primary or secondary to motor neuron degeneration in ALS.

Context: C-reactive protein (CRP) is an acute phase reactant, widely used as a biomarker for various infectious and inflammatory conditions. Guillain-Barrι syndrome (GBS) is an acute, autoimmune, polyradiculoneuropathy, triggered by infectious agents such as Campylobacter jejuni. GBS is generally precipitated 1-3 weeks following C. jejuni infection which suggests a humoral immunopathogenic mechanism. Aims: Basal CRP levels were estimated in sera of patients with GBS and compared with adequate controls. Settings & Design: The study population was divided into 4 groups: (i) GBS group included 45 newly diagnosed GBS patients; (ii) Neurological control (NC) group comprised of 59 patients with non-paralytic neurological symptoms/disorders; (iii) Non-neurological controls (NNC) comprised of 43 patients having no neurological symptoms and (iv) Healthy controls (HC) comprised of 101 healthy subjects. Materials and Methods: CRP was evaluated using slide latex agglutination test (LAT) and enzyme linked immunosorbent assay (ELISA). Statistical Analysis: Statistical analysis was done by the Chi-square test. Results: CRP by LAT was positive in 24.4% GBS group, 34% NC group and 44% NNC group. The range of titer in CRP positive samples in the three patient groups (GBS, NC, NNC) was at concentration of 0.6 mg/dl to 19.2 mg/dl. Similar results were also obtained by ELISA in the patient groups. None of the HC subjects was positive for detectable levels of CRP. High basal level of CRP was detected in patients with GBS. Conclusion: Autoimmune conditions like GBS can stimulate the production of a high level of inflammation resulting in an increase in the CRP production.

The present study was intended to explore the dynamics of viral and host factors determining the outcome of Japanese encephalitis viral infection. 223 patients with acute encephalitic syndrome, 126 with febrile illness suspected of JE and 79 apparently healthy individuals as control were enrolled. Elevated levels of TNF-α and IL-6 in encephalitis patients and IFN-γ in febrile JE patients without encephalitis were observed. A cutoff value of > 55 pg/ml of TNF-α and > 370 pg/ml of IL-6 in CSF was found as poor prognostic marker. Th1 shift (IFN-γ/IL-4: > 1) was observed in encephalitis patients.

HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm3) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population.

The pigmented ciliary epithelium (PCE) of mammalian eye harbors resident population of stem cells that lie in apposition with endothelial cells which release vascular endothelial growth factor (VEGF) that may influence the fate and function of these stem cells in ways that remain unclear. We examined the role of VEGF in proliferation of PCE stem cells and expression of Notch, Jagged, N-Cadherin and β-Catenin which are known to maintain proliferation state of neural stem cells. We cultured human PCE cells obtained from 12-20 weeks old fetal eyes. The neurospheres were analyzed for the proliferation capacity of PCE stem cells in presence of VEGF on 3,6 and 9 day. Real time PCR was used to quantitate the mRNA expression of above mentioned genes on PCE derived neurospheres on 3,6 and 9 day. We found increased number of neurospheres when PCE stem cells were stimulated with VEGF along with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) than EGF and bFGF. BrdU immunostaining was done to analyze the proliferation of CE cells and presence of neural and retinal progenitor markers such as Nestin and Pax6 were also investigated. An increased Notch and Jagged mRNA was observed on 6(th) day in VEGF, EGF and bFGF treated PCE cells as compared to 0,3 and 9 day. A similar pattern was noticed with N-cadherin and β-catenin mRNA levels. These findings may clarify the role of VEGF on PCE stem cell proliferation with possible involvement of Notch, Jagged, N-cadherin and β-Catenin. The data may suggest importance of harvesting 6(th) day neurospheres for transplantation purposes in preclinical investigations pertaining to retinal degenerative diseases, however, additional studies are needed to substantiate the findings.

Aim.The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1) in patients of age-related macular degeneration (AMD) and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD.Methods.115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve.Results.The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic (χ2=10.516,df=8,P=0.231) indicates the appropriateness of logistic regression model to predict AMD.Conclusion.Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827,P=.0001) with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model.

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.

Background Though animal studies have suggested a role for proinflammatory cytokines in pathogenesis their exact role in pathogenesis of human meningeal tuberculosis continues to be controversial with different studies yielding contradictory results. Aim and objectives To study the levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF) of patients with tubercular meningitis (TBM) and to determine whether these correlate with disease severity. Patients and methods Present study included 146 patients with TBM (90- Definite TBM; 56- Probable TBM), diagnosed according to criteria laid by Ahuja et al. which were modified to include CSF nucleic acid based tests. Serum ( n = 146) and CSF ( n = 140) levels of various proinflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α and IFNγ) were compared between TBM patients and healthy volunteers ( n = 99). These levels were correlated with various clinical, radiological and CSF parameters of TBM patients. Results Proinflammatory cytokines include cytokines which promote systemic inflammation. In current study, the serum and CSF levels of various cytokines (IL-2, IL-4, IL-6, IL-1β, IFN-γ and TNF-α) were significantly elevated in TBM patients compared to controls. A significant correlation was found between a) Higher stage of TBM and various cytokines (except for serum IL-6 and CSF IFN-γ); b) High CSF TNF-α, IL-4 and IL-1β with severity of hydrocephalus; c) High CSF IL1β and IFN-γ with presence of exudates on MRI; d) Serum and CSF levels of all cytokines with poor outcome as determined by death or as defined by S and E ADL (Schwab and England activities of daily living) score or by GOS (Glasgow outcome scale) (except for interferon gamma); and e) Serum and CSF IL-4 and IL1β with presence of infarcts on MRI brain. Conclusion Proinflammatory cytokines play an important role in the pathogenesis of TBM and contribute significantly towards severity of disease.

Age-related macular degeneration (AMD) is a leading cause of blindness and is the third leading cause of blindness. Genetic factors are known to influence an individual's risk for developing AMD. Linkage has earlier been shown to the vascular endothelial growth factor 2 (VEGF2) gene and AMD. To examine the role of VEGFR2 in north Indian population, we conducted a case control study. Total 176 subjects were enrolled in a case-control genetic study. Real-Time PCR was used to analyze the SNPs (rs1531289 and rs2305948) of VEGFR-2 gene. ELISA was conducted to determine the levels of VEGFR2. A non-parametric Mann-Whitney-U test was applied for comparison of the ELISA levels and pearson's Chi-square test was applied to study the association of polymorphism between various groups. The single SNP (rs1531289) AG genotype was significantly associated with AMD (OR= 2.13, 95%CI= 1.011-4.489, P=0.047). VEGFR2 levels were found to be increased significantly in AMD patients as compared to normal controls. We also found significant increase in the levels of wet AMD as compared to dry AMD. This study demonstrates higher levels of VEGFR2 and frequency of AG (rs1531289) genotype in AMD patient population, suggesting the role of VEGFR-2 in pathogenesis of AMD.

This report describes the clinical, radiological and autopsy findings of a young male suffering from acute, monophasic demyelinating disease presenting with acute onset of altered sensorium and a short past history of progressive multiple neurological deficits. The radiological findings revealed acute infarcts in the territory of anterior cerebral artery. The antemortem diagnosis centred on an infective (tubercular) aetiology leading to demyelination based on presence of tubercle bacilli in bronchoalveolar lavage (BAL) fluid. The autopsy revealed multiple subacute and acute plaques showing demyelination, giant astrocytes, numerous macrophages and little perivascular inflammation, thereby confirming the diagnosis of Marburg's type of multiple sclerosis. Marburg's type is a fulminant demyelinating disorder characterised by a severe, rapidly evolving clinical course. Death occurs due to brain stem involvement or severe widespread cerebral lesions.

Alzheimer's disease (AD) is the most common form of dementia, and is characterized by the degeneration of neurons and their synapses, and a higher number of amyloid plaques and neurofibrillary tangles (NFTs) compared with that found in non-demented individuals. Amyloid-β-peptides (Aβ) are major components of amyloid plaques in AD brain whereas NFTs are composed of Tau and associated with ubiquitin. The aim of the present study was to analyze the levels of Aβ42, hTau (total Tau) and ubiquitin in CSF of North Indian population. CSF Aβ42, Tau and ubiquitin were measured in CSF of AD patients as well as controls using ELISA assays. Here we report low Aβ42 levels in AD patients (324.24 ± 76.38 pg/ml) as compared to those in non-AD (NAD) (668.34 ± 43.13 pg/ml), neurological controls (NCs) (727.28 ± 46.49 pg/ml) and healthy controls (HCs) (976.47 ± 124.46 pg/ml). In contrast, hTau and ubiquitin levels were significantly high (568.65 ± 48.89 pg/ml and 36.82 ± 4.34 ng/ml, respectively) in AD patients compared to those in NAD, NC and HC. The hTau levels were 267.37 ± 36.64 pg/ml, 167.34 ± 44.27 pg/ml and 107.62 ± 24.27 pg/ml in NAD, NC and HC, respectively. Similarly, ubiquitin levels were 23.57 ± 2.32 ng/ml, 19.76 ± 3.64 ng/ml and 13.24 ± 4.56 ng/ml in NAD, NC and HC, respectively. In conclusion, low Aβ42 and high Tau–ubiquitin levels were found in North Indian AD patients.

SUMMARYJapanese encephalitis (JE) is an important arboviral infection of public health concern. There is a significant variation in mortality (10–30%) in JE viral infection. Epidemics of JE have become regular features in the northen states of India. The recent resurgence of the A226V mutation leading to a widespread Chikungunya epidemic motivated the investigators to search for any such mutational occurrence with Japanese encephalitis virus (JEV) isolated from this region. This study looked for mutation of clinical strains at amino-acid positions 176, 177, 227, 244, 264 and 279. A novel mutation S227T was detected corresponding to the loop region of domain II, E gene of JEV in comparison to Indian and other isolates from different parts of the world. Genotype III was found to be circulating in this geographical area. Further studies are required to ascertain its role in JE pathogenesis and vector competency.

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) within the Indian subcontinent continues to spread. Although the primary clade of HIV in India differs from that of most Western countries, recent evidence suggests that the Indian clade (Clade C) also impacts neurocognitive functioning. India also has extremely high illiteracy rates that may confound detection of neurocognitive impairment, since many assessments to detect such impairment are heavily influenced by formal schooling. Among those with HIV/AIDS who have had limited educational opportunities and who are in the early stage of infection, the confounding effects of education on tests for neurocognitive impairment may be particularly salient. We therefore tested influence of HIV serostatus and education on a commonly used tool to screen for cognitive impairment, the International HIV Dementia Scale (IHDS), among Indian men and women in the catchment area of the Post Graduate Institute of Medical Education and Research (PGIMER) located in Chandigarh, India. Adjusted analyses showed that from a sample of 295 HIV-positive and HIV-negative individuals, only education was significantly associated with performance on the IHDS. HIV-negative and HIV-positive individuals, who were in the early stages of infection, performed similarly. Further development of this test to account for the effects of education on cut-off scores used to indicate possible dementia are needed, particularly for use in resource-limited settings such as India where low levels of education are widespread.

Among several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra.In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, the authors screened 120,000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed.The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.

Event-related-potentials (especially P300) and cognitive functioning as potential endophenotypes have not been studied in opioid dependence. We compared auditory P300 and cognitive functions in opioid-dependent men, their brothers and normal controls in an exploratory study with a view to find shared genetic factors in the development of opioid dependence. Twenty abstinent opioid-dependent males, their brothers and twenty matched controls were administered Wisconsin card sorting test (WCST), digit span test, trail making test-B, and auditory event-related potentials (P300) from an oddball task were recorded. The opioid dependent group performed the worst, the brothers group was intermediate, and the control group performed the best on tests of WCST, digit span and trail making test-B. The opioid dependent group had the smallest amplitudes and longest latencies of P300, and was followed by the brothers group who had an intermediate position and the control group who had the largest amplitudes and the shortest latencies. P300 and executive neurocognitive functions can be considered endophenotypes for the genetic study of vulnerability to opioid dependence. These are reflective of executive dysfunction and disrupted behavioral inhibition and the intermediate position of brothers suggests a common genetic substrate as a component of the etiology.

The course and outcome of epilepsy following central nervous system (CNS) infections has been poorly characterized. Likewise, the impact of antimicrobial treatment as well as other preventative and therapeutic interventions on the development of epilepsy following neurological infectious disorders has been insufficiently studied. The CNS infections that can cause epilepsy may be either acute or chronic-recurrent. For most acute infections, for example, viral encephalitis and bacterial meningitis, the effect of specific antimicrobial treatment on the development of epilepsy cannot be studied in a controlled manner due to logistic and ethical reasons. In the specific case of neurocysticercosis (NCC), the risk of seizures in the short term is reduced following either anthelminthic or corticosteroid treatment or both. The effect of anthelminthic treatment on seizure outcome in the long term has not been studied. Finally, treatment with antiepileptic drugs (AEDs) needs to be optimally defined in the case of epilepsy associated with neurological infectious disorders.

Present study was to assess lipid peroxidation and antioxidant enzymes in the blood of the Parkinson's disease (PD) patients in the Indian population. It may be useful to develop peripheral markers, for the diagnosis and prognosis of Parkinson's disease during lifetime. Malondialdehyde content was increased in patients with PD (2 fold), with respect to the activity of superoxide-dismutase (p

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

We profiled 141 consecutive patients of writer's cramp (WC). Simple WC (n=108) had a mean (SD) disease duration of 3.65 (2.7) years and a severity score of 2.8 (0.91) by Burke-Fahn-Marden (BFM) scale (handwriting score: 0-4 ), whereas complex WC (n=33) had a disease duration of 5.8 (2.81) years and severity score of 3.6 (0.52). Compared with focal WC, generalized WC cases had longer disease duration, severer disability, and were older. Mirror dystonia was seen in 65 patients (46.1%). Co-existent Meige's syndrome (n=4) and cervical dystonia (n=6) were seen. Some patients had abnormal posturing of the neck (n=5) and of the oromandibular region (n=3) only while writing. Those receiving botulinum toxin fared significantly better than those on oral therapy, at 1 month post treatment.

Summary: Purpose: To assess the association of long-term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy. Methods: Clinical parameters, ovarian morphology, and serum reproductive hormone concentrations were evaluated in 30 clinically normal and eumenorrheic reproductive age women with generalized epilepsy who were newly initiated on valproate. Longitudinal evaluations were done in 25 of these women after 1 year, and in some of them after 2 and 3 years of therapy. Results: Of the 25 women who completed 1 year follow-up, we observed clinically relevant weight gain in 40%, hirsutism in 20%, menstrual abnormalities in 24%, polycystic ovaries (PCO) in 16%, polycystic ovarian syndrome (PCOS) in 20%, and a significant increase in mean serum testosterone (p = 0.046). A significant positive correlation existed between weight gain and the development of menstrual abnormalities (r = 0.66, p < 0.0001), hirsutism (r = 0.53, p = 0.006) and PCO (r = 0.51, p = 0.012). No correlation existed between weight change and serum reproductive hormonal changes. Yearly follow-up for next 2 years in some of these women revealed persistence of menstrual abnormalities, hirsutism and PCO, a significant linear increase in mean body weight, body mass index, and serum testosterone concentrations, and an increase in serum LH levels from second year onwards. Limitations: Limitations include small sample size and a high dropout rate on follow-up. Conclusions: Long-term valproate therapy in Indian women with generalized epilepsy is associated with development of hirsutism, significant weight gain, stable or progressive alterations in reproductive hormonal function, and ultimately a higher occurrence of PCOS. Key Words: Epilepsy—Menstrual disorders—Polycystic ovarian syndrome—Valproate—Druginduced reproductive abnormalities.

The purpose of this study was to compare cerebral CT venography with MR venography and determine the reliability of CT venography in the diagnosis of cerebral sinovenous thrombosis.Fifty patients who were clinically suspected of having cerebral sinovenous thrombosis, irrespective of age and sex, underwent cerebral CT venography and MR venography. Projection venograms were displayed using maximum-intensity-projection images for both CT venography and MR venography. The CT venograms were also displayed using the integral algorithm, which depicts the average intensity value of the first five voxels deep in relation to the model surface that is nearest the viewer, allowing direct visualization of the thrombus in the sinuses. All CT venograms and MR venograms were independently evaluated by experienced neuroradiologists.Of these 50 patients, 30 patients were diagnosed as having cerebral sinovenous thrombosis on both CT venography and MR venography. The total numbers of sinuses involved were 81 and 77 (CT venography and MR venography). When MR venography was used as the gold standard, CT venography was found to have both a sensitivity and a specificity of 75-100%, depending on the sinus and vein involved.CT venography is as accurate as MR venography for diagnosing cerebral sinovenous thrombosis.

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers. The objective of this study was to explore the effect of a single dose of piperine in patients with uncontrolled epilepsy on the steady-state pharmacokinetics of phenytoin. Two groups of 10 patients each receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected. Twelve hours after the night dose, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study day, piperine 20 mg was administered along with phenytoin and samples were collected similarly. The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test. Piperine increased significantly the mean plasma concentration of phenytoin at most of the time points in both dose groups. There was a significant increase in AUC((0-12h)) (p < 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and t(max) were not significant. The results showed that piperine enhanced the bioavailability of phenytoin significantly, possibly by increasing the absorption.

Importance: Allgrove syndrome is a rare autosomal recessive disorder characterised by achalasia, alacrima, adrenal insufficiency, autonomic dysfunction and amyotrophy. The syndrome has been described in childhood and adult presentation, as in our case, is very rare. There is a considerable delay in diagnosis due to lack of awareness about the syndrome. Observations: We report a single case of a 36year old man who was initially diagnosed and treated for achalasia cardia in our institute 14years before. After 8years he presented again with weakness and wasting predominantly distally. He had tongue fasciculations, brisk reflexes and extensor plantar. After supportive electrophysiological studies he was diagnosed as Amyotrophic lateral sclerosis. After 5years he presented with generalised fatigue without any significant worsening of his neurological status. On reevaluation he had alacrimia, autonomic dysfunction and mild ACTH resistance. Conclusions and relevance: Allgrove syndrome may be an underdiagnosed cause of multisystem neurological disease due to the heterogeneous clinical presentation as well as for ignorance of clinician about the syndrome. Based on our case, we also believe that there does exist a subgroup of patients who follow a less severe and chronic course. Recognition of syndrome allows for treatment of autonomic dysfunction, adrenal insufficiency and dysphagia.

Brucellosis remains an important public health problem especially in the underdeveloped countries as well as the Middle East. It may be a "master mimic" leading on to grave diagnostic dilemmas. Chronic neurobrucellosis is seldom associated with signs and symptoms of toxaemia due to multi organ dysfunction. We report the case of a 23-year-old man who presented with fever of 8 weeks associated with ascending weakness of lower limbs and sensorineural type of hearing loss of 6 weeks duration with prominent systemic findings in the form of hepatosplenomegaly and significant loss of weight. He responded well to treatment with combination antimicrobials with clinicoradiological resolution after 6 months of therapy. Even though a rare complication of brucellosis, neurobrucellosis causes significant morbidity if not promptly recognised and treated. Favourable outcomes can be achieved in neurobrucellosis with appropriate protracted polymicrobial antibiotic therapy as was illustrated in our patient.

Background and Aims: Neuropathy in association with chronic liver disease, including cirrhosis, is recognized; however, there are differences in the incidence and type of neuropathy reported. The causal relationship of liver disease to neuropathy has been questioned. This study was designed to evaluate the incidence and character of peripheral neuropathy in patients with liver cirrhosis. The effect of alcohol consumption, severity of liver disease and encephalopathy on the incidence and severity of neuropathy were also studied. Methods: Patients having an identifiable cause of peripheral neuropathy, except alcohol, were excluded from the study. Patients with evidence of vitamin B12 deficiency or diabetes were also excluded from the study. In this study, 33 patients with liver cirrhosis were evaluated clinically and electrophysiologically to detect any evidence of peripheral neuropathy. Nerve conduction studies were performed in the upper and lower limbs using surface electrodes. These patients also underwent a detailed clinical examination. Results: Clinical signs of peripheral neuropathy were found in seven (21%) patients. Nerve conduction studies were abnormal in 24 (73%) patients. The pattern of involvement was predominantly of an axonal sensory motor polyneuropathy. Neuropathy was found both in patients with alcohol-related and non-alcohol-related cirrhosis. The presence of encephalopathy did not have a significant bearing on the incidence and severity of neuropathy. The neuropathy was also not significantly related to the severity of liver disease. Conclusions: The present study reveals that a significant number of patients with liver cirrhosis show evidence of peripheral neuropathy, which is present regardless of the etiology of cirrhosis, and is subclinical in a majority of these patients. The cause of neuropathy was probably the liver disease itself, as the incidence and severity of neuropathy in the alcohol-related cirrhosis, although higher, was not significantly different from the neuropathy in patients with non-alcohol-related cirrhosis.

Alzheimer's disease (AD) is pathologically characterized by extracellular deposition of insoluble amyloid-β (Aβ) 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 Aβ-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 Aβ 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.

Neurolymphomatosis, a rare extranodal lymphoma, may involve the cranial nerves, peripheral nerves, spinal nerve roots, or nerve plexus. F-FDG PET/CT however shows increased FDG uptake in the nerves but is not specific for malignancy. We report a patient with neurolymphomatosis who underwent F-FDG PET/CT and F-fluorothymidine PET/CT where both the scans showed increased tracer uptake in the right sciatic nerve, proven later as neurolymphomatosis on nerve biopsy. Furthermore, the F-FDG avid mediastinal lymph nodes did not show F-fluorothymidine avidity, suggesting an inflammatory etiology.

Human umbilical cord blood (hUCB) is a primitive source of stem cells and is being banked worldwide for the purpose of future clinical use. Lineage negative (Lin-ve) stem cells are one of the primitive populations in hUCB which are capable of self-renewal and differentiation into multiple lineages. These cells have not been adequately investigated for their stem cell characteristics. We have analyzed the immunophenotypic expression of CD45, CD34 and CD117 markers on three different cell populations in hUCB viz., mononucleated cells (MNCs), Lineage positive (Lin+ve) and Lin-ve cells. The CD34 and CD117 expression was found to be 60 fold more in the Lin-ve population as compared to MNCs and Lin+ve cells. This expression was further enhanced in CD45+Lin-ve fraction. The CD34+ and CD117+ Lin-ve cells showed 99% positivity for CD45. Our data suggest that CD34+ CD117+ Lin-ve cells are reasonably enriched stem cell population in hUCB which can be clinically used for transplantation and other therapeutic purposes.

It has been postulated that there is a link between age related degenerative diseases and cancer. The TNF-related apoptosis-inducing ligand (TRAIL) has been shown to selectively kill tumor cells by binding to pro-apoptotic and anti-apoptotic receptors. Our aim was to study the levels of anti-apoptotic receptor (DcR1) in age related macular degeneration (AMD) and controls. AMD patients (115) were classified into two groups: Dry and Wet AMD. Wet AMDs were further classified into occult, predominant classic and minimal classic. 61 healthy individuals were recruited as normal controls. After normalization with total protein, DcR1 levels were analyzed by ELISA. Mann Whitney U-statistic was used for analysis of DcR1 ELISA results. We have observed DcR1 levels in serum sample which were significantly lower in AMD patients as compared to controls (p = 0.001). On the other hand, we did not find difference in DcR1 levels between wet and dry AMD. The present study defines the plausible role of DcR1 in AMD pathology signifying a new therapeutic target for AMD.

To evaluate intravenous immunoglobulin (IVIG) therapy in children with very severe Guilain-Barre syndrome (GBS) with reference to the need for respiratory support, ICU stay and long-term outcome, we studied 33 children with very severe GBS and quadriparesis and/or respiratory muscle weakness admitted to the Pediatric Intensive Care Unit (PICU) of PGIMER, Chandigarh. Cases (n = 22, IVIG group) were enrolled prospectively, and controls (n = 11), similar to cases in age and severity of illness, retrospectively. All children received similar supportive and respiratory care. In addition, cases were given IVIG (Sandoglobulin, Sandoz) 0.4 g/kg bodyweight per day for 5 days. The mean age, duration of symptoms prior to admission and severity of illness in the two groups were similar. In the IVIG group, onset of recovery of muscle power was significantly earlier (day 14.8 (6.8) of illness vs day 20.9 (8.6), p < 0.05) and the length of PICU stay significantly shorter (20.5 (13.0) days vs 50.5 (33.3) days, p < 0.01). Sixteen (72.7%) children in the IVIG group had improved by at least one functional grade after 1 month and 15 (68%) were walking independently after 3 months compared with two (18%) and four (36%) controls, respectively (p < 0.05). The number of children who needed endotracheal intubation and mechanical ventilation and the duration of mechanical ventilation was significantly less in the IVIG-treated group. We conclude that in very severe GBS in children IVIG therapy improves outcome to a remarkable extent, reduces the need for intubation and mechanical ventilation, shortens the length of stay in ICU, and promotes ambulation sooner.

Neurocysticercosis commonly presents with seizures, raised intracranial tension and dementia. The unusual location of the cysts may result in uncommon manifestations mimicking a host of neurological disorders. Ten patients with neurocysticercosis with rare clinical presentations have been described in this series. These include dorsal midbrain syndrome, isolated bilateral ptosis, papillitis, cerebral hemorrhage, painful cervical radiculopathy, progressive swelling of arm, paraplegia due to intramedullary cyst, third ventricular cyst, dystonia and nominal aphasia masquerading as transient ischaemic attacks. The clinical details and possible mechanisms for these rare presentations are discussed.

Importance Post-encephalitic parkinsonism (PEP) is believed to be caused by a viral illness which causes degeneration of the nerve cells in the substantia nigra, resulting in clinical parkinsonism. Although common during the period of the First World War, the diagnosis of PEP is rarely entertained today. Observation We report an adolescent boy of PEP, who was bedridden due to severe parkinsonism following the encephalitis attack. After relevant imaging and investigation, he was treated with levodopa which made him independent from a year long total dependent condition. Relevance and conclusion Encephalitis lethargica or PEP is one of the rare parkinsonian syndromes which may be amenable to treatment. Proper diagnosis and treatment may help the patient become ambulatory from the dreaded lethargic condition.

Age-related macular degeneration (AMD) is a devastating disease that results in irreversible central vision loss. TLRs signaling pathway has been found to play an important role in AMD pathogenesis as evidenced by several studies. The objective of the study was to determine the single nucleotide polymorphism (SNP) changes in TLR3 in North Indian AMD patients. We recruited 176 patients comprising 115 AMD patients and 61 controls. Real time PCR was used to evaluate the SNP changes at rs3775291 locus. Pearson's χ(2) test was used evaluate association between various groups. No significant association in genotype and allele frequency was found in AMD patients as compared to control. The results suggest that AMD pathology in North Indian AMD patients is not affected by TLR3 signaling but it could be influenced by other genetic or environmental factors unique to North India.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Although, many putative biomarkers are reported for AD, only a few have been validated in the clinical setting. Ubiquitin levels increase in cerebrospinal fluid (CSF) of patients with AD, but its diagnostic value is not clear. In this present study we evaluate the performance of ubiquitin as a diagnostic marker and deduce a statistical association with disease pathology in AD. Ubiquitin levels were estimated in subjects with AD, other forms of dementias, neurological disorders and healthy age matched population. The levels of ubiquitin were significantly higher in subjects with AD when compared with other groups (p

A 45-year-old male presented with progressive dysarthria and dysphagia for 1 year. Examination revealed bilateral facial (Figure 1A) and neck flexor weakness, with depressed gag and tongue fasciculations. Fasciculations, wasting and brisk reflexes were noted in upper limbs. Facial reflexes were not brisk, and pseudobulbar affect was not present. Bell’s …

The etiology of Alzheimer’s disease (AD) is multifactorial involving both genetic and environmental factors. Apolipoprotein E ( ApoE) gene plays a pivotal role in risk and age of onset of AD. Although it is broadly accepted that ApoE genotype is linked to the pathogenesis of AD, there are still controversial results regarding the association of ApoE levels in cerebrospinal fluid (CSF) with the occurrence of AD. Some studies have shown a positive correlation between CSF ApoE levels and AD, whereas others showed no link. In this study, we measured ApoE levels to assess the usefulness of CSF ApoE as a diagnostic marker of AD by comparing the levels in 3 patient groups and in control participants. No significant difference was observed in CSF ApoE concentrations between the patients with AD and the controls. So, it appears that CSF ApoE measurement does not offer any diagnostic advantage for AD.

A 24-year-old lady, recently married, was brought to our hospital by her husband when he incidentally noticed a tuft of hair in her lower back which he considered as a bad omen after consulting a rural Indian faith healer. On physical examination, she had a tuft of hair in her lower back which was present since birth and progressively increasing in size (figure 1A). Rest of the physical examination was normal with no neurological deficits …

407 patients (248 men, 159 women) of epilepsy attending the neurology clinic were evaluated to find out the profile of epilepsy, cost-effectiveness of various investigations, therapeutic regimens and efficacy of referring physicians in a developing country. At the time of onset of seizures 67.2% of patients were in the second and third decade. Generalised tonic clonic seizures were the commonest seizure type seen. Specific aetiology was established in 20.8% cases only. Neurocysticercosis was the commonest cause observed. The main source of referral (50.1%) was general practitioners. Referral diagnosis was incomplete in 52.8% of the cases. Investigations did not alter the diagnosis in 62.5% cases. The EEG was useful in the management of 15.1% cases of epilepsy. The skull x-ray and chest x-ray were abnormal in 1.7% and 2% cases respectively. CT scan revealed abnormality in 39.4% cases. Most of the patients were treated with monotherapy. Phenytoin, phenobarbitone and carbamazepine were the common drug used. Out of 246 cases who were started on anticonvulsant therapy prior to referral, the choice of drug was wrong in 78 (31.7%) cases and dose was inappropriate in 121 (49.2%) cases. It was concluded that most important factor for cost effective management of epilepsy is proper clinical evaluation and education of general physicians in this direction.