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Reason for withdrawal from publication At April 2015, this protocol has been withdrawn due to substantial delays in preparing the full review.

Reason for withdrawal from publication At April 2015, this protocol has been withdrawn due to substantial delays in preparing the full review.

Background: Hoarding is frequently conceptualized as a symptom of obsessive-compulsive disorder (OCD), but recent evidence indicates that, in most cases, hoarding may be better conceptualized as a distinct disorder that can coexist with OCD. Most of the research on hoarding is from the Western countries. This study aimed to provide data on the prevalence and correlates of clinically significant hoarding in a large sample of patients with OCD from the Indian subcontinent. Methods: We examined 200 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition OCD for clinically significant hoarding using the Saving Inventory–Revised, followed by a clinical interview. Results: Twenty patients (10%) had clinically significant hoarding. In all cases, hoarding did not appear to be related or secondary to other OCD symptoms. None of the cases consulted for their hoarding problems. Compared with nonhoarders, hoarders hailed exclusively from an urban background and had a significantly higher frequency of certain obsessions and compulsions, bipolar disorder, generalized anxiety disorder, cluster C personality disorders, and a higher number of lifetime suicidal attempts. They also had a more severe OCD along with poorer global functioning and somewhat poorer insight into obsessive-compulsive symptoms. Conclusions: The results suggest that clinically significant hoarding is relatively prevalent in Indian patients with OCD and that it appears to be largely unrelated to the OCD phenotype. However, the presence of comorbid hoarding is associated with more severe OCD, high comorbidity, more suicidal attempts, and a lower level of functioning. The results contribute to the current nosologic debate around hoarding disorder and provide a unique transcultural perspective.

Background and purpose To study the abnormalities of deep grey matter (GM) structures in patients with progressive supranuclear palsy (PSP) using MR volumetry and shape analysis techniques. Methods Twenty-eight patients with PSP and 25 matched controls (all were right handed) were evaluated using standard clinical scales. MRI was performed on a 3 tesla MRI scanner using standard protocol which included T1-3D Turbo Field-Echo images with 1-mm slice thickness. The volumes of GM and white matter, total brain and the deep subcortical GM structures, including hippocampus, amygdala, caudate, putamen, globus pallidus and thalamus were extracted using a fully automated tool. Univariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences. Shape analysis was also performed using automated software with age, sex and total brain volume as covariates of no interest in the statistical design at P

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization [WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM . We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 [83.3%] secondary, and 1/42 [2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P < . 001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P < .001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM.

Objective ApoE4 is a ‘risk factor’ for cognitive disorders like Alzheimer's dementia, and Late Onset Depression (LOD) is a forerunner of dementia. There is thus a need to study the association between ApoE4 allele and LOD. Method The study assessed the frequency of ApoE4 allele in 31 cases of LOD above the age of 50 years and 31 matched controls. The subjects were assessed on various clinical parameters towards diagnosis. Results There was a significant association between the ApoE4 allele and LOD in comparison to controls (Odd's ratio = 4.7, Confidence Interval = 1.12 to 19.79, P = 0.035). ApoE4 allele had no association with the age of onset of depression, cognitive functions and severity of LOD. Conclusion Individuals with LOD have a significantly higher frequency of the ApoE4 allele. In other words, elderly in India with an ApoE4 allele have 4.7 times more risk of developing depression in old age. Within LOD group there is no difference between those with and without ApoE4 accordingly in age of onset of depression, cognitive functions and severity of LOD.

Background: The occurrence of epilepsy is higher among elderly patients. The clinical manifestations of seizures, causes of epilepsy, and choice of anti-epileptic drugs (AEDs) are different in elderly people with epilepsy compared to the young. Aim: To evaluate the imaging (CT/MRI) observations in elderly patients manifesting with new-onset seizures. Materials and Methods: Two hundred and one elderly patients with new onset seizures, >60 years (age: 68.0 ± 7.5 years; M:F = 1.8:1) from Jan' 07 to Jan' 09, were prospectively recruited. Observations of cranial CT scan (n = 201) and MR imaging (n = 43) were analyzed. Results: The type of seizures included: Simple partial (42%), generalized tonic-clonic (30.3%), and complex partial (27.4%). The pattern of epilepsy syndromes were acute symptomatic (42.3%), remote symptomatic (18.4%), cryptogenic (37.8%), and idiopathic (1.5%). Seizures were controlled with monotherapy in 85%. The CT scan (n = 201) revealed cerebral atrophy (139), mild (79), moderate (43), and severe (18); focal lesions (98), infarcts (45), hemorrhages (18), granuloma (16), tumor (15) and gliosis (4), and hemispheric atrophy (1), white matter changes (75) and diffuse edema (21). An MRI (n = 43) showed variable degree of cerebral atrophy (31); white matter changes (20); focal cerebral lesions (24); - infarct (7); intracranial hemorrhage (6); granuloma (5); tumor (6); gliosis (1); hemispheric atrophy (1); and prominent Virchow-Robin spaces (7); and UBOs (12). Patients with focal lesions in neuroimaging more often had partial seizures, symptomatic epilepsy, past stroke, focal deficit, absence of diffuse atrophy, focal EEG slowing, abnormal CSF, seizure recurrence at follow-up (P < 0.05). Conclusions: Brain imaging observations in elderly patients with new-onset seizures revealed underlying symptomatic nature, hence the etiology and thereby assisted in deciding the specific therapy.

PURPOSE The authors evaluated the spectra of EEG observations in elderly patients with new onset seizures and correlated it with clinical, laboratory, and imaging findings. METHODOLOGY This prospective study involved 201 elderly individuals (age: 68.0 ± 7.5 years; male:female = 1.8:1) who manifested with new onset seizures. Data regarding clinical, laboratory, routine EEG (n = 201), and imaging (computerized tomography = 201; MRI = 43) observations were noted. Details of EEG findings were analyzed and correlated with other parameters. RESULTS Visual analysis of scalp EEG in 124 patients (61.7%) was abnormal, and the abnormalities included asymmetric background activity (3%) and diffuse slowing (32.8%) and focal slowing (7%) of the background activity. Dominant α-activity was more common in remote symptomatic group. Higher frequency of alpha waves was observed in patients with cryptogenic epilepsy compared with those with acute symptomatic epilepsy. Diffuse slowing and excess of β-fast activity were observed more often in acute symptomatic group. Epileptiform activities were evident in one third of patients and were noted in the temporal (38.8%) and frontotemporal (23.9%) regions. In univariate analysis of patients with and without EEG abnormalities, female gender, cluster attacks/status epilepticus, acute symptomatic epilepsy, longer duration of postictal state, lower Glasgow coma scale score, lower Mini-Mental State Examination score, focal deficits, diffuse edema (computerized tomography), and focal lesions (MRI) were significantly associated with abnormal EEG. Presence of epileptiform activity predicted the use of polytherapy (P = 0.004, odds ratio = 3.3). The significant factors associated with an abnormal EEG (multivariate) were female gender (P = 0.03, odds ratio = 2.32), lower Glasgow coma scale score (P = 0.03, odds ratio = 0.70), and lower frequency of α-waves (P = 0.04, odds ratio = 0.56). CONCLUSIONS Scalp EEG was abnormal in approximately two thirds of elderly patients, with the presence of epileptiform activities in one third of patients. Abnormal EEG significantly correlated with lower Glasgow coma scale score, suggesting its role in prognostication.

Purpose: Epilepsy following solitary cerebral cysticercosis(SCC)ispossiblycausedbyperilesionalgliosis,bestvisual-ized on magnetization transfer imaging (MTI).This studyaims to describe development of gliosis around SCC byprospective serial MTI and to correlate this gliosis withlong-termseizureoutcome.Methods: We randomized 123 patients with SCC andnew-onset seizures to treatment with albendazole plusantiepileptics (treatment), or antiepileptics only (con-trol), and performed magnetic resonance imaging (MRI)scans at 0, 3, 6, 12, and 24 months. Prospective follow-up data regarding seizure outcome up to 5 years laterwere collected. MRI studies were analyzed for lesioncharacteristics and perilesional magnetization transfer(MT) hyperintensity.Key Findings: Clinical and radiologic data of 77 patientswere analyzed. Demographic and seizure characteristicswere similar in treatment and control groups. Clinicaldata were available up to 64 months after enrollment. At12 months, 89.5% patients were seizure-free. MTI is moresensitive than routine imaging for detection of perilesion-algliosis.Albendazoletreatmentdidnotaffectimagingorclinical outcome, including development of gliosis. Inde-pendent of duration of follow-up, gliosis was associatedwith more seizures, and with seizure recurrence at12 months; duration of seizures and antiepileptic therapywas longer. Gliosis was not dependent on seizure type orstageofdegenerationatenrollmentorpersistence/calcifi-cationofthelesion.Significance: Perilesional gliosis around SCC helps prog-nosticate seizure outcome. Poorer outcome in patientswith persistent lesions is likely to be related to mecha-nisms other than gliosis. The lack of effect of albendazoleonseizureoutcomemaybeduetoitsinabilitytodecreaseformationofgliosis.KEYWORDS: Solitarycerebralcysticercallesion,Neuro-cysticercosis, Perilesional gliosis, Magnetic resonanceimaging,Magnetizationtransferimaging.

Introduction – Essential tremor (ET) is increasingly recognized to have several non-motor manifestations. The aim of this study was to determine the prevalence of non-motor manifestations in ET and its impact on the quality of life (QOL). Methods – This was a cross-sectional case–control questionnaire-based study. The subjects were 50 patients with ET and 50 matched healthy controls. All subjects were assessed by Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Parkinson Fatigue Scale, Brief Pain Inventory, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale. In addition, QOL in Essential Tremor questionnaire was administered to patients with ET. Results – Patients with ET, when compared with controls, had significantly higher prevalence and higher mean scores of sleep disturbances (46% vs 8%, P

Glioblastoma is the most common and malignant form of primary astrocytoma. Upon investigation of the insulin-like growth factor (IGF) pathway, we found the IGF2BP3/IMP3 transcript and protein to be up-regulated in GBMs but not in lower grade astrocytomas (p < 0.0001). IMP3 is an RNA binding protein known to bind to the 5′-untranslated region of IGF-2 mRNA, thereby activating its translation. Overexpression- and knockdown-based studies establish a role for IMP3 in promoting proliferation, anchorage-independent growth, invasion, and chemoresistance. IMP3 overexpressing B16F10 cells also showed increased tumor growth, angiogenesis, and metastasis, resulting in poor survival in a mouse model. Additionally, the infiltrating front, perivascular, and subpial regions in a majority of the GBMs stained positive for IMP3. Furthermore, two different murine glioma models were used to substantiate the above findings. In agreement with the translation activation functions of IMP3, we also found increased IGF-2 protein in the GBM tumor samples without a corresponding increase in its transcript levels. Also, in vitro IMP3 overexpression/knockdown modulated the IGF-2 protein levels without altering its transcript levels. Additionally, IGF-2 neutralization and supplementation studies established that the proproliferative effects of IMP3 were indeed mediated through IGF-2. Concordantly, PI3K and MAPK, the downstream effectors of IGF-2, are activated by IMP3 and are found to be essential for IMP3-induced cell proliferation. Thus, we have identified IMP3 as a GBM-specific proproliferative and proinvasive marker acting through IGF-2 resulting in the activation of oncogenic PI3K and MAPK pathways.

Tumors from a prospective cohort of adult patients with newly diagnosed glioblastoma (n=73), treated uniformly with radiochemotherapy, were examined for 10q23/PTEN deletion by fluorescence in situ hybridization (FISH). Statistical methods were employed to evaluate the degree of association between 10q23/PTEN deletion status and patient age. Survival analysis was performed using Kaplan-Meier log-rank test and multivariable Cox models to assess the prognostic value of 10q23/PTEN deletion. Interestingly, 10q23/PTEN homozygous deletion was frequent in patients >45 years of age (P=0.034) and the median age of patients harboring PTEN homozygous deletions was significantly higher than those with the retained status (P=0.019). 10q23/PTEN homozygous deletion was associated with shorter survival in the entire cohort as well in patients >45 years (P 45 years.

This study aimed to detect perilesional gliosis around solitary cerebral cysticerci (SCC) by magnetisation transfer imaging (MTI), to compare its incidence between patients administered and not administered albendazole. We prospectively randomised patients with SCC and new-onset seizures to treatment with albendazole plus antiepileptics (treatment), or antiepileptics only (control), and performed MRI scans at zero, three, six, 12 and 24 months. Data were analysed for lesion characteristics, perilesional MT hyperintensity and MT ratios, calculated from the lesion and perilesional area. Eighty-one patients' data were analysed (M-41, F-40; ages 6–52 years). About 13% scolices appeared hyperintense on MTI at baseline. T1-isointense cyst walls and perilesional area showed MT hyperintensity in 30 – 41.4%; this proportion increased over time. Persistently visible SCC and stage of degeneration at enrolment did not predict development of MT hyperintensity. MT ratios (range - 98.75 to 49.79) increased over time and differed significantly from normal parenchyma. No difference in MT ratios was noted between treatment and control groups. Qualitative perilesional MT hyperintensity was more often seen in control group. Perilesional gliosis is present in >20% of SCC at six months, and continues to appear on later scans. Gliosis is independent of lesion persistence and stage of degeneration. Pre- and post-contrast MT imaging is equally useful in detection of gliosis. MT ratios from the lesion and perilesional parenchyma are significantly lower than from normal brain tissue at all stages of degeneration, but increase as degeneration occurs and healing progresses. Albendazole therapy does not affect the formation of perilesional gliosis

This study aimed to explore subjective well-being (SWB) in an urban Indian sample. Adults (n = 1099) belonging to two wards in the city of Bangalore in South India, responded to a study-specific questionnaire. This paper is based on data generated as part of an ongoing larger study looking at correlates of SWB. Almost equal number of men and women responded to the study and their age ranged from 20 to 81 years (mean age 37 years). Majority of them were married, Hindus, from middle socio-economic status, had studied above pre-university level and more than half were earning. The mean scores on positive affect (40.9), negative affect (27.6) and life satisfaction (24) suggested above average levels of SWB. Higher age, being married, having higher education, higher income and working in a full time job seemed to improve life satisfaction and decrease negative affect. Religion was also significantly associated with negative affect. Step-wise regression analysis suggested that only education and income were important predictors of positive affect, while negative affect was better predicted by age, income, work status and religion. Life satisfaction was predicted by income, age and education. The important correlates of SWB for men and women were somewhat different. Overall, sociodemographic variables have minimal effect on SWB in urban India and research needs to explore other predictors of SWB.

Background: Insulin-like growth factor (IGF)–binding protein (IGFBP) isoforms have been implicated in the pathogenesis of human neoplasms including glioma. In view of this, we evaluated the expression of IGFBP isoforms (IGFBP-2, -3, and -5) during malignant progression of astrocytoma and their prognostic significance in glioblastoma. Methods: The expression of IGFBP isoforms was analyzed in diffusely infiltrating astrocytomas by real-time quantitative PCR (n = 203) and immunohistochemistry (n = 256). Statistical methods were used to assess their grade-specific expression pattern and mRNA-protein intercorrelation. Survival analyses were done on a uniformly treated, prospective cohort of adult patients with newly diagnosed glioblastoma (n = 136) by using Cox regression models. Results: The mean transcript levels of IGFBP-2 and -3 were significantly higher in glioblastomas (GBM) relative to anaplastic astrocytoma (AA), diffuse astrocytoma (DA), and controls whereas IGFBP-5 mRNA was higher in GBM relative to AA and controls (P < 0.05). By immunohistochemistry, the mean labeling index of all isoforms was significantly higher in GBM compared with AA, DA, and control (P < 0.05). A strong positive correlation was observed between their respective mRNA and protein expressions (P < 0.01). Multivariate analysis revealed IGFBP-3 expression (hazard ratio, 1.021; P = 0.030) and patient age (hazard ratio, 1.027; P = 0.007) to be associated with shorter survival in glioblastoma. Conclusions: This study shows the associations of IGFBP-2, -3, and -5 expression with increasing grades of malignancy in astrocytomas. IGFBP-3 is identified as a novel prognostic glioblastoma biomarker. The strong correlation between their mRNA and protein expression patterns suggests their role in the pathogenesis of these tumors. Impact: IGFBP isoforms have emerged as biomarkers with diagnostic and prognostic utility in astrocytomas. Cancer Epidemiol Biomarkers Prev; 19(6); 1399–408. ©2010 AACR.

Objective Quantitative assessment of balance in spinocerebellar ataxia type 1 (SCA1). Background Evaluation of balance in degenerative ataxias is often clinical and subject to bias. Quantification of balance is crucial for evaluating the efficacy of therapeutic and rehabilitative interventions. Methods The subjects were 20 patients (males: 14, females: 6) with genetically positive SCA1 and 20 age and gender matched healthy subjects. Ataxia was rated using the International Cooperative Ataxia Rating Scale (ICARS). Balance was assessed by dynamic posturography (Biodex, USA) which included: (a) ability to control balance in all directions (overall balance index, OBI), front to back (anterior–posterior index, API) and side-to-side (medio–lateral index, MLI); and (b) the limits of stability (LOS) in all directions. Balance index was considered abnormal if the actual value exceeded the predictive value. Results Impaired balance was found in 80% of patients (all indices in 35%, OBI + API in 25%, only OBI in 15%, and OBI + MLI in 5%). Compared to controls, SCA1 patients had significantly higher balance indices and lower LOS scores. Unlike in controls, the mean value of API was significantly higher than MLI in SCA1. LOS was found to the best predictor of balance abnormality. In patients, all balance indices had significant positive correlations with ICARS, static score of ICARS, body weight, severity and duration of illness, but not with the CAG repeat length. Conclusions Patients with SCA1 had global impairment of balance, with greater instability in anterior–posterior than medio–lateral directions. Apart from severity and duration of illness, body weight was detriment to maintenance of balance in SCA1. This information may be useful in planning balance rehabilitation in SCA.

Objective The objective of this study was to determine the correlation, if any, between the clinical rate of disease progression at presentation with the CAG repeat size in patients with spinocerebellar ataxias 1, 2 and 3 (SCA1, SCA2 and SCA3). Methods The severity of ataxia was measured using the International Cooperative Ataxia Rating Scale (IARS) in 31 patients of SCA1 (mean ± SD age: 35.1 ± 12.6 years; age at onset (AAO): 29.9 ± 10.7 years), 25 patients of SCA2 (age: 34.9 ± 14.9 years; AAO: 29.7 ± 14.0 years) and 15 patients of SCA3 (age: 40.9 ± 8.6 years; AAO: 36.9 ± 10.1). The rate of disease progression at presentation was measured by the age adjusted IARS (IARS/Age). For each SCA, correlations of AAO, raw scores of IARS, age adjusted IARS and duration adjusted IARS (IARS/Duration) with the CAG repeat size were determined. Results The number of CAG repeats of the abnormal allele ranged from 42 to 67 in SCA1, 38 to 66 in SCA2, and 69 to 79 in SCA3. In all the three types of SCAs, there were significant inverse correlations of AAO with CAG repeat size (SCA1: r = − 0.9, p

We performed a detailed evaluation of pulmonary function in 53 patients with idiopathic Parkinson's disease (PD) who did not have symptoms of pulmonary or cardiac dysfunction. There was a significant pulmonary dysfunction of restrictive type which partially responded to levodopa. Compared to men, women were more severely affected. Pulmonary function assessment is recommended in PD, irrespective of severity of disease.

ObjectiveSignificant differences in clinical profile and comorbidity patterns have been observed between “juvenile-onset” and “adult-onset” obsessive-compulsive disorder (OCD). There is little systematic research on onset of OCD after the fourth decade. The current study aims to compare the demographic, clinical, and comorbidity patterns of patients with “juvenile-onset” (MethodEight hundred two consecutive patients who consulted a specialty OCD clinic at a tertiary care hospital in India were evaluated with the Mini International Neuropsychiatric Interview, the Yale–Brown Obsessive-Compulsive Scale, and the Clinical Global Impression scale.Results37.4%, 57.4%, and 5.2% of patients had juvenile-, adult-, and late-onset OCD, respectively. Late-onset OCD was associated with female gender (χ2=42, p2=20.4, p2=18.16, p2=26.68, p2=19.41; p2=44.28; pConclusionLate-onset OCD is characterized by female gender, lesser familial loading for OCD, and presence of precipitating factors, suggesting that it may have a distinct pathophysiology compared to juvenile- and adult-onset OCD. Systematic research is required to understand the family-genetic, neuropsychological, and neurobiological correlates of late-onset OCD.

Our objective was to characterize the MR imaging features in a large and distinct series of distal bimelic amyotrophy (DBMA) from India. We utilized a retrospective and prospective study on 26 cases. Results demonstrated that upper limb distal muscle wasting and weakness was predominantly symmetrical in onset. Mean age at onset was 20.9 ± 7.0 years, mean duration 83.0 ± 102.6 months. MRI carried out in 22 patients with flexion studies showed forward displacement of posterior dura in 19 (86.4%). Crescent shaped epidural enhancement on contrast was seen in 20/24 cases (83.3%), and bilateral T2W hyperintensities of cord in17 (65.4%) - symmetrical in15 cases. Maximum hyperintensity was noted at C5-C6, C6-C7 levels. Cord atrophy was noted in 24 (92.3%) cases (most affected: C5-C6, C6-C7) - symmetrical atrophy in 21cases. Cervical spine straightening occurred in six (23.1%) cases and reversal of lordosis in 15 (57.7%). In conclusion, this study confirms that DBMA is phenotypically distinct but pathophysiologically the same as brachial monomelic amyotrophy (BMMA) on MR imaging. Typical MRI features were seen in all. It is important to differentiate this disorder from ALS, which could present at a younger age as often seen among Indians. The clinical and MR imaging features are highly suggestive that DBMA, as with BMMA/Hirayama disease, occurs due to dynamic alterations at the cervical spine level.

Madras motor neuron disease (MMND) and Madras motor neuron disease variant (MMNDV) have an unique geographic distribution with concentration of majority of cases in the southern states of India. They have the characteristic features of onset in young, weakness and wasting of the limbs, multiple cranial nerve palsies particularly involving the 7th, 9th to 12th and sensorineural hearing impairment. In addition, all patients with MMNDV have bilateral optic atrophy. During the past 32 years, a total of 104 patients were diagnosed to have MMND and among these 25 patients with the familial form were further evaluated. In this report, we describe the clinical features of these 25 patients diagnosed to have familial Madras motor neuron disease (FMMND) or familial Madras motor neuron disease variant (FMMNDV), belonging to 15 families hailing from southern India. There were 10 patients diagnosed to have FMMND and 15 with FMMNDV. There were 14 males and 11 females with mean age at onset of 13.0 ± 6.2 years and mean duration of illness of 73.6 ± 74.0 months. Notably, the occurrence of MMNDV in the familial group (15 of 25 patients) was significantly more as compared to occurrence in the group with sporadic MMND (SMMND) [12 of 79 patients] ( p = 0.0002).

Yoga is an ancient Indian science and way of life that has been described in the traditional texts as a systematic method of achieving the highest possible functional harmony between body and mind. Yogic practices are claimed to enhance the quality of sleep. Electrophysiological correlates associated with the higher states of consciousness have been reported in long-term practitioners of transcendental meditation during deep sleep states. The present study was carried out to assess sleep architecture in Sudarshan Kriya Yoga (SKY) and Vipassana meditators. This was to ascertain the differences, if any, in sleep architecture following yogic practices. Whole night polysomnographic recordings were carried out in 78 healthy male subjects belonging to control and yoga groups. The groups studied were aged between 20 and 30-years-old (younger) and 31 to 55-years-old (middle-aged). The sleep architecture was comparable among the younger control and yoga groups. While slow wave sleep (non-REM (rapid eye movement) S3 and S4) had reduced to 3.7 percent in the middle-aged control group, participants of the middle-aged yoga groups (both SKY and Vipassana) showed no such decline in slow wave sleep states, which was experienced by 11.76 and 12.76 percent, respectively, of the SKY and Vipassana groups. However, Vipassana practitioners showed a significant enhancement (P < 0.001) in their REM sleep state from that of the age-matched control subjects and also from their SKY counterparts. Yoga practices help to retain slow wave sleep and enhance the REM sleep state in the middle age; they appear to retain a younger biological age as far as sleep is concerned. Overall, the study demonstrates the possible beneficial role of yoga in sleep-wakefulness behavior.

Previous studies have suggested that schizophrenic psychopathology segregates into three orthogonal dimensions, viz., psychosis, negative and disorganization. Most of these reports were based on studies on medicated patients with varying degrees of chronicity. The present study aimed at exploring the dimensionality of psychopathology rated on the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in a sample of 43 neuroleptic-naïve patients with recent-onset schizophrenia/schizophreniform disorder. Principal Components Analysis (PCA) of SANS and SAPS global ratings, excluding inattention but including inappropriate affect as a separate global rating, revealed that the symptoms segregated into three dimensions, viz., negative (affective flattening, alogia, avolition anhedonia and inappropriate affect), psychosis (delusions and hallucinations) and disorganization (positive formal thought disorder and bizarre behavior). Cumulatively these three dimensions explained 74.07% of the variance. The results suggest that the three dimensions of schizophrenic psychopathology are valid even in neuroleptic-naïve, recent-onset patients with schizophrenia/schizophreniform disorder. PCA of the SANS and SAPS individual items revealed similar findings, but psychotic symptoms loaded under two components, thus yielding a four-factor solution; however, this observation needs to be confirmed in a larger sample of neuroleptic-naïve schizophrenic patients.

We describe the evolution of quantitative T2 relaxometry values on serial MRI in patients with a solitary cerebral cysticercal lesion (SCCL), and determine whether albendazole therapy affects T2 relaxation (T2R) values. Patients with new-onset seizures and MRI-confirmed SCCL were randomized to treatment with albendazole and antiepileptics (“treatment group”) or antiepileptics only (“controls”). Serial MRI including T2 relaxometry was performed at baseline, three, six, 12, and 24 months. Of 123 patients recruited, 81 had more than three MRI scans (treatment group: 37; controls: 44; 58 patients had five scans). The lesion wall at baseline showed a mean T2R value of 152.3 ms, centre 474.9 and perilesional parenchyma 338.5 ms. These were significantly higher than those from normal parenchyma (114 ms). Over time, most sharply in the initial three months, T2R values fell but even at 24 months, they remained above those from normal parenchyma. A slight increase in T2R values from the lesion centre at six months was thought to represent the initiation of gliosis. In the treatment group, T2R values approached normal at 24 months, while controls had persistently higher T2R values. The decline in T2R values at six months was more prominent in the treatment group. T2R values at baseline and at three months differed significantly depending on the stage of the lesion, being higher in stage 2 SCCL. T2R values from SCCL declined over 24 months, being significantly higher in earlier stages of degeneration. A mild increase after six months may be due to the initiation of gliosis. T2R values appear to decline faster in patients who receive albendazole.

Our objective was to study the clinical characteristics and natural history of monomelic amyotrophy (MMA). We used a retrospective study of 279 patients diagnosed to have either upper (Hirayama disease) or lower limb MMA. Results showed that brachial MMA (BMMA) occurred in 224 patients (male:female, 9:1). Mean age of onset was 19.5 ± 4.18 years. Progression occurred over less than five years in the majority (95.9%) of patients. Duration at the last follow-up was: up to five years in 61.4%, 5-10 in 21.3%, 10-15 in 7.2%,15 years in 10.1%. MRI showed asymmetrical lower cervical cord atrophy in 44.6% of patients. Crural MMA (CMMA) occurred in 55 patients (male:female, 13:1). Mean age of onset was 21.38 ± 5.3 years. Similar to BMMA, most cases (65.5%) had onset between 15 and 25 years of age. Total duration of illness at the last follow-up was up to five years in 52.7%, 10 and beyond in 47.3%. In conclusion, a large cohort of patients with monomelic amyotrophy seen over 35 years (1976-2010) is described. Study data support the clinical findings and its natural history with long term follow-up, and the findings emphasize that monomelic amyotrophy is a 'benign' condition with a self-limiting course.

Background: Insulin-like growth factor binding proteins (IGFBPs) are known to be differentially expressed in brain tumours. The role of some IGFBPs in malignant CNS tumours, except glioblastoma, is unknown. We evaluated the protein expression of 3 IGFBP isoforms (IGFBP-2, -3, -5) in medulloblastoma and correlated them with histological subtypes and clinical parameters. Methods: The expression of IGFBP-2, -3 and -5 was analysed in 67 samples of medulloblastoma by immunohistochemistry and correlated with histological subtypes and patient prognosis. Results: IGFBP-3 expression was seen in 37.3% of cases and IGFBP-5 expression in 80.6% of cases. IGFBP-2 expression was totally absent in medulloblastoma. The extent of IGFBP-3 expression was higher in anaplastic when compared to classical and desmoplastic subtypes (p < 0.05). IGFBP-5 expression was significantly higher in classical and anaplastic subtypes when compared to desmoplastic medulloblastoma (p < 0.05). No influence of IGFBPs on survival was noted. Conclusions: This is the first study to report expression of 3 cancer-related biomarkers - IGFBP-2, -3, -5 in medulloblastoma. Significantly higher extents of expression of IGFBP-3 in large cell variant and IGFBP-5 in classical and anaplastic subtypes suggest a plausible role of these molecules in specific molecular pathways of medulloblastoma.

Nitric oxide (NO) plays a significant role in the inflammatory process and has been implicated in several autoimmune disorders. This study was carried out prospectively to estimate the levels of nitrite and citrulline in the serum and urine, as surrogate markers of NO production, among patients with systemic lupus erythematosus (SLE). Forty-seven patients and 44 age- and sex-matched, healthy volunteers were studied. Nitrite and citrulline were measured in serum and urine by spectrophotometry.Median serum nitrite and citrulline levels and urine citrulline levels were higher among patients as compared with controls (p0.05). Patients with skin involvement stood out and had higher median serum and urine citrulline levels (p0.05). Disease activity correlated with steroid dosage, serum nitrite levels, and serum and urine citrulline levels (p0.05). Steroid dosage correlated with serum citrulline level (p0.05). Serum and urine citrulline levels correlated with each other (p0.01). In the subset of 13 individuals with renal involvement, serum and urine citrulline levels correlated with each other (p0.01) as did urine nitrite and citrulline levels (p0.05).NO production is increased among patients with SLE, and this increase correlates with disease activity and dosage of steroids used. The addition of a urine test to measure NO production as a marker of disease activity using simple spectrophotometry can be a valuable adjunct to other tests, can obviate the need for drawing a blood sample for this purpose, and can be repeated as often as necessary.

OBJECTIVE To study the long-term rate and predictors of remission in adults with obsessive-compulsive disorder (OCD), using meta-analysis. DATA SOURCES The MEDLINE database was searched to May 2013 using the search terms obsessive-compulsive disorder, prospective, outcome study, clinical course, remission, prognosis, follow-up, and long-term and limits for language (English), species (humans), and age (adults). This was supplemented by manual bibliographic cross-referencing. STUDY SELECTION English-language studies from peer-reviewed journals on adults with DSM-III-R, DSM-IV, DSM-IV-TR, ICD-9, or ICD-10 diagnosis of OCD followed up for ≥ 1 year and treated with serotonin reuptake inhibitors and/or cognitive-behavioral therapy that reported rate of remission (Yale-Brown Obsessive Compulsive Scale [YBOCS] score < 16 at longest follow-up) were included. DATA EXTRACTION Data were gathered as numbers/means/percentages/categories on sample size, study design, follow-up duration, age at assessment, illness duration, age at illness onset, gender, marital status, inpatient/outpatient status, family history, baseline YBOCS score, comorbidities, and remission. RESULTS Seventeen studies (pooled N = 1,265) fit the selection criteria and were used for the meta-analysis. The pooled sample had a mean follow-up duration 4.91 years and was predominantly male and outpatient and had onset of illness in the second decade, illness duration more than 10 years, and moderate-to-severe OCD. Pooled remission rate was 53% (95% CI, 42%-65%). Prospective studies showed higher pooled remission rate than retrospective studies (55% [95% CI, 45%-65%] vs 50% [95% CI, 27%-73%], P < .001). Indian studies showed higher pooled remission rate than others (71% [95% CI, 59%-83%] vs 48% [95% CI, 37%-59%], P < .001). Age at onset (t = -7.08, P = .019), illness duration (t = -8.13, P = .015), baseline YBOCS score (t = -6.81,P = .021), and male gender (t = -5.92, P = .027) had significant negative association with remission on meta-regression. CONCLUSION A high long-term remission rate found in this meta-analysis is contrary to generally held beliefs about poor outcome of individuals with OCD. Multicenter, prospective, long-term studies should systematically examine course and outcome in larger samples, emphasizing symptomatic and functional recovery.

OBJECTIVE There are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency. METHODS Nondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented. RESULTS Thirty-seven patients with 25-OHD deficiency participated in the study. The baseline and post-vitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (-0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (-20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (-4.88 ± 10.65 mg/dL); and homeostasis model assessment-2-percent β-cell function C-peptide secretion (HOMA-2-%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, -3.751; P

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization [WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM. We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 [83.3%] secondary, and 1/42 [2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P. 001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P.001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM.

The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (P = 0.043; HR = 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.

We investigated age-related differences in neuropsychological performance in 400 Indian school children (5–15 years of age). Functions of motor speed, attention, executive functions, visuospatial functions, comprehension, learning, and memory were examined. Growth curve analysis was performed. Different growth models fitted different cognitive functions. Neuropsychological task performance improved slowly between 5 and 7 years, moderately between 8 and 12 years and slowly between 13 and 15 years of age. The overall growth patterns of neuropsychological functions in Indian children have been discussed with the findings reported on American children. The present work describes non-linear, heterogeneous, and protracted age trends of neuropsychological functions in Indian children and adolescents.

Evidence of efficacy of cognitive behavior therapy (CBT) in obsessive-compulsive disorder (OCD) non-responsive to multiple trials of serotonin reuptake inhibitors (SRI) is limited. We examined the efficacy of CBT in 31 adult patients with DSM-IV OCD who were non-responders to at least two SRI trials. They received 20-25 sessions of CBT over 3-month duration. The primary outcome measure was "response" to treatment [Clinical Global Impressions-Improvement score 1 or 2 and ≥35% reduction in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) severity score]. Patients were assessed at baseline, post-treatment and at 3-, 6- and 12-month follow-up. Twenty-six (84%) patients completed treatment and number of responders at post-treatment, 3-, 6- and 12-month follow-up were 23 (74%), 20 (64%), 20 (64%) and 19 (61%) respectively. Quality of homework compliance and baseline Y-BOCS severity predicted remission (Y-BOCS

Glioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes that showed specific upregulation in GBM along with their protein-protein interaction information. A system level analysis was used to construct GBM-specific network. Computation of topological parameters of networks showed scale-free pattern and hierarchical organization. From the large network involving 1,447 proteins, we synthesized subnetworks and annotated them with highly enriched biological processes. A careful dissection of the functional modules, important nodes, and their connections identified two novel intermediary molecules CSK21 and protein phosphatase 1 α (PP1A) connecting the two subnetworks CDC2-PTEN-TOP2A-CAV1-P53 and CDC2-CAV1-RB-P53-PTEN, respectively. Real-time quantitative reverse transcription-PCR analysis revealed CSK21 to be moderately upregulated and PP1A to be overexpressed by 20-fold in GBM tumor samples. Immunohistochemical staining revealed nuclear expression of PP1A only in GBM samples. Thus, CSK21 and PP1A, whose functions are intimately associated with cell cycle regulation, might play key role in gliomagenesis. Cancer Res; 70(16); 6437–47. ©2010 AACR.

Presurgical evaluation of children with mesial temporal sclerosis has shown severe neurocognitive impairments. There is debate about lateralized material-specific deficits in memory in children with mesial temporal sclerosis. The authors examined lateralization of brain dysfunction and age appropriate development of cognitive functions in 17 children (7-15 years) with mesial temporal sclerosis who had histories of uncontrolled epilepsy. The National Institute of Mental Health and Neurosciences (NIMHANS) neuropsychological battery for children was employed and each participant’s performance was compared with the norms. Results showed that the battery was sensitive to deficits in learning and memory associated with mesial temporal sclerosis. However, a lack of clearly lateralized material-specific memory deficits in children with left/right mesial temporal sclerosis was also observed. Performance on tests that assess learning, attention, working memory, and visuospatial functions was found to be below the age appropriate level. Children with mesial temporal sclerosis showed widely distributed neuropsychological deficits.

Over the past decade preventive endovascular treatment is increasingly being considered for intracranial aneurysms irrespective of whether ruptured or unruptured. Few studies have dealt with in-vivo characteristics of intracranial aneurysms. We compare the angiographic morphology of ruptured and unruptured intracranial aneurysms using short interval serial DSA. 37 patients with intracranial aneurysms and who underwent at least two digital subtraction angiograms were included in the study. Based on the clinical presentation there were two subgroups of patients, Group A patients presenting acutely with Sub arachnoid haemorrhage (SAH) and Group B patients who had no clinical or imaging features suggestive of bleed. Clinical and serial angiographic data were correlated. Aneurysms in Group A (1.04 mm3) were significantly (p=0.010) smaller than in Group B (4.53 mm3). Aneurysms in group A showed increase in size and those in Group B showed a decrease in size (p=0.019). Hypertensive patients in both the groups showed a tendency for a decrease in the size of the aneurysms. Aneurysms having stasis at the time of initial angiogram had significantly reduced in size on follow up (p=0.013) at a faster rate (p=0.017). Presence of spasm in adjacent vessels was associated with increase in size of aneurysm on follow up in both Groups. There are significant differences between a ruptured aneurysm and an unruptured one. Ruptured aneurysms are small and show rapid increase in size. The presence of spasm increased the size of the aneurysm in the post rupture period and anti hypertensive medication and stasis were associated with decrease in size.

Electroencephalogram spectral power was estimated at 30 scalp locations in 28 neuroleptic-naive, recent-onset schizophrenia (NRS) patients and 25 healthy comparison subjects in the resting eyes closed condition. Weighted relative power values in the various bandwidths were initially compared between NRS subjects and comparison subjects and subsequently between the positive symptom subgroup, negative symptom subgroup, and comparison subjects, to look for characteristic spectral power profiles of the homogeneous symptom subgroups. Significant differences were noted especially in alpha2, delta, and theta bands between NRS patients and healthy comparison subjects, while the positive symptom and negative symptom subgroups showed characteristic spectral power profiles in alpha1, alpha2, delta, and theta bands.