As per the estimates of the World Health Organization, aging population is increasing in developing countries and dementia is going to become epidemic among elderly in the coming decades. This demands early action to prevent the disease and treatment of the affected persons, which is poorly existent in middle- and low-income countries. The need of the hour to tackle dementia in India is to estimate disease burden in the community, search for risk and protective factors of dementia, and undertake measures to provide social benefits to the sufferers and those who are at risk. Raising awareness among the public and general physicians is an important task ahead. In India, there is lack of good longitudinal studies which can provide true trend of the disease and determine risk factors, paucity of basic and clinical researches on dementia, poor awareness, and inadequate availability of social benefit. India, being a country of diverse ethnicity and cultures, has great advantages to carry out genetic epidemiological study. The information may be useful for undertaking remedial measure. This article will highlight the existing state of the above medical and social issues and deficiencies, so that the stakeholders can make adequate preparation to provide relief to the dementia patients and those who are at risk. It is expected that the medical and scientific community will draw attention to the medical problem with the help of governmental and non-governmental agencies, and the political leadership will be motivated to undertake the issue of providing socioeconomic benefit to families of the victims.

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Objective: To determine overall and age-specific incidence rates of Alzheimer's disease (AD) in a southern Indian province, Kerala. Materials and Methods: A 10-year (2001-2011) prospective epidemiologic study of community residing subjects aged ≥55 years at enrollment. The catchment area included four urban and semi-urban regions of Trivandrum city in Kerala, India, was selected to provide a range of demographic and socioeconomic representation. Cognitive and functional ability screening were done at baseline and 24-month follow-up assessments. Consensus diagnostic procedures were done using the Diagnostic and Statistical Manual of Mental Disorders, 4 ^th edition (DSM-IV), and the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria for the diagnosis of dementia and AD. Results: Among the 1066 eligible participants who were cognitively normal at baseline, 104 developed dementia (98 with AD) over a follow-up period of 8.1 years. The incidence rates per 1000 person-years for AD was 11.67 (95% CI: 10.9-12.4) for those aged ≥55 years and higher for those aged ≥65 years (15.54, 95% CI: 14.6-16.5). In those aged ≥65 years, the world age standardized incidence rate was 21.61 per 100,000, and standardized against the age distribution for the year 2000 U.S. Census, the age-adjusted incidence rate was 9.19 (95% CI: 9.03-9.35) per 1000 person-years. Incidence rate of AD increased significantly and proportionately with increasing age. Conclusion: These are the first AD incidence rates to be reported from southern India. The incidence rates appear to be much higher than that reported from rural north India, comparable with that reported from China, and marginally lower than that reported from the western world.

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Background: Recovery in stroke is mediated by neural plasticity. Neuro-restorative therapies improve recovery after stroke by promoting repair and function. Mirror neuron system (MNS) has been studied widely in humans in stroke and phantom sensations. Materials and Methods: Study subjects included 20 patients with chronic stroke and 10 healthy controls. Patients had clinical disease-severity scores, functional magnetic resonance imaging (fMRI) and diffuse tensor imaging (DTI) at baseline, 8 and at 24 weeks. Block design with alternate baseline and activation cycles was used with a total of 90 whole brain echo planar imaging (EPI) measurements (timed repetition (TR) = 4520 ms, timed echo (TE) = 44 ms, slices = 31, slice thickness = 4 mm, EPI factor 127, matrix = 128 × 128, FOV = 230 mm). Whole brain T1-weighted images were acquired using 3D sequence (MPRage) with 120 contiguous slices of 1.0 mm thickness. The mirror therapy was aimed via laptop system integrated with web camera, mirroring the movement of the unaffected hand. This therapy was administered for 5 days in a week for 60-90 min for 8 weeks. Results: All the patients showed statistical significant improvement in Fugl Meyer and modified Barthel Index (P < 0.05) whereas the change in Medical Research Council (MRC) power grade was not significant post-therapy (8 weeks). There was an increase in the laterality index (LI) of ipsilesional BA 4 and BA 6 at 8 weeks exhibiting recruitment and focusing principles of neural plasticity. Conclusions: Mirror therapy simulated the "action-observation" hypothesis exhibiting recovery in patients with chronic stroke. Therapy induced cortical reorganization was also observed from our study.

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One of the most basic functions in every individual and species is memory. Memory is the process by which information is saved as knowledge and retained for further use as needed. Learning is a neurobiological phenomenon by which we acquire certain information from the outside world and is a precursor to memory. Memory consists of the capacity to encode, store, consolidate, and retrieve information. Recently, memory has been defined as a network of connections whose function is primarily to facilitate the long-lasting persistence of learned environmental cues. In this review, we present a brief description of the current classifications of memory networks with a focus on episodic memory and its anatomical substrate. We also present a brief review of the anatomical basis of memory systems and the most commonly used neuroimaging methods to assess memory, illustrated with magnetic resonance imaging images depicting the hippocampus, temporal lobe, and hippocampal formation, which are the main brain structures participating in memory networks.

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Background: Genetic polymorphisms of CYP2C9 can lead to wide inter-individual variations in drug metabolism. Decreased metabolism leads to higher plasma levels, causing adverse drug reactions (ADRs). Polymorphic alleles CYP2C9 * 2 and CYP2C9 * 3 occur in the Indian population and this may serve as the basis for using genotyping as a tool to predict phenytoin toxicity. Aims: To evaluate the association between the presence of polymorphic alleles CYP2C9 * 2 and *3 and phenytoin toxicity in Indian patients with epilepsy. Settings and Design: A case-control study with cases defined as those who had plasma phenytoin concentrations above 20 μg/ml. Materials and Methods: The study population included 259 patients with epilepsy on phenytoin. Phenotyping was done using High Performance Liquid Chromatography. Those with plasma phenytoin levels above 20 μg/ml were taken as cases and the rest as controls. Genotyping was done by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism. Statistics: Numerical data between groups was compared using unpaired-'t' test. Between-group comparison of categorical data was done using Chi square for trend with crude odds ratio (OR). Adjusted OR was calculated using binary logistic regression. Results: There were 40 cases and 219 controls. Mean phenytoin dosage between groups was not statistically significant. Of the 40 cases, 25 (62.5%) cases had wild alleles versus 178 (81.3%) controls. We found a significant association between polymorphic alleles CYP2C9 * 2 and *3 and toxic phenytoin levels. After adjusting for age, sex and dose, a significant association between polymorphic alleles and phenytoin toxicity was still found. Conclusions: This study shows significant association between polymorphic alleles and phenytoin toxicity in this study population. However, until technology for genotyping becomes cost-effective, we would recommend Therapeutic Drug Monitoring to guide dosing.

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In chordoma, complete surgical removal of the epidural tumor should be the first choice of treatment. Numerous surgical approaches to clival chordoma have been described: anterior approaches, lateral approaches, and posterolateral approaches. A multistaged operation with a combination of these approaches is generally performed. We used three approaches to remove a clival chordoma extending from the lower clivus anteriorly to the anterior perivertebral space and inferiorly to the C2 level. The epidural posterolateral approach through the vertebral artery (VA)-C2 interval space after resection of the C2 dorsal ganglion was the most effective. To our knowledge, the epidural posterolateral approach below VA, referred to as C2 ganglion sectioning epidural approach has not been reported as an independent approach in detail. We report a two-year-old girl with a lower clival chordoma which has been excised using C2 ganglion sectioning epidural approach.

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A 42-year-old woman, a diagnosed case of systemic lupus erythematosus (SLE), developed severe headache followed by left hemiparesis and cortical blindness. Magnetic resonance imaging (MRI) of brain demonstrated right parieto-occipital infarct and the patient was initiated on high-dose steroids and antiplatelet agents with which the patient had clinical and radiological deterioration. Magnetic Resonance angiography showed severe narrowing of bilateral anterior, middle, and posterior cerebral arteries (PCA) suggestive of reversible cerebral vasoconstriction syndrome (RCVS). Patient was treated with IV nimodipine and she recovered over a period of 2 weeks. Repeat MR-angiography done on day-30 was normal. The diagnosis of RCVS in patients with SLE is of practical importance, because treatment and prognosis for SLE-associated cerebral vasculitis differ strongly from the treatment of RCVS. Empirical high-dose glucocorticoid therapy should be avoided in patients with typical features of RCVS.

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Background: Bypass patency is critical for patients undergoing superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. Near-infrared indocyanine green video-angiography (ICGA) is an excellent method to assess vessels during cerebrovascular surgery. Objective: The aim of the present study is to analyze the effectiveness of ICGA in patients undergoing STA-MCA anastomosis for moyamoya disease. Materials and Methods: This study was a retrospective review of case records and operation records of patients who underwent STA-MCA bypass for moyamoya disease at our institute. Concordance of ICGA with intraoperative micro-Doppler and postoperative angiography, whenever available, was assessed. Results: In all, 22 STA-MCA anastomoses were performed in 13 patients. ICGA was used to assess patency in 14 surgeries (10 patients). No patient required revision of anastomosis following ICGA. Postoperative angiography was done in five anastomoses (three patients) at three months follow-up and correlated well with ICGA findings in all cases. Conclusion: ICGA is an effective technique to assess bypass patency during cerebrovascular surgery. Routine use of ICGA in cerebral bypass surgery improves graft patency and minimizes complications due to graft occlusion.

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Background: Hedgehog/Gli1 (HH/Gli1) pathway plays an important role in the patterning and development of the central nervous system during embryogenesis. Recent data have shown its potential involvement in a subset of human gliomas and inhibition of the pathway resulted in tumor suppression in both in vitro and in vivo studies. The underlying mechanisms of tumor suppression, however, remain to be fully elucidated. Materials and Methods: Gli1 expression was investigated in 60 surgically resected glioma tissues (World Health Organization (WHO) III-IV). Results: Gli1 was expressed in 43 gliomas with high Gli1 expression in nine cases, moderate expression in 21 cases, and low expression in 13 cases. Additionally, microvessel counts were higher in Gli1 positive gliomas than those in Gli1 negative gliomas. Gli1 expression in gliomas was positively correlated with microvessel density (MVD). To explore the molecular mechanisms of the phenotypic changes, we performed quantitative real-time polymerase chain reaction (PCR) and Western blot analysis to monitor the changes of a series of genes, which play critical roles in the regulation of glioma angiogenesis. In conclusion, HH/Gli1 pathway inhibition resulted in down-regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) expressions, whereas this pathway activation led to up-regulation of VEGF, MMP2, and MMP9 expressions. These molecular changes of the HH/Gli1 pathway inhibited by indirect drug approach were consistent with Gli1 RNA-interference (RNAi) in glioma cell lines. Conclusion: Our findings demonstrated that the aberrantly active HH/Gli1 pathway contributed to angiogenesis in part through induction of VEGF, MMP2, and MMP9.

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Objective: Decompressive hemicraniectomy is accepted as the most effective life-saving treatment for malignant middle cerebral artery (MCA) infarction. However, the outcome remains hard to predict. This study examined the efficacy of using the Glasgow Coma Scale (GCS) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores before emergency craniectomy for predicting clinical outcome in malignant MCA infarction. Materials and Methods: Seventy-nine consecutive patients with malignant MCA infarction treated from January 2006 to October 2010 were retrospectively analyzed. The GCS and APACHE II scores within the first 24 h of neurological deterioration or before decompressive hemicraniectomy, were used to predict short-term functional outcome rated by the modified Rankin Scale (mRS). The receiver operating characteristic (ROC) curve was obtained to determine the accuracy and best cut-off value for each scoring system. Results: At 6 months, there was dramatic life-saving effect of surgery, with a significant reduction in mortality rate (from 71% to 19%, P < 0.001). After the ROC analysis, cut-off values of pre-operative GCS > 8 (P = 0.003) and APACHE II <13 (P = 0.006) were sufficiently sensitive and specific to predict favorable outcome (mRS 0-3). Conclusions: Pre-operative GCS and APACHE II scores are useful tools in predicting outcomes for patients with malignant MCA infarction who underwent decompressive hemicraniectomy.

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Distal myopathy with rimmed vacuoles (DMRV) is a major entity of distal myopathy. It is an autosomal recessive disorder and is due to mutations in the GNE gene that regulates the synthesis of sialic acid. Although reported predominantly from Japan, cases have been reported from other parts of the world. We report the first genetically proven case of DMRV from India in a 23-year-old male with gradual onset, progressive distal weakness of both lower limbs with features of inflammation in muscle biopsy.

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Background: Large size, and location in posterior circulation, both individually portend high risk in the endovascular management of intracranial aneurysms. Aim: The purpose of this study was to investigate the outcome of endovascular management of giant posterior circulation aneurysms at our centre. Materials and Methods: This is a retrospective analysis of 22 consecutive patients with giant posterior circulation aneurysms, who were managed by endovascular techniques between 1997 and 2009. The aneurysms included: Vertebral-6 (27%), basilar or vertebrobasilar - 7 (32%) and nine posterior cerebral artery (PCA) - 9 (41%). Results: There were 14 males and eight females with a mean age of 37 years. Treatment modalities included: Parent vessel sacrifice (PVS), coil embolization, flow reversal, stent-assisted coiling, and telescopic stent placement. Angiographic cure or stasis was achieved in 21 (95%) patients and no recurrence was observed in 17 of the 18 patients who had follow-up. Complications occurred in 9 (41%) patients, death in 4 and morbidity in 5 (3 with good eventual outcome). Overall, good clinical outcome was noted in 16 (73%) patients. The majority of the poor outcomes were observed in the management of basilar/vertebrobasilar aneurysms and flow reversal. Parent vessel sacrifice showed the best outcomes with stable results. Conclusions: Our results suggest that PVS remains the procedure of choice wherever possible and is relatively safe, particularly for giant vertebral and PCA aneurysms. When PVS is not feasible, stent-assisted coiling is a reasonable and safe option and requires follow-up. Management of basilar or vertebrobasilar aneurysms is complicated and still evolving.

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Background: Single nucleotide polymorphisms (SNPs) in the Reelin gene (RELN) are likely candidates to confer risk for autism. The objective of the present study is to investigate the association of RELN gene SNPs with autism. Materials and Methods: A total of 367 Chinese Han subjects were recruited, including 186 autism patients and 181 unrelated healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods were used to detect RELN gene polymorphisms. The association between SNPs and autism was analyzed in this study. Results: The g.333509A>C in intron12 and g.504742G>A in exon60 were detected in the RELN gene and a significant association was found between the g.504742G>A polymorphism and autism. Allele and genotype frequencies for the g.504742G>A polymorphism in autistic patients were significantly different for healthy subjects. There was no significantly difference in g.333509A>C polymorphism and autism in the studied populations. Conclusions: Our findings indicated that g.333509A>C was not significantly associated with autism. The g.504742G>A polymorphic variant in the RELN gene might affect subjects susceptibility toward autism in Chinese Han population.

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Background: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy syndrome with genetic basis and accounts for 10% of all forms of epilepsy. Despite the existence of rare mutations responsible for some familial forms inherited in a Mendelian pattern, the genetics of JME is complex and probably involves multiple genes. Because of widespread distribution in the central nervous system (CNS) and their ability to produce postsynaptic inhibition, GABA (A) receptor subunits (GABRs) encoding genes represent high ranking candidates for epilepsy susceptibility. Aim: This case/control study was designed to investigate whether the rs211037 of the GABRG2 gene is a risk factor for JME in the Brazilian population. Materials and Methods: The polymorphism was genotyped in 98 patients and 130 controls using polymerase chain reaction-restriction fragment length polymorphism method. Descriptive and statistical analyses were performed using SNP stat software. Results: Genotype proportions and allele frequencies for the rs211037 polymorphism of the GABARG2 gene did not differ significantly between the groups, even when the odds ratio was adjusted for clinical variables. Conclusion: These results present no evidence for an association of rs211037 with JME. Further studies are required to investigate the involvement of the GABRG2 gene in the genetic susceptibility to this epileptic syndrome.

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