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We report the potential role of 1H Nuclear Magnetic Resonance (NMR) based metabolomics in tuberculous meningitis (TBM). We also correlate the significant metabolites with clinical-radiological parameters. Forty-three patients with TBM were included, and their severity of meningitis was graded as stages I to III, and patients with positive Mycobacterium tuberculosis or its nucleic acid was considered as definite TBM. 1H NMR-based metabolomic study was performed on (CSF) samples, and the significant metabolites compared to healthy controls were identified. Outcome at three months was defined as death, poor and good based on the modified Rankin Scale. These metabolites were compared between definite and probable groups of TBM, and also correlated with MRI findings. About 11 metabolites were found to be significant for distinguishing TBM from the controls. In TBM, lactate, glutamate, alanine, arginine, 2-hydroxyisobutyrate, formate, and cis-aconitate were upregulated, and glucose, fructose, glutamine, and myo-inositol were downregulated compared to the controls. For differentiating TBM from the controls, the AUC of the ROC curve generated using these significant metabolites was 0.99, with a 95% confidence interval from 0.96 to 1, demonstrating that these metabolites were able to classify cases with good sensitivity and specificity. Lactate concentration in CSF correlated with hemoglobin, CSF glucose, and infarction. The outcome did not correlate with metabolomics parameters. NMR-based CSF metabolomics have a potential role in differentiating TBM from the controls. [ABSTRACT FROM AUTHOR]

Purpose: To document magnetic resonance imaging (MRI) changes in Pott's spine and to correlate these with clinical findings and outcome. Methods: Patients with Pott's spine having more than one set of MRI were included in the study. Patients were grouped according to timing of their second MRI. The MRI findings included changes in bone, disc, spinal cord, and soft tissue. The MRI changes were categorized into improvement, no change, or worsening. "Paradoxical worsening" was defined as radiological worsening in setting of clinical improvement, as described by improvement of Nurick's grade. Outcome was defined by mRS scale at three, six, and 12 months. The MRI findings and outcome were correlated. Results: The results are based on 36 patients. The MRI changes included vertebral changes in form of spondylodiscitis in 33 (92%), epidural abscess in 29 (81%), spinal cord changes including edema and granuloma in 17 (47%), paravertebral abscess in 29 (81%), and vertebral body collapse in 12 (33.3%) patients. At three months, clinical improvement occurred in eight out of 12 patients, deterioration in two, and no change in two. Spinal MRI revealed improvement in one patient only; whereas eight had deterioration and three had no change. At six months, all nine patients improved clinically, but MRI showed improvement in only four, while another four showed deterioration and one had no change. In the nine and 12 months group, while all patients clinically improved, MRI showed minimal worsening. Conclusion: In Pott's spine, the clinical improvement precedes the radiological improvement. [ABSTRACT FROM AUTHOR]

The expression of matrix metalloproteinases (MMPs) is tightly regulated at the level of gene transcription, conversion of pro-enzyme to active MMPs, and the action of tissue inhibitors of metalloproteinases (TIMPs). The present study aimed to investigate the expression of some specific MMPs (2, 7, 9) and TIMPs (1, 2, 3) in serum and cerebrospinal fluid (CSF) of children with Japanese encephalitis virus (JEV) infection. Serum and CSF levels of MMPs and TIMPs in children with JEV infection and disease control (DC) were compared. The CSF and serum concentrations of MMP-2, TIMP-2 and TIMP-3 were significantly higher in children with JEV infection compared to DC. The concentration of MMP-9 in serum was significantly higher in children with JEV infection than in the DC and healthy control (HC), while in the CSF, no significant difference was observed compared to DC. The MMP-7 serum concentration was significantly higher in children with JEV infection compared to HC, but no significant difference was observed compared to DC. MMP-7 concentration was undetectable in CSF in both groups. The TIMP-1 CSF concentration was significantly higher, while the serum concentration was significantly lower, in children with JEV infection compared to DC. No correlation was found between the levels of each biomolecule measured in CSF and serum, suggesting that the levels in CSF represent local production within the CNS rather than production in the periphery. We also observed leucocytosis, mononuclear pleocytosis and elevated protein concentrations in the CSF of children with JEV infection compared to DC. [ABSTRACT FROM AUTHOR]

The mortality in intracerebral hemorrhage (ICH) is mainly due to raised intracranial pressure, and its complications mediated by sympathetic overactivity. There is paucity of studies evaluating the role of β-blockers in the outcome of ICH. This study reports the role of atenolol in reducing mortality, pneumonia, systemic inflammatory response syndrome (SIRS), and 3 months outcome in the patients with hypertensive ICH. 138 consecutive patients with hypertensive ICH were included and their stroke risk factors and clinical details were recorded. Consciousness was assessed by Glasgow Coma Scale and severity of stroke by Canadian Neurological Scale. Volume of hematoma was measures on CT scan and occurrence of SIRS and pneumonia were noted. 3 months outcome was categorized into good (Barthel index >12) and poor (BI < 12). The patients were categorized into those receiving atenolol and nonatenolol. The effects of atenolol on stroke outcome parameters were evaluated. Seventy-nine patients received atenolol and 59 did not and they mainly received amlodipine. There was no difference in the base line clinical characteristics between the two groups except smoking (P = 0.01) and baseline blood pressure (P = 0.007). Atenolol significantly reduced the mortality (11.4 vs 37.3 %, P < 0.0001), SIRS (16.4 vs 40.9 %, P = 0.007), and pneumonia (8.9 vs 30.5 %, P = 0.002) compared to those not receiving atenolol. At 3 months, patients with atenolol had insignificantly better outcome compared to nonatenolol group (49.1 vs 31.9 %, P = 0.11). Use of atenolol in hypertensive ICH results in reduction in mortality, SIRS, and pneumonia which may be due to its β-adrenergic blocking effect. [ABSTRACT FROM AUTHOR]

There is a paucity of data on the prevalence of elevated homocysteine and its relation with plasma folate and the methylenetetrahydrofolate reductase ( MTHFR) gene in the population of North India. This study evaluates MTHFR gene polymorphism and its relationship with plasma homocysteine and folate levels in a healthy North Indian population. The age of the 200 subjects included in this study was in the range 18–73 (mean 39.4) years. The plasma homocysteine level was elevated in 56.5%, and the plasma folate level was low in 49.5% of the subjects. Heterozygous MTHFR gene polymorphism (CT) was present in 15.5%, and homozygous (TT) in 3.5% of the subjects. Age, diet, and MTHFR gene polymorphisms were related to homocysteine level. All the subjects with the TT and 79% with the CT genotype had a high level of plasma homocysteine, whereas 51% with the CC genotype had a high homocysteine level. After adjustment for the effect of covariates, however, homocysteine was not related to MTHFR gene polymorphism. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the clinical and radiological characteristics and the outcome of status epilepticus (SE). 117 consecutive patients with SE were evaluated including their demographics, history of epilepsy, antiepileptic drug (AED) default, comorbidities, SE type and duration. The study included 22 children, 77 adults and 18 elderly patients with SE. Blood counts, serum chemistry, ECG, cranial MRI, cerebrospinal fluid and EEG were done. Patients were treated with IV phenytoin, valproate, lorazepam or diazepam as per a fixed protocol and responses to first and second drugs were noted. Death during hospital was recorded. The etiology of SE was infection in 53.8%, drug default in 7.9%, metabolic in 14.5%, stroke in 12.8% and miscellaneous in 11% of patients. 92.3% of patients had convulsive and 7.7% nonconvulsive SE. Cranial MRI was abnormal in 62%. Infection as an etiology was more common in children, drug default and metabolic causes in adults and stroke in adults and elderly. Following first AED, SE was controlled in 50%. 30% of patients remained refractory to second AED which was related to duration of SE and mortality. 29% patients died and death was higher in elderly (44%) compared to children (14%). Acute symptomatic SE is more common in developing countries. Refractory SE is associated with SE duration and mortality. [ABSTRACT FROM AUTHOR]

Increased generation of free radicals resulting in brain injury is a feature of many viral infections. The present study has been undertaken to evaluate the level of free radicals in Japanese encephalitis. Twelve days old Wistar rats were inoculated intracerebrally with 3 × 106 pfu of JE virus and were sacrificed on 3, 6, 10, and 20 days post inoculation (dpi). The neuronal levels of reactive oxygen species (ROS), nitric oxide (NO), peroxinitrite (OONO−), necrotic and apoptotic cell population were estimated by flow cytometry. Hematoxylin-eosin staining was also performed. Maximum level of neuronal ROS and OONO− was observed on 6 dpi; however, NO levels peaked on 10 dpi. Free radical generation significantly declined on 20 dpi as compared to control. Apoptotic cell death gradually increased over the time. Neuronal shrinkage and necrosis was also observed. The results of our study indicate that free radicals increased in acute JE and declined at later stage, which may contribute to cell death. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with <8 attacks/months were included. One hundred and fifty-five migraine patients were randomised to rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability. [ABSTRACT FROM AUTHOR]

In view of the paucity of deletion studies of survival of motor neuron ( SMN) and neuronal apoptosis inhibitor protein ( NAIP) genes in Indian SMA patients, this study has been undertaken to determine the status of SMN1, SMN2 and NAIP gene deletions in Indian SMA patients. Clinically and neurophysiologically diagnosed SMA patients were included in the study. A gene deletion study was carried out in 45 proximal SMA patients and 50 controls of the same ethnic group. Both SMN1 and NAIP genes showed homozygous absence in 76 % and 31 % respectively in proximal SMA patients. It is proposed that the lower deletion frequency of SMN1 gene in Indian patients may be due to mutations present in other genes or population variation, which need further study. [ABSTRACT FROM AUTHOR]

Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood-brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies - including corticosteroids, aspirin and thalidomide - has not been extensively explored. To address this deficit, two expert meetings were held in 2009 and 2015 to share findings and define research priorities. This Review summarizes historical and current research into TBM and identifies important gaps in our knowledge. We will discuss advances in the understanding of inflammation in TBM and its potential modulation; vascular and hypoxia-mediated tissue injury; the role of intensified antibiotic treatment; and the importance of rapid and accurate diagnostics and supportive care in TBM. [ABSTRACT FROM AUTHOR]