U.K. Misra

Tuberculous meningitis: a uniform case definition for use in clinical research

Tuberculous meningitis causes substantial mortality and morbidity in children and adults. More research is urgently needed to better understand the pathogenesis of disease and to improve its clinical management and outcome. A major stumbling block is the absence of standardised diagnostic criteria. The different case definitions used in various studies makes comparison of research findings difficult, prevents the best use of existing data, and limits the management of disease. To address this problem, a 3-day tuberculous meningitis workshop took place in Cape Town, South Africa, and was attended by 41 international participants experienced in the research or management of tuberculous meningitis. During the meeting, diagnostic criteria were assessed and discussed, after which a writing committee was appointed to finalise a consensus case definition for tuberculous meningitis for use in future clinical research. We present the consensus case definition together with the rationale behind the recommendations. This case definition is applicable irrespective of the patients age, HIV infection status, or the resources available in the research setting. Consistent use of the proposed case definition will aid comparison of studies, improve scientific communication, and ultimately improve care.

Mannitol in intracerebral hemorrhage: a randomized controlled study

OBJECTIVE To study the usefulness of mannitol in spontaneous intracerebral hemorrhage (ICH) patients. METHOD 128 CT proven supratentorial ICH patients within 6 days of ictus were randomized into study and control groups. The study group received mannitol 20%, 100 ml every 4 h for 5 days, tapered in the next 2 days. The control group received sham infusion. Primary endpoint was 1-month mortality and secondary endpoint functional disability at 3 months assessed by Barthel index score. RESULTS There were 65 patients in study and 63 in control groups. The study and control groups were evenly matched regarding age, Glasgow coma scale (GCS) score, Canadian Neurological Scale (CNS) score, pupillary asymmetry, pyramidal signs on non-hemiplegic side, and location, midline shift and ventricular extension of hematoma. At 1 month, 16 patients died in each group. The primary and secondary endpoints were not significantly different between the two groups. CONCLUSION Low dose mannitol does not seem to be beneficial in patients with ICH.

Prognosis of tuberculous meningitis: a multivariate analysis

Twenty-six clinical, laboratory and CT scan features in 49 patients with tuberculous meningitis (TBM) were analysed to identify the parameters of prognostic significance. Employing univariate analysis, seven variables were found to correlate with three month outcome; these variables included the stage of TBM on admission, focal weakness, Glasgow coma scale (GCS), incontinence, infarction, hydrocephalus and shunt surgery. Analysing all 26 variables, a conditional logistic regression model was derived. In this model stage of TBM, age, focal weakness, cranial nerve palsy and hydrocephalus were found to be contributing to the three month outcome of TBM patients as assessed by the Barthel index.

Predictors of long-term neurological sequelae of tuberculous meningitis: a multivariate analysis.

There is paucity of studies on predictors of long‐term sequelae of tuberculous meningitis (TBM). We report the neurological sequelae of TBM at 1 year and their predictors. Patients with TBM who were followed up for 1 year were included. The diagnosis of TBM was based on clinical, cerebrospinal fluid (CSF) and computed tomography (CT) scan findings. Detailed neurological examinations at admission and at 1 year were carried out. All the patients received four‐drug antitubercular therapy. The frequency of sequelae at 1 year were noted and the role of various demographic (age, sex, duration of illness, BCG vaccination), clinical (weakness, seizure, extra central nervous system tuberculosis, Glasgow Coma Scale (GCS) score, cranial nerve palsy, stage, corticosteroid, drug‐induced hepatitis, shunt surgery), and laboratory findings (erythrocyte sedimentation rate (ESR), CSF cell and protein, CT scan evidences of hydrocephalus, basal exudates, infarctions and tuberculoma) at presentation were evaluated employing logistic regression analysis. Sixty‐five patients with TBM were included in this study whose age ranged between 13 and 80 years (mean 33.2), 27 of whom were females. Complete neurological recovery at 1 year occurred in 21.5% patients only although about 50% were independent for activities of daily living. Neurological sequelae were observed in 78.5% patients, which included cognitive impairment in 55%, motor deficit in 40%, optic atrophy in 37% and other cranial nerve palsy in 23%. On logistic regression analysis, focal motor deficit at admission was the most important predictor of neurologic deficits at 1 year. GCS score predicted the cognitive and motor sequelae. Neurological sequelae at year occurred in 78.5% patients with TBM in the form of cognitive impairment, motor deficit and optic atrophy. Sequelae were common in patients who had focal motor deficit and altered sensorium at admission.

Evaluation of MTHFR C677T polymorphism in ischemic and hemorrhagic stroke patients. A case–control study in a Northern Indian population

OBJECTIVE The present study was aimed to evaluate MTHFR C677T gene polymorphism in patients with ischemic stroke (IS) and intracerebral hemorrhage (ICH) and compare it with controls. METHODS 207 patient with IS and 215 with CT/MRI proven ICH were included and compared with 188 healthy controls. The stroke risk factors, location of IS, its vascular territory and in ICH the location of hematoma were noted. MTHFR C677T polymorphism was studied by polymerase chain reaction. RESULTS Hypertension was present in 65.9% of ICH and 48.8% of IS. Other stroke risk factors were not significantly different. The frequency of the CC genotype in controls was 68.6%. CT in 28.7% and TT in 2.7%, whereas it was 75.3%, 20.5% and 4.2% in ICH and 66.2%, 39.4% and 2.4% respectively in IS. The frequency of these genotypes as well as allele frequency was not different in IS, ICH as compared to controls, however variant allele was more frequent in IS compared to ICH. Homocysteine level was higher in IS patients with variant genotype INTERPRETATION MTHFR C677T gene polymorphism was neither associated with hemorrhagic nor ischemic stroke. However raised homocysteine levels were found to be associated with MTHFRC677-TT genotype in IS patients.

A randomized placebo controlled trial of ranitidine versus sucralfate in patients with spontaneous intracerebral hemorrhage for prevention of gastric hemorrhage

AIM Due of paucity of studies on stress ulcer prophylaxis in intracerebral hemorrhage (ICH), we have evaluated the usefulness of ranitidine and sucralfate in preventing gastric hemorrhage (GH) in patients with ICH. SUBJECTS AND METHODS In a hospital-based randomized placebo-controlled study, patients with CT-proven ICH within 7 days of ictus were randomized into ranitidine 50 mg i.v. eight hourly, sucralfate 1 g six hourly and placebo groups. Patients were conservatively managed. Primary endpoint was occurrence of GH within 15 days of ictus and secondary endpoint 1-month mortality. RESULTS The mean age of the patients was 57.2 (range 25-90) years and 40 were females. There were 45 patients in ranitidine, 49 in sucralfate and 47 in placebo group. Demographic, clinical and radiological features were not significantly different in 3 groups. GH occurred in 11 (23.4%) patients in placebo, 5 (11.1%) in ranitidine and 7 (14.3%) in sucralfate group, which was not significant. Only one female had GH. There were 13 (27.7%) deaths in placebo, 5 (11.1%) in ranitidine and 12 (24.5%) in sucralfate group. Pneumonia occurred in placebo group in 5 (10.6%), ranitidine in 2 (4.4%) and sucralfate in 5 (10.2%) patients, which was not significantly different. CONCLUSION Ranitidine and sucralfate do not seem to significantly prevent GH or reduce 1-month mortality.

Effect of mannitol on regional cerebral blood flow in patients with intracerebral hemorrhage.

AIM To evaluate the regional cerebral blood flow (rCBF) changes following IV mannitol bolus in patients with intracerebral hemorrhage (ICH). METHODS In a hospital based randomized placebo controlled study, 21 CT proven ICH patients with Glasgow coma scale (GCS) score of 5 or more were subjected to clinical evaluation including GCS and Canadian Neurological stroke (CNS) scale. Cranial SPECT study was undertaken before and 60 min after 20% mannitol 100 ml IV in 20 min or sham infusion. The SPECT images were semi-quantitatively analyzed and asymmetry index of basal ganglia, frontal, parietal and occipital regions were calculated. RESULTS There were 12 patients in mannitol and nine in control group who were evenly matched for age, mean arterial blood pressure, GCS score and size of hematoma. Only one patient died in mannitol group. Following mannitol, GCS score improved in six, worsened in two and remained unaltered in four patients. In the control group, GCS improved in seven, worsened in none and was unchanged in two patients. SPECT studies revealed reduction in asymmetry index in basal ganglia in four, frontal region in six, parietal in four and occipital region in five patients in mannitol group. In control group, asymmetry index was reduced in basal ganglia in one, frontal and parietal region in three each and occipital region in five patients. These differences between control and study group were not significant. CONCLUSION Mannitol does not seem to significantly change the regional cerebral blood flow (rCBF) in ICH patients as evaluated by SPECT study.

Thallium poisoning: emphasis on early diagnosis and response to haemodialysis

Thallium poisoning is known for its diverse manifestations and these can delay the diagnosis if a clear history of poisoning is not forthcoming. A 42 year old man presented on the third day of illness with flaccid quadriparesis and paresthesia, which were confused with Guillain-Barré syndrome. Because of associated loose motions, skin lesions, and liver and kidney dysfunction arsenic poisoning was considered. In the second week he developed ophthalmoplegia, nystagmus, and neck tremor and later developed alopecia, and thallium poisoning was suspected. His serum thallium level on the 18th day of illness was 40 980 μg/ml. He was subjected to haemodialysis, potassium supplementation, laxatives, and B complex supplementation. He showed significant improvement after haemodialysis and at three months he was able to walk with support. At six months of follow up he was independent for activities of daily living. Severe paresthesia, ophthalmoplegia, cerebellar and extrapyramidal signs, and alopecia are highly suggestive of thallium poisoning. Haemodialysis may be effective even in the third week of poisoning.

Predictors of gastrointestinal bleeding in acute intracerebral haemorrhage

BACKGROUND Gastrointestinal (GI) haemorrhage is an important and sometimes serious complication in critically ill neurological patients who suffered from stroke and head injury and those in intensive care. There is no study evaluating frequency, severity and risk factors of GI haemorrhage in patients with primary intracerebral haemorrhage (ICH). AIMS To evaluate the frequency, severity and predictors of GI haemorrhage in patients with ICH. METHODS In a prospective hospital-based study, consecutive CT-proven ICH patients within 10 days of the ictus were included. The patients with history of peptic ulcer, GI haemorrhage, liver and kidney disease, bleeding diathesis and those on antiplatelet, anticoagulant or nonsteroidal antiinflammatory drugs (NSAIDS) were excluded. A detailed neurological evaluation was carried out. Glasgow coma scale (GCS) was used for assessment of consciousness level and Canadian neurological scale (CNS) for severity of stroke. The haematomas were classified into small (<20 ml), medium (20-40 ml) and large (>40 ml). The occurrence of GI haemorrhage during 14 days of ictus was considered due to ICH. To evaluate the predictors of GI haemorrhage, various clinical and CT scan findings were evaluated by univariate followed by multivariate logistic regression analysis. RESULTS Fifty-one patients with ICH were included whose age ranged between 30 and 80 years and 14 were female. The mean GCS score was 8.9 (3-15) and CNS score was 2.2 (2-4). Haematoma was small (<20 ml) in 11 patients and medium (20-40 ml) and large (>40 ml) in 20 patients each. Evidences of septicemia were present in 20 patients. Gastric haemorrhage (GH) was noted in 15 patients which was more than 40 ml in 4 patients and one of these patients needed blood transfusion. On univariate analysis, the size of haematoma, septicemia, motor signs on the nonhemiplegic side and pupillary asymmetry were significantly related to GI haemorrhage. On multivariate analysis, the best set of predictors of gastric haemorrhage included size of haematoma, septicemia and GCS score. CONCLUSION GI haemorrhage is more likely present in patients with larger haematoma having septicemia. Our study highlights the importance of septicemia, which is an important and modifiable risk factor for GI bleeding in ICH patients.

SCN1AIVS5-91G>A polymorphism is associated with susceptibility to epilepsy but not with drug responsiveness

Sodium channel alpha subunit type 1 (SCN1A) is voltage gated ion channel which plays critical role in membrane excitability. A common SCN1A IVS5-91G>A (rs3812718) allele has been attributed to be a possible modifying factor for epilepsy susceptibility and therapeutic response. In the present study, we enrolled 485 epilepsy patients and 298 age-sex matched controls free of neurological deficits. Therapeutic response of carbamazepine/oxcarbamazepine (CBZ/OXC) and other antiepileptic drugs were observed in terms of drug responsiveness and drug resistance. Genotyping of SCN1A IVS5-91G>A is done by Taqman custom designed assay; in a real time7500HT System. We observe highly significant association [(P-values for GA (P = 6.58 × 10(-5), OR = 2.13, 95% CI = 1.47-3.09) and AA (P = 4.11 × 10(-9), OR = 3.59, 95% CI = 2.35-5.50)] at variant genotypes as well as A allele (P = 6.92 × 10(-11)), OR = 1.99, 95%, CI = 1.62-2.45) in epilepsy patients versus control subjects. The relative risk for epilepsy susceptibility due to variant containing genotypes (GA + AA) was also significant (P = 1.64 × 10(-5); OR = 2.56; 95% CI = 1.80-3.65) when compared with homozygous wild-type GG. The risk in recessive model (P = 1.34 × 10(-5); OR = 2.12; 95% CI = 1.51-2.97) was also apparent when compared with GA + GG. In case-only analysis, we evaluated the effect of SCN1A IVS5-91G>A polymorphism with drug resistance of anti-epileptic drug therapies. However, we did not observe significant associations either with patients showing drug resistance to CBZ/OXC monotherapy or polytherapy. In conclusion, we report that SCN1AIVS5-91G>A polymorphism is associated with epilepsy susceptibility but not with drug responsiveness in epilepsy patients from North India.