Study of neurological deficits in patients with tuberculous meningitis and its association with urodynamic study

Background: Tuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. The objective of this study was to study neurological symptoms in TBM patients using clinical diagnosis and MRI of spine and comparing with urodynamic study.Methods: Fifty one patients diagnosed with TBM were studied in Neurology Department of KGM Medical University, Lucknow. Uroflowmetry and urodynamic study were done to divide the patients into normal and abnormal. A detailed history taking, general physical and neurological examination using MRI spinal cord was done and recorded on a predesigned proforma.Results: Visual impairment, hemiparesis, paraparesis, abnormal tone and reflexes in lower limbs showed significant association with abnormality in urodynamic study. MRI spine showed significant relationship of spinal meningeal enhancement, lumbosacral arachnoiditis, with abnormal urodynamic study.Conclusions: We found a significant association between neurological symptoms and abnormal urodynamic

Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population.

BACKGROUND: In epilepsy, in spite of the best possible medications and treatment protocols, approximately one-third of the patients do not respond adequately to anti-epileptic drugs. Such interindividual variations in drug response are believed to result from genetic variations in candidate genes belonging to multiple pathways. MATERIALS AND METHODS: In the present pharmacogenetic analysis, a total of 402 epilepsy patients were enrolled. Of them, 128 were diagnosed as multiple drug-resistant epilepsy and 274 patients were diagnosed as having drug-responsive epilepsy. We selected a total of 10 candidate gene polymorphisms belonging to three major classes, namely drug transporters, drug metabolizers and drug targets. These genetic polymorphism included CYP2C9 c.430C>T (*2 variant), CYP2C9 c.1075 A>C (*3 variant), ABCB1 c.3435C>T, ABCB1c.1236C>T, ABCB1c.2677G>T/A, SCN1A c.3184 A> G, SCN2A c.56G>A (p.R19K), GABRA1c.IVS11 + 15 A>G and GABRG2 c.588C>T. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, and each genotype was confirmed via direct DNA sequencing. The relationship between various genetic polymorphisms and responsiveness was examined using binary logistic regression by SPSS statistical analysis software. RESULTS: CYP2C9 c.1075 A>C polymorphism showed a marginal significant difference between drug resistance and drug-responsive patients for the AC genotype (Odds ratio [OR] = 0.57, 95% confidence interval [CI] = 0.32–1.00; P = 0.05). In drug transporter, ABCB1c.2677G>T/A polymorphism, allele A was associated with drug-resistant phenotype in epilepsy patients (P = 0.03, OR = 0.31, 95% CI = 0.10-0.93). Similarly, the variant allele frequency of SCN2A c.56 G>A single nucleotide polymorphism was significantly higher in drug-resistant patients (P = 0.03; OR = 1.62, 95% CI = 1.03, 2.56). We also observed a significant difference at the genotype as well as allele frequencies of GABRA1c.IVS11 + 15 A > G polymorphism in drug-resistant patients for homozygous GG genotype (P = 0.03, OR = 1.84, 95% CI = 1.05–3.23) and G allele (P = 0.02, OR = 1.43, 95% CI = 1.05–1.95). CONCLUSIONS: Our results showed that pharmacogenetic variants have important roles in epilepsy at different levels. It may be noted that multi-factorial diseases like epilepsy are also regulated by various other factors that may also be considered in the future.

Assessment of genetic diversity of Clarias batrachus using RAPD markers in three water bodies of Bhopal.

To assess the extent of genetic diversity within and between three populations of the catfish, Clarias batrachus, an analysis for random amplified polymorphic DNA (RAPD) variations were carried out. Five out of ten random primers produced constant and reproducible pattern of RAPD products. These five primers produced 72 scorable DNA fragments out of which 68 (86.66%) were polymorphic. Populations showed significant differences in their degree of polymorphism. Differences however, were observed in the primers in producing similarities in the populations.

Water quality and conservation management of Ramsagar reservoir, Datia, Madhya Pradesh.

The aim of this study is to assess physico-chemical characteristics, trophic status, pollution studies and macrophytic community of Ramsagar reservoir from April 2003 to March 2005. The range of various parameters of reservoir water (water temperature 15.92-31.87 oC, water depth 2.90-8.25 m, transparency 66.59-116.00 cm, electrical conductivity 108-246.30 µS cm-1, turbidity 2.17-16.72 NTU, total dissolved solids 166.37-239.00 mg l-1, pH 7.41-8.95, dissolved oxygen 6.78-11.59 mg l-1, free carbon dioxide nil-6.32 mg l-1, total alkalinity 64.25-146.25 mg l-1, total hardness 34.00-75.25 mg l-1, chlorides 13.13-22.36 mg l-1, calcium 11.21-33.81 mg l-1, sulphates 1.50-8.87 mg l-1, nitrates 0.011-0.033 mg l-1, nitrites 0.004-0.029 mg l-1, phosphates 0.013-0.054 mg l-1, silicates 0.65-8.42 mg l-1, ammonia nil-0.84 mg l-1, biochemical oxygen demand 0.93-4.68 mg l-1, chemical oxygen demand 3.60-17.40 mg l-1, magnesium 1.17-5.60 mg l-1, sodium 16.75-34.30 mg l-1 and potassium 1.97-4.86 mg l-1) exhibit monthly as well as seasonal fluctuations. The nutrients including silicates, sulphates, phosphates, nitrates and potassium are in sufficient quantities for the growth of aquatic plants and animals in the reservoir. In all 13 species of macrophytes were recorded from the reservoir. Macrophytic diversity was higher at the points where nallahas join the reservoir and in the areas where agricultural practices are performed. This was due to allocthonous nutrients brought in to the reservoir from the surrounding catchments area. The above study indicated that the Ramsagar reservoir is under the category of mesotrophic water body slightly inclined towards eutrophication. Therefore, the conservation and management of this water body are very much required.

Identification of lysine positive non-fermenting gram negative bacilli (Stenotrophomonas maltophilia and Burkholderia cepacia complex).

BACKGROUND: The Burkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia are closely related groups of non-fermenting gram-negative bacilli (NFGNBs) having a similar spectrum of infections ranging from superficial to deep-seated and disseminated infections. Identification of these lysine decarboxylase-positive NFGNBs lags behind in most Indian laboratories. A simplified identification scheme was devised for these two pathogens that allowed us to isolate them with an increasing frequency at our tertiary care institute. MATERIALS AND METHODS: A simple five-tube conventional biochemical identification of these bacteria has been standardized. In the beginning, some of the isolates were confirmed from the International B. cepacia Working group, Belgium. Molecular identification and typing using recA polymerase chain reaction-restriction fragment length polymorphism was also standardized for BCC. For short-term preservation of BCC, an innovative method of preserving the bacteria in Robertson's cooked medium tubes kept in a domestic refrigerator was developed. RESULTS: Thirty-nine isolates of BCC isolates were obtained from various specimens (30 from blood cultures) and 22 S. maltophilia (13 blood cultures and 9 respiratory isolates) were isolated during the year 2007 alone. CONCLUSIONS: BCC and S. maltophilia can be identified with relative ease using a small battery of biochemical reactions. Use of simplified methods will allow greater recognition of their pathogenic potential and correct antimicrobials should be advised in other clinical laboratories and hospitals.

Water quality and pollution status of Chambal river in National Chambal Sanctuary, Madhya Pradesh.

The physico-chemical characteristics of Chambal river water in National Chambal sanctuary (Madhya Pradesh) have been studied. The stretch of Chambal river contained in the National Chambal sanctuary (located at 25 degrees 23'-26 degrees 52'N, 76 degrees 28'-79 degrees 15'E) is extending up to 600 km downstream from Kota (Rajasthan) to the confluence of the Chambal with Yamuna river (Etawah). The river flow in Madhya Pradesh spans up to approximately 400 km. Three sampling stations viz., Station A--near Palighat, district Sheopurkalan, Station B--near Rajghat, district Morena and Station C--near Baraighat, district Bhind were established for the collection of water samples during April, 2003 to March, 2004. The water quality parameters namely transparency (12.12-110 cm), colour (transparent-very turbid), turbidity (1-178 TNU), electrical conductivity (145.60-884 microS cm(-1)), total dissolved solids (260-500 mgl(-1)), pH (7.60-9.33), dissolved oxygen (4.86-14.59 mgl(-1)), free carbon dioxide (0-16.5 mgl(-1)), total alkalinity (70-290 mgl(-1)), total hardness (42-140 mgl(-1)), chloride (15.62-80.94 mgl(-1)), nitrate (0.008-0.025 mgl(-1)), nitrite (0.002-0.022 mgl(-1)), sulphate (3.50-45 mgl(-1)), phosphate (0.004-0.050 mgl(-1)), silicate (2.80-13.80 mgl(-1)), biochemical oxygen demand (0.60-5.67 mgl(-1)), chemical oxygen demand (2.40-26.80 mgl(-1)), ammonia (nil-0.56 mgl(-1)), sodium (14.30-54.40 mgl(-1)) and potassium (2.10 mgl(-1)-6.30 mgl(-1)) reflects on the pristine nature of the river in National Chambal sanctuary. On the basis of various parameters studied, Chambal river in this stretch can be placed under the category of oligosaprobic. The water quality analysis, indicated that the riverwater in the sanctuary area is pollution free and can serve as a good habitat for many aquatic animals including endangered species.

Predictive efficacy of nalidixic acid resistance as a marker of fluoroquinolone resistance in Salmonella enterica var Typhi.

BACKGROUND AND OBJECTIVES: Resistance in Salmonella enterica var Typhi (S. Typhi) to chloramphenicol, amoxicillin and co-trimoxazole has posed a challenge to treatment of typhoid fever. Ciprofloxacin has been the empirical therapy of choice, but the recent increase in minimum inhibitory concentration (MIC) to ciprofloxacin in S. Typhi, not detectable by disc diffusion (DD) tests, may result in delayed response and serious complications. Nalidixic acid (NA) resistance has been used as an indirect evidence of increased ciprofloxacin MIC in S. Typhi. We evaluated the predictive value of NA resistance for fluoroquinolone resistance in clinical isolates of S. Typhi. METHODS: A total of 70 clinical isolates of S. Typhi were tested for antimicrobial susceptibility according to the National Committee for Clinical Laboratory Standards (NCCLS) method. MIC to fluoroquinolones was carried out by the agar dilution method. RESULTS: Thirteen (18.6 %) isolates were resistant to amoxicillin, chloramphenicol and cotrimoxazole; all were sensitive to ciprofloxacin and cefotaxime. Fifty (71.4%) were resistant to NA. Nineteen (27.1 %) isolates were resistant to ciprofloxacin by MIC tests. The MIC for ciprofloxacin was 0.03-4 microg/ml for NA(S) and 0.25-4 microg/ml for NA(R) isolates. NA susceptibility showed a predictive value of 95 per cent for ciprofloxacin susceptibility while NA resistance had a predictive value of 36 per cent for ciprofloxacin resistance. Thirty isolates studied were sensitive to gatifloxacin; MIC values were 0.03-0.5 microg/ml for NA(S) and 0.25-0.5 microg/ml for NA(R) isolates. INTERPRETATION AND CONCLUSION: NA susceptibility was a good marker for fluoroquinolone susceptibility but NA resistance had a poor predictive value for ciprofloxacin resistance. NA resistant isolates should be tested for ciprofloxacin MIC before deciding a change in therapeutic regimen. Higher MIC for gatifloxacin was also noticed in NA resistant isolates.

Predictive value of routine hematological and biochemical parameters on 30-day fatality in acute stroke.

OBJECTIVE: This prospective study was planned to study the prognostic value of routine clinical, hematological and biochemical parameters, including platelet aggregation in patients of acute stroke, on fatality occurring during the first 30 days. MATERIAL AND METHODS: In this study 116 consecutive patients (77 males and 39 females) of stroke (within 72 hours of onset) were included. After clinical evaluation and neuroimaging, blood investigations, hemoglobin, total leukocyte count, platelet count, platelet aggregation, erythrocyte sedimentation rate (ESR), blood sugar, urea, creatinine, sodium, potassium, serum cholesterol, serum bilirubin, aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), albumin, and globulin estimations were performed. The patients were followed up for a maximum period of 30 days from the onset of stroke, and patients who expired were grouped as 'expired' and the rest as 'survivors'. Logistic regression analysis was carried out among the significant parameters to identify independent predictors of 30-day fatality. RESULTS: Univariate analysis demonstrated that among hematological parameters, high total leukocyte count and ESR, at admission, correlated significantly with an undesirable outcome during the initial 30 days. Among biochemical parameters, elevated urea, creatinine, serum transaminases (SGOT and SGPT) and globulin levels correlated significantly with death. Logistic regression analysis demonstrated that a low Glasgow Coma Scale (GCS) score along with biochemical parameters such as high serum creatinine, SGPT, ESR and total leukocyte count correlated with death. CONCLUSION: Impaired consciousness, high total leukocyte count, raised ESR, elevated creatinine and SGPT levels, estimated within 24 hours of hospitalization, are the most important indicators of 30-day mortality in patients with first-time ischemic stroke.

Postpartum posterior leukoencephalopathy syndrome.

In this report we are presenting three patients of posterior leukoencephalopathy syndrome developing in postpartum period. Two of these patients had persistent imaging abnormalities in posterior parietal and occipital regions leading to focal atrophy of brain along with permanent cortical blindness and recurrent seizures. In both the patients the syndrome was either unrecognized, or remained untreated on initial presentation. In third patient also the syndrome was not recognized for 10 days, initial clinical manifestations and computed tomographic (CT) abnormalities remained unchanged even after two months. Failure to early recognition and treatment can produce permanent brain damage and syndrome of posterior leukoencephalopathy may become irreversible.

Posterior leukoencephalopathy in a girl with acute haemorrhagic leukoencephalitis.

In children, posterior leukoencephalopathy is frequently associated with hypertensive encephalopathy, anticancer chemotherapy, treatment with immunosuppressive drugs in patients with organ transplantation, transfusion or human immunodeficiency virus infection. Posterior leukoencephalopathy in these children appears as a complicating illness and resolves once precipitating factor (e.g. cancer chemotherapy) is removed. Here we are reporting a fatal case of acute haemorrhatic leukoencephalitis in a 13 year old girl, imaging abnormalities are also suggestive of posterior leukoencephalopathy. Posterior leukoencephalopathy in our patient possibly, is a part of post-infectious haemorrhagic leukoencephalitis, rather than because of ischaemia or cerebral oedema secondary either to abrupt increase in blood pressure or following administration of immunosuppressive drugs.

Medical management of neurocysticercosis.

Neurocysticercosis is the most common parasitic disease of the central nervous system. Praziquantel and albendazole, the two antiparasitic drugs, have been reported to be effective against cysticercosis. Both the drugs effectively destroy the cerebral parenchymal cystic lesions. However, albendazole is possibly more effective in subarachnoidal, ventricular and spinal forms of cysticercosis, and frequently obviates the need for surgery. Initially, longer courses of albendazole and praziquantel had been advocated. Now even shorter treatment regimens are found equally effective. Complete course of praziquantel therapy can be administered in a single day with comparable efficacy instead of conventional treatment of 15 days. Similarly, one week therapy of albendazole is as effective as 30 days' treatment regimen. Recently, there is an intense debate whether anticysticercal treatment is useful and safe. Opponents of anticysticercal therapy argue that effectiveness of therapy is possibly a reflection of natural course of the disease. It has been observed that even if cysticercal lesions are left untreated, they either disappear spontaneously or calcify. Anticysticercal therapy is potentially risky, it may aggravate cerebral oedema, and may produce vasculitis and stroke, and several deaths have also been reported. To minimise these risks, concomitant corticosteroids should be administered especially, if there is a massive parasitic load. It is better to avoid anticysticercal treatment in patients with cysticercotic encephalitis. Doubts have been expressed that anticysticercal therapy really affects ultimate long-term clinical outcomes (e.g. control of seizure and possibility of seizure free state after discontinuation of antiepileptic drugs). So far, definite evidences in this regard, based on finding of well planned placebo-controlled studies, are lacking and an opinion that, there is an urgent need for such a study, has been expressed. Measures for effective prevention like provision for safe drinking water and safe excreta disposal should be emphasisfxed.

Calcification of the thoracic ligamentum flavum: a rare cause of myelopathy.

Compressive myelopathy secondary to ossification or calcification of the ligamentum flavum is a rare entity. Clinical features and magnetic resonance imaging findings of a patient of dorsal cord compression who improved remarkably with surgery are reported.

Pathological laughter as heralding manifestation of left middle cerebral artery territory infarct: case report and review of literature.

Clinical, radiological and pathological studies in patients with stroke, presenting with pathological laughter as heralding manifestation, have shown lesions in the internal capsule and thalamus, basal ganglion, hypothalamus and ventral pons. In this report a patient with similar manifestation and having a cortical infarct in the territory supplied by superior division of middle cerebral artery is being presented. Our case suggests possible influence of dominant cerebral hemisphere, especially of Broca's area, on the motor control of laughter.

Cerebral malaria.

Cerebral malaria is a rapidly progressive potentially fatal complication of Plasmodium falciparum infection. It is characterized by unarousable and persistent coma along with symmetrical motor signs. Children, pregnant women and non-immune adults are more susceptible to have cerebral malaria. Several clinical, histopathological and laboratory studies have suggested that cytoadherence of parasitized erythrocytes (mechanical hypothesis), and neuronal injury by malarial toxin and excessive cytokine (e.g. tissue necrosis factor-alpha) production (cytotoxic hypothesis) are possible pathogenic mechanisms. Several associated systemic complications like hypoglycemia, hypovolemia, hyperpyrexia, renal failure, bleeding disorders, anemia, lactic acidosis and pulmonary oedema may contribute in the pathogenesis of coma, and are responsible for high mortality. The meticulous supportive care along with intravenous administration of antimalarial drugs are corner-stone of the treatment. Quinine is currently, drug of choice. Artimisinin derivatives are equally effective and can be used by intramuscular route. In severe cases exchange blood transfusion may be an effective alternative. Corticosteroids has no place in the management of cerebral malaria. The occurrence of convulsions are common in children, these can be prevented with the use of single intramuscular administration of phenobarbitone. Despite advances in the management mortality and morbidity have not changed much. A large number of surviving patients are left with permanent neurological sequelae. There is a need to search for effective malaria prevention and interventional strategies to avert high mortality and morbidity associated with cerebral malaria.

Neurocysticercosis like presentation in a case of CNS tuberculosis.

A clinical picture consisting of seizures, multiple non-tender subcutaneous nodules, and multiple 'nodular or ring' enhancing lesions in computed tomography of the brain is considered characteristic of neurocysticercosis in an endemic area. 1,2 A case with a similar clinical picture, in whom serological tests and histopathological examination of subcutaneous nodule established tuberculosis as a cause, is presented.