Sudesh Prabhakar

Intravenous Autologous Bone Marrow Mononuclear Stem Cell Therapy for Ischemic Stroke: A Multicentric, Randomized Trial

Background and Purpose— Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. Methods— This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of 18fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days. Results— Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (−11.1 versus −7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of 18fluorodeoxyglucose uptake. Conclusions— With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome. Clinical Trial Registration— URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.

Comparison of CT venography with MR venography in cerebral sinovenous thrombosis

OBJECTIVE The purpose of this study was to compare cerebral CT venography with MR venography and determine the reliability of CT venography in the diagnosis of cerebral sinovenous thrombosis. SUBJECTS AND METHODS Fifty patients who were clinically suspected of having cerebral sinovenous thrombosis, irrespective of age and sex, underwent cerebral CT venography and MR venography. Projection venograms were displayed using maximum-intensity-projection images for both CT venography and MR venography. The CT venograms were also displayed using the integral algorithm, which depicts the average intensity value of the first five voxels deep in relation to the model surface that is nearest the viewer, allowing direct visualization of the thrombus in the sinuses. All CT venograms and MR venograms were independently evaluated by experienced neuroradiologists. RESULTS Of these 50 patients, 30 patients were diagnosed as having cerebral sinovenous thrombosis on both CT venography and MR venography. The total numbers of sinuses involved were 81 and 77 (CT venography and MR venography). When MR venography was used as the gold standard, CT venography was found to have both a sensitivity and a specificity of 75-100%, depending on the sinus and vein involved. CONCLUSION CT venography is as accurate as MR venography for diagnosing cerebral sinovenous thrombosis.

Bacterial meningitis and epilepsy

The high incidence and prevalence of epilepsy in developing countries has partly been attributed to an increased frequency of central nervous system (CNS) infections. Of the CNS infections, bacterial meningitis is endemic in many countries and several epidemics have also been reported in these regions. Unprovoked seizures and epilepsy (recurrent unprovoked seizures) can be long‐term sequelae of bacterial meningitis. The probability of developing an unprovoked seizure or epilepsy varies according to the etiologic agent responsible for meningitis and this probability appears to be higher for Streptococcus pneumoniae. The risk factors for late unprovoked seizures/epilepsy include early seizures during the acute phase of meningitis and persistent neurological deficits other than sensorineural hearing loss. The majority of unprovoked seizures occur within 5 years of the meningitis episode and tend to be recurrent. The burden of epilepsy associated with bacterial meningitis depends upon the incidence of the latter and hence is to some extent preventable. Implementing vaccination programs against the three most important meningeal pathogens can reduce the incidence of bacterial meningitis. In developed countries, a decline in the incidence of bacterial meningitis has been accomplished with the implementation of vaccination programs.

Ophthalmoplegia With Migraine in Adults: Is It Ophthalmoplegic Migraine?

Objective.— Ophthalmoplegic migraine (OM) is a rare disorder characterized by recurrent oculomotor nerve palsy in children, following migraine headaches. We report 62 adults, seen consecutively, who developed acute ophthalmoplegia with severe attacks of migraine over a 10‐year (1996‐2005) period. An overwhelming majority of these patients had an antecedent worsening in severity of migraine headaches, before the ophthalmoplegic attack.

Bacopa monniera Attenuates Scopolamine-Induced Impairment of Spatial Memory in Mice

Scopolamine, an anticholinergic, is an attractive amnesic agent for discerning the action of candidate antiamnesic drugs. Bacopa monniera Linn (Syn. Brahmi) is one such antiamnesic agent that is frequently used in the ancient Indian medical system. We have earlier reported the reversal of diazepam-induced amnesia with B. monniera. In this study we wanted to test if scopolamine-induced impairment of spatial memory can also be ameliorated by B. monniera using water maze mouse model. The objective of study was to study the effect of B. monniera on scopolamine-induced amnesia. We employed Morris water maze scale to test the amnesic effect of scopolamine and its reversal by B. monniera. Rotarod test was conducted to screen muscle coordination activity of mice. Scopolamine significantly impaired the acquisition and retrieval of memory producing both anterograde and retrograde amnesia. Bacopa monniera extract was able to reverse both anterograde and retrograde amnesia. We propose that B. monnieras effects on cholinergic system may be helpful for developing alternative therapeutic approaches for the treatment of Alzheimers disease.

Neuroprotective effect of Bacopa monniera on ischemia induced brain injury.

PURPOSE Brain stroke is a leading cause of death without effective treatment. B. monniera, an Indian herbal medicine, exerts antioxidant activity and antistress activity by modulating the antioxidative defence system. We wanted to test if B. monniera could alleviate the ischemia induced brain injury and cognitive dysfunction in Wistar rats. PROCEDURE We studied the effect of B. monniera (120mg kg(-1), 160mg kg(-1) and 240mg kg(-1) P.O.) on transient intracarotid artery (ICA) occlusion induced ischemia by testing the neurobehavioral and biochemical parameters on treated and control rats. FINDINGS B. monniera attenuated the reduced transfer latency in ischemic rats in a step through test and showed a protective effect on ischemia induced memory impairment in the plus maze task. It also showed a marginal improvement in neurodeficit score and fore limb muscle grip strength. B. monniera reduced the infarct size in the ischemic brain. It also decreased nitrite, nitrate and lipid peroxidation and significantly improved catalase activity. CONCLUSION These observations suggest the neuroprotective and antioxidant activity of B. monniera on ischemia induced brain injury and pave the way for future investigations.

Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients.

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability‐enhancer. The present study aimed at evaluating the effect of piperine on the steady‐state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t‐test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC0‐12hr (p < 0.001), average Css (p < 0.001), t1\2el (p < 0.05) and a decrease in Kel (p < 0.05), in both the dose groups, whereas changes in Ka and t1\2a were not significant. Cmax (p < 0.01) and tmax (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption. Copyright

Sodium Valproate, Hyperandrogenism and Altered Ovarian Function in Indian Women with Epilepsy: A Prospective Study

Summary:  Purpose: To assess the association of long‐term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy.

Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no effective treatment. Stem cell therapy may be one of the promising treatment options for such patients. AIM To assess the feasibility, efficacy and safety of autologous bone marrow-derived stem cells in patients of ALS. SETTINGS AND DESIGN We conducted an open-label pilot study of autologous bone marrow-derived stem cells in patients with ALS attending the Neurology Clinic of a tertiary care referral centre. MATERIALS AND METHODS Ten patients with ALS with mean revised ALS Functional Rating Scale (ALSFRS-R) score of 30.2 (± 10.58) at baseline received intrathecal autologous bone marrow-derived stem cells. Primary end point was improvement in the ALSFRS-R score at 90, 180, 270 and 365 days post therapy. Secondary endpoints included ALSFRS-R subscores, time to 4-point deterioration, median survival and reported adverse events. Paired t-test was used to compare changes in ALSFRS-R from baseline and Kaplan-Meier analysis was used for survival calculations. RESULTS There was no significant deterioration in ALSFRS-R composite score from baseline at one-year follow-up (P=0.090). The median survival post procedure was 18.0 months and median time to 4-point deterioration was 16.7 months. No significant adverse events were reported. CONCLUSION Autologous bone marrow-derived stem cell therapy is safe and feasible in patients of ALS. Short-term follow-up of ALSFRS-R scores suggests a trend towards stabilization of disease. However, the benefit needs to be confirmed in the long-term follow-up period.

Apo-E4 Allele in Conjunction with Aβ42 and Tau in CSF: Biomarker for Alzheimers Disease

The objective of this study was to elucidate an association between Apo- E4 allele and CSF biomarkers Aβ42 and tau for the diagnosis of Alzheimers Disease (AD) patients. Aβ42 and tau protein concentrations in CSF were measured by using ELISA assays. The levels of Aβ42 were found to be decreased where as tau levels increased in AD patients. Moreover in AD patients Apo-E4 allele carriers have shown low Aβ42 levels (328.86 ± 99.0 pg/ml) compared to Apo- E4 allele non-carriers (367.52 ± 57.37 pg/ml), while tau levels were higher in Apo-E4 allele carriers (511 ± 44.67 pg/ml) compared to Apo-E4 allele non-carriers (503.75 ± 41.08 pg/ml). Combination of Aβ42 and tau resulted in sensitivity of 75.38% and specificity of 94.82% and diagnostic accuracy of 84.30% for AD compared with the controls. Therefore low Aβ42 and elevated tau concentrations in CSF may prove to be a better diagnostic marker for AD along with the Apo-E4 allele.