Sundararajan Baskar Singh

Hyperacute thrombolysis with IV rtPA of acute ischemic stroke: Efficacy and safety profile of 54 patients at a tertiary referral center in a developing country

BACKGROUND Given the constraints of resources, thrombolysis for acute ischemic stroke (AIS) is under evaluation in developing countries. Prothrombin time (PT), platelet count and activated partial thromboplastin time (aPTT) may not be feasible within the time window. AIM To evaluate the safety and efficacy of thrombolysis in selected patients without the coagulation profile. DESIGN Open, nonrandomized, observational study. MATERIALS AND METHODS Fifty-four stroke patients were classified using TOAST criteria (large artery atherosclerotic = 13; cardioembolic = 12; small vessel occlusion = 22; other determined etiology =three; undetermined etiology = four). The mean time to reach emergency was 2.4h (1.15-3.4), the mean door to CT, 24 min (10-47) and the door to recombinant tissue plasminogen activator (r-tPA) injection, 26.8 min (25-67). The NIHSS scores ranged from 11 to 22 (mean = 15.5 +/- 2.7). Patients with history of liver or renal disease or those on anticoagulants were excluded. The PT, aPTT and platelet count were not done. Recombinant tissue plasminogen activator was administered at a dosage of 0.9 mg/Kg. RESULTS Thirty-five patients (65%) significantly improved on NIHSS at 48 h (> or =4 points) (mean change = 10; range= 4-17). At one month, 43 (79%) improved on Barthel Index (mean change = 45%). One each developed small frontal lobe hemorrhage and recurrent stroke; one died of aspiration; and eight showed no improvement. CONCLUSIONS Hyperacute thrombolysis was found useful and safe in selected patients with AIS even without the coagulation studies.

Validity of the Berlin Questionnaire in identifying obstructive sleep apnea syndrome when administered to the informants of stroke patients

Given the high prevalence of sleep-disordered breathing (SDB) in stroke and its importance as a vascular risk factor, a clinical instrument to assess its incidence would be useful. Acute stroke patients (n=121) were stratified into high- and low-risk groups for SDB using a modified Berlin Questionnaire (BQ) administered to the informants who were living with the patient. After a minimum of 4 weeks from stroke onset, patients who were fit underwent overnight polysomnography (PSG). On stratifying risk of obstructive sleep apnea (OSA) in these patients based on the BQ, 53% belonged to the high-risk group and 47% belonged to the low-risk group. There was poor correlation between the clinical questionnaire results and PSG findings, with sensitivity of 66.7%, specificity of 55.6%, a positive predictive value of 63.4%, and a negative predictive value of 58.8%.

Clinical speech impairment in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy

CONTEXT Speech abnormalities are common to the three Parkinsonian syndromes, namely Parkinsons disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), the nature and severity of which is of clinical interest and diagnostic value. AIM To evaluate the clinical pattern of speech impairment in patients with PD, PSP and MSA and to identify significant differences on quantitative speech parameters when compared to controls. DESIGN AND SETTING Cross-sectional study conducted in a tertiary medical teaching institute. MATERIALS AND METHODS Twenty-two patients with PD, 18 patients with PSP and 20 patients with MSA and 10 age-matched healthy controls were recruited over a period of 1.5 years. The patients were clinically evaluated for the presence and characteristics of dysarthria. This was followed by quantitative assessment of three parameters: maximum phonation time (MPT), semantic fluency and reading speed. The outcome measures were compared between the patient groups and with controls. RESULTS Patients with PD had hypophonic monotonous speech with occasional rushes of speech while patients with MSA and PSP had mixed dysarthria with ataxic and spastic elements respectively. All quantitative parameters were affected when compared to controls (P values<0.001, 0.012 and 0.008 respectively). Maximum phonation time was significantly less in PSP when compared to MSA and PD (P=0.015). Reading speed also showed a similar trend which was not statistically significant. Semantic fluency was comparable in all three groups. CONCLUSION Dysarthria in PD, PSP and MSA have many overlapping but certain distinctive features as well which could serve as a diagnostic clue. Patients with PSP had profound speech impairment probably indicative of the more severe frontostriatial pathology.

Detection of the membrane attack complex as a diagnostic tool in dermatomyositis

Jain A, Sharma MC, Sarkar C, Bhatia R, Singh S, Gulati S, Handa R. Detection of the membrane attack complex as a diagnostic tool in dermatomyositis.
Acta Neurol Scand: 2011: 123: 122–129.
© 2010 John Wiley & Sons A/S.

Effect of fluoroquinolones on the expression of matrix metalloproteinase in debrided cornea of rats

Matrix metalloproteinases (MMPs) are implicated in regenerative and healing processes in corneal injuries. Based upon reports that topical fluoroquinolones (FQs) may cause perforations during corneal healing by modulating MMPs, this study evaluated the comparative effects of commercially available FQs eye drops on the expression of MMP-2 and MMP-9 in the cornea after ethanol injury. Uniform corneal epithelial defects were created using 70% ethanol in the right eye of the rats (n = 6). The groups studied were (I) sham, (II) normal saline with benzalkonium chloride (NS-BKC), (III) norfloxacin 0.3%, (IV) ciprofloxacin 0.3%, (V) lomefloxacin 0.3%, (VI) sparfloxacin 0.3%, (VII) gatifloxacin 0.3%, and (VIII) moxifloxacin 0.5%. Each treatment was instilled six times/day up to 48 h and rats were sacrificed using excess of anesthesia. The corneas were excised to study the expression of MMP-2 and MMP-9 using gelatin zymography and real-time PCR. All the FQs significantly increased the expression of MMP-2 and MMP-9 as compared to the sham and NS-BKC-treated group. NS-BKC did not show a significant effect on MMPs expression compared to the sham group. Among the studied FQs, ciprofloxacin was observed to exhibit maximal induction of MMP-2 and MMP-9, whereas lomefloxacin exhibited an equivocal effect on both MMP-2 and MMP-9 expression. Findings of the present study demonstrate that topical application of FQs may induce the expression of MMP-2 and MMP-9 in debrided corneal epithelium and, therefore, may delay corneal wound healing. Thus, it can be concluded that selecting a FQ for ophthalmic use having minimal effect on MMPs may impact wound healing in injured or vulnerable cornea.

Group III PLA2 from the scorpion, Mesobuthus tamulus: cloning and recombinant expression in E. coli

Phospholipases A 2 (PLA 2 ) are enzymes that specifically hydrolyze the sn-2 fatty acid acyl bond of phospholipids, producing a free fatty acid and a lyso-phospholipid. We report the cloning and expression of a secretory phospholipase A 2 (sPLA 2 ) from Mesobuthus tamulus , Indian red scorpion. The nucleotide sequence codes for a 167 residue enzyme. The open reading frame codes for a 31 amino acid signal peptide followed by a mature portion of the protein. The primary structure shows the calcium binding motif, catalytic residues, 8 highly-conserved cysteines and C-terminal extension which classify it as a group III PLA 2 . The entire transcript was expressed in Escherichia coli and was purified by metal affinity chromatography under denaturing conditions. The protein was refolded by serial dilutions in the refolding buffer to its active form. Hemolytic assays indicate that the protein adopts a functional conformation. The functional requisites such as optimum pH of 8 and calcium dependency are shown. This report provides a simple but robust methodology for recombinant expression of toxic proteins.

Long-term outcome of decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A prospective observational study

BACKGROUND Malignant middle cerebral artery (MCA) infarction is associated with high mortality and morbidity. Decompressive hemicraniectomy (DH) reduces mortality significantly but evidence for long-term functional benefit is sparse and contradictory. MATERIALS AND METHODS A total of 60 patients with malignant MCA infarction were prospectively enrolled. 36 (60%) patients underwent DH and 24 (40%) patients received best medical therapy alone. Both groups were followed-up for 1 year for improvement in disability and aphasia using modified Rankin score (mRS) and Western Aphasia Battery respectively. Good outcome was defined as mRS ≤ 3. Secondary analysis using mRS ≤ 4 was also performed. RESULTS An absolute risk reduction of 45% was observed in mortality at 1 year; 38% (14/36) in the surgical group died versus 83% (20/24) in the medical group. Good outcome at 1 year was achieved in 20% (7/35) patients in the surgical group compared with none in the medical group (P = 0.025). Repeated measures regression suggested increased proportion of patients improving over time (discharge, 3, 6 and 12 months). Surgery reduced the odds of moderate to severe disability (mRS ≥ 4) by 93.5% (odds ratio: 0.064, 95% confidence interval: 0.01-0.045, P = 0.006). CONCLUSIONS DH in malignant MCA infarction not only reduces mortality but also increases chances of a better functional outcome. The benefit of surgery in motor and aphasia recovery is progressive and sustained until 1 year.

Development and validation of a highly sensitive LC-MS/MS method for organic cation transporter (OCT) substrate tetraethylammonium (TEA) in rabbits.

Tetraethylammonium is widely used as a probe in organic cation transporters studies. A simple, highly sensitive, and specific method using direct protein precipitation was developed using Hydrophilic Interaction Liquid Chromatography coupled with positive electrospray ionization tandem mass spectrometry for the determination of tetraethylammonium (TEA) in rabbit plasma. Isocratic separation was achieved using a ZIC-HILIC column with acetonitrile and 5mM ammonium acetate in the ratio of 8:2 containing 0.1% formic acid. Acquisition was performed in multiple reaction monitoring mode with the transitions: m/z 130→100 and 130→86 for TEA and m/z 276.1→142.2 for internal standard (homatropine). This method was validated to determine selectivity, linearity, sensitivity, precision, accuracy, recovery and stability. A good linearity was found within a range of 1.53-784.6 ng/mL. The above method has been demonstrated for its capability to estimate the plasma levels of TEA after its topical instillation in rabbit eyes. This method provides an accurate, precise and sensitive tool for determining TEA levels for transporter studies.

Clinical spectrum of Hallervorden-Spatz syndrome in India.

Hallervorden-Spatz syndrome is a rare autosomal recessive disorder that involves progressive extrapyramidal manifestations. Classical and atypical clinical presentations are known. Clinical details of patients admitted to the neurology ward or attending the movement disorder clinic of the All India Institute of Medical Sciences between January 2001 and July 2007 were reviewed. Sixteen patients (9 males and 7 females) were included in the study (median age 14 years; range 6-25). The most common clinical presentation was limb or cranial onset progressive dystonia. The patients with early onset had more frequent truncal and axial dystonia, including retrocollis, oromandibular-facial dystonia and chorea, dysarthria, pyramidal signs, gait disturbance, cognitive impairment, delay in milestones, retinitis pigmentosa, optic atrophy, oculomotor abnormalities, positive family history and acanthocytosis. Although rare, cerebellar ataxia, behavioural abnormalities, parkinsonism and apraxia of eyelid opening were exclusively seen in late onset patients. The present study highlights the heterogeneity of this disease entity and also describes certain unusual clinical features.

IgM anti-GM1 antibody titers in patients with monomelic amyotrophy

BACKGROUND Monomelic amyotrophy (MMA) is a benign motor neuron disorder, which particularly affects young people and the etiology is still unknown. Gangliosides are located on the outer surface of motor neurons. Anti-GM1 antibodies have been found to be elevated in multi-focal motor neuropathy with conduction block and other neurological diseases, which may have therapeutic implication. AIM To evaluate IgM anti-GM1 antibody titers in patients of monomelic amyotrophy. SETTING AND DESIGN prospective controlled study. MATERIALS AND METHODS Forty-six clinically and electrophysiologically diagnosed cases of MMA were assessed for IgM anti-GM1 antibody titers by enzyme-linked immunosorbent assay (ELISA) method and compared with titers in healthy controls, cases of amyotrophic lateral sclerosis (ALS) and acute inflammatory demyelinating polyneuropathy (AIDP). Titer of 800 units was taken as upper limit of normal (Buhlmann Laboratories AG, Switzerland). STATISTICAL ANALYSIS USED one-way ANOVA. RESULTS The mean age of 46 patients with MMA was 24.5 (+/- 7.3) years, with male female ratio of 44:2. The mean age of 19 healthy controls was 24.1 (+/- 3) years with male: female ratio of 18:1. Five (26%) individuals in the healthy control group, 22 (48%) patients of MMA, four (30%) of ALS and five (50%) of AIDP had high titers of IgM anti-GM1 antibody (P> 0.05). CONCLUSIONS Although larger number of patients with MMA had higher IgM anti-GM1 antibody titers, the difference was not statistically significant from titers of healthy individuals and of patients in the ALS and AIDP group.