Mv Padma

Molecular analysis of autosomal dominant hereditary ataxias in the Indian population: high frequency of SCA2 and evidence for a common founder mutation.

Abstract. Expansion of CTG/CAG trinucleotide repeats has been shown to cause a number of autosomal dominant cerebellar ataxias (ADCA) such as SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA8 and DRPLA. There is a wide variation in the clinical phenotype and prevalence of these ataxias in different populations. An analysis of ataxias in 42 Indian families indicates that SCA2 is the most frequent amongst all the ADCAs we have studied. In the SCA2 families, together with an intergenerational increase in repeat size, a horizontal increase with the birth order of the offspring was also observed, indicating an important role for parental age in repeat instability. This was strengthened by the detection of a pair of dizygotic twins with expanded alleles showing the same repeat number. Haplotype analysis indicates the presence of a common founder chromosome for the expanded allele in the Indian population. Polymorphism of CAG repeats in 135 normal individuals at the SCA loci studied showed similarity to the Caucasian population but was significantly different from the Japanese population.

Usefulness of short-term video EEG recording with saline induction in pseudoseizures.

Objectives ‐ To study the usefulness of short‐term recording of video electroencephalography (VEEG) as an outpatient procedure with placebo induction (PLIN) and intravenous saline in cases of pseudoseizures (Psz). Material and methods ‐ Fifty cases of suspected Psz were enrolled. They were divided into 2 groups: Group 1 consisted of patients with frank Psz, Group 2 those where diagnosis was uncertain. VEEG recording was done and 10 ml of saline used for placebo‐induction. Results ‐ Of 50 patients, 24 (48%) were in Group 1 and 26 (52%) in Group 2. Fifteen (30%) had a spontaneous event during VEEG and 33% had an event only on PLIN. The diagnosis was confirmed in 60%. In 24% of patients anti‐epileptic drugs were discontinued. Conclusion ‐ Short‐term monitoring with VEEG using PLIN is a useful initial screening procedure and in patients where it is inconclusive, long term recordings may be done.

Normobaric oxygen therapy in acute ischemic stroke: A pilot study in Indian patients

Purpose: Clinical and radiological assessment of effects of normobaric high-flow oxygen therapy in patients with acute ischemic stroke (AIS). Materials and Methods: Patients with anterior circulation ischemic strokes presenting within 12 h of onset, ineligible for intravenous thrombolysis, an National Institute of Health Stroke Scale (NIHSS) score of >4, a mean transit time (MTT) lesion larger than diffusion-weighted image (DWI) (perfusiondiffusion mismatch), and an evidence of cortical hypoperfusion on magnetic resonance imaging (MRI) were included into the trial. Active chronic obstructive pulmonary disease (COPD), requirement of >3/L min oxygen delivery to maintain SaO2 > 95%, rapidly improving neurological deficits, pregnancy, contraindications to MRI, or unstable medical conditions were excluded. The experimental group received humidified oxygen at flow rates of 10 L/min for 12 h. The NIHSS, modified Rankin Score (mRS), Barthel Index (BI) were measured at 0, 1, 7 day of admission and at 3 months follow-up. MRI with DWI/PWI was performed at admission, 24 h later and at 3 months follow-up. Results: Of 40 patients (mean age = 55.8 years ± 13.2) (range, 26–82), 20 patients were randomized to normobaric oxygen (NBO). The mean NIHSS in NBO and control groups were 14.25 and 12.7 at admission which decreased to 11.6 and 9.5 on the seventh day, and 9.4 and 9.05 at 3 months, respectively. The mean mRS (3.7/3.7) and BI (58.2/53.9) in NBO and control groups improved to 2/2.2 and 73.05/73.8 at the end of 3 months, respectively. Conclusions: NBO did not improve the clinical scores of stroke outcome in Indian patients with AIS.

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.

Memory and intelligence outcome following surgery for intractable temporal lobe epilepsy: relationship to seizure outcome and evaluation using a customized neuropsychological battery

The main objectives of this prospective study were to (1) assess memory and intelligence outcome following surgery for intractable temporal lobe epilepsy, (2) correlate this with seizure outcome and side of surgery, and (3) perform (1) and (2) using an indigenously developed battery customized to the Indian population. Prior to use in our epilepsy surgery program, the test-retest and interexaminer variance reliability of this battery had been established in both normal and cognitively compromised populations. The memory scores were overall rather than material-specific. The battery was administered to right-handed adults undergoing surgery for intractable temporal lobe epilepsy without any evidence of opposite temporal lobe abnormality, both presurgery and postsurgery at a mean follow-up of 8 months. Twenty-five consecutive patients were included; 13 underwent right and 12 underwent left temporal surgery. Seizure outcome was assessed using Engels classification. Among 13 patients who underwent right temporal surgery, although 4 patients with poor seizure outcome had insignificant changes in scores, 7 of 9 patients with good seizure outcome exhibited considerable (> 20% over preoperative) improvement in their memory and intelligence scores. Statistical analysis using Students t test and the Mann-Whitney test revealed that the patients who underwent right temporal surgery with good seizure outcome had significant improvement in both memory (P = 0.007) and intelligence (P = 0.043) scores compared with those with poor seizure outcome. In contrast, patients who underwent left temporal surgery had no significant change in cognitive scores irrespective of seizure outcome. Cognitive improvement seems to occur in patients with good seizure outcome following nondominant temporal lobe surgery for intractable epilepsy with no evidence of pathology in the opposite temporal lobe. The same finding was not observed in patients undergoing left temporal surgery.

Occurrence of only myoclonic jerks in juvenile myoclonic epilepsy

Objectives ‐ The clinical data on individuals who were diagnosed to have juvenile myoclonic epilepsy (JME) on the basis of myoclonic jerks alone has been analysed. The points in favour and against individuals with only myoclonic jerks being classified as “affected” for research on JME are discussed.

Quantification of Circulating Plasma DNA in Friedreich's Ataxia and Spinocerebellar Ataxia Types 2 and 12

DNA triplet repeat expansion-associated ataxias, Friedreichs ataxia, and different types of spinocerebellar ataxias (SCAs) are progressive multisystem neurodegenerative disorders. The diagnosis of this wide group of inherited ataxias is essentially based on clinical findings. Cell-free circulating DNA in plasma has been considered as a powerful tool in clinical diagnosis and prognosis of several human diseases. In the present study, clinically suspected patients were assessed on the International Co-operative Ataxia Rating Scale and further confirmed by molecular analysis of DNA triplet repeats. Quantification of plasma DNA using a highly sensitive and DNA-specific PicoGreen fluorescent assay was done. We found significantly high levels (p < 0.001) of plasma DNA of 167 ± 43 ng/mL in Friedreichs ataxia patients (n = 15), 148 ± 29 ng/mL in SCA2 patients (n = 10), and 137 ± 29 ng/mL in SCA12 patients (n = 25), whereas those of healthy controls (n = 20) was only 59 ± 15 ng/mL. Therefore, we were able to distinguish between ataxia patients and healthy controls using plasma DNA. Although the precise mechanism by which plasma DNA enters into circulation is not known, significantly higher concentrations of plasma DNA appears to be due to neuronal and muscular degeneration in these patients. Identification of genes in plasma DNA, which are overexpressed or novel, can be a promising tool for the prognosis of these diseases.

Surgical outcome of cortical dysplasias presenting with chronic intractable epilepsy: a 10-year experience.

BACKGROUND There has been sparse description of cortical dysplasias (CDs) causing intractable epilepsy from India. AIM Clinical retrospective study of CDs causing intractable epilepsy that underwent surgery. MATERIALS AND METHODS Fifty-seven cases of CDs reviewed (1995 till July 2006) are presented. All patients had intractable epilepsy, and underwent a complete epilepsy surgery workup (inter ictal electroencephalography (EEG), video EEG, MRI as per epilepsy protocol, SPECT {interictal, ictal with subtraction and co-registration when required}, and PET when necessary). Surgical treatment included a wide exposure of the pathology with a detailed electrocorticography under optimal anesthetic conditions. Mapping of the sensori-motor area was performed where indicated. Procedures included resection either alone or combined with multiple subpial transactions when extending into the eloquent areas. RESULTS Our study had 28 (49.12%) cases of isolated focal CDs, and 29 (50.67%) with dual pathology. Average age at the time of onset of seizures in our series was 7.04 years (three months to 24 years), and average age at the time of surgery was 10.97 years (eight months to 45 years). Among coexistent pathologies, one had associated MTS, 16 had coexistent gangliogliomas and 12 (dysembryonic neuroepithelial tumor) DNTs. At an average follow-up of 3.035 years (range 5-10 years), three patients were lost to follow-up. Fifty-one per cent (29/57) patients had a good outcome (Engel Grade I) and 26%(15/57) had a Grade II outcome. CONCLUSION Cortical dysplasias have a good outcome if evaluated and managed with concordant electrical and imaging modalities.

Family Studies and Human Leukocyte Antigen Class II Typing in Indian Probands with Seizures in Association with Single Small Enhancing Computed Tomography Lesions

Summary: Purpose: To define the clinical features of the syndrome of seizures associated with single, small, enhancing computed tomography (CT) lesions (SSELs) in 235 Indian probands and seizure types among their family members. Human leukocyte antigen (HLA) class II genomic typing in randomly selected 41 probands was done to identify the role of hereditary factors in this syndrome.

Occurrence of Epilepsies in Family Members of Indian Probands with Different Epileptic Syndromes

Summary: Purpose: Large numbers of families with many members having seizures have been used to understand the role of hereditary factors in the pathogenesis of human epileptic syndromes. We aimed to establish a genetic database to form a hypothesis on the possible genetic contributions in different epileptic syndromes.