The Effect of Dual Tasking and Deep Brain Stimulation Frequency Parameters on Gait in Advanced Parkinson's Disease.

OBJECTIVE: To study the effect of dual tasking and deep brain stimulation frequency parameters on gait in advanced Parkinson's disease. MATERIALS AND METHODS: This is an open label interventional study evaluating 40 post STN-DBS patients with gait disturbances. All patients were diagnosed as PD by a movement disorder specialist using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria. Patients underwent bilateral subthalamic deep brain stimulation by a qualified neurosurgeon. Patients were managed on a combination of dopamine replacement therapy as well as deep brain stimulation. Patients were assessed by stand walk sit (SWS) test for a 5 meter distance and FOG scoring during medication 'ON' state and device "ON" state, at four frequencies 180, 130, 90, 60 HZ and device "OFF" state. RESULTS: Out of 40 patients, 38 patients showed a significant improvement in gait at a single frequency (best response frequency) which is different for each patient. The mean FOG score showed significant improvement at all stimulation frequencies when compared to OFF stimulation (P < 0.05). The mean number of steps was 18.9 at best response frequency and 21.48 at 130 Hz (P < 0.0001). Number of freezing episodes also were significantly less with best frequency when compared to 130 Hz stimulation (0.28 and 0.65 respectively, (P < 0.0001). The mean FOG score was 6.45 at best frequency and 9.48 at 130 Hz (P < 0.0001). Mean Dual tasking score was 3.53 at best frequency and 5.15 at 130 Hz (P < 0.0002). CONCLUSION: Optimization of frequency setting for each patient can improve gait and that each patient may have a different optimal frequency.

Oxidative Stress in the Development of Genetic Generalised Epilepsy: An Observational Study in Southern Indian Population.

INTRODUCTION: Oxidative stress resulting from excessive generation of Reactive Oxygen Species (ROS) plays a significant role in neurodegeneration associated with seizures/epilepsy. AIM: To evaluate oxidative stress markers and antioxidant enzymes in Genetic Generalised Epilepsy (GGE) and to know the extent of oxidative stress induced by Anti-Epileptic Drugs (AEDs) with the time duration of treatment. MATERIALS AND METHODS: In this case-control study, 310 GGE patients (male:female=203:107), who were on AED treatment (n=235) and 75 untreated patients (male:female=49:26) along with 310 age and sex matched healthy controls were recruited. Oxidative stress markers such as Nitric Oxide (NO), Malondialdehyde (MDA) and antioxidant enzyme activities namely Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT) were measured spectrophotometrically. RESULTS: Significantly higher levels of serum NO, MDA and low levels of plasma Total Antioxidant Capacity (TAC) were found in patients as compared to controls (p<0.001) whereas erythrocyte SOD, CAT and GPx activities were found to be significantly low in patients when compared to the control group (p<0.001). Statistically significant higher levels of NO, MDA and lower levels of SOD, CAT and TAC were observed in patients subgroup, who were on AEDs for more than >5 years compared to other groups (≤ 1 year and 1-≤ 5 years) (p=0.02, p=0.01, p=0.001, p=0.01 and p=0.05 respectively). Further, significant increase in the levels of NO, MDA and decreased activities of SOD, CAT were found in treated patients compared to untreated patients (p<0.05) denoting that additional oxidative stress induced by AEDs which results in seizure recurrence and drug intractability. CONCLUSION: Our study demonstrated that GGE patients have additional oxidative stress due to AEDs and decreased antioxidant enzyme activities causing an imbalance between oxidant and antioxidant status, which might contribute to the pathogenesis of GGE.

Risk Factors, Vascular Lesion Distribution, Outcome and Recurrence of Strokes Due to Intracranial Atherosclerosis: One Year Data from Hyderabad Stroke Registry.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is a common cause of ischemic stroke in Asian countries and probably in India. AIM: The aim of this study was to describe the risk factors, distribution of vascular lesions, recurrence and outcome of stroke due to ICAS. METHODOLOGY: A total of 100 consecutive patients of ischemic stroke due to ICAS were enrolled prospectively from January 1, 2015, to December 31, 2015, and followed for 1 year for treatment compliance and recurrence. The details about demographics, risk factors, and vascular lesions were noted. RESULTS: There were 68 males and 32 females. Hypertension (HTN), diabetes, alcohol, smoking, hyperlipidemia, and hyperhomocysteinemia was present in 82%, 52%, 34%, 33%, 28%, and 23%, respectively. The number of arteries involved were middle cerebral artery, 53 (37.3%); posterior cerebral artery, 24 (16.9%); internal cerebral artery, 21 (14.8%); vertebral artery, 18 (12.7%); basilar artery, 6 (4.2%); and anterior cerebral artery, 6 (4.2%). Seventeen (17%) patients had a recurrent stroke during 1 year follow-up. The presence of uncontrolled HTN and diabetes mellitus after discharge were significantly associated with stroke recurrence (P < 0.05). The use of dual antiplatelet agents and statins was found to have a significant effect in the prevention of recurrent stroke (P < 0.05). Severe stroke at presentation and presence of hemiparesis were the predictors for unfavorable outcome at 3 months (P < 0.05). CONCLUSION: Risk factors, distribution of vascular lesions and high recurrence of stroke due to ICAS in this study is similar to that reported from other Asian countries. Aggressive medical management and risk factor control remains the best strategy for preventing recurrence.

Association of GABRA6 1519 T>C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy.

The idiopathic generalized epilepsy (IGE) is a neurological disorder which accounts for approximately 30% of all epilepsy cases. Patients identified with IGE syndromes have pharmacoresponsive epilepsies without abnormal neurological symptoms, structural brain lesions and are of unknown origin. A genetic etiology to IGEs has been proposed. Gamma amino butyric acid (GABA), a major inhibitory neurotransmitter acts by binding to transmembrane GABAA and GABAB receptors of both pre- and postsynaptic neurons. Synapsin II (SynII), a neuron specific phosphoprotein plays a major role in synaptogenesis and neurotransmitter release. The present study was carried out with an aim to evaluate the association of GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G gene polymorphisms with IGE. Molecular analysis revealed that the frequency of 'CC' genotype and 'C'allele of GABRA6 (rs3219151) T>C gene polymorphism was significantly higher in IGE patients compared to healthy controls [CC vs. TT, χ2=26; p<0.001; Odds ratio=3.6 (95% CI; 2.1-5.9); C vs T, χ2=24.7; p<0.001; Odds ratio=1.78 (95% CI; 1.4-2.2)]. The frequency of 'GG' genotype and 'G' allele of the intronic polymorphism A>G in Syn II gene was also found to be significantly associated with the disease when compared to controls [GG vs AA, χ2=64.52; p<0.001; Odds ratio=7.37 (95% CI; 4.4-12.3); G vs. A, χ2=65.78; p<0.001; Odds ratio=2.57 (95% CI; 2.0-3.2)]. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. The gene-gene interaction at two loci involving GABRA6 and Syn II revealed a significant association [χ2=36.6, p<0.001, Odds ratio=3.17 (95% CI; 2.2-4.6)] with IGE. Therefore, the present study clearly indicates that both GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh. The gene-gene interaction studies demonstrated significant interactive effects of these two loci in the development of the disease.

Association of genetic variants of fibrinolytic system with stroke and stroke subtypes.

Genetic variants of tPA (PLAT) and PAI-1 genes have been suggested to be the risk factors for stroke. In the present case-control study we investigated the association of -7351C/T polymorphism (rs2020918) and I/D polymorphism of tPA gene and Insertion/deletion polymorphism (4G/5G) of PAI-1 gene with genetic predisposition to ischemic stroke. 516 stroke patients and 513, sex and age matched healthy controls were involved in the study. We did not find a significant association of tPA -7351C/T polymorphism and PAI-1 4G/5G polymorphism with stroke. However, in case of I/D polymorphism significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. DD genotype and D allele associated significantly with stroke (p=0.002 and <0.001 respectively). We also found significant association of I/D polymorphism with intracranial large artery atherosclerosis and stroke of undetermined etiology. Exploring the association between gene-gene interaction (26 combinations including the three variants) and stroke, we found that individuals with CC+4G4G+DD, CC+5G5G+ID, CT+4G5G+ID, CT+5G5G+II, CT+5G5G+ID and TT+4G5G+II had a significantly higher risk of stroke. The results of this study suggest that -7351C/T polymorphism of tPA and 4G/5G polymorphism of PAI-1 are not associated with stroke, while as DD genotype and D allele of tPA gene are important risk factors for ischemic stroke. Further we found that the subjects with different tPA and PAI genotype combinations displayed a significantly high risk for overall ischemic stroke suggesting that gene-gene interaction involving more variants may change the susceptibility of particular subjects to the disease.

Association of C3435T multi drug resistance gene-1 polymorphism with aspirin resistance in ischemic stroke and its subtypes.

Aspirin is the most commonly used antiplatelet drug for treatment of a serious vascular event, most notably myocardial infarction and stroke. Significant fraction of aspirin treated patients is resistant to the antiplatelet effects of the drugs. Previous studies have suggested that a genetic basis for aspirin resistance exists. Therefore the present study was taken up to investigate the role of C3435T polymorphism (rs 1045642) of multiple drug resistance-1 (MDR-1) gene with aspirin resistance in stroke patients. Five hundred and sixty ischemic stroke patients and 560 age and sex matched healthy controls were involved in the study. Baseline clinical data were collected and follow-up telephone interviews were conducted with patients at 3, 6 and 12 months post event to determine stroke outcome. Blood samples were collected and genotypes determined. Significant difference was observed in the genotype distribution and allele frequency between patients and controls. The results were confirmed by a step wise multiple logistic regression analysis controlling all other confounding risk factors [adjusted Odds ratio=3.132 (95% CI; 2.043-4.800; p<0.001)]. There was a significant difference in genotype distribution between drug responders and non-responders. The risk of aspirin resistance was significantly high in patients with TT genotype in comparison to those with CC genotype [(TT vs. CC, χ(2)=6.268; p=0.012, Odds ratio=1.85) (95% CI; 1.142-3.017) (adjusted Odds ratio=2.465; 95% CI; 1.895-4.625 and p<0.001)]. As far as the stroke subtypes are concerned TT genotype associated significantly with aspirin resistance in intracranial large artery atherosclerosis. Our results indicate that the risk of aspirin resistance is more in patients with 3435TT genotype than in those with CC genotype. However, this is a preliminary study and a large study of replication is needed to confirm our results.