Browsing by Author "Kishore, Asha"

Now showing 1 - 8 of 8
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    Acute dopamine boost has a negative effect on plasticity of the primary motor cortex in advanced Parkinson's disease
    (BRAIN, 2012)
    Plasticity of primary motor cortex is severely impaired in Parkinson's disease and chronic dopaminergic treatment is reported not to rescue it. The effect of an acute dose of levodopa on cortical plasticity reported so far is variable. In this study, it was hypothesized that cortical plasticity would be restored in Parkinson's disease as a long duration response to treatment in stable responders while those with motor complications would have a reduction or loss of plasticity similar to the decay of long duration response of motor signs. Patients were carefully stratified based on their motor response to levodopa into stable responders (n = 17), fluctuating non-dyskinetics (n = 18) and fluctuating dyskinetics (n = 20). Theta burst stimulation was applied to the motor cortex to induce long-term potentiation and long-term depression-like plasticity in both OFF and ON conditions. In OFF, stable responders could express both types of plasticity, fluctuating non-dyskinetics had long-term potentiation, but no long-term depression and both types of plasticity were lost in fluctuating dyskinetics. This suggests the presence of a long duration response in early stages of levodopa treatment and a gradual loss of chronic treatment benefit on plasticity, particularly for long-term depression, when motor complications develop. An acute dose of levodopa led to a worsening of long-term potentiation in fluctuating non-dyskinetic patients, and it did not have any effect on the plasticity that was absent in OFF in the fluctuating dyskinetic patients. Acute dosing led to a worsening of long-term depression in all the groups. In the fluctuating dyskinetic patients, there was a paradoxical potentiation instead of depression. Our results suggest that an acute non-physiological dopamine boost has a negative effect on cortical plasticity as disease advances. We propose that the loss of long duration response and the negative effect of acute doses on cortical plasticity with progression of disease may contribute to the pathophysiology of motor complications. Repeated non-physiological surges in synaptic dopamine during acute levodopa dosing could potentially lead to persistent dysfunction of key enzymes of the intracellular signalling cascade that are involved in the induction and maintenance of both forms of plasticity.
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    Co-occurrence of radiological features of progressive supranuclear palsy and corticobasal degeneration
    (NEUROLOGY INDIA, 2007)
    We report an interesting case demonstrating co-occurrence of radiological features of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). The clinical features were typical of PSP but magnetic resonance imaging (MRI) showed both typical brainstem changes of PSP and an atypical pattern of cortical atrophy. While the MRI had markers of CBD, the clinical features were not classical of CBD.
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    Do Nonmotor Symptoms in Parkinson's Disease Differ from Normal Aging?
    (MOVEMENT DISORDERS, 2011)
    Background: Nonmotor symptoms in Parkinson's disease are frequent and affect health-related quality of life of patients. The severity and domains of nonmotor symptoms involved in Parkinson's disease and normal aging have not been compared before.Methods: We performed a prospective case-control study to assess the frequency and severity of nonmotor symptoms in patients with Parkinson's disease (n = 174) and age-matched normal controls (n = 128) using the Non-Motor Symptoms Scale.Results: Nonmotor symptoms in Parkinson's disease were ubiquitous, more frequent, and more severe than in normal aging, particularly in women. Cardiovascular, mood/cognition, and perceptual problems/hallucinations domains were rarely involved in age-matched controls. Age had no effect and sex some influence on nonmotor symptoms in Parkinson's disease. In contrast, in controls, nonmotor symptoms increased with age, and sex had no effect.Conclusions: Nonmotor symptoms in Parkinson's disease differ from those in aging in frequency, severity, sex predilection, and domain involvement. (C) 2011 Movement Disorder Society
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    Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson's disease
    (CLINICAL NEUROPHYSIOLOGY, 2012)
    Objective: To test the plasticity of bilateral motor cortices (M1) in treatment-nave (de novo) Parkinson's disease (PD) patients and its response to single dose of L-DOPA.Methods: Twenty-one de novo PD patients with only unilateral motor symptoms were recruited to eliminate the effects of advanced disease and chronic treatment and were tested with intermittent (n = 10) and continuous theta burst stimulation (iTBS and cTBS) (n = 11) protocols to induce LTP and LTD-like plasticity on both M1 cortices. They were compared with two groups of 10 each, age-matched, healthy volunteers (HV). Severity of motor signs and effectiveness of TBS were measured bilaterally in the untreated state and after a uniform dose of L-DOPA in all patients.Results: iTBS and cTBS induced significant LTP and LTD-like plasticity in M1 of HV. In de novo patients, there was no plasticity in both M1. Acute L-DOPA challenge did not improve plasticity in either M1 cortices, though motor signs of PD improved. There was no correlation of motor signs with M1 plasticity.Conclusion: The early, severe and bilateral loss of plasticity in M1 in de novo PD patients is a primary disease-related cortical dysfunction. The contrasting L-DOPA response of motor signs and M1 plasticity could arise from differences in neural circuits mediating them or differing effects of acute dopamine replacement on circuits recruited by specific plasticity-induction techniques, particularly in treatment nave PD.Significance: M1 plasticity defect occurs early in PD and might affect motor learning. Acute vs. chronic dopamine replacement could have different effects on plasticity in PD or in the networks recruited by a specific plasticity induction technique. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
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    Long-Term Stability of Effects of Subthalamic Stimulation in Parkinson's Disease: Indian Experience
    (MOVEMENT DISORDERS, 2010)
    Reports of long-term effects of subthalamic (STN) stimulation for Parkinson's disease (PD) are few, mostly open-label evaluations and from Western centers. We used single-blind and open-label motor, cognitive and quality of life (QOL) evaluations to study the effects of bilateral STN stimulation in 45 patients over 5 years. Our patients showed a stable and substantial reduction in the cardinal signs of PD, motor fluctuations, and dyskinesias but less so for axial signs. The reduction in medications and the intensity of electrical stimulation needed also remained stable during follow up. Although the total QOL and its parkinsonism and social components showed sustained benefits till 5 years, the gains in emotional and systemic subsets were short lasting. Global scores for mood and cognition did not show significant worsening. Benefits of STN stimulation on the cardinal signs, motor complications, and QOL of advanced PD were substantial and sustained till 5 years. The initial benefits in axial motor signs and emotional and psychological aspects of QOL did not show similar stability. In general, the procedure had insignificant impact on cognition and mood. This is the first report of STN stimulation in Asian patients with PD. (C) 2010 Movement Disorder Society
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    LRRK2 G2019S mutation does not contribute to Parkinson's disease in South India
    (NEUROLOGY INDIA, 2011)
    Background: The frequency of leucine-rich repeat kinase 2 (LRRK2) G2019S mutation, the most common genetic cause of Parkinson's disease (PD), shows significant variation based on ethnicity. Earlier reports suggest a very low frequency or absence of this mutation in Asians. Objective: To analyze the frequency of LRRK2 G2019S mutation in sporadic and familial cases of PD and normal controls of common ethnicity from South India. Patients and Methods: We used direct sequencing technique of all DNA samples in a clinic-based study of sporadic (n = 100) and familial PD patients (n = 86 index cases) and normal controls (n = 100) of common ethnicity from South India. Results: None among the patients or controls had the G2019S mutation. Conclusion: The founding events that influenced a number of other populations/ethnicities had no impact on the genetic makeup of PD patients from South India. Our findings support the current view that G2019S-associated PD may be population-specific. This has implications in genetic testing for PD and selection of subjects for potential future gene-based therapeutic trials for G2019S carriers in such populations.
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    Neuropsychological functions in progressive supranuclear palsy, multiple system atrophy and Parkinson's disease
    (NEUROLOGY INDIA, 2006)
    Background: Few studies have compared cognitive functions in multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and Parkinson's disease (PD). Aim: To compare the results of cognitive function tests in the three diseases and examine their relation with the severity of parkinsonism. Settings and Design: Clinic-based open prospective study. Materials and Methods: Global cognitive function tests and tests specific for frontal lobe functions were used in 25 cases of each disease. UPDRS III was used to measure the severity of parkinsonism. Statistical Analysis: ANOVA was done for group comparisons, followed by t-test for independent samples with Bonferroni correction. Pearson's correlation test was done to assess the relation between severity of parkinsonism and cognitive functions. Results: The severity of parkinsonism was worst in PD followed by PSP and least in MSA. Patients with PSP exhibited the worst performance in both sets of cognitive tests. Even though patients with MSA did better than PD in global function tests, they performed worse than PD in some frontal function tests. There was a negative correlation between severity of parkinsonism and scores in cognitive tests in the MSA group but not in others. Conclusions: Global and frontal dysfunction was worst in PSP. The frontal dysfunction in MSA was more severe than PD, correlated with the severity of parkinsonism and was worse in clinically probable than possible cases of MSA. The severity of cognitive dysfunction in these diseases may be related to the distribution and extent of pathological changes affecting the striato-frontal circuits in them.
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    Utility of susceptibility-weighted MRI in differentiating Parkinson's disease and atypical parkinsonism
    (NEURORADIOLOGY, 2010)
    Neuropathological studies report varying patterns of brain mineralization in Parkinson's diseases (PD), progressive supranuclear palsy (PSP), and Parkinson variant of multiple system atrophy (MSA-P). Susceptibility-weighted imaging (SWI) is the ideal magnetic resonance imaging (MRI) technique to detect mineralization of the brain. The purpose of this study was to test if SWI can differentiate PD, PSP, and MSA-P.Eleven patients with PD, 12 with PSP, 12 with MSA-P, and 11 healthy controls underwent SWI of the brain. Hypointensity of putamen, red nucleus, substantia nigra, and dentate nucleus in all groups were measured using an objective grading scale and scored from 0 to 3.In PSP, hypointensity score of red nucleus was higher than that in MSA-P (p = 0.001) and PD (p = 0.001), and a score of a parts per thousand yen2 differentiated the PSP group from the PD and MSA-P groups. Putaminal hypointensity score was higher in PSP when compared to that in PD (p = 0.003), and a score of a parts per thousand yen2 differentiated PSP from PD groups. SWI hypointensity scores of red nucleus and putamen had an excellent intrarater and interrater correlation. Substantia nigra hypointensity score of the PSP group was higher than that of the MSA-P (p = 0.004) and PD (p = 0.006) groups, but the scores had only a moderate intrarater and interrater correlation.SWI shows different patterns of brain mineralization in clinically diagnosed groups of PD, PSP, and MSA-P and may be considered as an additional MR protocol to help differentiate these conditions.