Browsing by Author "Sarma, G"

Now showing 1 - 3 of 3
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    Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients
    (Parkinsonism Relat Disord., 2016-12) Krishnamoorthy, S; Rajan, R; Banerjee, M; Kumar, H; Sarma, G; Krishnan, S; Sarma, S; Kishore, A
    Introduction: Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson’s disease (PD) patients. Methods: We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Results: Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR ¼ 2.22, 95% CI: 1.03e4.86, p ¼ 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR ¼ 1.14, 95% CI: 1.01e1.29, p ¼ 0.041), current dopamine agonist but not Levodopa use (OR ¼ 2.16, 95% CI: 1.03e4.55, p ¼ 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05e4.18, p ¼ 0.035) were independently associated with ICD. Conclusion: DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.
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    Impulse Control Disorders and Related Behaviors in Indian Patients With Parkinson's Disease
    (MOVEMENT DISORDERS, 2013) Sarathchandran, P; Soman, S; Sarma, G; Krishnan, S; Kishore, A
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    The decade after subthalamic stimulation in advanced Parkinson's disease: A balancing act
    (NEUROLOGY INDIA, 2016) Krishnan, S; Prasad, S; Pisharady, KK; Sarma, G; Sarma, SP; Kishore, A
    Aim: The duration of improvement in quality of life after subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) and the presurgical identification of factors predicting sustained clinical benefits have implications in patient selection and timing of surgery. These aspects were assessed in patients who underwent yearly assessment for at least 7 years after surgery. Materials and Methods: The quality of life, motor and cognitive outcomes of 25 patients who completed the 7-year assessment, and 12 patients who completed the 10-year assessment, were analyzed. Results: The improvement in quality of life was sustained only for 5 years, while the severity of motor signs and motor fluctuations remained reduced at 7 and 10 years. Tremor and rigidity showed more enduring reduction than bradykinesia and axial signs. The dose reduction in medications could be maintained until 7 years, by which time, the axial scores were worse than that seen at the pre-DBS levels. At 10 years, a higher levodopa requirement and recurrence of dyskinesias were noted. Patients with greater pre-DBS levodopa-responsive motor signs had greater long-term motor improvement. Conclusions: STN DBS performed in patients with advanced motor fluctuations and severe dyskinesias provide only an average of 5 years of quality of life improvement. STN DBS in patients with motor signs that are less responsive to levodopa results in shorter duration of clinical benefits. The improvements in the severity of motor fluctuations, rigidity, and tremor are the most enduring benefits of STN DBS that last a decade. However, these are offset by worsening axial and cognitive functions, bradykinesia, a higher levodopa requirement, and recurrence of dyskinesias by the end of the decade.