Browsing by Author "Kumar, H"

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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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    Surgery for "Long-term epilepsy associated tumors (LEATs)": Seizure outcome and its predictors
    (Clin Neurol Neurosurg, 2016-02) Radhakrishnan, A; Abraham, M; Vilanilam, G; Menon, R; Menon, D; Kumar, H; Cherian, A; Radhakrishnan, N; Kesavadas, C; Thomas, B; Sarma, SP; Thomas, SV
    Objectives: “Long-term epilepsy associated tumors (LEATs)” by definition are tumors primarily causing drug-resistant seizures for two years or more. They include low-grade glial and glioneuronal tumors with normal life expectancy. We studied a large cohort of patients with LEATs who underwent surgery through our epilepsy program. Patients & methods: From 1998–2011, 105 patients with LEATs underwent surgery in our center. We utilized their data archived in a prospective registry to evaluate their electro-clinical-imaging characteristics affecting the long-term seizure outcome. Results: Of 105patients (age 3–50 years),meanage at surgery was 20 years andmeanpre-surgicalduration of epilepsy was 10.9 years. 66 (62.8%) had secondary generalized seizures. 82 had temporal tumors, 23 had extra temporal (13 frontal, 3 parietal, 2 occipital and 5 multilobar lesions) and four had associated hippocampal sclerosis. The interictal discharges and ictal onset were concordant to the lesion in 82 (78%) and 98 (93%) patients respectively. Lesionectomy and/or adjoining corticectomy or temporal lobectomy was done. Ganglioglioma was the most dominant pathological substrate in 61 (58%). During a mean follow-up of 7.5 years (range 3–16 years), 78/105 (74.2%) were seizure-free and 45 (57.4%) were totally off drugs. Secondary generalized seizures (p-0.02), temporal location of tumor (p-0.008) and spikes in third month post-operative EEG (p-0.03) caused unfavorable seizure outcome. A pre-surgical duration of epilepsy of more than 6.6 years caused less than optimal surgical outcome Conclusions: Early surgery should be considered a priority in LEATs. Presence of secondary generalized seizures is the single most important predictor of a poor seizure outcome