NESSCA Validation and Responsiveness of Several Rating Scales in Spinocerebellar Ataxia Type 2.

Spinocerebellar ataxia type 2 (SCA2), caused by a CAG expansion (CAGexp) at ATXN2, has a complex clinical picture. While validated ataxia scales are available, comprehensive instruments to measure all SCA2 neurological manifestations are required. This study aims to validate the Neurological Examination Score for the assessment of Spinocerebellar Ataxias (NESSCA) to be used in SCA2 and to compare its responsiveness to those obtained with other instruments. NESSCA, SARA, SCAFI, and CCFS scales were applied in symptomatic SCA2 patients. Correlations were done with age at onset, disease duration, CAGexp, and between scales. Responsiveness was estimated by comparing deltas of stable to worse patients after 12 months, according to Patient Global Impression of change, and the area under the curve (AUC) of the Receiver Operating Characteristics curve of scores range. Eighty-eight evaluations (49 patients) were obtained. NESSCA had an even distribution and correlated with disease duration (r = 0.55), SARA (r = 0.63), and CAGexp (rho = 0.32): both explained 44% of NESSCA variance. Deltas (95% CI) after 1 year in stable and worse patients were only significantly different for SARA. NESSCA, SARA, SCAFI, and CCFS AUC were 0.63, 0.81, 0.49, and 0.48, respectively. NESSCA is valid to be used in SCA2. However, the only instrument that presented good responsiveness to change in 1 year was SARA. We suggest that NESSCA can be used as a secondary outcome in future trials in SCA2 due to the burden of neurological disabilities related to disease progression.

Polymorphisms in the dopamine transporter gene are associated with visual hallucinations and levodopa equivalent dose in Brazilians with Parkinson's disease.

The requirement for dopaminergic drugs in Parkinson's disease (PD) is highly variable. Visual hallucinations are a frequent and serious complication of chronic levodopa therapy. Polymorphisms in the DAT1 gene might affect the reuptake of dopamine in the synaptic cleft, but the influence of this variability on adverse effects or levodopa equivalent dose on PD patients is still poorly investigated. Therefore, the aim of the present study was to investigate DAT1 gene polymorphisms on levodopa equivalent dose and visual hallucination occurrence in PD patients. Altogether, 196 PD patients in treatment with at least 200 mg levodopa equivalent dose for at least 1 yr were included. These patients were genotyped for the -839 C > T and 3' VNTR DAT1 polymorphisms by PCR-based methodologies. Visual hallucinations occurred in 25.5% of the sample. After controlling for confounders, the dopamine transporter (DAT) -839 C allele was associated with visual hallucinations (prevalence ratio 2.5, 95% confidence intervals 1.13-5.5, p = 0.02). Levodopa equivalent dose was lower in carriers of the nine repeat allele of the DAT 3'UTR VNTR (741.2 ± 355.0 vs. 843.4 ± 445.7), explaining 21% of dose variability (p = 0.01). Our results support an effect of DAT1 polymorphisms in adverse effects of anti-Parkinsonian drugs and in levodopa equivalent dose usage.

DRD2 haplotype is associated with dyskinesia induced by levodopa therapy in Parkinson's disease patients.

AIM: Dyskinesia and motor fluctuation are frequent and serious complications of chronic levodopa therapy in patients with Parkinson's disease. Since genetic factors could play a role in determining the occurrence of these problems, the aim of the present study was to investigate whether possible functional polymorphisms among DRD2 and ANKK1 genes are associated with the risk of developing dyskinesia and motor fluctuations in Parkinson's disease patients. PATIENTS & METHODS: One hundred and ninety nine patients in treatment with levodopa were genotyped for the -141CIns/Del, rs2283265, rs1076560, C957T, TaqIA and rs2734849 polymorphisms at the DRD2/ANKK1 gene region. RESULTS: Carriers of the TTCTA haplotype showed an increased risk for the presence of dyskinesia (p = 0.007; 1.538 [95% CI: 1.126-2.101]). CONCLUSION: Our data suggest an influence of the DRD2/ANKK1 gene region on levodopa-induced dyskinesia.

S100B and NSE serum concentrations in Machado Joseph disease.

BACKGROUND: NSE and S100B are considered as neuronal and glial peripheral markers of central nervous system pathologies, respectively. We evaluated the potential use of S100B and NSE serum concentrations as peripheral markers of symptomatic patients with Machado Joseph disease (MJD). METHODS: We measured S100B and NSE peripheral concentrations of 22 MJD patients and compared with healthy subjects concentrations. The correlations of both markers with CAG repeat size, age of onset, disease duration, and the scores of the Extended Disability Status Scale of Kurtzke, Unified Parkinson's Disease Rating Scale, and the Montgomery-Asberg depression rating scale were also assessed. RESULTS: S100B serum concentrations between control and MJD subjects were not statistically different, whereas NSE serum concentrations were higher in MJD patients than in control subjects (p=0.00001). S100B presented a moderate correlation with disease duration and depression score, whereas NSE presented a moderate correlation with depression score and a good negative correlation with EDSS score. CONCLUSIONS: Symptomatic MJD patients present increased concentrations of NSE and normal concentrations of S100B in blood.