Testosterone Levels Are Decreased and Associated with Disease Duration in Male Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Despite clinical and experimental evidence indicating the relevance of the gonadotropic axis to the prognosis and therapeutics for several late-onset neurodegenerative disorders, its functioning and association with disease severity have not been previously explored in SCA2. To assess serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and their clinical relevance in SCA2 patients. A case-control study involving 94 Cuban SCA2 patients and 101 gender- and age-matched healthy controls was conducted. Testosterone, LH, and FSH serum levels were determined by radioimmunoassay or immunoradiometric assay systems. Clinical outcomes included age at onset, disease duration, Scale for the Assessment and Rating of Ataxia (SARA) score, and progression rate. Univariate general linear models were generated. Testosterone, LH, and FSH serum levels were significantly reduced in male SCA2 patients relative to control individuals. On average, there was a 35% reduction in testosterone levels in male patients versus male control individuals. Testosterone levels were associated with disease duration (r = 0.383; p = 0.025) and age at onset (r = 0.414; p = 0.011) in male SCA2 patients, but no association was observed between testosterone and CAG expansion size, SARA score, or progression rate. Testosterone levels might be a biomarker of disease progression in male SCA2 patients. Further studies are needed to explore the effects of low testosterone levels on non-motor symptoms, and to assess the potential of testosterone replacement therapy in male SCA2 patients.

Spinocerebellar Ataxia Type 2 Is Associated with the Extracellular Loss of Superoxide Dismutase but Not Catalase Activity.

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is an inherited and still incurable neurodegenerative disorder. Evidence suggests that pro-oxidant agents as well as factors involved in antioxidant cellular defenses are part of SCA2 physiopathology. AIM: To assess the influence of superoxide dismutase (SOD3) and catalase (CAT) enzymatic activities on the SCA2 syndrome. METHOD: Clinical, molecular, and electrophysiological variables, as well as SOD3 and CAT enzymatic activities were evaluated in 97 SCA2 patients and in 64 age- and sex-matched control individuals. RESULTS: Spinocerebellar ataxia type 2 patients had significantly lower SOD3 enzymatic activity than the control group. However, there were no differences between patients and controls for CAT enzymatic activity. The effect size for the loss of patients' SOD3 enzymatic activity was 0.342, corresponding to a moderate effect. SOD3 and CAT enzymatic activities were not associated with the CAG repeat number at the ATXN2 gene. SOD3 and CAT enzymatic activities did not show significant associations with the age at onset, severity score, or the studied electrophysiological markers. CONCLUSION: There is a reduced SOD3 enzymatic activity in SCA2 patients with no repercussion on the clinical phenotype.

Spinocerebellar ataxia type 2 neurodegeneration differentially affects error-based and strategic-based visuomotor learning.

There are different types of visuomotor learning. Among the most studied is motor error-based learning where the sign and magnitude of the error are used to update motor commands. However, there are other instances where individuals show visuomotor learning even if the sign or magnitude of the error is precluded. Studies with patients suggest that the former learning is impaired after cerebellar lesions, while basal ganglia lesions disrupt the latter. Nevertheless, the cerebellar role is not restricted only to error-based learning, but it also contributes to several cognitive processes. Therefore, here, we tested if cerebellar ataxia patients are affected in two tasks, one that depends on error-based learning and the other that prevents the use of error-based learning. Our results showed that cerebellar patients have deficits in both visuomotor tasks; however, while error-based learning tasks deficits correlated with the motor impairments, the motor error-dependent task did not correlate with any motor measure.

Couples at risk for spinocerebellar ataxia type 2: the Cuban prenatal diagnosis experience.

Cuba reports the highest worldwide prevalence of spinocerebellar ataxia type 2 (SCA2) and the greatest number of descendants at risk. A protocol for genetic counseling, presymptomatic testing, and prenatal diagnosis of hereditary ataxias has been under development since 2001. Considering that the revision of the experience with prenatal diagnosis for SCA2 in Cuba would enable comparison of ours with international findings, we designed a descriptive study, based on the retrospective revision of the medical records belonging to the 58 couples that requested their inclusion in the program, during an 11-year period (2001-2011). Most of the participants in the prenatal diagnosis program were known presymptomatic carriers, diagnosed through the presymptomatic testing in the same period of study, for an uptake among them of 22.87 % (51 out of 223). In 28 cases, the fetuses were carriers, 20 of these couples (71.43 %) decided to terminate the pregnancy; the rest continued the pregnancy to term, this resulting in a predictive test for their unborn children. A predominance of females as the at-risk progenitor was observed. Except for a slightly lower average age, the results attained in the Cuban SCA2 prenatal diagnosis program resulted similar to the ones reported for Huntington disease in other countries. It is necessary to have easy access to the Cuban program through its expansion to other genetic centers along the island. Future research is needed to evaluate the long-term impact of both the predictive testing in unborn children and the selection of other reproductive options by the at-risk couples.