Motor decline in clinically presymptomatic spinocerebellar ataxia type 2 gene carriers.

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents.

Motor Decline in Clinically PresymptomaticSpinocerebellar Ataxia Type 2 Gene Carriers

Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxiatype 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomaticgene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we testedpresymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motorperformance and their motor learning capabilities. Findings: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of controlvolunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation taskknown to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that althoughmotor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation ofthe disease start.The results show a clear deficit in motor performance that can be detected years before the clinical onset ofthe disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease.These observations identify the performance coefficient as an objective and quantitative physiological biomarker that couldbe useful to assess the efficiency of different therapeutic agents...(AU)

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents(AU)

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities...(AU)

Prism adaptation in spinocerebellar ataxia type 2.

Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form of autosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterized in these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prism adaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather, patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degree of adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly, SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect. Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia.

Prism adaptation in spinocerebellar ataxia type 2

Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form ofautosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterizedin these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prismadaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather,patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degreeof adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly,SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect.Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia...(AU)

Spinocerebellar ataxia type 2 olfactoryimpairment shows a pattern similar toother major neurodegenerative diseases

Olfactory function isaffected in different neurodegenerativediseases. Recently, it hasbeen found that some hereditaryataxias are also associated withsignificant olfactory impairment.However, the initial findings didnot examine the nature of theolfactory impairment associatedwith these ataxias. In the presentarticle the effect of spinocerebellarataxia type 2 (SCA2) on olfactoryfunction was studied in 53 SCA2patients and 53 healthy controlsubjects from Holguý´n, Cuba.Several tests were applied to evaluateolfactory threshold, description,identification anddiscrimination. The results showsignificant impairment in SCA2patients on all olfactory measurements,and the pattern of olfactorydeficits found suggests that theyhave much in common with thosereported for other neurodegenerativediseases such as Parkinsonsand Alzheimers diseases...(AU)

Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2.

We assessed maximal saccade velocity (MSV) in 82 spinocerebellar ataxia type 2 (SCA2) patients and 80 controls, correlating it to disease duration, polyglutamine expansion size, age at onset, ataxia score, age, and sex. Little overlap with normal values was found even at earliest stages. Stepwise linear regression analysis showed that 60-degree MSV was strongly influenced by polyglutamine size and less by disease duration, whereas the reverse was found for ataxia score. Saccade velocity thus is a sensitive, quite specific, and objective endophenotype, useful to search polyglutamine modifier genes.

Saccade Velocity isControlled by PolyglutamineSize in SpinocerebellarAtaxia 2

We assessed maximal saccade velocity (MSV) in 82 spinocerebellarataxia type 2 (SCA2) patients and 80 controls,correlating it to disease duration, polyglutamine expansionsize, age at onset, ataxia score, age, and sex. Littleoverlap with normal values was found even at earlieststages. Stepwise linear regression analysis showed that 60-degree MSV was strongly influenced by polyglutaminesize and less by disease duration, whereas the reverse wasfound for ataxia score. Saccade velocity thus is a sensitive,quite specific, and objective endophenotype, useful tosearch polyglutamine modifier genes...(AU)