The average age of symptom onset was significantly higher in the parkinsonism group of SCA2 (51.5 ± 8.9 vs. 35.3 ± 12.6 years, p = .007) than those with pure ataxia.
We identified a SCA1 intermediate allele in a MSA-C subject (36 CAG), a SCA2 intermediate allele in a MSA-P patient (31 CAG), and a pathologically expanded SCA2 allele (36 CAG) in a patient initially misdiagnosed as MSA-C. No intermediate or expanded SCA alleles were detected in controls.
Parkinsonism in SCA2 has unique genetic characteristics, such as low number of expansions and interrupted structures, which may explain the sporadic cases with low penetrance.
Our observation that lesions of the motor territory of the subthalamic nucleus were consistently associated with the prevention of parkinsonism in our SCA2 and SCA3 patients matches the clinical experience that selective targeting of the motor territory of the subthalamic nucleus by focal lesions or deep brain stimulation can ameliorate parkinsonian motor features and is likely to counteract the manifestation of parkinsonism in SCA2 and SCA3 despite a severe neurodegeneration of the dopaminergic substantia nigra.
In the preclinical stage of SCA2parkinsonism, the connectivity of a part of the basal ganglia motor loop is weakened as a consequence of dopaminergic deficits; meanwhile, the connectivity of other large-scale brain networks is strengthened presumably to compensate for the dysfunction of the basal ganglia to maintain brain function in the early stage of dopaminergic deficits.
Progression was faster in patients with SCA2 mutations and normal alleles with 22 or fewer repeats (P = .02) and in patients with SCA3 mutations with parkinsonism and/or dystonia at baseline (P = .003).
Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing.
In order to define if mutation at these loci is a common cause of clinically defined parkinsonism we typed the SCA-2 and SCA-3 repeats for expansion in a series of 280 patients diagnosed with PD or parkinsonism.
We report on a young woman from the United Kingdom with L-dopa-responsive parkinsonism with a trinucleotide repeat expansion in her spinocerebellar ataxia 2 (SCA2) gene.
Interestingly, 4 patients (1 with SCA2, 1 with SCA3, and 2 with SCA6) were misdiagnosed as having multiple-system atrophy because of the absence of family history and the presence of parkinsonism and urinary incontinence.
We have previously shown in several pedigrees that SCA-2 and SCA-3 can cause both parkinsonism and typical Parkinson's disease in the absence of prominent ataxia; a finding which has been confirmed by others.
Recent reports have shown trinucleotide repeat expansions in the spinocerebellar ataxia 2 (SCA2) gene in patients with levodopa-responsive parkinsonism.