Dopa‐responsive parkinsonism phenotype of spinocerebellar ataxia type 2

Abstract

We report on 2 brothers, Patients 1 and 2, who presented with a similar clinical syndrome consisting of resting tumor, bradykinesia, rigidity, and dysarthria at the ages of 40 and 43 years, respectively. An excellent response to levodopa therapy was observed throughout the disease course. No gait or limb ataxia, slow saccades, or decreased tendon reflexes were detected, but unsteadiness of gait with propulsion developed recently in Patient 1 approximately 25 years after disease onset. Magnetic resonance imaging demonstrated mild atrophy of the pons and cerebellum in Patient 1 and cerebellar atrophy in Patient 2. Expanded CAG repeats, numbering 36, in one allele of the ataxin-2 gene were identified in Patient 1 only; his brother was not available for this investigation. With [(99m)Tc]TRODAT-1 single photon emission computed tomography of the brain, a significant bilateral and asymmetrical reduction of striatal dopamine transporters was found in Patient 1 compared to healthy controls. This bilateral reduction of striatal dopamine transporters resembled that observed in a set of controls with Parkinson's disease who had asymmetrical impairment. These results suggest that patients with familial parkinsonism who present with typical Parkinson's disease should be screened for the genetic defect of spinocerebellar ataxia type 2. The presynaptic impairment of nigrostriatal function is very likely to be the reason for levodopa responsiveness.

Genetic and clinical analysis in a Chinese parkinsonism-predominant spinocerebellar ataxia type 2 family

“…12). The sign of dopamine-responsive just has been seen in some Chinese families 13,14 and some white families. 15,16 We described here a large family from Hubei, China, that showed primarily autosomal dominant inheritance of parkinsonism symptoms acrossing four generations.…”

Distal Tumors Elicit Distinctive Gene Expression Changes in Mouse Brain, Different from Those Induced by Arthritis

“…We observed down-regulation of Gabarapl2, a protein involved in vesicle transport and axonal elongation in mammalian neurons [26] and ataxin-2, a protein associated with spinocerebellar ataxia type 2; it is of note that a subset of patients with parkinsonian phenotype responded to dopamine treatment suggesting a link between ataxin-2 and dopamine [39]. On the other hand, previous studies have shown both decreased dopaminergic activity and increase in DOPAC:DA ratio in the hypothalamus of mice injected with mammary tumor cells and lymphoma cells, respectively [11,40].…”

The Multiple Faces of Spinocerebellar Ataxia type 2

“…One patient was diagnosed as progressive supranuclear palsy because of the presence of bradykinesia, lack of response to L‐Dopa, prominent vertical gaze palsy but not ataxia signs. Several other families with parkinsonian phenotype have been described since then 90, 91, 92, 93, 94. Number of CAG repeats was <40 repeats and the sequence was interrupted by CAA when explored.…”

“…It is not known the prevalence of asymptomatic cerebellar atrophy in parkinsonian patients. SCA2 expansions explained 0–2% of familial parkinsonism in Caucasian94, 95, 96 and up to 10% in Asian population 92, 93…”