Spinocerebellar ataxia type 3
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common spinocerebellar ataxia (SCA) worldwide. SCA3 presents with cerebellar ataxia in association with pyramidal signs, peripheral amyotrophy, nystagmus, ophthalmoparesis, fasciculations of the face and tongue, dystonia, and parkinsonism.
Disease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for the Assessment and Rating of Ataxia (SARA) sum score, but little is known about the contributions and progression patterns of individual items.
Objectives: To investigate the temporal dynamics of SARA item scores in SCA3 patients and evaluate if clinical and demographic factors are differentially associated with evolution of axial and appendicular ataxia.
Methods: In a prospective, multinational cohort study involving 11 European and 2 US sites, SARA scores were determined longitudinally in 223 SCA3 patients with a follow-up assessment after 1 year.
Results: An increase in SARA score from 10 to 20 points was mainly driven by axial and speech items, with a markedly smaller contribution of appendicular items. Finger chase and nose-finger test scores not only showed the lowest variability at baseline, but also the least deterioration at follow-up. Compared with the full set of SARA items, omission of both tests would result in lower sample size requirements for therapeutic trials. Sex was associated with change in SARA sum score and appendicular, but not axial, subscore, with a significantly faster progression in men. Despite considerable interindividual variability, the average annual progression rate of SARA score was approximately three times higher in subjects with a disease duration over 10 years than in those within 10 years from onset.
The findings provide evidence for a difference in temporal dynamics between axial and appendicular ataxia in SCA3 patients, which will help inform the design of clinical trials and the development of new (etiology-specific) outcome measures. 1).
Oromandibular dystonia (OMD) with facial grimacing (FG) in SCA3 has seldom been reported in the literature and in a series of SCA3 patients.
We evaluated 104 patients with SCA (59 patients with SCA3, 20 with SCA2, 20 with SCA7 and 5 with SCA6) and assessed dystonia frequency and types.
Thirteen cases of SCA3, one of SCA2 and two of SCA7 had dystonia. OMD in the form of FG was present in seven SCA3 patients (11.9%). Patients with FG were significantly younger, had earlier disease onset and a significantly higher CAG repetition length when compared to the SCA3 sample. Parkinsonism, dysphagia and pyramidal signs were significantly more frequent in the FG group than the non-FG group of the SCA3 sample.
Patients with SCA3 presenting with FG are younger, with earlier disease onset and higher CAG repetition length. They present with parkinsonism, dysphagia and pyramidal signs more frequently than SCA3 patients without FG 2).