Comprehensive Study of Early Features in Spinocerebellar Ataxia 2: Delineating the Prodromal Stage of the Disease

Abstract

The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main findings come from a homogeneous SCA type 2 (SCA2) population living in Cuba. The aim of this study was to characterize extensively the prodromal phase of SCA2 by several approaches. Thirty-seven non-ataxic SCA2 mutation carriers and its age- and sex-matched controls underwent clinical assessments, including standardized neurological exam, structured interviews and clinical scales, and looking for somatic and autonomic features, as well as a neuropsychological battery, antisaccadic recordings, and MRI scans. Main clinical somatic features of non-ataxic mutation carriers were cramps, sensory symptoms, sleep disorders, and hyperreflexia, whereas predominating autonomic symptoms were pollakiuria/nocturia, constipation, and frequent throat clearing. Cognitive impairments included early deficits of executive functions and visual memory, suggesting the involvement of cerebro-cerebellar-cerebral loops and/or reduced cholinergic basal forebrain input to the cortex. Antisaccadic task revealed impaired oculomotor inhibitory control but preserved ability for error correction. Cognitive and antisaccadic deficits were higher as carriers were closer to the estimated onset of ataxia, whereas higher Scale for the Assessment and Rating of Ataxia (SARA) scores were associated most notably to vermis atrophy. The recognition of early features of SCA2 offers novel insights into the prodromal phase and physiopathological base of the disease, allowing the assessment of its progression and the efficacy of treatments, in particular at early phases when therapeutical options should be most effective.

Autonomic function testing in spinocerebellar ataxia type 2

“…This finding is in agreement with previous studies, reporting bladder and gastrointestinal symptoms as the most common autonomic features among SCA 2 patients [14, 15, 22]. …”

SCA2 predictive testing in Cuba: challenging concepts and protocol evolution

“…There are 163 affected families in Cuba, encompassing almost 600 SCA2 living patients and approximately 8 000 at-risk individuals; among them, 2060 subjects are SCA2 patients' first-degree relatives (Velázquez-Pérez et al 2014b). For this reason, in 2000, the National Center for the Research and Rehabilitation of Hereditary Ataxias (CIRAH) was created at Holguín province, to provide these families with specialized health care services.…”

The preclinical stage of spinocerebellar ataxias

“…Moreover, an inverse correlation between the volume of the vermis and SARA score was shown. 15 Using arterial spin labeling perfusion MRI and diffusion-weighted imaging, Xing and coworkers 27,28 found decreased regional cerebral blood flow in the cerebellar cortex and dentate nucleus and an elevated apparent diffusion coefficient in the latter only in preclinical SCA3 carriers. In contrast to clinically manifest patients, pontine perfusion remained uncompromised.…”

“…Impairments in this task reflect a loss of inhibitory control and thus preclinical involvement of the (pre)frontal cortex and cortico-cerebellar pathways. 15 Various eye movement abnormalities were observed in preclinical SCA6 carriers. Hypometric saccades, impaired pursuit tracking, and square-wave jerks are all indicative of cerebellar dysfunction and/or degeneration at this stage.…”