Cerebellar ataxias: an update

Abstract

Purpose of review Providing an update on the pathophysiology, cause, diagnosis and treatment of cerebellar ataxias. This is a group of sporadic or inherited disorders with heterogeneous clinical presentation and notorious impact on activities of daily life in many cases. Patients may exhibit a pure cerebellar phenotype or various combinations of cerebellar deficits and extracerebellar deficits affecting the central/peripheral nervous system. Relevant animal models have paved the way for rationale therapies of numerous disorders affecting the cerebellum. Recent findings Clinically, the cerebellar syndrome is now divided into a cerebellar motor syndrome, vestibulocerebellar syndrome and cerebellar cognitive affective syndrome with a novel clinical scale. This subdivision on three cornerstones is supported by anatomical findings and neuroimaging. It is now established that the basal ganglia and cerebellum, two major subcortical nodes, are linked by disynaptic pathways ensuring bidirectional communication. Inherited ataxias include autosomal recessive cerebellar ataxias (ARCAs), autosomal dominant spinocerebellar ataxias and episodic ataxias and X-linked ataxias. In addition to the Movement Disorders Society genetic classification of ARCAs, the classification of ARCAs by the Society for Research on the Cerebellum and Ataxias represents major progress for this complex subgroup of cerebellar ataxias. The advent of next-generation sequencing has broadened the spectrum of cerebellar ataxias. Summary Cerebellar ataxias require a multidisciplinary approach for diagnosis and management. The demonstration of anatomical relationships between the cerebellum and basal ganglia impacts on the understanding of the cerebello-basal ganglia-thalamo-cortical system. Novel therapies targeting deleterious pathways, such as therapies acting on RNA, are under development.

Essential tremor: the most common form of cerebellar degeneration?

“…conducted a PubMed search on April 22, 2020. The goals of this search were to systematically identify papers that provided [ 1 ] data on the links between ET and the cerebellum, [ 2 ] data and discussion on the degenerative hypothesis of ET, and [ 3 ] data on the prevalence of ET. It was not a systematic search of all papers on disease mechanisms in ET, although the only other mechanistic disease model for ET is the olivary hypothesis, which has fallen out of favor in recent years [ 55 – 57 ].…”

“…Given that [ 1 ] ET is highly prevalent, [ 2 ] clinical, neuroimaging and postmortem studies have linked ET to the cerebellum, and [ 3 ] clinical and postmortem features suggest that it is neurodegenerative, then one would conjecture that it might be the most common form of cerebellar degeneration. Before reaching this conclusion, we must compare the prevalence of ET with that of other cerebellar degenerations.…”

Cerebellar Astrocytes: Much More Than Passive Bystanders In Ataxia Pathophysiology

“…This is due to the functional anatomy of the cerebellum, according to which distinct lobules in both the vermis and hemispheres are connected with distinct brain areas and are involved in diverse motor and non-motor functions [4]. Based on this functional anatomy, cerebellar ataxia is now clinically subdivided into (i) cerebellar motor syndrome, (ii) vestibulocerebellar syndrome, and (iii) cerebellar cognitive affective syndrome [5].…”

Rehabilitation for Spinocerebellar Ataxia

“…For the clinical diagnosis of cerebellar ataxia, specific blood studies and magnetic resonance imaging (MRI) have been performed [9]. Furthermore, genetic techniques improve the diagnosis of degenerative cerebellar ataxia [10].…”

“…Furthermore, genetic techniques improve the diagnosis of degenerative cerebellar ataxia [10]. Although the details of the findings of these genetic and blood studies are beyond the scope of this review of rehabilitation, cerebellar atrophy and cerebellar motor deficits are traditionally common observations in patients with degenerative cerebellar ataxia [9]. Furthermore, recently, the absence of motor cerebellar symptoms has also been recognized as being important for rehabilitation [11].…”