Movement Disorders in Autosomal Dominant Cerebellar Ataxias: A Systematic Review

Abstract

Autosomal dominant cerebellar ataxias (ADCAs) are clinically heterogeneous disorders classified according to genetic subtype and collectively known as SCAs. In a few SCAs, movement disorders can be the most frequent extracerebellar sign. The aim of this article is to perform a systematic review of movement disorders frequency and characteristics in ADCAs. This work consisted of a structured search of electronic databases up to January 2013. Publications containing descriptions of ADCA clinical features written in several languages were selected initially based on title and abstract screening, followed by full-text reading of potentially relevant publications. Clinical findings and demographic data on genetically confirmed patients were extracted. Analysis of individual patient data from subjects with movement disorders was performed using the chi-square test and logistic regression. One thousand and sixty-six publications reviewing 12,151 patients from 30 different SCAs were analyzed. Individual data were available from 755 patients with at least one type of movement disorder during overall disease course. Of 422 patients in whom onset symptom data were available, one third referred a movement disorder as the initial symptom. During overall disease course, parkinsonism was common in many SCA subtypes, frequently described in the absence of ataxia and characterized as responding to dopaminergic medications. Motor complications developed occasionally in some patients as did nigrostriatal imaging alterations. Other frequent features were dystonia, chorea, and myoclonus. Rare conditions, such as akathisia, paroxysmal nonkinesigenic dyskinesia, or stiff person-like syndrome, were also reported. ADCA descriptions included a full range of movement disorders. Aside from postural or intention tremor, dopamine-responsive parkinsonism and dystonia were the most common.

Genetic Dystonia‐ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

“…Different types or forms of dystonia were described in the genetic diseases listed: focal, segmental, generalized, and hemidystonia (e.g., in autosomal dominant progressive external ophthalmoplegia type 1 due to POLG mutations and in Coats plus syndrome) as well as task‐specific dystonia (e.g., in several spinocerebellar ataxias, mitochondrial disorders, ataxia‐telangiectasia‐like disorder type 1, and in L‐2‐hydroxyglutaric aciduria), paroxysmal, or episodic dystonia (paroxysmal kinesigenic dyskinesia due to PRRT2 mutations, episodic ataxia type 2, and biotin‐thiamine‐responsive basal ganglia disease due to SLC19A3 mutations). Supporting Table 1 lists the various forms of dystonia described in genetic dystonia‐ataxia syndromes.…”

Deep brain stimulation for dystonia: a novel perspective on the value of genetic testing

“…Another example is ataxia telangiectasia, which may first present in adults with isolated dystonia rather than ataxia (Meneret et al 2014; Charlesworth et al 2013; Saunders-Pullman et al 2012; Verhagen et al 2009). Similarly, dystonia may be the dominating clinical feature of several spinocerebellar ataxias (Neychev et al 2011; Rossi et al 2014). There is little information regarding DBS in these populations.…”

Dystonia in Patients With Spinocerebellar Ataxia Type 2

“…Interestingly enough, dystonia in SCA2 may, at least transiently, respond to l ‐dopa . Although 1 of our patients developed rest tremor (case 1) and parkinsonism was described in SCA 2 patients, we believe that this tremor was probably the result of damage to cerebellar outflow pathways.…”

“…Dystonia has been described in various genetically proven spinocerebellar ataxias (SCAs), most often in SCA3, SCA17, and SCA2 patients, but also, less commonly, in SCA1, SCA14, and SCA6 . Dystonic features in SCA often emerge in the context of already developed cerebellar ataxia, when they do not pose a significant diagnostic problem.…”

“…The prevalence of dystonia in SCA2, an autosomal‐dominant cerebellar ataxia caused by the trinucleotide cytosine‐adenine‐guanine (CAG) repeat expansion in the ataxine‐2 gene, varied from 14% to 17%, although Boesch et al . reported an estimate of up to 61%.…”