Autosomal dominant cerebellar ataxias (ADCAs) share features of progressive, usually adult-onset, spinocerebellar degeneration, including gait and limb ataxia, dysarthria, and oculomotor control impairment. The presence of peripheral nerve involvement in ADCAs has been reported, suggesting that disease mechanisms are not solely confined to the central nervous system compartment. In a large study, covering twenty-seven genotyped ADCA patients electrophysiological evidence of involvement of the peripheral nervous system was found in 70% of patients. Findings were compatible with a dying-back axonopathy in 30%, while in 40% of patients a neuronopathy was diagnosed. SCA1 and SCA2 patients mostly displayed features of a neuronopathy, while in SCA3 and SCA7 both neuronopathies and axonopathies were encountered. In SCA6, no significant peripheral nerve involvement was demonstrated.

Authors

H.J. Schelhaas, M.D., Ph.D.
B.P. van de Warrenburg, M.D., Ph.D.

Clinical features
Autosomal dominant cerebellar ataxias (ADCAs) share features of progressive, usually adult-onset, spinocerebellar degeneration, including gait and limb ataxia, dysarthria, and oculomotor control impairment. Genetic studies have now identified 30 SCA loci (http://www.gene.ucl.ac.uk/nomenclature) and around 20 genes. Read more

Natural course and prognosis

Van de Warrenburg et al did not find any correlation between the sum of CMAPs/SNAPs and age, disease duration, or ataxia severity. Previously, the severity of the axonal polyneuropathy in SCA3 patients was found to be related to age and not to CAG repeat length or disease duration.⁴ SCA2 patients with a later age-at-onset (> 40 years) and small CAG repeat expansions, both suggesting milder disease, were found to display a more severe peripheral neuropathy.²⁰ Van alfen et al. recently reported a SCA3 family, carrying intermediate repeat expansions, with a syndrome encompassing restless legs, fasciculations, and a sensorimotor axonal polyneuropathy.²¹ Apparently, peripheral nerve involvement, both neuronopathies and axonopathies, can be an early disease feature, can occur in patients with relatively small repeat expansions, and is not related to disease progression. Whether the neuropathy in the individual patient with SCA is stable or slowly progressive is currently unknown.

Epidemiology

International prevalence estimates of autosomal dominant cerebellar ataxias (ADCA) vary from 0.3 to 2.0 per 100,000. The estimated minimal prevalence of ADCA in the Netherlands is 3.0 per 100,000 inhabitants.¹

Differential diagnosis
In case of a late onset autosomal dominant hereditary ataxia one should consider Dentato-Rubro Pallido-Luysian Atrophy (DRPLA), Gerstmann-Straussler-Scheinker (GSS) disease and, familiar hemiplegic migraine (FHM). In this last disorder ataxia is rare and if present it develops many years after the onset of migraine. There are patients with a late onset autosomal recessive ataxia, like Friedreich’s ataxia but this is unusual and the differential diagnostic considerations in these patients are beyond the scope of this document. In case of a sporadic presentation the most likely diagnosis is multi system atrophy (MSA) or idiopathic late onset cerebellar ataxia (ILOCA). Read more

Ancillary investigations

DNA analysis, nerve conduction studies, and EMG. Further ancillary investigations depends on the differential diagnostic considerations.

Genetics
The pathogenesis varies according to the underlying mutation. Electrophysiological evidence of peripheral nerve pathology was found in 19 of 27 patients (70.3%). In eight patients, abnormalities were compatible with a typical dying-back axonal neuropathy, which was purely sensory in one and mixed sensorimotor in seven patients. Read more

Therapy

Therapy is symptomatic and supportive.

Links

 

References
Van de Warrenburg BP, Notermans NC, Schelhaas HJ, van Peripheral nerve involvement in spinocerebellar ataxias. Archives Neurol. 2004 (in press) Read more