Aktuelle Neurologie 2008; 35 - V222
DOI: 10.1055/s-0028-1086589

Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6

L Schöls 1, C Globas 1, T Schmitz-Hübsch 1, D Timmann 1, S Szymanski 1, A Dürr 1, C Dupont 1, B Melegh 1, C Mariotti 1, S Boesch 1, B van de Warrenburg 1, A Filla 1, M Rakowicz 1, T Klockgether 1, S Tezenas du Montcel 1, P Bauer 1
  • 1EUROSCA

Onset of genetically determined neurodegenerative diseases is difficult to specify due to the insidious and slowly progressive nature of these disorders. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms.

We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3 or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (i) the definition of disease onset, (ii) people defining onset and (iii) duration of symptoms.

Gait difficulty was the initial symptom in about two thirds of SCA patients. Symptoms preceding gait ataxia were in the order of frequency cramps, dysarthria, sleep disturbance, double vision, impaired hand writing, episodic vertigo, neuropathic symptoms, restless legs syndrome, urinary urgency, reduced visual acuity and frequent throat clearing. Episodic vertigo occurred especially frequent as the initial symptom in SCA6 patients. Data about onset of disease varied for 1 year or more in 44% of cases between SCA patients and their relatives and for more than 5 years in 8.5% of cases.

Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance after discussion between patients and relatives and when cases who had symptoms for more than 10 years were excluded. Even under these conditions the number of CAG repeats determined only 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3 and 41% in SCA6.

This study demonstrates substantial influence of non-repeat factors on disease onset in all SCA subtypes but especially in SCA3 and SCA6. Identification of these factors will be interesting since they may provide potential therapeutic targets for disease modifying compounds. In this respect recognition of early symptoms that develop before onset of gait ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA as early as possible.