Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6.
Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. 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 (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms. Gait difficulty was the initial symptom in two-thirds of patients. Double vision, dysarthria, impaired hand writing, and episodic vertigo preceded ataxia in 4% of patients, respectively. Frequency of other early symptoms did not differ from controls and was regarded unspecific. Data about disease onset varied between patients and relatives for 1 year or more in 44% of cases. Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance and cases with symptoms for more than 10 years were excluded. Under these conditions, CAG repeat length determined 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3, and 41% in SCA6 demonstrating substantial influence of nonrepeat factors on disease onset in all SCA subtypes. Identification of these factors is of interest as potential targets for disease modifying compounds. In this respect, recognition of early symptoms that develop before onset of ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA.
Globas
Christoph
C
Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
du Montcel
Sophie Tezenas
ST
Baliko
Laslo
L
Boesch
Syliva
S
Depondt
Chantal
C
DiDonato
Stefano
S
Durr
Alexandra
A
Filla
Alessandro
A
Klockgether
Thomas
T
Mariotti
Caterina
C
Melegh
Bela
B
Rakowicz
Maryla
M
Ribai
Pascale
P
Rola
Rafal
R
Schmitz-Hubsch
Tanja
T
Szymanski
Sandra
S
Timmann
Dagmar
D
Van de Warrenburg
Bart P
BP
Bauer
Peter
P
Schols
Ludger
L