THE NATURAL-HISTORY OF DEGENERATIVE ATAXIA - A RETROSPECTIVE STUDY IN466 PATIENTS

The aim of the present study was (i) to compare disease progression an d survival in different types of degenerative ataxia, and (ii) to iden tify variables that may modify the rate of disease progression. We inc luded patients suffering from Friedreich's ataxia (FRDA, n = 83), earl y onset cerebellar ataxia (EOCA, n = 30), autosomal dominant cerebella r ataxia (ADCA) type I (ADCA-I n = 273), ADCA-III (n = 13) and multipl e system atrophy (MSA, n = 67). Molecular genetic testing allowed us t o assign 202 ADCA-I patients to one of the following subgroups. spinoc erebellar ataxia type I (SCAI, n = 36), SCA2 (n = 56) and SCA3 (n = 11 0). To assess disease progression we defined the following disease sta ges: stage 0 = no gait difficulties; stage I = disease onset, as defin ed by onset of gait difficulties; stage 2 = loss of independent gait; stage 3 = confinement to wheelchair; stage 4 = death. Disease progress ion was most rapid in MSA, intermediate in FRDA, ADCA-I and ADCA-III a nd slowest in EOCA. The rate of progression was similar in SCA1, SCA2 and SCA3. The CAG repeat length was a significant risk factor for fast er progression in SCA2 and SCA3, but not in SCA1. In FRDA, the time un til confinement to wheelchair was shorter in patients with earlier dis ease onset, suggesting that patients with long GAA repeats and early d isease onset have a poor prognosis. Female gender increased the risk o f becoming dependent on walking aids or a wheelchair, but it did not i nfluence survival in FRDA, SCA3 and MSA. IN SCA2, female gender was as sociated with shortened survival. In MSA, later age of onset increased the risk of rapid progression and death.