From anti-GAD to ataxia with ocular motor apraxia type 2: through the looking glass.

Dear Sirs,Elevated levels of anti-glutamic acid decarboxylase anti-bodies (GAD-Ab) are found in serum and cerebrospinalfluid in various autoimmune diseases such as diabetesmellitus and stiff-man syndrome. GAD-Abs also have beenreported in 14 patients presenting with cerebellar ataxiaand ocular motor disturbances [1, 2]. We report newinsights about one patient of the first published series ([1],patient 1) who came to our examination at age 57. Sinceshe was adopted, her neonatal and familial history was notknown. Since age 16, she showed progressive cerebellarataxia associated with axonal sensory-motor neuropathy,leading to use of a wheelchair at age 43. In 1995, when thepatient was 38 years old, further investigations revealedelevated levels of plasmatic GAD-Ab [1, 2]; her levelsremained significantly elevated and pathological in a sec-ond laboratory examination at 282 U/mL at age43, 115 U/mLat age 57 (positive rate[1 U/mL), and 3,911 cpm (positiverate[200 cpm) in a third laboratory at age 58. Each of thelaboratories used radioimmunoassay for measurement, asin the initial report of 1995. Indeed, her condition hadworsened and elevated plasmatic GAD-Ab levels persistedover time despite treatment by IV Immunoglobulin [3],plasmapheresis, cyclophosphamide then azathioprine,which had been started at age 38. At age 57, she hadmarked cerebellar ataxia (scale for the assessment andrating of ataxia (SARA) score at 23.5/40) with disablingdysarthria, dysmetria, hypotonia and severe distal amyot-rophy. Oculographic recording confirmed ocular motorapraxia. Electroneuromyography found severe axonalsensory motor neuropathy; brain MRI showed markedcerebellar atrophy. Her alpha-fetoprotein (AFP) serumlevel was elevated at 52.5 lg/L (normal\7 lg/L). Becauseof the combination of progressive cerebellar atrophyoccurring at around 15 years old with axonal sensory motorpolyneuropathy, ocular motor apraxia and elevated AFPserum level [4], we suspected the diagnosis of ataxia with