Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients.
BACKGROUND
Antibodies to glutamic acid decarboxylase (GAD-Ab) are described in patients with insulin-dependent (type 1) diabetes mellitus (IDDM), in stiff-man syndrome, and, recently, in a few patients with cerebellar ataxia.


OBJECTIVE
To show a link between GAD-Ab and some patients with cerebellar ataxia and to clarify their clinical and immunologic profiles.


METHODS
Serum samples were selected from 9000 samples of 4 laboratories. The selection criterion was an immunohistochemical pattern compatible with GAD-Ab that was confirmed by radioimmunoassay. We identified 22 patients with stiff-man syndrome and 14 with cerebellar ataxia and GAD-Ab.


RESULTS
Thirteen of the 14 patients with cerebellar ataxia and GAD-Ab were women, and 11 had late-onset IDDM. Patients did not have clinical or radiologic evidence of brainstem involvement. Ten patients had oligoclonal IgG bands in the cerebrospinal fluid, and intrathecal GAD-Ab synthesis was observed in 5 of the 6 patients studied. The level of GAD-Ab of these patients was similar to those with stiff-man syndrome and significantly higher than those with IDDM or with polyendocrine autoimmunity (P<.001). However, the GAD-Ab levels of 6 of the 9 patients with polyendocrine autoimmunity overlapped with those of patients with cerebellar ataxia.


CONCLUSIONS
These results suggest a link between high level of GAD-Ab and some cases of cerebellar ataxia, particularly women with IDDM. If high serum levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluated for the presence of oligoclonal IgG bands and intrathecal synthesis of GAD-Ab to further prove an autoimmune origin of the syndrome.
Honnorat
J
J
Service of Neurology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.
Saiz
A
A
Giometto
B
B
Vincent
A
A
Brieva
L
L
de Andres
C
C
Maestre
J
J
Fabien
N
N
Vighetto
A
A
Casamitjana
R
R
Thivolet
C
C
Tavolato
B
B
Antoine
J
J
Trouillas
P
P
Graus
F
F
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D001284:Atrophy; D002524:Cerebellar Ataxia / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D002531:Cerebellum / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood* / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D043025:Oligoclonal Bands; D016750:Stiff-Person Syndrome / Q000097:blood*
D000888:Antibodies, Anti-Idiotypic; D007136:Immunoglobulins; D043025:Oligoclonal Bands; D005968:Glutamate Decarboxylase