Background: Antibodies to glutamic acid decarboxylase (GAD-Ab) are describe
d in patients with insulin-dependent (type 1) diabetes mellitus (IDDM), in
stiffman syndrome, and, recently, in a few patients with cerebellar ataxia.
Objectives: 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. T
he selection criterion was an immunohistochemical pattern compatible with G
AD-Ab that was confirmed by radioimmunoassay. We identified 22 patients wit
h 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 radio
logic evidence of brainstem involvement. Ten patients had oligoclonal IgG b
ands in the cerebrospinal fluid, and intrathecal GAD-Ab synthesis was obser
ved in 5 of the 6 patients studied. The level of GAD-Ab of these patients w
as similar to those with stiff-man syndrome and significantly higher than t
hose with IDDM or with polyendocrine autoimmunity (P < .001). However, the
GAD-Ab levels of 6 of the 9 patients with polyendocrine autoimmunity overla
pped 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 seru
m levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluate
d for the presence of oligoclonal IgG bands and intrathecal synthesis of GA
D-Ab to further prove an autoimmune origin of the syndrome.