Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy.
BACKGROUND
Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in type 1 diabetes and stiff man syndrome (SMS), and have also been reported in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A, implying that epilepsy sometimes is associated with anti-GAD autoimmunity.


METHODS
The authors investigated the prevalence of GAD-A in patients with therapy-resistant localization-related epilepsy (n = 51) and generalized epilepsy (n = 49) by a radiobinding assay. The positive samples were confirmed by immunohistochemistry and immunoblotting of recombinant human GAD65.


RESULTS
GAD-A were found in eight patients with localization-related epilepsy, whereas none of the patients with generalized epilepsy, other neurologic disorders (n = 38), or the control subjects (n = 48) had GAD-A. Two patients had high levels of GAD-A, similar to SMS, whereas six patients had significantly lower titers, characteristic of type 1 diabetes. The two patients with high levels of GAD-A had GAD-A both in serum and CSF by immunohistochemistry and immunoblotting. Both of them had longstanding therapy-resistant temporal lobe epilepsy but did not have diabetes. One had a history of autoimmune disease, whereas the other had serologic evidence of multiple autoantibodies without any clinical signs of autoimmune disease.


CONCLUSIONS
GAD autoimmunity may be associated with refractory localization-related epilepsy.
Peltola
J
J
Department of Neurology, Tampere University Hospital, Finland. lljupe@uta.fi
Kulmala
P
P
Isojärvi
J
J
Saiz
A
A
Latvala
K
K
Palmio
J
J
Savola
K
K
Knip
M
M
Keränen
T
T
Graus
F
F
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002531:Cerebellum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004351:Drug Resistance / Q000276:immunology*; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay
D001323:Autoantibodies; D005968:Glutamate Decarboxylase