Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis.
OBJECTIVE
Antibodies to glutamic acid decarboxylase (GAD) have been described in a few patients with temporal lobe epilepsies consistent with limbic encephalitis (LE). We studied a cohort of patients with recent-onset temporal lobe epilepsy caused by LE to test for GAD antibody positivity and response to immunotherapies.


METHODS
Over a period of 3.75 years, 138 patients aged >or=18 years investigated at the Department of Epileptology, University of Bonn, for recent-onset epilepsy were prospectively collected and studied for cliniconeuroradiological features of LE, autoantibodies, and treatment responses.


RESULTS
Fifty-three adult patients fulfilled the criteria for LE: (1) limbic signs and symptoms for <or=5 years and (2) brain MRI revealing mediotemporal encephalitis (T2/fluid attenuated inversion recovery hyperintensity without atrophy). Nine had high-titer GAD antibodies; 10 had voltage-gated potassium channel (VGKC) antibodies. Patients with GAD antibodies were younger (median age, 23 years; range, 17-66 years) (p = 0.003) and presented with seizures only, whereas polymorphic limbic features were more common in the VGKC antibody-positive group (p < 0.001). None had tumors. Patients with GAD antibodies more frequently had cerebrospinal fluid oligoclonal bands (p = 0.009) and intrathecal secretion of the specific antibody (p = 0.01). Following monthly intravenous methylprednisolone pulses, GAD antibodies remained highly elevated in 6/6 patients, whereas VGKC antibodies normalized in 6/9 patients (p = 0.03). Despite more intense anticonvulsive treatment in the GAD antibody-positive group (p = 0.01), none of these patients became seizure free, unlike all of the patients with VGKC antibodies (p < 0.001).


CONCLUSIONS
High-titer GAD antibodies define a form of nonparaneoplastic LE. This is a chronic, nonremitting disorder and should be included in the differential diagnosis of patients with TLE and mediotemporal encephalitis. Therapeutic trials of other immunotherapies should be undertaken.
Malter
Michael P
MP
Department of Epileptology, University of Bonn Medical Center, Bonn, Germany.
Helmstaedter
Christoph
C
Urbach
Horst
H
Vincent
Angela
A
Bien
Christian G
CG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D020363:Limbic Encephalitis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology; D011446:Prospective Studies; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult
D000906:Antibodies; D016756:Immunoglobulins, Intravenous; D024642:Potassium Channels, Voltage-Gated; D019788:Fluorodeoxyglucose F18; D005968:Glutamate Decarboxylase