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July 12, 2000; 55 (1) Article

Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy

J. Peltola, P. Kulmala, J. Isojärvi, A. Saiz, K. Latvala, J. Palmio, K. Savola, M. Knip, T. Keränen, F. Graus
First published July 12, 2000, DOI: https://doi.org/10.1212/WNL.55.1.46
J. Peltola
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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P. Kulmala
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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J. Isojärvi
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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A. Saiz
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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K. Latvala
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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J. Palmio
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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K. Savola
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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M. Knip
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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T. Keränen
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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F. Graus
From the Departments of Neurology (Drs. PeltolaPalmio, and Keränen) and Pediatrics (Dr. Knip), Tampere University Hospital, Finland; the Departments of Neurology (Drs. Isojärvi and Latvala) and Pediatrics (Drs. Kulmala and Savola), Oulu University Hospital, Finland; and the Service of Neurology (Drs. Saiz and Graus), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain.
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Full PDF
Citation
Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy
J. Peltola, P. Kulmala, J. Isojärvi, A. Saiz, K. Latvala, J. Palmio, K. Savola, M. Knip, T. Keränen, F. Graus
Neurology Jul 2000, 55 (1) 46-50; DOI: 10.1212/WNL.55.1.46

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Abstract

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.

  • Received August 27, 1999.
  • Accepted in final form March 31, 2000.
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