Abstract
Antibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab. We report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapies that were initially administered for 6 months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLA-DR(+) CD8(+) T-lymphocytes (fCD8(+)TL) when compared to controls. Thus, a second, intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/month was started. After 3 months, the fCD8(+)TL in the CSF normalized; after 6 months, the psychological impulse-control deficits normalized; and after 11 months the patient was seizure free. However, 7 weeks later, seizures and, later on, psychological deficits recurred and fCD8(+)TL was once again present in the CSF. Flumazenil PET, magnetic resonance imaging-volumetry, and neuropsychological changes during therapy are described. The correlation of the fCD8(+)TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximab strongly argues in favor of the putative pathogenic role fCD8(+)TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti-drug ABs, a well-known complication of therapy with chimeric ABs.
Highlights
In 2009, a male patient with temporal lobe epilepsy (TLE) that started at the age of 18 was admitted to the Department of Epileptology, University of Bonn, 2 years after his initial diagnosis
Limbic encephalitis is an autoimmune encephalitis with mediotemporal lobe symptoms caused by inflammatory lesions in limbic structures, which leads to a TLE, impairment of recent memory, and affective disturbances, which have mostly been observed in adults
GAD65-ABs were above the limit of 2000 IU before, during, and after initial Cortisone pulse therapy in the peripheral blood (PB)
Summary
In 2009, a male patient with temporal lobe epilepsy (TLE) that started at the age of 18 was admitted to the Department of Epileptology, University of Bonn, 2 years after his initial diagnosis He displayed some clinical signs compatible with limbic encephalitis (LE): seizures of temporal semiology starting in adult age but lasting no longer than 5 years, as well as affective disturbances with prominent mood lability, or disinhibition [1, 2]. Case presentation: We report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. These interventions resulted in the concentration of ABs being reduced to only 57% (69–3%) of the initial concentration
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