Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis

Malter, Michael P.; Helmstaedter, Christoph; Urbach, Horst; Vincent, Angela; Bien, Christian G.

doi:10.1002/ana.21917

Cited by 446 publications

(465 citation statements)

References 38 publications

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“…However, centers that perform a lot of antibody testing report that only 10 % of the tested cases have more than 1 single antibody [85]. Another interesting point is that the persistence of antibodies over time is different across the antigenic specificities: LGI1 antibodies are often monophasically formed, whereas onconeural antibodies [86] and GAD antibodies [46] persist for long periods, that is they are continuously produced. Another issue is how and why the antibodies reach the brain.…”

Section: Discussionmentioning

confidence: 99%

“…The findings in brain tissue from such GAD antibody-positive patients are less clear, but also consistent with a cytotoxic mechanism [27]. A nerve cell destroying T-cell effect is certainly compatible with the progressive focal or generalized brain atrophy in patients with GAD antibodies [31,46]. In analogy to other CNS disorders with neuronal degeneration, that is mediotemporal epilepsy with hippocampal sclerosis, such neuronal loss could explain both the patients' epilepsies and their memory problems [47].…”

Section: Studies With Antibodies Against Intracellular Antigensmentioning

confidence: 93%

“…In some patients, there is also evidence for progressive loss of brain tissue, mainly in the medial temporal lobe [46]. The findings in brain tissue from such GAD antibody-positive patients are less clear, but also consistent with a cytotoxic mechanism [27].…”

Section: Studies With Antibodies Against Intracellular Antigensmentioning

confidence: 97%

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Autoimmune Epilepsies

Bien

Bauer

2014

Neurotherapeutics

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In patients with immune-associated disorders of the gray central nervous system matter (including recurrent seizures), antibodies against intracellular antigens have been discovered since the 1980s/1990s. In recent years, new antibodies against surface antigens have also been discovered. In two respects, these antibodies are even more interesting than the ones to intracellular antigens as, first, they promise a better response to immunotherapy; and, second, these antibodies contribute greatly to the understanding of the disease mechanisms. Whereas in encephalitides with antibodies against intracellular antigens, a cytotoxic T-cell-mediated response seems to be responsible for neuronal cell loss, in encephalitides with autoantibodies against surface antigens these antibodies are probably the relevant pathogenic agents in the associated disease conditions. On the one hand, antibodies to the NR1 subunit of N-methyl-D-aspartate receptors have been suggested to cause internalization and loss of these receptors without any cell destruction. This mechanism can explain the reversible functional effects caused by these antibodies. On the other hand, antibody-and complement-mediated destructive, and the irreversible effects of antibodies against the voltage-gated potassium channel antigens have been noted. These emerging findings make it plausible that immunological therapies, preferably early after characterization of the antibodies, offer opportunities to restore the health of affected patients.

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Section: Discussionmentioning

confidence: 99%

Section: Studies With Antibodies Against Intracellular Antigensmentioning

confidence: 93%

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Autoimmune Epilepsies

Bien

Bauer

2014

Neurotherapeutics

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“…Antibodies to voltage-gated potassium channels (VGKCs) were identified in a number of patients with non-paraneoplastic limbic encephalitis, but further studies have shown that the real antigens in these patients are leucine-rich glioma inactivated 1, contactinassociated protein-like 2, and contactin-2, all of which are associated with VGKCs [230,231]. The spectrum of autoantigens associated with in limbic encephalitis, however, continues to expand, and now includes the N-methyl-D-aspartate receptor (NMDAR), the AMPA receptor, the GABA = gamma-aminobutyric acid receptor, and glutamic acid decarboxylase [232][233][234][235]. It is quite likely that many other pathologic autoantigens will be identified.…”

Section: Limbic Encephalitismentioning

confidence: 99%

“…For noncancer-related limbic encephalitides, immunomodulatory therapies, such as corticosteroids, plasmapheresis, and IVIG have all been used with success [234,238]. As opposed to NMDAR antibody encephalitis, outcome in limbic encephalitis is generally better in patients without an identified tumor [239].…”

Section: Limbic Encephalitismentioning

confidence: 99%

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

Geldern¹,

McPharlin

Becker

2012

Neurotherapeutics

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This chapter will review the spectrum of immunemediated diseases that affect the nervous system and may result in an admission to the neurological intensive care unit. Immunomodulatory strategies to treat acute exacerbations of neurological diseases caused by aberrant immune responses are discussed, but strategies for long-term immunosuppression are not presented. The recommendations for therapeutic intervention are based on a synthesis of the literature, and include recommendations by the Cochrane Collaborative, the American Academy of Neurology, and other key organizations. References from recent publications are provided for the disorders and therapies in which randomized clinical trials and large evidenced-based reviews do not exist. The chapter concludes with a brief review of the mechanisms of action, dosing, and side effects of commonly used immunosuppressive strategies in the neurocritical care unit.

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Encephalitis Associated With Glutamic Acid Decarboxylase Autoantibodies in a Child

et al. 2011

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To increase the recognition of glutamic acid decarboxylase autoantibodies-related encephalitis in childhood. Design: Case report and review of the literature. Patient: A 6-year-old girl who had developed refractory seizures, developmental regression, and type 1 diabetes mellitus at age 25 months. Interventions: Blood analysis, electroencephalogram, cerebral magnetic resonance imaging, positron emission tomography scan, lumbar puncture, and measurement of glutamic acid decarboxylase activity were performed. Treatment with repeated plasmapheresis and rituximab, with concomitant antiepileptic drugs, was administered. Results: Highly elevated titers of glutamic acid decarboxylase autoantibodies were found in the serum, as well as in the cerebrospinal fluid. Major clinical improvement in parallel with a decrease in the levels of serum and cerebrospinal fluid antibodies was observed with treatment. Conclusions: Encephalitis associated with glutamic acid decarboxylase autoantibodies is a severe epileptic disorder that occurs in young children as well as adults. It may be partially reversible with aggressive immunomodulatory treatment, including plasmapheresis and rituximab. Studies are warranted to determine whether early treatment leads to complete remission.

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Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis

Abstract: 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.

Cited by 446 publications

References 38 publications

Autoimmune Epilepsies

Autoimmune Epilepsies

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

Encephalitis Associated With Glutamic Acid Decarboxylase Autoantibodies in a Child

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