Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies

Joubert, Bastien; Belbézier, Aude; Haesebaert, Julie; Rheims, Sylvain; Ducray, François; Picard, Géraldine; Rogemond, Véronique; Psimaras, Dimitri; Berzero, Giulia; Desestret, Virginie; Honnorat, Jérôme

doi:10.1007/s00415-020-09807-2

Cited by 35 publications

(47 citation statements)

References 17 publications

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“…Neurological syndromes have instead been associated the HLA class II haplotype DQA1*05:01-DQB1*02:01-DRB1*03:01 (DQ2-DR3), detected in 41% of patients in a mixed cohort of SPS, CA, and LE [89]. Consistently, the HLA alleles DQB1*02:01 and DRB1*03:0 were formerly detected in 44%-72% of patients in cohorts with SPS [92,93]. Further studies analyzing larger cohorts are needed to clarify whether the different neurological syndromes are associated with particular HLA alleles.…”

Section: Genetic Predispositionmentioning

confidence: 91%

“…Patients with neurological disorders associated with GAD Ab typically have a personal or familial history of autoimmunity. Family history of autoimmune diseases, including T1DM or thyroiditis, is common (43%-55% for SPS/CA [79,87] and 23% for TLE [93]). A personal history of T1DM is present in about half of cases (between 43 and 71% in the main cohorts [15,18,28,45,87]) and it usually precedes neurological manifestations [28,45,87].…”

Section: Coexisting Autoimmune Disordersmentioning

confidence: 99%

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Neurological Syndromes Associated with Anti-GAD Antibodies

Dade

Berzero

Izquierdo

et al. 2020

IJMS

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Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter within the central nervous system. GAD antibodies (Ab) have been associated with multiple neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and limbic encephalitis, which are all considered to result from reduced GABAergic transmission. The pathogenic role of GAD Ab is still debated, and some evidence suggests that GAD autoimmunity might primarily be cell-mediated. Diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid. Due to the relative rarity of these syndromes, treatment schemes and predictors of response are poorly defined, highlighting the unmet need for multicentric prospective trials in this population. Here, we reviewed the main clinical characteristics of neurological syndromes associated with GAD Ab, focusing on pathophysiologic mechanisms.

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Section: Genetic Predispositionmentioning

confidence: 91%

Section: Coexisting Autoimmune Disordersmentioning

confidence: 99%

Neurological Syndromes Associated with Anti-GAD Antibodies

Dade

Berzero

Izquierdo

et al. 2020

IJMS

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“…Furthermore, only one type of receptors, mainly located in the postsynaptic site, is attacked by these autoantibodies (one to one action). On the other hand, autoantibodies-induced impairments in the release machinery are associated with poor prognosis [ 161 ]. For example, anti-GAD65 Ab decreases GABA release, resulting in dysfunction in the GABA A and GABA B receptors at postsynaptic sites and GABA B receptor in the presynaptic site of neighboring excitatory synapses.…”

Section: Fundamental Pathophysiology Of Autoantibodies Targeting Imentioning

confidence: 99%

Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias

Mitoma

Honnorat

Yamaguchi

et al. 2020

IJMS

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In the last years, different kinds of limbic encephalitis associated with autoantibodies against ion channels and synaptic receptors have been described. Many studies have demonstrated that such autoantibodies induce channel or receptor dysfunction. The same mechanism is discussed in immune-mediated cerebellar ataxias (IMCAs), but the pathogenesis has been less investigated. The aim of the present review is to evaluate what kind of cerebellar ion channels, their related proteins, and the synaptic machinery proteins that are preferably impaired by autoantibodies so as to develop cerebellar ataxias (CAs). The cerebellum predictively coordinates motor and cognitive functions through a continuous update of an internal model. These controls are relayed by cerebellum-specific functions such as precise neuronal discharges with potassium channels, synaptic plasticity through calcium signaling pathways coupled with voltage-gated calcium channels (VGCC) and metabotropic glutamate receptors 1 (mGluR1), a synaptic organization with glutamate receptor delta (GluRδ), and output signal formation through chained GABAergic neurons. Consistently, the association of CAs with anti-potassium channel-related proteins, anti-VGCC, anti-mGluR1, and GluRδ, and anti-glutamate decarboxylase 65 antibodies is observed in IMCAs. Despite ample distributions of AMPA and GABA receptors, however, CAs are rare in conditions with autoantibodies against these receptors. Notably, when the autoantibodies impair synaptic transmission, the autoimmune targets are commonly classified into three categories: release machinery proteins, synaptic adhesion molecules, and receptors. This physiopathological categorization impacts on both our understanding of the pathophysiology and clinical prognosis.

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“…GAD65 antibodies have been associated with a variety of autoimmune neurological syndromes, from stiffperson syndrome and cerebellar ataxia to limbic encephalitis (LE) and epilepsy. [1][2][3][4][5][6][7][8][9][10] However, the pathogenic role of the antibodies has often been questioned due to variability of the clinical presentation and the high prevalence of GAD65 antibodies in patients without any neurological manifestation. They are found in up to 80% patients with type 1 diabetes mellitus.…”

Section: Commentarymentioning

confidence: 99%