Anti-GAD antibodies in a cohort of neuropsychiatric patients

Vinke, Anita M; Schaper, Frédéric; Vlooswijk, Mariëlle C.G.; Nicolai, Joost; Majoie, Marian; Martinez, Pilar Martinez; Hoffmann, Carolin; Damoiseaux, Jan; Rouhl, Rob P.W.

doi:10.1016/j.yebeh.2018.03.004

Cited by 14 publications

(17 citation statements)

References 19 publications

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“…Case-series in TIDM also reported an association between the GAD epitope pattern and the occurrence of epilepsy [67,68]. One recent case-control study indicated that TIDM was more likely in people with epilepsy who were anti-GAD positive compared to those who were negative [69].…”

Section: Type 1 Diabetes Mellitus (Tidm)mentioning

confidence: 97%

Seizures as a clinical manifestation in somatic autoimmune disorders

Amanat

Thijs

Salehi

et al. 2019

Seizure

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A B S T R A C TThe risk of epileptic seizures seems increased in several systemic autoimmune disorders including systemic lupus erythematosus, type 1 diabetes mellitus, myasthenia gravis, celiac disease, rheumatoid arthritis, Hashimoto's encephalopathy, psoriasis, multiple sclerosis, neuromyelitis optica, and bullous pemphigoid. Immune dysfunction may be partly responsible for this association. Elevated levels of pro-inflammatory cytokines, autoantibodies seen in these autoimmune disorders and antibodies against neuronal antigens may contribute to the etiopathogenesis of seizures and epilepsy associated to immune conditions. Other unknown factors, the effect of different co-morbid conditions of epilepsy as well as shared risk factors such as common etiological factors, environmental triggers, or a common genetic predisposition may also explain the association. We review different autoimmune disorders which may present with co-morbid seizures and discuss possible underlying mechanisms of this co-occurrence focusing on a potential role of immune system dysfunction.

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Section: Type 1 Diabetes Mellitus (Tidm)mentioning

confidence: 97%

Seizures as a clinical manifestation in somatic autoimmune disorders

Amanat

Thijs

Salehi

et al. 2019

Seizure

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“…Here, we report on a large consecutive series of patients newly referred to a large Epilepsy Center over more than three years suffering from temporal lobe adult-onset seizures (TAOS) with clinical findings suggestive of an autoimmune origin. Compared to previous studies on ABs in highly selected epilepsy patient cohorts [20][21][22][23], here, we have assessed for the first time the clinical results in a patient group, in which the presence of autoABs is suspected but has not been identified yet, and compared this group to patients positive for 'neuroABs'.…”

Section: Introductionmentioning

confidence: 99%

Adult-onset temporal lobe epilepsy suspicious for autoimmune pathogenesis: Autoantibody prevalence and clinical correlates

et al. 2020

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Temporal lobe adult-onset seizures (TAOS) related to autoimmunity represent an increasingly recognized disease syndrome within the spectrum of epilepsies. In this context, certain autoantibodies (autoABs) were often associated with limbic encephalitis (LE). Here, we aimed to gain insights into (a) the distribution of ‘neurological’ autoABs (neuroABs, defined as autoABs targeting neuronal surface structures or ‘onconeuronal’ ABs or anti-glutamate acid decarboxylase 65 (GAD65) autoABs) in a large consecutive TAOS patient cohort, to characterize (b) clinical profiles of seropositive versus seronegative individuals and to find (c) potential evidence for other autoABs. Blood sera/cerebrospinal fluid (CSF) of TAOS patients (n = 800) and healthy donors (n = 27) were analyzed for neuroABs and screened for other autoABs by indirect immunofluorescence on hippocampal/cerebellar sections and immunoblots of whole brain and synaptosome lysates. Serological results were correlated with clinico-neuropsychological features. 13% of TAOS patients (n = 105) were neuroAB + , with anti-GAD65 and anti-N-methyl-D-aspartate receptors (NMDAR) as most frequent autoABs in this group. In our screening tests 25% of neuroAB - patients (n = 199) were positive (screening + ), whereas all control samples were negative (n = 27). Intriguingly, key clinico-neuropsychological characteristics including magnetic resonance imaging (MRI) findings, epileptiform electroencephalographic (EEG) activity, and inflammatory cellular infiltrates in CSF were shared to a greater extent by neuroAB + with neuroAB - /screening + patients than with neuroAB - /screening - patients. Serological testing in a large consecutive TAOS patient series revealed seropositivity for anti-GAD65 autoABs as the most frequent neuroAB. Intriguingly, neuroAB + individuals were virtually indistinguishable from neuroAB - /screening + patients in several major clinical features. In contrast, neuroAB - /screening - TAOS patients differed in many parameters. These data support the potential presence of so far unrecognized autoABs in patients with TAOS.

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“…In our series, orofacial dyskinesia was noted in 7/11 cases. 5 Journal of Immunology Research AE with anti-GAD65 antibodies is a rare condition in children, and to the best of our knowledge, only 16 pediatric cases were reported [11][12][13][14][15]. It is characterized by limbic involvement with refractory seizures, cognitive impairment, and behavioral disturbances [16].…”

mentioning

confidence: 99%

Autoimmune Encephalitis in Tunisia: Report of a Pediatric Cohort

Douma

Younes

Benrhouma

et al. 2021

Journal of Immunology Research

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Background. Autoimmune encephalitis (AE) is a rapidly progressive encephalopathy caused by antibodies targeting neurons in the central nervous system generating specific immune responses. It is increasingly recognized in children. Objective. To describe clinical, neuroimaging, and laboratory features, treatment, and outcome in a cohort of Tunisian children with AE. Methods. We conducted a retrospective review of the medical records of all children attending the Department of Child and Adolescent Neurology (Tunis) with autoimmune encephalitis between 2004 and 2020. Clinical, neuroimaging, laboratory features, therapeutic data, and outcome were analyzed. Results. Nineteen children were included in the study (12 girls and 7 boys). The median age at diagnosis was 7.68 years (range: 10 months-13 years). The most frequent manifestations were seizures and behavioral disorders. Eleven cases were diagnosed with anti-NMDA receptor encephalitis, 4 cases with anti-Ma2 encephalitis, 3 cases with anti-GAD encephalitis, and 1 case with anti-SOX1 encephalitis. Brain MRI showed increased T2 and fluid-attenuated inversion recovery (FLAIR) signal of the temporal lobe in 5 patients. Eighteen patients showed improvement following first-line immunotherapy (high-dose corticosteroids, intravenous immunoglobulin). One patient with anti-GAD encephalitis died despite escalating immunotherapy. Conclusion. Diagnosis of autoimmune encephalitis is challenging in children, because of misleading presentations. An early and accurate diagnosis is important to enable proper therapeutic interventions.

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Anti-GAD antibodies in a cohort of neuropsychiatric patients

Abstract: Antiglutamate decarboxylase (anti-GAD) antibodies relate to epilepsy with or without cognitive complaints. However, psychiatric symptoms were almost absent in anti-GAD positive patients, and the presence of anti-GAD antibodies contributed little to the prognosis in our cohort.

Cited by 14 publications

References 19 publications

Seizures as a clinical manifestation in somatic autoimmune disorders

Seizures as a clinical manifestation in somatic autoimmune disorders

Adult-onset temporal lobe epilepsy suspicious for autoimmune pathogenesis: Autoantibody prevalence and clinical correlates

Autoimmune Encephalitis in Tunisia: Report of a Pediatric Cohort

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