Limbic Encephalitis Associated With GAD65 Antibodies: Brief Review of the Relevant literature

AbstractRecently, many cases of autoimmune limbic encephalitis with positive GAD65 (glutamic acid decarboxylase) antibodies have been described in the scientific literature. However, it remains an understudied topic of great relevance to practicing neurologists. Thus, we report here a review of published cases, in English, of autoimmune limbic encephalitis with this type of antibodies, focusing on presenting symptoms and signs, associated conditions, and findings upon investigation. We also report treatment responses. We aim to offer a better description of the clinical spectrum of autoimmune limbic encephalitis associated with GAD65 antibodies as well as to expose its paraclinical features and outcome.

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Type 1 diabetes and GAD65 limbic encephalitis: a case report of a 10-year-old girl

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0016 ◽

2016 ◽

Vol 29 (8) ◽

Cited By ~ 3

Author(s):

Ema Grilo ◽

Joana Pinto ◽

Joana Serra Caetano ◽

Helena Pereira ◽

Patrícia Cardoso ◽

...

Keyword(s):

Type 1 Diabetes ◽

Limbic Encephalitis ◽

Acid Decarboxylase ◽

High Dose ◽

Cerebral Magnetic Resonance Imaging ◽

Temporal Lobe Seizures ◽

Glutamic Acid Decarboxylase 65 ◽

Gad65 Antibodies

AbstractLimbic encephalitis is a rare neurological disorder that may be difficult to recognize. Clinical features include memory impairment, temporal lobe seizures and affective disturbance. We report the case of a 10-year-old girl with type 1 diabetes mellitus that presented with seizures, depressed mood and memory changes. The diagnosis of glutamic acid decarboxylase 65 (GAD65) mediated limbic encephalitis relied on cerebral magnetic resonance imaging lesions and high serological and cerebrospinal fluid GAD65-antibodies titers. High-dose steroidal therapy was started with clinical improvement. Relapse led to a second high-dose steroid treatment followed by rituximab with remission. A correlation between serum GAD65-antibodies levels and symptoms was found, demonstrating GAD65-antibodies titers may be useful for clinical follow-up and immunotherapy guidance. This report raises awareness of this serious neurological condition that may be associated with type 1 diabetes, underlining the importance of an early diagnosis and prompt treatment for a better prognosis.

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P.050 Autoimmune encephalitis associated with GAD65 antibodies: brief review of the relevant literature

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.154 ◽

2016 ◽

Vol 43 (S2) ◽

pp. S33-S33

Author(s):

M Gagnon ◽

M Savard

Keyword(s):

Memory Impairment ◽

Brain Mri ◽

Relevant Literature ◽

Clinical Manifestations ◽

Autoimmune Encephalitis ◽

Systemic Autoimmune Disease ◽

Acid Decarboxylase ◽

Distinctive Pattern ◽

Temporal Lobes ◽

Gad65 Antibodies

Background: Recently, many cases of autoimmune encephalitis with positive GAD65 (Glutamic acid decarboxylase) antibodies have been described in the literature. However, it remains an understudied topic. Methods: We conducted a search on reported cases of anti-GAD65 encephalitis. Specific variables were identified as general characteristics, clinical manifestations, MRI and EEG findings, concomitant systemic autoimmune disorders and cancer, and outcome and autoantibodies findings. Results: We identified a total of 58 cases, from one to 70 years old. It most frequently presented with seizures (97%) and memory impairment (59%). It commonly occurred in association with systemic autoimmune disease, particularly diabetes (28%). Brain MRI was usually abnormal (78%); involvement of temporal lobes was more frequent than multifocal abnormalities (59% vs 16%). GAD65 antibodies were reported positive in CSF and/or serum (31% in serum only). Other antibodies such as GABABR, GABAAR and VGKC were concurrently reported positive in some cases (19%). However, we found that the vast majority of cases were not tested for all those cell-surface antibodies. Overall, no distinctive pattern of clinical and paraclinical findings was found. Persistent impairments were common. Optimal treatment remained undefined. Conclusions: Prospective studies recruiting patients with autoimmune encephalitis are needed to better elucidate the contributions of GAD65 autoantibodies, and to evaluate treatment and outcomes in this population.

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Autoimmune Limbic Encephalitis Associated with Glutamic Acid Decarboxylase Antibodies

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/435 ◽

2021 ◽

Vol 10 (28) ◽

pp. 2131-2133

Author(s):

Krishnan Balagopal

Keyword(s):

Cell Surface ◽

Glutamic Acid ◽

Glutamic Acid Decarboxylase ◽

Limbic Encephalitis ◽

Neuropsychiatric Symptoms ◽

Surface Antigens ◽

Clinical Syndrome ◽

Acid Decarboxylase ◽

Cell Surface Antigens ◽

Autoimmune Limbic Encephalitis

Limbic encephalitis (LE) is a clinical syndrome characterized by the progressive development of neuropsychiatric symptoms including personality changes, memory loss followed by seizures, autonomic dysfunction, and involvement of the medial temporal lobes.1 Limbic encephalitis most commonly presents secondary to an autoimmune aetiology which can be further subclassified into autoimmune and paraneoplastic. Autoimmune LE can be classified according to the presence of autoantibodies into two categories. The first one is associated with antibodies to intracellular neuronal antigens and the other with antibodies to cell surface antigens.2 Intracellular antigens include Hu, Ma2, Collapsin response - mediator protein 5 (CRMP - 5) and cell surface antigens like the voltage-gated potassium channel (VGKC), N - methyl - D - aspartate receptor (NMDA) and others. The autoimmune form of LE is important because it can be treated with immunotherapy if detected early. We present a case of a patient with recurrent vertigo followed by progressive cognitive dysfunction and involuntary movements. She was diagnosed with autoimmune limbic encephalitis associated with glutamic acid decarboxylase (GAD) 65 antibodies. Her symptoms showed improvement following immunomodulatory therapy.

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Anti-GAD65 antibody-associated hemiataxia

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000939 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000939

Author(s):

Emily J. Hill ◽

Joseph Jankovic

Keyword(s):

Cerebellar Ataxia ◽

Limbic Encephalitis ◽

Acid Decarboxylase ◽

Intracellular Membrane ◽

Limb Ataxia ◽

High Concentrations ◽

Gad65 Antibody ◽

Glutamic Acid Decarboxylase 65 ◽

Improved Methods ◽

Gad65 Antibodies

Autoimmune and paraneoplastic movement disorders are increasingly recognized as a result of improved methods in detecting antibodies directed against intracellular, membrane, and other antigens.1 High concentrations of anti-glutamic acid decarboxylase 65 (GAD65) antibodies are associated with several neurologic syndromes including stiff-person syndrome, epilepsy, limbic encephalitis, and cerebellar ataxia.2 Anti-GAD65-associated cerebellar ataxia is typically generalized with prominent gait disturbance and eye movement abnormalities.1 Limb ataxia is present in 60-70% of patients.3 Here we present 2 unusual cases of hemiataxia associated with high concentrations of anti-GAD65 antibodies.

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Neurologic syndromes related to anti-GAD65

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000696 ◽

2020 ◽

Vol 7 (3) ◽

pp. e696 ◽

Cited By ~ 14

Author(s):

Amaia Muñoz-Lopetegi ◽

Marienke A.A.M. de Bruijn ◽

Sanae Boukhrissi ◽

Anna E.M. Bastiaansen ◽

Mariska M.P. Nagtzaam ◽

...

Keyword(s):

Limbic Encephalitis ◽

Serum Antibody ◽

Complete Recovery ◽

Acid Decarboxylase ◽

Antibody Concentration ◽

High Concentration ◽

Neurologic Symptom ◽

Low Concentrations ◽

Treatment Responses ◽

Glutamic Acid Decarboxylase 65

ObjectiveAntibodies against glutamic acid decarboxylase 65 (anti-GAD65) are associated with a number of neurologic syndromes. However, their pathogenic role is controversial. Our objective was to describe clinical and paraclinical characteristics of anti-GAD65 patients and analyze their response to immunotherapy.MethodsRetrospectively, we studied patients (n = 56) with positive anti-GAD65 and any neurologic symptom. We tested serum and CSF with ELISA, immunohistochemistry, and cell-based assay. Accordingly, we set a cutoff value of 10,000 IU/mL in serum by ELISA to group patients into high-concentration (n = 36) and low-concentration (n = 20) groups. We compared clinical and immunologic features and analyzed response to immunotherapy.ResultsClassical anti–GAD65-associated syndromes were seen in 34/36 patients with high concentration (94%): stiff-person syndrome (7), cerebellar ataxia (3), chronic epilepsy (9), limbic encephalitis (9), or an overlap of 2 or more of the former (6). Patients with low concentrations had a broad, heterogeneous symptom spectrum. Immunotherapy was effective in 19/27 treated patients (70%), although none of them completely recovered. Antibody concentration reduction occurred in 15/17 patients with available pre- and post-treatment samples (median reduction 69%; range 27%–99%), of which 14 improved clinically. The 2 patients with unchanged concentrations showed no clinical improvement. No differences in treatment responses were observed between specific syndromes.ConclusionMost patients with high anti-GAD65 concentrations (>10,000 IU/mL) showed some improvement after immunotherapy, unfortunately without complete recovery. Serum antibody concentrations' course might be useful to monitor response. In patients with low anti-GAD65 concentrations, especially in those without typical clinical phenotypes, diagnostic alternatives are more likely.

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Case Report: Autoimmune Encephalitis Associated With Anti-glutamic Acid Decarboxylase Antibodies: A Pediatric Case Series

Frontiers in Neurology ◽

10.3389/fneur.2021.641024 ◽

2021 ◽

Vol 12 ◽

Author(s):

Changhong Ren ◽

Haitao Ren ◽

Xiaotun Ren ◽

Weihua Zhang ◽

Jiuwei Li ◽

...

Keyword(s):

Glutamic Acid ◽

Clinical Data ◽

Glutamic Acid Decarboxylase ◽

Limbic Encephalitis ◽

Refractory Epilepsy ◽

Autoimmune Encephalitis ◽

Acid Decarboxylase ◽

Long Term Outcome ◽

Gad65 Antibody ◽

Gad65 Antibodies

Background: Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extralimbic encephalitis. There have been some case reports and investigations regarding anti-GAD65 antibody-associated encephalitis in adult populations, but pediatric cases are rare. We retrospectively analyzed the clinical data of three anti-GAD65 antibody-positive patients to explore the diversity and clinical features of anti-GAD65 antibody-associated pediatric autoimmune encephalitis.Methods: The clinical data of a series of three patients positive for anti-GAD65 antibody were retrospectively analyzed. GAD65 antibodies were determined in serum and CSF using a cell-based assay.Results: All three patients were female, and the onset ages were 4 years and 9 months, 6 years, and 16 years old. Their clinical phenotypes included autoimmune limbic encephalitis, extralimbic encephalitis, and encephalitis combining limbic and extralimbic encephalitis. The clinical symptoms included seizures, memory deficits, drowsiness, dysautonomia, and headache. All patients had abnormal carinal MRI and EEG. All patients received immunotherapy and had transiently good responsiveness, but one patient then experienced relapse. In follow-up, one patient with extralimbic encephalitis recovered completely, while two patients with limbic involvement had poor outcomes with refractory focal epilepsy.Conclusion: In addition to limbic encephalitis, extralimbic encephalitis is also an important phenotype in patients who are positive for anti-GAD65 antibodies. Early diagnosis and immunotherapy can improve the symptoms. However, patients with limbic encephalitis often have refractory epilepsy in the chronic phase and have a poor long-term outcome.

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