Anti-GAD65 antibody-associated hemiataxia

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.

scholarly journals Clinical spectrum of high-titre GAD65 antibodies

2021 ◽  
pp. jnnp-2020-325275
Author(s):  
Adrian Budhram ◽  
Elia Sechi ◽  
Eoin P Flanagan ◽  
Divyanshu Dubey ◽  
Anastasia Zekeridou ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Antibody Titre ◽  
Clinical Manifestations ◽  
High Titre ◽  
Acid Decarboxylase ◽  
Poor Outcome ◽  
Atypical Presentations ◽  
Gad65 Antibody ◽  
Glutamic Acid Decarboxylase 65 ◽  
Gad65 Antibodies

ObjectiveTo determine clinical manifestations, immunotherapy responsiveness and outcomes of glutamic acid decarboxylase-65 (GAD65) neurological autoimmunity.MethodsWe identified 323 Mayo Clinic patients with high-titre (>20 nmol/L in serum) GAD65 antibodies out of 380 514 submitted anti-GAD65 samples (2003–2018). Patients classified as having GAD65 neurological autoimmunity after chart review were analysed to determine disease manifestations, immunotherapy responsiveness and predictors of poor outcome (modified Rankin score >2).ResultsOn review, 108 patients were classified as not having GAD65 neurological autoimmunity and 3 patients had no more likely alternative diagnoses but atypical presentations (hyperkinetic movement disorders). Of remaining 212 patients with GAD65 neurological autoimmunity, median age at symptom onset was 46 years (range: 5–83 years); 163/212 (77%) were female. Stiff-person spectrum disorders (SPSD) (N=71), cerebellar ataxia (N=55), epilepsy (N=35) and limbic encephalitis (N=7) could occur either in isolation or as part of an overlap syndrome (N=44), and were designated core manifestations. Cognitive impairment (N=38), myelopathy (N=23) and brainstem dysfunction (N=22) were only reported as co-occurring phenomena, and were designated secondary manifestations. Sustained response to immunotherapy ranged from 5/20 (25%) in epilepsy to 32/44 (73%) in SPSD (p=0.002). Complete immunotherapy response occurred in 2/142 (1%). Cerebellar ataxia and serum GAD65 antibody titre >500 nmol/L predicted poor outcome.InterpretationHigh-titre GAD65 antibodies were suggestive of, but not pathognomonic for GAD65 neurological autoimmunity, which has discrete core and secondary manifestations. SPSD was most likely to respond to immunotherapy, while epilepsy was least immunotherapy responsive. Complete immunotherapy response was rare. Serum GAD65 antibody titre >500 nmol/L and cerebellar ataxia predicted poor outcome.

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

2016 ◽  
Vol 29 (8) ◽  
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.

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

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.

scholarly journals Anti–Glutamic Acid Decarboxylase Limbic Encephalitis Without Epilepsy Evolving Into Dementia With Cerebellar Ataxia

2012 ◽  
Vol 69 (8) ◽  
Author(s):  
Marisol Mirabelli-Badenier ◽  
Giovanni Morana ◽  
Francesca Pinto ◽  
Antonio Uccelli ◽  
Edvige Veneselli ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Cerebellar Ataxia ◽  
Glutamic Acid Decarboxylase ◽  
Limbic Encephalitis ◽  
Acid Decarboxylase

scholarly journals Neurologic syndromes related to anti-GAD65

2020 ◽  
Vol 7 (3) ◽  
pp. e696 ◽  
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.

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

2016 ◽  
Vol 43 (4) ◽  
pp. 486-493 ◽  
Author(s):  
Maude-Marie Gagnon ◽  
Martin Savard
Keyword(s):  
Limbic Encephalitis ◽  
Relevant Literature ◽  
Acid Decarboxylase ◽  
Presenting Symptoms ◽  
Associated Conditions ◽  
Autoimmune Limbic Encephalitis ◽  
Great Relevance ◽  
Treatment Responses ◽  
Symptoms And Signs ◽  
Gad65 Antibodies

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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