Neurological disorders associated with glutamic acid decarboxylase 65 antibodies: Clinical spectrum and prognosis of a cohort from China

Abstract

ObjectiveTo describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China.MethodIn this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients.ResultsFifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) (n = 34, 61.82%), stiff-person syndromes (SPS) (n = 18, 32.73%), autoimmune cerebellar ataxia (ACA) (n = 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis (n = 17, 53.13%), T1DM (n = 11, 34.78%), vitiligo (n = 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6–33.75 month, range 3–96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients.ConclusionsLE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes.

A case of severe paraneoplastic glutamic acid decarboxylase antibody‐spectrum disorder with improvement through prior immunotherapy before surgical intervention

“…1,3 GAD-SD typically presents as either SPS or CA alone, with an overlap between SPS and CA observed in approximately 2%-15% of cases. [5][6][7] In the present case, CA preceded the onset of SPS symptoms. MRI findings did not show significant cerebellar atrophy or reduced blood compared with the severity of cerebellar symptoms.…”

“…The exact role of GAD antibodies in the pathology of these disorders is still not fully understood, and as GAD is localized in the cytoplasm of presynaptic nerve endings, it appears to be more of a marker rather than a pathogenic factor 1,3 . GAD‐SD typically presents as either SPS or CA alone, with an overlap between SPS and CA observed in approximately 2%–15% of cases 5–7 . In the present case, CA preceded the onset of SPS symptoms.…”

“…Most previous reports have shown improvement after tumor removal in cases of thymoma complications, whereas the optimal timing for tumor removal remains unknown 11,13 . In contrast, there have also been reports of worsened neurological symptoms after thymoma removal 7,14 . In cases of tumor complications, it might be advisable to prioritize immunotherapy and consider whether the patients' activities of daily living have improved.…”

“…11,13 In contrast, there have also been reports of worsened neurological symptoms after thymoma removal. 7,14 In cases of tumor complications, it might be advisable to prioritize immunotherapy and consider whether the patients' activities of daily living have improved.…”