Case Report: Extraocular muscles paralysis associated with GAD65 antibody: a case series study

Heyu Zhang; Jiajia Yue; Chun Lian; Youming Long; Dan He

doi:10.3389/fimmu.2023.1256089

Case Report: Extraocular muscles paralysis associated with GAD65 antibody: a case series study

Front Immunol. 2023 Dec 1:14:1256089. doi: 10.3389/fimmu.2023.1256089. eCollection 2023.

Authors

Heyu Zhang¹, Jiajia Yue², Chun Lian², Youming Long², Dan He¹

Affiliations

¹ Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.
² Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and The Ministry of Education of China, Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Abstract

Objective: To explore the clinical manifestations of glutamic acid decarboxylase 65 (GAD65) antibody-positive patients with extraocular symptoms and the possible mechanism.

Method: Assays for the presence of GAD65 antibodies were performed on patients' serum and cerebral spinal fluid (CSF). The brain and ocular structures involved in eye movement were assessed via magnetic resonance imaging (MRI). Tests such as electromyography (EMG), particularly repetitive nerve stimulation (RNS), and neostigmine tests were utilized for differential diagnosis. Additionally, the interaction of GAD65 antibodies with muscle tissue was confirmed using immunofluorescence techniques.

Result: Each patient exhibited symptoms akin to extraocular myasthenia gravis (MG), with two individuals reporting diplopia and two experiencing ptosis. GAD65 antibodies were detected in either the serum or CSF, which were shown to bind with monkey cerebellum slides and mouse muscle slides. Neuroimaging of the brain and extraocular muscles via MRI showed no abnormalities, and all patients tested negative for the neostigmine test, RNS via EMG, and the presence of MG antibodies. However, thyroid-related antibodies were found to be abnormal in four of the patients.

Conclusion: Our results showed that GAD65 antibodies are not only associated with encephalitis, cerebellum ataxia or stiff-person syndrome caused by the decrease of GABAergic transmission but also diplopia and ptosis. Therefore, we should pay more attention to extraocular muscle paralysis patients without pathogenic antibodies directed against the components of neuromuscular junctions.

Keywords: GAD65 antibody; autoimmune; extraocular muscles paralysis; neuro-immune; neuromuscular disorder.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies
Diplopia
Humans
Mice
Myasthenia Gravis* / diagnosis
Neostigmine
Oculomotor Muscles*
Paralysis

Substances

Neostigmine
Antibodies

Grants and funding

This study was supported by grants from National Natural Science Foundation (82001234) and the Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases (2020B1212060017), Guangdong Provincial Clinical Research Center for Neurological Diseases (2020B1111170002), Southern China International Joint Research Center for Early Intervention and Functional Rehabilitation of Neurological Diseases (2015B050501003 and 2020A0505020004), Guangdong Provincial Engineering Center for Major Neurological Disease Treatment, Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease, Guangzhou Clinical Research and Translational Center for Major Neurological Diseases (201604020010).