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Medical Student
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Internal Medicine
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Patient Care
Abstract
Autoimmune encephalitis (AE) is a rare group of neurological disorders in which antibodies are directed against intracellular or surface antigens. The incidence of AE ranged from between 0.4-1.2 per 100,000 person-years between 1995 and 2015. A subset of these autoimmune encephalitides that target glutamic acid decarboxylase (GAD) are termed anti-GAD related neurological disorders. GAD is the rate-limiting enzyme involved in the synthesis of GABA from glutamate, and is expressed in neurons of the cerebral cortex, cerebellum, and hippocampus. In addition, it is found in the B-islets of the pancreas, epithelial cells of the fallopian tube, and spermatocytes of the testes. Antibodies directed against GAD have been linked to a group of autoimmune neurological syndromes such as stiff person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis, and temporal lobe epilepsy. In the following case report, a 62-year-old-male presented to the emergency department with dysphagia and drooling. On this admission, he had multiple neurological findings including right gaze palsy, diminish facial sensation on the right V1 branch, moderate left facial droop, and left leg dysmetria on Heel-Knee-Shin Test.
We began the workup to determine the pathogenicity of the autoimmune response. We ordered several antibody titers from CSF and serum (anti-aquaporin4 IgG, anti-MOG IgG, anti-Ma 1 and 2, anti-amphiphysin, anti-gly5, anti- NMDAR, anti-VGKC). All antibodies were negative, and no oligoclonal bands were found on CSF analysis. Anti-GAD65 titers were elevated, giving us strong suspicion for anti-GAD immune-mediated neurologic disorders, which include stiff person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis, and temporal lobe epilepsy. From these disorders, cerebellar ataxia aligned with our patient’s clinical presentation. There were concerns that elevated anti-GAD65 antibodies could be due to underlying type 1 diabetes because B-islets in the pancreas also contain these antigens. Previous studies have demonstrated that highly elevated quantitative titer levels of anti-GAD65 (threshold >10,000 units/mL) are associated with anti-GAD65 associated neurologic syndromes. This is particularly important because lower levels of anti-GAD65 help differentiate between an incidental finding of T1DM and these neurologic syndromes. However, similar studies demonstrate that even with low anti-GAD65 titers, 1-8% of patients still present with neurologic findings. Our case highlights the necessity for a systematic approach workup of autoimmune encephalitis. Currently, there are no established criteria for the diagnosis of these autoimmune neurologic syndromes, particularly in relation to GAD65 syndromes. Multiple in-vivo studies have shown limited evidence for the autoimmune pathogenicity of anti-GAD65 antibodies in stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and temporal lobe epilepsy. This was evident in our management due to our patient’s limited clinical response to immunotherapy (IVIG and steroids). Our case report elucidates the need for scientific exploration into molecular mechanisms of anti-GAD65 neurologic syndromes.
Presentation Type
Poster
Recommended Citation
Masood, Areeb; Appareddy, Nina; Tovar Castro, Raul; Shareef, Zan; and Garcia, Laura, "A Puzzling Case of Glutamic Acid Decarboxylase 65 (GAD65) Neurologic Syndrome" (2023). Research Colloquium. 44.
https://scholarworks.utrgv.edu/colloquium/presentation/poster/44
Included in
A Puzzling Case of Glutamic Acid Decarboxylase 65 (GAD65) Neurologic Syndrome
Autoimmune encephalitis (AE) is a rare group of neurological disorders in which antibodies are directed against intracellular or surface antigens. The incidence of AE ranged from between 0.4-1.2 per 100,000 person-years between 1995 and 2015. A subset of these autoimmune encephalitides that target glutamic acid decarboxylase (GAD) are termed anti-GAD related neurological disorders. GAD is the rate-limiting enzyme involved in the synthesis of GABA from glutamate, and is expressed in neurons of the cerebral cortex, cerebellum, and hippocampus. In addition, it is found in the B-islets of the pancreas, epithelial cells of the fallopian tube, and spermatocytes of the testes. Antibodies directed against GAD have been linked to a group of autoimmune neurological syndromes such as stiff person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis, and temporal lobe epilepsy. In the following case report, a 62-year-old-male presented to the emergency department with dysphagia and drooling. On this admission, he had multiple neurological findings including right gaze palsy, diminish facial sensation on the right V1 branch, moderate left facial droop, and left leg dysmetria on Heel-Knee-Shin Test.
We began the workup to determine the pathogenicity of the autoimmune response. We ordered several antibody titers from CSF and serum (anti-aquaporin4 IgG, anti-MOG IgG, anti-Ma 1 and 2, anti-amphiphysin, anti-gly5, anti- NMDAR, anti-VGKC). All antibodies were negative, and no oligoclonal bands were found on CSF analysis. Anti-GAD65 titers were elevated, giving us strong suspicion for anti-GAD immune-mediated neurologic disorders, which include stiff person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis, and temporal lobe epilepsy. From these disorders, cerebellar ataxia aligned with our patient’s clinical presentation. There were concerns that elevated anti-GAD65 antibodies could be due to underlying type 1 diabetes because B-islets in the pancreas also contain these antigens. Previous studies have demonstrated that highly elevated quantitative titer levels of anti-GAD65 (threshold >10,000 units/mL) are associated with anti-GAD65 associated neurologic syndromes. This is particularly important because lower levels of anti-GAD65 help differentiate between an incidental finding of T1DM and these neurologic syndromes. However, similar studies demonstrate that even with low anti-GAD65 titers, 1-8% of patients still present with neurologic findings. Our case highlights the necessity for a systematic approach workup of autoimmune encephalitis. Currently, there are no established criteria for the diagnosis of these autoimmune neurologic syndromes, particularly in relation to GAD65 syndromes. Multiple in-vivo studies have shown limited evidence for the autoimmune pathogenicity of anti-GAD65 antibodies in stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and temporal lobe epilepsy. This was evident in our management due to our patient’s limited clinical response to immunotherapy (IVIG and steroids). Our case report elucidates the need for scientific exploration into molecular mechanisms of anti-GAD65 neurologic syndromes.