Objective: To describe a novel phenotype of glutamic acid decarboxylase-65 (GAD65) antibody-associated neurological disease in which an older patient initially presented with levodopa-unresponsive hemiparkinsonism and then subsequently developed cerebellar ataxia and stiff-person syndrome (SPS).

Background: GAD65 autoimmunity is associated with a well-recognized spectrum of neurological phenotypes, the most common of which is SPS characterized by axial and symmetric proximal muscle hyperactivity. Other neurologic syndromes include cerebellar ataxia, progressive encephalomyelitis with rigidity and myoclonus (PERM), and limbic encephalitis (1). Parkinsonism is seen infrequently, so we aim to present an atypical case of GAD65 antibody-associated neurologic disorder initially presenting with hemiparkinsonism.

Method: Case report.

Results: A 60-year old otherwise-healthy left-handed man presented with six months of loss of dexterity in the left hand and feeling of “heaviness” in the left leg when he exercised. On exam, he had slow and deliberate speech and mild parkinsonism with bradykinesia and rigidity of the left arm and leg. MRI brain was normal. He was initially diagnosed with suspected idiopathic Parkinson’s disease and levodopa was initiated for symptomatic treatment. At 6-month follow-up, he reported poor response to levodopa therapy and described new symptoms of disequilibrium, speech changes, and back stiffness. His exam continued to demonstrate hemiparkinsonism, but he also developed new dysarthric scanning speech, limb ataxia affecting the left side, and gait ataxia. Additionally, he had lordosis of the lower back with hypertrophic lumbar paraspinal muscles. Diagnostic work-up revealed elevated GAD65 antibody titers in the serum and cerebrospinal fluid. Paraneoplastic antibody and malignancy work-up were negative. He did not have a history of autoimmune disorders, thyroid disease, or type 1 diabetes. He was admitted to the hospital and treated acutely with intravenous immunoglobulin which lead to symptomatic improvement.

Conclusion: GAD65 autoimmunity is associated with a wide spectrum of neurologic syndromes, yet parkinsonism is described infrequently (2,3). We report a case of a GAD65 antibody-associated syndrome initially presenting with asymmetric parkinsonism. Levodopa-unresponsiveness and subsequent development of dysarthria, ataxia, and stiffness were clues to the diagnosis that prompted further investigation.

References: References: 1. Mckeon A, Tracy JA. GAD65 neurological autoimmunity. Muscle Nerve. 2017;56(1):15-27. 2. Pittock SJ, Yoshikawa H, Ahlskog JE, et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc. 2006;81(9):1207-14. 3. A.P . Mentreddi, S. Chitnis, P . Khemani. A unique phenotype associated with anti-GAD antibodies [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/a-unique-phenotypeassociated-with-anti-gad-antibodies/. Accessed February 28, 2020.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gad65-antibody-neurologic-syndrome-presenting-with-hemiparkinsonism/