Oculomotor phenotypes and longitudinal video-oculography dynamics in anti-GAD65 antibody-associated neurological syndromes: a case series and literature review.
Source: PubMed, NCBI / U.S. National Library of Medicine
Anti-glutamic acid decarboxylase (GAD) antibody-associated neurological syndromes encompass a heterogeneous group of immune-mediated disorders in which ocular involvement is increasingly recognized but remains insufficiently characterized. Data on clinical features, neuroimaging, and longitudinal ocular motor findings are limited. We retrospectively reviewed four patients diagnosed with anti-GAD antibody-associated neurological syndromes presenting with ocular manifestations at our center between 2019 and 2025. Clinical features, ocular motor findings, laboratory and neuroimaging results, treatment, and outcomes were collected. Longitudinal video-oculography (VOG) was analyzed in one patient. A literature review was performed to summarize reported ocular and vestibulo-ocular abnormalities. All four patients (2 males, 2 females; onset age 53-68 years) exhibited ocular symptoms, three presented with ocular symptoms early in the disease course; however, in one case (Case 4), the temporal association between the initial ocular symptom and the final diagnosis remained uncertain. Diplopia, nystagmus, and ptosis were the predominant findings. Early brain and orbital Magnetic Resonance Imaging (MRI) were unremarkable, while cerebellar atrophy developed in one patient during relapse. All patients were positive for serum anti-GAD65 antibodies; one also had anti-titin antibodies with elevated creatine kinase(CK). VOG in one patient demonstrated worsening saccadic velocity and pursuit ga
Abstract
Anti-glutamic acid decarboxylase (GAD) antibody-associated neurological syndromes encompass a heterogeneous group of immune-mediated disorders in which ocular involvement is increasingly recognized but remains insufficiently characterized. Data on clinical features, neuroimaging, and longitudinal ocular motor findings are limited. We retrospectively reviewed four patients diagnosed with anti-GAD antibody-associated neurological syndromes presenting with ocular manifestations at our center between 2019 and 2025. Clinical features, ocular motor findings, laboratory and neuroimaging results, treatment, and outcomes were collected. Longitudinal video-oculography (VOG) was analyzed in one patient. A literature review was performed to summarize reported ocular and vestibulo-ocular abnormalities. All four patients (2 males, 2 females; onset age 53-68 years) exhibited ocular symptoms, three presented with ocular symptoms early in the disease course; however, in one case (Case 4), the temporal association between the initial ocular symptom and the final diagnosis remained uncertain. Diplopia, nystagmus, and ptosis were the predominant findings. Early brain and orbital Magnetic Resonance Imaging (MRI) were unremarkable, while cerebellar atrophy developed in one patient during relapse. All patients were positive for serum anti-GAD65 antibodies; one also had anti-titin antibodies with elevated creatine kinase(CK). VOG in one patient demonstrated worsening saccadic velocity and pursuit gain during relapse, consistent with cerebellar dysfunction. Literature review of 61 articles showed that diplopia and nystagmus were the most frequently reported features, with characteristic vestibulo-ocular abnormalities including multistep saccades and square-wave oscillations. Based on clinical and literature findings, we further identified recurrent oculomotor patterns across cases. Ocular symptoms may represent early clinical features of anti-GAD antibody-associated neurological syndromes, although the temporal relationship may vary across patients and should be interpreted with caution in atypical cases. Downbeat nystagmus may serve as an early marker of cerebellar involvement. Longitudinal VOG provides objective insights into disease evolution. Importantly, we propose a structured oculomotor phenotype framework and highlight longitudinal VOG as a tool for tracking dynamic cerebellar dysfunction, which may facilitate earlier recognition and monitoring of disease progression.