Probable Seronegative Myasthenia Gravis With Initially Negative Diagnostic Testing: A Case Report

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction characterized by fluctuating, fatigable weakness. Diagnosis can be particularly challenging when symptoms are initially non-specific and standard serological and neurophysiological investigations are unrevealing. We report the case of a 27-year-old woman who initially developed progressive fatigue and exercise intolerance, followed by fluctuating left eyelid ptosis that worsened with exertion and improved with rest. Initial laboratory testing and cranial imaging were unrevealing. Persistence and progression of ocular symptoms prompted neurological assessment, during which an ice-pack test produced clear improvement in ptosis. Anti-acetylcholine receptor, anti-muscle-specific kinase, and anti-low-density lipoprotein receptor-related protein 4 antibodies were negative, thoracic imaging excluded thymoma, and single-fiber electromyography of the orbicularis oculi was normal, providing no objective electrophysiological confirmation of MG. A trial of pyridostigmine provided only limited symptomatic benefit. In the context of the characteristic fluctuating phenotype, positive bedside test, exclusion of relevant alternative diagnoses, and despite the absence of objective electrophysiological confirmation, a working diagnosis of probable seronegative MG (SNMG) was established, and immunosuppressive treatment was initiated. Over the following two years, symptoms generalized, with limb fatigability, difficulty climbing stairs, occasional dysphagia, and substantial functional limitation. This case highlights the diagnostic uncertainty inherent to suspected SNMG and the importance of longitudinal clinical assessment. Negative antibody and neurophysiological results should prompt careful reassessment and consideration of mimics rather than automatic exclusion or confirmation of MG. In primary care, recognizing true muscle fatigability, diurnal fluctuation, and evolving focal signs may facilitate timely specialist evaluation.