Clinical Features, Diagnostic Implications, And Outcomes of Amyotrophic Lateral Sclerosis and Myasthenia Gravis Overlap Syndrome: A Systematic Review

• Published in: Medical principles and practice pp. 1 - 18
• Main Authors: Hawas, Yousef, Hamad, Abdullah Ashraf, Meshref, Mostafa, Elbehary, Mohamed, Mohamed, Rashad G., Elshahat, Ahmed, Mabrouk, Manar Alaa, Nashwan, Abdulqadir J., Fouda, Basem Hamdy
• Format: Journal Article
• Language: English
• Published: Switzerland S. Karger AG 10.04.2025
• Subjects: Systematic Review; Amyotrophic lateral sclerosis; Myasthenia gravis; Neuromuscular junction; Motor neuron disease; Overlap syndrome
• ISSN: 1011-7571; 1423-0151; 1423-0151
• DOI: 10.1159/000545806

Objective: This review aims to summarize the current evidence of reported myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS) overlap syndrome regarding clinical and laboratory features, diagnostic implications, management, outcomes, and comorbid conditions to raise awareness among healthcare providers and aid in proper care provision. Methods: Recently, a few cases of an unusual association between both diseases have been reported. PubMed, Scopus, and Web of Science were searched from inception until May 2024 to identify eligible studies. After the screening and data extraction, 20 studies with 42 cases suffering from ALS and MG were included. Results: 42 cases were categorized into four groups as follows: The first group had 26 cases with MG onset (range 26-82 years) preceding ALS (range 46-83 years). The second group had 9 cases with ALS (range 34-89) preceding MG (range 40-89 years). The third group comprised 5 cases of ALS with positive acetylcholine receptor antibodies but without clinical manifestations of MG. The fourth group involved 2 cases of ALS with initial ocular symptoms that were unresponsive to MG treatments. Conclusion: The onset of new ptosis or diplopia in ALS patients should prompt clinicians to consider the possibility of a coexisting condition or alternative diagnosis. Additionally, positive acetylcholine receptor antibodies alone are insufficient to diagnose MG if ALS coexists. In patients with ALS, repetitive nerve stimulation tests may be less sensitive for detecting MG. Thus, diagnosing MG in ALS patients should rely on clinical presentation and response to empirical treatment.