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.

PubMed, EBSCO, Scopus, and Web of Science databases 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.

The 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). Most MG symptoms resolved with treatment, ALS symptoms worsened despite therapy except for a case who showed significant improvement after receiving autologous enhanced mesenchymal stem cells. The second group had 8 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.

This review summarizes the current evidence and underscores the need for heightened awareness among healthcare providers to facilitate early recognition, accurate diagnosis, and individualized management strategies. Future research efforts should focus on unraveling the underlying mechanisms driving this intriguing association. Also, they should reconsider the role of peripheral targets in neurodegenerative diseases as ALS, where the focus has traditionally been centrally.