2024 American Academy of Neurology Abstract Website

Objective:

This study aims to retrospectively characterize a cohort of children with seronegative myasthenia gravis, compared to those with seropositive disease.

Background:

Myasthenia gravis is associated with antibodies that target epitopes in the neuromuscular junction, particularly the acetylcholine receptor, MuSK and LRP4 proteins. In spite of advances in the sensitivity of antibody tests and identification of antibodies beyond the acetylcholine receptor, about 15 % of patients are still classified as seronegative. In these individuals, diagnosis is made by a pattern of fluctuating weakness and one or more of the following: positive response to an acetylcholinesterase inhibitor such as pyridostigmine and/or a > 10% decremental response with low-frequency RNS or positive SFEMG. Electrodiagnostic testing is often not well tolerated in children, making diagnosis challenging when antibodies are negative. Reaching a diagnosis of myasthenia is critical in these cases to appropriately treat a child's symptoms.

Design/Methods:

We analyzed patients’ symptoms, co-existing diagnoses, exam findings, results of antibody and electrodiagnostic findings , and response to treatments among a cohort of 35 children with myasthenia gravis over 7 years, and compared seronegative to seropositive patients.

Results:

We identify several distinct phenotypes among seronegative patients. These include children with autoinflammatory disorders, children with pain-associated myasthenia, those with a slow channel syndrome-like phenotype, and ocular myasthenia. Several children in the seronegative group required ICU care and plasma exchange, underscoring the severity of seronegative MG. Furthermore, some seronegative children without characteristic 10% decremental response on repetitive nerve stimulation showed severe symptoms and a robust response to immunotherapies, including IVIg, plasma exchange and rituximab.

Conclusions:

Children with seronegative myasthenia manifest with diverse phenotypes, and sometimes lack characteristic findings on repetitive nerve stimulation, making diagnosis more challenging. Nonetheless, they can suffer from severe disease and may respond well to immunotherapy, highlighting the need to correctly diagnose children with MG early in their disease course.