An algorithm to assist diagnostic for seronegative autoimmune myasthenia gravis

At the 275th workshop of the European Neuromuscular Centre (ENMC), held in February 2024 in the Netherlands, experts and patient representatives met to review the diagnosis and management of seronegative autoimmune myasthenia gravis in the light of the latest advances. They concluded that :

• seronegative autoimmune myasthenia (undetectable autoantibodies) affects 10 to 15% of patients with autoimmune myasthenia (10 to 40% for children and adolescents) ;
• early diagnosis is crucial for appropriate treatment;
• diagnosis is heterogeneous;
• in the absence of a specific test and recommendations, there are considerable challenges to be faced in improving diagnosis;
• several differential diagnoses need to be taken into account, in particular certain myopathies, congenital myasthenic syndromes and functional disorders.
• response to treatment and long-term prognosis vary greatly from one individual to another.

In order to improve the diagnosis of patients with seronegative autoimmune myasthenia, a consensus decision-making algorithm has been developed.

• The starting point for this algorithm is the presence of clinical features strongly suggestive of myasthenia combined with negative serological tests (including cell-based assays or CBA).
• A neuromuscular transmission defect (EMGTracé rendant compte de l’activité électrique produite par la contraction musculaire, enregistré à l’aide d’une aiguille fine implantée dans le muscle. Il permet de savoir si le problème musculaire est dû à une atteinte des muscles ou à une atteinte des nerfs., neostigmine test, etc.) and an immune mechanism (response to immunotherapy) are essential to establish a definitive diagnosis.
• Conversely, an unclear response to immunotherapy and limited electrophysiological results are associated with a high risk of misdiagnosis.

It is vital that neurologists are made more aware of the diagnosis of seronegative autoimmune myasthenia to avoid delays in diagnosis and management.

275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management, 9-11 February 2024, Hoofddorp, the Netherlands. Evoli A, Palace J, Spagni G et al. Neuromuscul Disord. 2024 Oct.