Myasthenic Crisis

ABSTRACT

Myasthenia gravis (MG) is an acquired autoimmune disorder of the neuromuscular junction, caused by antibodies that target the post-synaptic membrane. These antibodies most commonly bind to the nicotinic acetylcholine receptor (AChR), but in a smaller proportion of cases, antibodies to muscle specific tyrosine kinase (MuSK)(1-10%) or to lipoprotein receptor-related protein 4 (Lrp-4)(1-3%) can be present instead. These antibodies act on the receptors, prevent neuromuscular transmission and induce weakness of skeletal muscles. In 10-15% of MG patients, no antibodies are detected and these patients are designated as seronegative. Weakness can be generalized or localized, is usually more proximal than distal, and nearly always includes eye muscles, causing diplopia and/or ptosis. The pattern of involvement is usually symmetric, except for the eye involvement, which is mostly markedly asymmetric. The muscle weakness typically increases with exercise and repetitive muscle use (fatigue) and varies over the course of a day and from day to day. Patients commonly present first with ocular manifestations, however, the majority develop generalized muscle weakness, involving the facial and bulbar muscles (dysarthria, dysphagia), the limbs, the neck and axial muscles (dropped head, bent spine), and in severe cases the diaphragmatic and intercostal muscles. MuSK-MG predominantly appears in women, who show weakness in mostly cranial and bulbar muscles, commonly with an acute onset and a tendency to rapid progression in comparison to AchRMG. Myasthenic crisis (MC), the severe end of the disease spectrum, can occur at any age and is potentially life-threatening. This is a clinical emergency that requires management in an intensive care setting. MC is mostly provoked by infections or inadequate treatment. In 15-40% of the reported patients with COVID-19 infection a MC occurred. MC appears in around 15-20% of MG patients in the first 2 years after diagnosis. MC can be the first manifestation of MG. Up to a half of MuSK-MG patients develop a MC in their disease course and it is also common in patients with thymoma-associated disease, or AChR-positive late-onset disease;after surgery (including thymectomy);during or after childbirth;in patients taking a contraindicated medication;at the start of corticosteroid treatment or during the tapering of immunosuppression. In approximately 20% the cause of an exacerbation remains unknown. Characteristic symptoms for the impending MC include rapidly progressive muscle weakness, 'inverse aspiration', dysphagia with choking, and dyspnoea associated with orthopnoea and/or tachypnoea which can result in respiratory insufficiency. The clinical management of MC with mechanical ventilation, extended intensive care management and intravenous immunoglobulins (IVIg) or plasmapheresis (PLEX) or in case of persistent MC escalation with rituximab has led to a significant decline in mortality from around 40% in the early 1960s to 5-22% in recent studies with negative prognostic factors including older age at onset, prolonged intubation, and associated comorbidities. At present IVIg and PLEX are considered the gold standard treating MC. However, it may be conceiv- able that newly developed monoclonal antibody therapy (eculizumab, efgartigimod), could be used as rescue therapy to achieve a significant and rapid clinical improvement.