Clinical review of muscle-specific tyrosine kinase-antibody positive myasthenia gravis

Antibodies to muscle-specific receptor tyrosine kinase (MuSK-Ab) are detected in approximately 40% of generalized acetylcholine receptor antibody (AChR-Ab)-negative myasthenia gravis (MG). Based on a growing number of clinical series, a MuSK-Ab-positive phenotype is emerging. Although these clinical patterns are not wholly distinct from either AChR-Ab-positive or seronegative (both AChR-Ab- and MuSK-Ab-negative) MG, they are still helpful in identifying these patients. Patients with MuSK-Ab-positive MG are predominantly female with more prominent cranial and bulbar involvement and more frequent crises than other populations of people with MG. Disease onset tends to be earlier, generally by the third or fourth decade. The yield of repetitive nerve stimulation with conventional limb muscles is lower in these patients, but at least three-fourths demonstrate decrements in facial-innervated muscles. Similarly, single-fiber electromyography of distal limb muscles tends to have a lower yield of abnormality in patients who are MuSK-Ab-positive than either AChR-Ab-positive or seronegative MG, whereas jitter is increased in nearly all patients who are MuSK-Ab-positive when proximal limb or cranial musculature is studied. Patients who are MuSK-Ab-positive are more likely to display poor tolerance of or a lack of improvement with anticholinesterase agents. Most are managed successfully with immunomodulatory therapies, although a higher proportion of patients with MuSK MG have a refractory course when compared to other generalized populations.