MuSK-MG Tied to Poorer Outcomes in Myasthenic Crisis, Study Reports

Patients with myasthenia gravis (MG) and self-reactive antibodies against the muscle-specific kinase (MuSK) protein are more likely to have poorer outcomes when experiencing a myasthenic crisis than other MG patients, a study suggests.

Outcomes linked to MuSK antibody production include longer periods of hospitalization or admittance to intensive care, as well as a greater need for prolonged mechanical ventilation for breathing support. Its researchers recommended that disease-specific therapies be initiated early in this patient group.

The study, “MuSK-antibodies are associated with worse outcome in myasthenic crisis requiring mechanical ventilation,” was published in the Journal of Neurology.

Myasthenic crisis is a complication of MG characterized by a worsening of muscle weakness, resulting in respiratory failure that may require the temporary use of a respirator to assist with breathing.

In MG, muscle weakness occurs when self-reactive antibodies drive the immune system to attack and destroy certain proteins that play a key role in the nerve-muscle communication. While most MG patients have antibodies against acetylcholine receptor (AChR), some have antibodies against another protein called MuSK.

Antibodies against MuSK are found in about 6% of all MG patients, and in around 36–37% of those who are negative for AChR antibodies. However, their role in the development of myasthenic crisis is still unclear.

To investigate this further, researchers looked at the medical records of MG patients treated for a myasthenic crisis between 2006 and 2015 at 12 different centers in Germany.

Their study included 15 MuSK-MG patients (mean age of 66), eight of whom also had antibodies against AChR, who experienced a total of 19 myasthenic crises during those years. It also included 144 AChR-MG patients (mean age of 66.8) who had a total of 161 myasthenic crises.

Compared with AChR-MG patients, MuSK-MG patients were almost three times more likely to be female, and more than three times more likely to have severe muscle weakness — meeting class IV criteria of the Myasthenia Gravis Foundation of America (MGFA) — before a crisis.

Chronic diseases, including diabetes, cancer, kidney, heart, and lung diseases, were more also frequent in those with MuSK antibodies.  MuSK-MG patients were almost five times more likely to have three or more chronic diseases compared with AChR-MG patients.

Analyses revealed that MuSK-MG patients remained on mechanical ventilation about 26 days longer than did those with AChR-MG (mean of 43 vs. 17.4 days). They also remained in an intensive care unit (ICU) about 24 days longer than those with AChR-MG (mean of 45.3 vs. 21.2 days).

The time MuSK-MG patients remained hospitalized was nearly double that of those with AChR-MG (mean of 55.9 vs. 28.8 days). These differences were maintained even after factors such as age, sex, and MGFA class were accounted for.

Interestingly, these differences were mainly due to the nine patients who only had antibodies against MuSK. People with antibodies against both MuSK and AChR had outcomes similar to those of AChR-MG patients.

Overall, MuSK-MG was linked to a longer time on mechanical ventilation and lengthier ICU and hospital stays, reflecting “a more severe course” of myasthenic crisis, the researchers noted.

Based on these findings, “we recommend early initiation of a focused therapy,” the scientists wrote, adding that testing for the presence of MuSK antibodies during a crisis “may represent an important tool to estimate prolonged [mechanical ventilation] and the need for an intensified treatment.”