Case Report Describes Late-onset MG in Man Treated for Multiple Myeloma

A 60-year-old man being treated for multiple myeloma was found to have myasthenia gravis (MG) caused by antibodies against muscle-specific tyrosine kinase (MuSK), a study reports.

This unusual case indicates that cancer treatments may mask the symptoms of MG, complicating diagnosis, researchers said.

The case was described in the journal BMC Neurology, in report , “Myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies during therapy for multiple myeloma: a case report.”

MG is caused by the immune system attack against proteins found at the neuromuscular junction, the site where nerve and muscle cells communicate.

About 10% of all cases are caused by antibodies targeting the MuSK protein (MuSK-MG). which usually appears during the late 30s and is uncommon at older ages. MuSK-MG rarely has been described in people with cancer, and never had been reported in a person with the blood cancer multiple myeloma.

A team in Japan described a 60-year-old man who was diagnosed with multiple myeloma at age 56. He received the chemotherapy Velcade (bortezomib) along with the corticosteroid dexamethasone, and then Thalomid (thalidomide) as maintenance therapy, but cancer treatment had to be modified at several points due to side effects and infections.

The patient went to the hospital following prolonged neurological symptoms. About six months before hospital admission, he started experiencing double vision while working at a desk. A test at a neurology clinic showed no antibodies against acetylcholine receptors (AChRs), the most common cause of MG.

His double vision then became more persistent. He also developed weakness in the neck and limbs, as well as persistent drooping eyelid in both eyes. The patient’s breathing and swallowing were not affected significantly.

At the hospital, he also showed bilateral gaze limitations and a blood test revealed an anti-MuSK antibody level of 21.6 nanomoles (nmol) per liter. (For context, a normal level would be below 0.05 nmol/L.) Along with evidence of impaired muscle function, this supported a diagnosis of MuSK-MG. According to the Myasthenia Gravis Foundation of America (MGFA) scale, he had MG class IIa, meaning mild weakness predominantly affecting limb and/or axial muscles (in the trunk and head).

“To the best of our knowledge, this is the first report of an MM [multiple myeloma] patient who developed serologically-proven MuSK-MG,” the researchers wrote.

The patient was treated with the anti-inflammatory steroid prednisolone, and was discharged from the hospital after about a month. At the time of discharge, his status was classified as minimal manifestations based on the MGFA scale. with eased limb weakness and fatigue.

Overall, the scientists said that vision complaints starting in the 60s and limb weakness without symptoms affecting the face and throat (e.g., difficulty swallowing) are atypical in patients with MuSK-MG.

In addition, they suggested that MG diagnosis may have been complicated by the ongoing cancer treatments. “Although the pathophysiological [disease-related] mechanism in the patient described in this case report remains unclear, we hypothesize that an autoimmune condition had already existed before MG manifested clinically,” the investigators wrote.

“In conclusion,” they added, “this case emphasizes the need to still consider testing for anti-MuSK antibodies in older MM patients where there is clinical suspicion for possible MG despite negative AChR antibodies and lacking classic MuSK MG phenotype [manifestations].”