Myasthenia gravis (MG) is a neuromuscular junction disorder caused by nicotinic acetylcholine receptors/muscle specific kinase antibodies causing fluctuating, fatigable muscle weakness.  

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressively severe muscle weakness.  

We present a case of MG who developed ALS after prolonged stable disease.

Patient is an 84 year old male who developed fatigable weakness of eyelids, slurred speech and difficulty chewing in 2003. He tested positive for acetylcholine binding/blocking antibodies and was diagnosed with MG. He started azathioprine and stayed in prolonged remission. 

Around November 2019, he developed progressive weakness of both legs, L>R and subsequent falls. He denied family history of ALS/FTLD. Examination revealed left leg weakness, wasting and hyperreflexia of left arm and leg.

MRI brain +/- contrast ruled out leptomeningeal/infiltrative disease, MRI C spine +/- contrast ruled out cervical myelopathy and showed mild-moderate C4-T1 neuroforaminal narrowing. MRI L spine showed L5 radiculopathy. EMG revealed active denervation/fasciculations and neurogenic units in left leg and thoracic paraspinals. Sensory responses were absent in left leg.  

He was diagnosed with clinically probable ALS and started riluzole. Initial FVC (sitting) was 56% requiring non-invasive ventilation. He was transitioned to hospice in February 2021 and passed away in May 2021.

Some studies show an increased risk of ALS in MG patients. Although rare, the coexistence has been attributed to low-density lipoprotein receptor-related protein-4 and heat shock protein-70 antibodies disrupting normal neuronal protein conformation. Regulatory T cell deficiencies and neuronal nitric oxide synthase abnormalities found in both raise possibility of pathophysiological commonalities.  

Through this case, we emphasize the importance of ALS as a differential in MG cases and vice versa along with increased comorbidity associated with their coexistence. There is also a need for a larger study to investigate their shared pathophysiological attributes.