To review cases of immune checkpoint inhibitor (ICI) induced neurological side effects.

ICIs are immunotherapies used in cancer treatments to enhance the body’s immune system to target cancer cells. These therapies can activate the immune system against normal tissues.

We collected a list of neurology consults for ICI related side effects and narrowed down the list to patients who experienced symptoms of myasthenia gravis (MG), myositis, and myocarditis (triple overlap syndrome).

We identified 10 patients diagnosed with MG, of which 5 were diagnosed with triple overlap syndrome. The 5 patients had a median age of 74 and had been diagnosed with non-small cell lung cancer, melanoma, mesothelioma, rectal adenocarcinoma, and penile squamous cell carcinoma. The patients had no history of MG or autoimmune disorder and presented with proximal muscle weakness and dyspnea. The median time to symptom onset was 11 days after ICI therapy. All patients had elevated CK and troponin, with four patients having elevated acetylcholine receptor antibodies. All patients discontinued the ICI, and received high dose steroids and IVIG. Two of the patients died due to rapid progression of symptoms, one has not followed up at our institution, and the other two patients are well managed on pyridostigmine.

The incidence of ICI induced myasthenia gravis is less than 1% and about 20 - 30% of these patients may have overlap syndrome such as myositis and myocarditis. The development of MG, myositis, and myocarditis from ICI therapy is reported to occur within the first few doses. There is typically a median delay of about 17 to 34 days for onset of symptoms. It is important to be aware that older patients and those with metastatic melanoma and lung cancer are more at risk for developing these adverse reactions. Patients with triple overlap syndrome are at higher risk for severe outcomes.