Pembrolizumab-induced peripheral nervous system damage: A combination of myositis/myasthenia overlap syndrome and motor axonal polyneuropathy

Abstract

Introduction – Immune-checkpoint inhibitors (ICI) are effective drugs in cancer treatment that block immune checkpoints and stimulate an attack on cancer cells. However, various side effects were reported with ICIs. Peripheral nervous system (PNS) side effects are three times more frequent than those in the central nervous system. Case report – A 63-year-old male patient was admitted to our department with a 10-day history of dyspnea, diplopia, and generalized weakness. He had a diagnosis of non-small cell lung cancer, which was treated with pembrolizumab. His neurological symptoms appeared one week after the second course of pembrolizumab, and gradually worsened. His neurological examination showed nasal speech, bilateral ptosis, tongue and neck flexor weakness, prominent asymmetrical upper limb weakness, and mild lower limb weakness. Deep tendon reflexes and sensory examination were normal. He had an elevated creatine kinase level (4430 U/L). Needle electromyography (EMG) showed a myopathic pattern, and single fiber EMG demonstrated an increased jitter in the right frontal muscle. Pembrolizumab treatment was discontinued, and intravenous methylprednisolone followed by intravenous immunoglobulin (IVIg) were initiated. His symptoms gradually improved. However, his weakness began to worsen after a month, and repeated nerve conduction studies showed a predominantly motor axonal polyneuropathy. Thereafter, the patient was treated with IVIg infusions (0.4 g/every two weeks) to maintain his motor function. Conclusion – Our case showed that ICIs could simultaneously or sequentially cause damage in multiple domains of the PNS. Early recognition of these adverse events is essential since the outcome is favorable with rapid cessation of the causative ICI and administration of immune-modulator treatment.