Case Presentation: A 72-year-old male with a history of ischemic cardiomyopathy, infectious endocarditis, subarachnoid hemorrhage, and esophageal cancer presented with symptoms of fever, altered mental status, bilateral lower extremity weakness, spasms and pain. Of note, the patient was on nivolumab, undergoing targeted radiation therapy for esophageal cancer; and vancomycin and cefepime for infectious endocarditis. The examination was notable for spastic lower extremity, hyperreflexia and myoclonus. CT head imaging was negative for acute findings. MRI of the cervical, thoracic and lumbar spine was non-diagnostic and did not explain the weakness in his lower extremities. MRI brain showed age-related degenerative changes and an EEG demonstrated diffuse background slowing without epileptiform discharges. Lumbar puncture yielded an elevated protein of 126, normal cell count and glucose levels. Findings are unremarkable for meningitis or encephalitis. Antibody testing for paraneoplastic syndromes, autoimmune encephalitis, and anti-Glutamic Acid Decarboxylase were all negative. Unfortunately, anti-Glycine Receptor antibody testing was not available at our institution at the time. A diagnosis of PERM related to checkpoint inhibitor therapy was made, and a decision was made to treat the patient with a 5-day course of IVIG and intravenous steroids. With the above interventions, there was a rapid improvement in muscle weakness and spasticity, followed by improvement in his mental status with continued treatment. The patient was successfully discharged to inpatient rehab for further therapy and conditioning.
Discussion: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological syndrome that presents with myoclonus, autonomic symptoms and excessive tactile response. Most patients have anti-GAD antibodies and some GlyR antibodies. It is postulated to be paraneoplastic due to its close association with thymoma, Hodgkin lymphoma, small-cell lung cancer and breast cancer. Diagnosis is mainly clinical after exclusion of common causes. Nivolumab, a checkpoint inhibitor, may have triggered an immunological cascade predisposing this patient to the development of PERM. However, no such associations have been reported in the literature, and no guidelines for management have been established due to the rarity of this condition. Current immunosuppressive therapies include intravenous immunoglobulins, plasma exchange, and B-cell depletion using rituximab.
Conclusions: PERM remains a rare and complex autoimmune condition with fewer than ten published cases. Further investigation of biological markers and the cross-reactivity with paraneoplastic antibodies is needed. This case report emphasizes the possibility of developing this neurological syndrome in patients receiving checkpoint inhibitor therapy.