Very high-dose methylprednisolone for treatment of nivolumab-induced limbic encephalitis: A case report

Abstract

Introduction Nivolumab is a programmed death 1 (PD-1) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of eight different cancers including metastatic melanoma. Immune checkpoint blockade may lead to a range of neurologic immune-related adverse events (irAEs) with severity varying from mild to life-threatening, including encephalitis. Case report We describe a case of a 68-year-old man who developed alteration in mental status, physical weakness and fatigue after nine cycles of nivolumab 3 mg/kg every two weeks. These symptoms were compatible with a clinical diagnosis of autoimmune limbic encephalitis, although no specific antibodies were detected and the initial MRI was normal. Management and outcome The patient received intravenous methylprednisolone 1 g daily for 5 days, which was then converted to a maintenance dose of oral prednisone. The patient made a full clinical recovery but relapsed clinically upon steroid tapering, while hypersignal in the left mesial temporal suggestive of limbic encephalitis was observed on repeated MRI. Discussion Because of the prevailing usage of nivolumab in many cancer protocols, this case highlights the importance of rapidly recognising neurological impairment in patients treated with nivolumab and of initiating very high doses of corticosteroids.

Encephalitis Induced by Immune Checkpoint Inhibitors

“…Electroencephalography results were reported mostly for patients with clinical or subclinical seizures; electroencephalographic changes included focal or generalized slowing or less-frequent nonconvulsive seizures or status epilepticus . For 3 patients, a positron emission tomography scan was performed, and the results showed increased metabolism in the mesial temporal lobe during the acute phase (patient 2; Figure 2) and hypometabolism after clinical improvement . Results of N -isopropyl-p-[ 123 I]iodoamphetamine single-photon emission computed tomography showed marked hyperperfusion in the entire cerebellum improving after immunosuppressive treatment in a patient with cerebellitis …”

“…6,[11][12][13][14][15][16] Patients with meningoencephalitis typically had an acute altered mental status, accompanied by fever and headache in approximately half the patients (Figure 1). [17][18][19] Conversely, the group of patients with focal encephalitis presented with syndromes involving limbic structures, memory loss, and behavioral and personality changes, which could be isolated 5,9,14,[20][21][22][23][24][25][26][27][28][29] or associated with diencephalic and/or brainstem involvement. 5,6,[30][31][32][33][34] For these patients, diplopia or eye movement abnormalities, hyperphagia, or impaired consciousness were present.…”

“…9,29,40,42,46,47 For 3 patients, a positron emission tomography scan was performed, and the results showed increased metabolism in the mesial temporal lobe during the acute phase (patient 2; Figure 2) and hypometabolism after clinical improvement. 21,28 Results of N-isopropyl-p-[ 123 I]iodoamphetamine single-photon emission computed tomography showed marked hyperperfusion in the entire cerebellum improving after immunosuppressive treatment in a patient with cerebellitis. 37…”

“…Among add-on therapies, 10,53 plasma exchange was more frequently indicated among patients with antineuronal autoantibodies (Table 1). For 10 patients (12%), a relapse of ICI-iE was described during the tapering phase of corticosteroids (n = 3) 28,33 or after completing the tapering phase (n = 5) 25,30,31 at a median of 10 weeks (IQR, 4-23 weeks) after the first episode. For 1 of the patients at our center and for another patient from the study by Galmiche et al, 54 ICI-iE relapse occurred after completely resuming ICI treatment (Table 2).…”

Encephalitis in a patient with hypopharynx cancer treated with immune checkpoint inhibitors and radiotherapy: a case report and review of the literature

“…If positive for autoimmune encephalopathy, paraneoplastic antibody, or limited or no improvement, consider rituximab in consultation. Continuous vigilance is necessary since ICI-associated encephalitis is susceptible to relapse despite receiving steroid therapy (Taillefer et al 2020 ). In our report, the patient was administered intravenous methylprednisolone at a daily dose of 120 mg for 3 days, and underwent a tapering course of corticosteroids over 6 weeks.…”