Autoimmune Encephalitis Related to Cancer Treatment With Immune Checkpoint Inhibitors

Abstract

OBJECTIVE:To determine the clinical and laboratory features of immune checkpoint inhibitor (ICPI)-associated autoimmune encephalitis (ICPI-AIE), an increasingly recognized adverse event with ICPI treatment.METHODS.We searched PubMed, The Cochrane Library and Embase for ICPI-AIE cases from the first description in 2015 until 01/2020 using standard bibliographic measures including PRISMA guidelines and pre-registration with PROSPERO (CRD42019139838).RESULTS.Thirty-nine studies met inclusion criteria, resulting in 54 ICPI-AIE patients (mean age 58.6 years; 43% females). Common cancers included melanoma (30%) and non-small cell lung cancer (30%). Brain metastases were found in 16 patients (30%). The most frequent ICPI was nivolumab (61%). Onset of ICPI-AIE occurred after a median of 3.5 treatment cycles, but very early and late presentations were common. Non-limbic AIE was roughly twice as frequent as limbic AIE (p<0.05). The most common laboratory abnormalities included bitemporal FLAIR lesions on MRI, continuous slow waves and diffuse slowing on EEG, and monocytic pleocytosis on cerebrospinal fluid analysis. Of note, intraneuronal antibodies were more frequent than neuronal surface antibodies, and a significant predictor for lack of improvement after 1st line immunotherapy (p<0.05).CONCLUSIONS.ICPI-AIE consists of a heterogenous group of conditions. Neurologists will likely encounter ICPI-AIE more often in the future, but important unresolved questions include the exact pathophysiological mechanisms, the epidemiology and the best treatment approaches associated with ICPI-AIE.

Anti-GAD65 Antibody-Associated Autoimmune Encephalitis With Predominant Cerebellar Involvement Following Toripalimab Treatment: A Case Report of a Novel irAE of Toripalimab

“…Compared with myositis and peripheral neuropathies, autoimmune encephalitis (AIE) is not a common n-irAE, but it accounts for more than half of the irAEs in the central nervous system (CNS) (7). The clinical symptoms of autoimmune encephalitis related to ICIs include altered mental status, focal CNS deficits, psychiatric symptoms, seizures, autonomic dysfunction, working memory deficits, ataxia, and dyskinesia (8). According to current studies, most n-irAEs occur early in ICI treatment, usually within 6 months of treatment initiation (9,10).…”

“…Regarding autoimmune antibodies of AIE related to ICIs, antibodies against intracellular antigens (anti-Ma2, anti-Hu, anti-GAD, an unspecified Purkinje cell antibody, anti-Ri, anti-GFAP) were more frequent than those against cell-surface antigens (anti-NMDA receptor and anti-CASPR2) (4,6,8,(16)(17)(18)(19)(20)(21)(22). As an autoimmune antibody against intracellular antigens, the anti-GAD65 antibody is associated with several neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and epilepsy (3,(23)(24)(25).…”

Pembrolizumab-Related Side Effects: Acute Renal Failure and Severe Neurological Toxicity

“…Neurological toxicity appears typically within three months of therapy initiation and includes a wide range of pathologies [6][7][8][9][10][11] (headache, Guillain-Barré syndrome, myasthenia gravis, PRES, aseptic meningitis, transverse myelitis, pancerebellitis, autoimmune encephalitis, cranial, and peripheral neuropathies) [7][8][9][10]. ASCO (American Society of Clinical Oncology) guidelines and SITC (Society for Immunotherapy of Cancer) suggest treatment with high-dose glucocorticoids, intravenous immunoglobulins, and plasmapheresis [4,6].…”

Neurological Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Perspectives and New Development

“… 41 A systematic review also reported that early and late ICI-related encephalitis were possible. 42 In addition, not all irAEs will disappear when antitumor treatment is stopped; some late-irAEs could occur a year after first application. Interestingly, a multicenter study identified that neurological late-irAEs are the only type of irAEs which tends to occur late (>12 months) rather than early (⩽12 months) in melanoma and NSCLC patients.…”