Neurologic Adverse Events of Immune Checkpoint Inhibitors

Abstract

Objective:To define the clinical characteristics, management, and outcome of neurological immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs).Methods:Systematic review of the literature following the PRISMA guidelines.Results:A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on central nervous system (CNS) disorders (109/428, 25%). The most common n-irAEs reports were: myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared to the whole sample, myasthenic syndromes were significantly more Ab-positive (33/56, 59%; p<0.001). Anti-PD-1/PD-L1 were more frequent in myasthenic syndromes (50/58, 86%; p=0.005) and less common in meningitis (2/13, 15%; p<0.001) and cranial neuropathies (13/31, 42%; p=0.005).Anti-CTLA-4 ICIs were more frequent in meningitis (8/13, 62%; p<0.001) and less common in encephalitis (2/56, 4%; p=0.009) and myositis (12/136, 9%; p=0.01). Combination of different ICIs was more frequent in cranial neuropathies (12/31, 39%; p=0.005). Melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; p=0.003) and less common in encephalitis (19/56, 34%; p=0.001). The highest mortality rate was reached in myasthenic syndromes (28%).Conclusion:Considering the increasing use of ICI therapy in the forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.

Chemotherapy-Induced Peripheral Neuropathy: Mechanisms and Clinical Assessment

“…More recently, the introduction of the checkpoint inhibitors as a treatment for advance melanoma have opened the possibility of different immune-mediated neuromuscular manifestations reported as complication of the treatment in 75% of Chemotherapy-Induced Peripheral Neuropathy: Mechanisms and Clinical Assessment DOI: http://dx.doi.org/10.5772/intechopen.100495 patients [15]. In this case acute demyelinating polyneuropathy (Guillain-Barré syndrome), demyelinating sensorimotor neuropathy, myositis or myasthenic syndrome have to be considered.…”

A review of neurotoxicities associated with immunotherapy and a framework for evaluation

“…Immune-related encephalitis (irEncephalitis) is the most reported irAE-N affecting the CNS, with 56 cases in a recent systematic review. 25 Patients may present with mental status changes, cognitive impairment, seizures, movement disorders, and psychiatric disturbances (ordered highest to lowest frequency). 25 Recommended work-up includes contrast-enhanced MRI of the brain, lumbar puncture (LP), electroencephalogram (EEG) to assess for subclinical seizures, and autoantibody evaluation.…”

“… 25 Patients may present with mental status changes, cognitive impairment, seizures, movement disorders, and psychiatric disturbances (ordered highest to lowest frequency). 25 Recommended work-up includes contrast-enhanced MRI of the brain, lumbar puncture (LP), electroencephalogram (EEG) to assess for subclinical seizures, and autoantibody evaluation. 24 Diagnosis requires ruling out infectious causes of encephalitis and cytology to rule out disease progression.…”

The Price of Success: Immune-Related Adverse Events from Immunotherapy in Lung Cancer

“…There are a wide variety of neurotoxicities at various degrees of severity that can occur due to ICI therapy, but occur in <5% of patients [ 65 , 66 ]. These include potential antibody-mediated toxicities such as paresthesias, Guillian–Barre syndrome, and myasthenia gravis, or other sensory, motor, and CNS toxicities like enteric neuropathy, inflammatory myopathy, lymphocytic meningitis, cerebral vasculitis, and optic neuritis [ 65 , 66 ]. Neurologic irAEs usually occur within one to six weeks of starting ICI treatment [ 65 , 66 ].…”

“…These include potential antibody-mediated toxicities such as paresthesias, Guillian–Barre syndrome, and myasthenia gravis, or other sensory, motor, and CNS toxicities like enteric neuropathy, inflammatory myopathy, lymphocytic meningitis, cerebral vasculitis, and optic neuritis [ 65 , 66 ]. Neurologic irAEs usually occur within one to six weeks of starting ICI treatment [ 65 , 66 ]. If grade 1, the ICI can be continued, and the patient monitored closely for progression.…”