Neurologic Complications of Cancer Immunotherapy

Abstract

Immunotherapy has revolutionized cancer treatment over the past decade. As it is increasingly introduced into routine clinical practice, immune-related complications have become more frequent. Accurate diagnosis and treatment are essential, with the goal of reduced patient morbidity. This review aims to discuss the various clinical manifestations, diagnosis, treatments, and prognosis of neurologic complications associated with the use of immune checkpoint inhibitors, adoptive T-cell therapies, and T-cell redirecting therapies. We also outline a suggested clinical approach related to the clinical use of these agents.

Neurological Adverse Events Related to Immune Checkpoint Inhibitors: A Practical Review

“…irEncephalitis often presents with aspecific symptoms [43]. Two main presentation types have been described [42,43,52]:…”

“…The recommended workup includes -Brain, orbit, and/or spinal MRI with contrast, which typically shows enhancements and/or hyperintense T2/FLAIR lesions, although no definitive imaging feature has been identified [43]; -Lumbar puncture, usually revealing lymphocytic pleocytosis and elevated protein levels [56]; -Autoantibody testing, including demyelinating antibodies (i.e., AQP4 and MOG) in serum and spinal fluid, although the impact on sensitivity is limited compared to serum analysis alone. While most patients test negative for these antibodies, AQP4, CRMP5, Hu, or other neural antibodies can be present in some patients [10,43,56,57]; -Other diagnostic tools include EEG, neuro-ophthalmologic evaluation and evoked potentials; -Brain biopsy-exceptionally-to allow definitive proof of CNS demyelination.…”

“…Long-term immunosuppression is often necessary, except in a few patients who experience minor manifestations confined to ocular or facial muscles [ 14 ]. Distinguishing between MG and myositis can be challenging, as myositis can mimic MG, leading to a clinical presentation referred to as “pseudo-myasthenia” [ 8 , 42 , 43 ]. In such cases, myopathy can display weakness patterns in the oculo-bulbar, respiratory, and axial muscles.…”

“…The symptoms may be aspecific, ranging from headache only to meningeal syndrome (headache, neck stiffness, photophobia, vomiting, with or without fever) [ 10 ]. The signs and symptoms of encephalitis (confusion, behavioral changes, aphasia, seizure-like activity, short-term memory disturbances, or other focal neurological deficits) are associated with a worse prognosis [ 14 , 43 ].…”

“…irEncephalitis often presents with aspecific symptoms [ 43 ]. Two main presentation types have been described [ 42 , 43 , 52 ]: Diffuse, meningoencephalitis-like picture, with general symptoms (fever, headache, altered consciousness, and/or seizures) and without focal signs; Focal presentations, including limbic encephalitis (neuropsychiatric disturbances, memory issues, behavioral changes, delusions, hallucinations, temporal epilepsy), cerebellitis (ataxia, dysmetria), brainstem encephalitis (altered vigilance, cranial nerve paresis, vertigo, bulbar syndromes), basal ganglia encephalitis (extrapyramidal syndrome with abnormal movements), dysphasia, pyramidal syndrome, sensory disturbances, and dysautonomia. …”