Immune checkpoint inhibitors (ICI) have had a dramatic effect on cancer outcomes with their use increasing as indications expand. Despite impressive efficacy across a range of tumour types, their role in activating the immune system results in frequent immune-related adverse events (irAE). While gastrointestinal, endocrine, respiratory and cutaneous toxicities are common, neurological irAEs (N-irAEs) occur more rarely. N-irAEs have been well reported in the literature, can affect any part of the nervous system and are associated with significant morbidity and mortality. Treating oncologists have a high index of suspicion for irAEs and a low threshold for initiating treatment. The role of the neurologist is to consider the differential diagnosis, direct investigation according to the clinical syndrome and guide management, efficacy monitoring and rehabilitation. Once alternative aetiologies have been excluded, the ICI should be either paused or discontinued depending on clinical severity, and immunosuppressive treatment commenced. There is no high-level evidence for toxicity management in this emerging field, so there is much variation in clinical practice and the medical literature. While describing the range of neurological toxicities related to ICIs and current experience of management and outcome, this review focuses on the potential utility of predictive biomarkers, the risk of re-ignition of pre-existing neurological autoimmune disease and the question of rechallenge after a N-irAE. Given the paucity of data specifically relating to N-irAE, we also discuss cancer outcomes in the context of irAEs and associated immunosuppression and consider some outstanding questions pertinent to ICI-related neurotoxicity and potential future directions for research.

Background and ObjectivesPatients with brain tumors face an increased risk of arterial and venous thromboembolic events. However, owing to risk of intracranial hemorrhage (ICH), clinician practice patterns vary on preference for anticoagulation treatment. ...

Background and ObjectivesIn patients with mechanical heart valves (MHVs), anticoagulation (AC) interruption after intracranial hemorrhage (ICH) poses a clinical dilemma because of competing risks of ischemic complications and hemorrhagic recurrence. To ...

BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at Tmax (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome (P<0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS. Graphical Abstract

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Neurocritical Care - There is a growing consensus that blood in the cerebrospinal fluid (CSF) is deleterious to outcomes in patients with aneurysmal subarachnoid hemorrhage. The extracorporeal...

Neurocritical Care - For patients with increased intracranial pressure, prompt initiation of hyperosmolar therapy with 23.4% sodium chloride may minimize permanent neurological damage and prevent...