Lancet neurology
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Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. ⋯ Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation.
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Immune checkpoint inhibitors, a class of oncological treatments that enhance antitumour immunity, can trigger neurological adverse events closely resembling paraneoplastic neurological syndromes. Unlike other neurological adverse events caused by these drugs, post-immune checkpoint inhibitor paraneoplastic neurological syndromes predominantly affect the CNS and are associated with neural antibodies and cancer types commonly found also in spontaneous paraneoplastic neurological syndromes. Furthermore, post-immune checkpoint inhibitor paraneoplastic neurological syndromes have poorer neurological outcomes than other neurological adverse events of immune checkpoint inhibitors. ⋯ Importantly, the neural antibodies found in patients with post-immune checkpoint inhibitor paraneoplastic neurological syndromes are sometimes detected before treatment, indicating that these antibodies might help to predict the development of neurological adverse events. Experimental and clinical evidence suggests that post-immune checkpoint inhibitor paraneoplastic neurological syndromes probably share immunological features with spontaneous paraneoplastic syndromes. Hence, the study of post-immune checkpoint inhibitor paraneoplastic neurological syndromes can help in deciphering the immunopathogenesis of paraneoplastic neurological syndromes and in identifying novel therapeutic targets.
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Established by brain endothelial cells, the blood-brain barrier (BBB) regulates the trafficking of molecules, restricts immune cell entry into the CNS, and has an active role in neurovascular coupling (the regulation of cerebral blood flow to support neuronal activity). In the early stages of multiple sclerosis, around the time of symptom onset, inflammatory BBB damage is accompanied by pathogenic immune cell infiltration into the CNS. ⋯ Damage to brain endothelial cells leads to an influx of deleterious molecules into the CNS, accelerating leakage across the BBB. Potential future therapeutic approaches might help to prevent BBB damage (eg, monoclonal antibodies targeting cell adhesion molecules and fibrinogen) and help to repair BBB dysfunction (eg, mesenchymal stromal cells) in people with multiple sclerosis.