Checkpoint Inhibitor-Induced Neurotoxicity in a Case of Metastatic Melanoma.

Checkpoint inhibitors (CPIs) are increasingly being used in the treatment of malignant melanoma. While showing promise in metastatic melanoma treatment, CPIs are associated with immune-related adverse events in various organ systems. Among these events, checkpoint inhibitor-induced neurotoxicity stands out as a particularly rare yet diagnostically challenging and potentially life-threatening occurrence. We report a unique case of checkpoint inhibitor-induced neurotoxicity in a patient with metastatic melanoma directly after beginning treatment with checkpoint inhibitor encorafenib. The patient presented with an unclear clinical course, with features of Guillain-Barré syndrome, myasthenia gravis, and brainstem encephalitis.  We followed a recently established management algorithm for checkpoint inhibitor-induced neurotoxicity with positive outcomes. This case report highlights the importance of recognizing checkpoint inhibitor-induced neurotoxicity as a potential adverse effect of CPIs when treating metastatic melanoma. J Drugs Dermatol. 2023;22(12):e25-e27.     doi:10.36849/JDD.7991e.

Contemporary Neuroscience Core Curriculum for Medical Schools.

Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also, because the nervous system plays such a critical role in the function of every organ system. Due to the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field. It is also unnecessary, as students can expect to have ready access to electronic reference sources no matter where they practice. In the pre-clerkship phase of medical school, the focus should be on providing students with the foundational knowledge to use those resources effectively and interpret them correctly. This article describes an organizational framework for teaching the essential neuroscience background needed by all physicians. This is particularly germane at a time when many medical schools are re-assessing traditional practices and instituting curricular changes such as competency-based approaches, earlier clinical immersion, and increased emphasis on active learning. This article reviews factors that should be considered when developing the pre-clerkship neuroscience curriculum, including goals and objectives for the curriculum, the general topics to include, teaching and assessment methodology, who should direct the course, and the areas of expertise of faculty who might be enlisted as teachers or content experts. These guidelines were developed by a work group of experienced educators appointed by the Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN). They were then successively reviewed, edited, and approved by the entire UES, the AAN Education Committee, and the AAN Board of Directors.

Diffusion-weighted magnetic resonance imaging in symptomatic vertebrobasilar atherosclerosis and dissection.

BACKGROUND: Acute multiple brain infarction (AMBI) pattern on diffusion-weighted imaging (DWI) is associated with arterial and cardiac sources of embolism. The DWI characteristics of patients with stroke due to vertebrobasilar arterial dissection and atherosclerotic disease have not been reported in detail. OBJECTIVE: To describe the DWI stroke patterns in patients with posterior circulation occlusive disease to determine mechanisms of ischemia. DESIGN: Retrospective analysis of infarct patterns in patients with symptomatic vertebrobasilar disease. SETTING: Large community-based teaching hospital. PATIENTS: Patients admitted with stroke due to vertebrobasilar disease were identified retrospectively. Patients were included if DWI was obtained within 7 days of symptom onset. MAIN OUTCOME MEASURE: Infarct patterns were analyzed according to established templates of vascular territories. RESULTS: Eleven patients with vertebral dissection and 39 patients with atherothrombosis were identified. An AMBI pattern was present in 8 (72%) of 11 patients with arterial dissections and 25 (64%) of 39 patients with atherosclerotic disease (P = .48). Distal embolism to the terminal branches of the basilar artery occurred with equal frequency in both groups and was found in half of all cases. Isolated thalamic infarction did not occur. Pontine infarction was noted in 2 (18%) of 11 patients with dissections and 18 (46%) of 39 patients with atherosclerosis (P = .09). Cerebellar border zone involvement was found in 14 (36%) of 39 patients with atherosclerosis and 4 (37%) of 11 patients with dissections (P = .6). CONCLUSIONS: Large arterial disease is frequently associated with AMBI in the posterior circulation. The incidence of AMBI was comparable to that reported in the anterior circulation. This DWI study supports the importance of embolism as the main mechanism of infarction in patients with vertebrobasilar occlusive disease. On the basis of our experience, large-vessel vertebrobasilar disease rarely causes isolated small-vessel thalamic infarction.

Obesity and intracranial in-stent thrombosis.

A morbidly obese, diabetic, hypertensive patient, with severe intracranial left middle cerebral artery (MCA) stenosis, suffered recurrent stereotyped transient ischemic attacks over 2 months, despite taking daily antiplatelet agents, high dose statin, insulin and an angiotensin converting enzyme inhibitor. A left MCA (M1) Wingspan stent-assisted angioplasty was performed after standard loading, and daily doses of clopidogrel were given 3 days prior to the procedure. Immediately after the procedure, the patient developed a left hemispheric ischemic stroke syndrome. Urgent re-angiography identified an acute intracranial in-stent thrombosis. This complication was immediately treated successfully with abciximab and balloon angioplasty. The patient had persistent residual stroke despite complete recanalization of the thrombosed stent within 3 h of occlusion. The patient was subsequently found to have incomplete inhibition of platelet activity despite being on clopidogrel 150 mg and aspirin 81 mg daily and having a normal CYP-2C19 genotype, suggesting that suboptimal antiplatelet inhibition, secondary to morbid obesity, contributed to his in-stent thrombosis. Obese patients undergoing coronary artery stenting routinely receive larger loading and maintenance doses of clopidogrel. Our case suggests that obese patients undergoing intracranial stenting may also benefit from higher than conventional clopidogrel doses prior to intracranial stenting, to decrease risk of acute in-stent occlusion.