Background Immune checkpoint inhibitors (ICIs) represent an effective cancer immunotherapy yet are associated with immune-related adverse events (irAEs). The aim of this study was to characterize irAEs involving the peripheral nervous system (PNS-irAEs) in a real-world cohort of ICI-treated patients. Methods Cancer patients treated with ICIs between January 2014 and March 2022 were included. Patients with PNS-irAEs were identified and divided into two groups: (1) cranial/peripheral neuropathies and (2) myasthenia gravis (MG) and/or myositis. Clinical characteristics and outcomes, measured with the modified Rankin Scale (mRS), were compared among the two groups. Results Among 920 ICI-treated patients, 20 patients (2.17%) developed a PNS-irAEs. The median latency from ICI exposure was 8.8 weeks and the median time from onset to clinical nadir was 3.5 weeks. Eleven patients developed a neuropathy: polyneuropathy (n = 4), cranial neuropathy (n = 3), small-fiber neuropathy (n = 3), brachial plexopathy (n = 1). Nine patients presented MG and/or myositis: concomitant MG and myositis (n = 6), isolated myositis (n = 2), exacerbation of MG (n = 1). Immunosuppressive treatment and/or ICI withdrawal determined a significant clinical improvement, expressed by a mRS reduction, in the neuropathy group (p = 0.004), but not in the MG/myositis group (p = 0.11). Overall, death due to irAEs occurred in four patients (20%), all with MG/myositis. Compared to patients with neuropathies, those with MG/myositis had a shorter latency onset (p = 0.036), developed more frequently concomitant non-neurologic irAEs (p = 0.028) and showed a higher mortality rate (p = 0.026). Conclusions In our large cohort of ICI-treated patients, 2.17% developed PNS-irAEs. Compared to ir-neuropathies, ir-MG/myositis tend to occur earlier from ICI exposure and present a worse response to treatment and a higher mortality.

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IntroductionNeurosurgical education should start during medical school to involve more students, favoring the recruitment of the most prepared and motivated ones and spreading this subject to the future medical generations. Despite multiple investigations, a dedicated educational plan does not exist. This study aims to assess the undergraduates' interests, needs, and perceptions of this subject.Materials and MethodsThe survey was structured to collect demographic data of the participants, and to explore their interest in neurosurgery, their consideration of its importance in medical school, their opinions about the role of this subject in medical education, their needs in this training, and, the usefulness of this subject for their future career.ResultsA total of 156 students participated in the survey. Interest in neurosurgery was shown by 76 (48.7%) participants, however, this subject was also perceived as intimidating by 86 (55.1%). Attending the first 2 years of medical school (p < 0.02), previous interest in neuroscience (p < 0.01), and in a surgical subject (p < 0.01) were the factors associated with a greater interest in this subject. Neurosurgery should be included in all students' education, according to 117 (75.0%) participants and practical operating room training should involve all students, according to 96 (61.5%). The most effective learning methods were considered internship (134, 85.9%), followed by participation in meetings or seminars (113, 72.4%). Online seminars were considered useful by 119 participants (76.3%). Neurosurgery was assessed as a potentially interesting career by 99 students (63.5%), who also considered that it can increase their preparation for other subjects (116, 74.4%).ConclusionsNeurosurgery was positively considered by medicals students, who, however, also perceived it as intimidating and hardly approachable. Demonstration that knowledge of neurosurgical concepts can improve their preparation also in general medical settings and, not only in the field of neuroscience, can be useful to promote their interest toward this subject. A combination of lectures and practical internships is considered an effective learning method, which can be fruitfully associated with new technologies.

Background. Increasing evidence support the clinical implementation of plasma biomarkers of neurodegeneration and neuroinflammation for the screening and diagnosis of patients with dementia. However, confirmatory studies are required to demonstrate their usefulness in the real-world clinical setting, in which co-existence of multiple pathologies in dementia is common.Methods. We evaluated plasma and cerebrospinal fluid (CSF) samples from consecutive patients with frontotemporal dementia (FTD) (n=59), progressive supranuclear palsy (PSP) (n=31), corticobasal syndrome (CBS) (29), dementia with Lewy bodies (DLB) (49), and Alzheimer disease (AD) (n=97). Plasma samples from 60 healthy controls were also analysed. We measured neurofilament light chain (NfL), phospho-tau181 (p-tau181), and glial fibrillary acid protein (GFAP) using Simoa (all plasma biomarkers and CSF GFAP), CLEIA (CSF p-tau181), and ELISA (CSF NfL) assays. To assess the effect of AD and Lewy body co-pathologies, we stratified the non-AD groups according to the A/T/N classification and the results of the CSF alpha-synuclein real-time quaking-induced conversion assay.Results. We found good correlations between CSF and plasma biomarkers for NfL (rho=0.651, p<0.001) and p-tau181 (rho=0.637, p<0.001). Plasma NfL was significantly higher in disease groups than in HC, and showed a greater increase in FTD than in AD [44.9 (28.1-68.6) vs. 21.9 (17.0-27.9) pg/ml, p<0.001]. Conversely, plasma p-tau and GFAP levels were significantly higher in the AD than in FTD [3.2 (2.4-4.3) vs. 1.1 (0.7-1.6) pg/ml, p<0.001; 404.7 (279.7-503.0) vs. 198.2 (143.9-316.8) pg/ml, p<0.001]. GFAP also allowed discriminating disease groups from HC. In the distinction between FTD and AD, plasma p-tau showed better accuracy (AUC 0.964) than NfL (AUC 0.791) and GFAP (AUC 0.818). In DLB and CBS, CSF amyloid positive (A+) subjects had higher plasma p-tau181 and GFAP levels than A- individuals.Conclusions. In a clinical setting, we confirm the high diagnostic value of plasma p-tau181 for distinguishing FTD from AD, and plasma NfL for discriminating degenerative dementias from HC. Plasma GFAP alone combines the value of distinguishing both AD from FTD and neurodegenerative dementias from HC, but with a lower accuracy than p-tau181 and NfL. In CBS and DLB, both plasma ptau181 and GFAP levels are significantly influenced by amyloid co-pathology.