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.

The clinical course and the risk of chronicity of neurologic immune-related adverse events (n-irAEs) associated with immune checkpoint inhibitors (ICIs) are not well documented. This study aimed to characterize the clinical course of n-irAEs and assess the prevalence of chronic events. This nationwide, multicenter, retrospective study included patients with n-irAEs identified at 7 Italian hospitals. The clinical course of n-irAEs was categorized into fulminant (if resulted in death within 12 weeks), monophasic (if resolved within 12 weeks), and chronic (if persisted beyond 12 weeks). Chronic n-irAEs were further subdivided into active (if there was indirect evidence of ongoing inflammation [i.e., required ongoing immunosuppression, relapsed on steroid tapering, or exhibited neurologic progression]) and inactive (if patients had neurologic sequelae without ongoing inflammation). Comparisons between groups and time-to-death analyses were performed. Sixty-six patients were included (median age: 69 years [IQR 62-75]; 53 [80%] men). n-irAEs involved the peripheral nervous system in 48 patients (73%), the central nervous system in 14 (21%), and both in 4 (6%). Twelve patients (18%) had a fulminant course, with the risk being significantly higher in those with concurrent myocarditis (OR 5.4; 95% CI [1.02-28.31]). Among 54 patients with a nonfulminant course, 23 (43%) had a monophasic n-irAE and 31 (57%) had a chronic n-irAE, of which 16 of 31 (52%) were chronic active (due to ongoing immunosuppression [69%], relapses at corticosteroid tapering [19%], or neurologic disease progression [12%]) and 15 of 31 (48%) were chronic inactive. In patients with chronic inactive n-irAEs, neurologic sequelae included cerebellar ataxia (33%), neuromuscular weakness (27%), visual loss (13%), sensory disturbances (13%), focal neurologic signs (7%), and cognitive impairment (7%). Compared with patients with monophasic events, those with chronic n-irAEs had a higher rate of severe neurologic disability at the last evaluation (p < 0.01), shorter survival (p < 0.01), and higher overall mortality (p < 0.01), primarily due to cancer progression. More than half of the patients with n-irAEs who survived the acute phase developed a chronic condition. Patients with chronic n-irAEs were at higher risk of death, mainly due to cancer progression. Future studies are needed to further characterize chronic n-irAEs and identify optimal long-term management strategies.

Introduction: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet.Methods: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation.Results: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years;p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL;p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3–10) days, following aggressive treatment and glucose normalization.Conclusions: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings.

Telemonitoring, a branch of telemedicine, involves the use of technological tools to remotely detect clinical data and evaluate patients. Telemonitoring of patients with Parkinson's disease (PD) should be performed using reliable and discriminant motor measures. Furthermore, the method of data collection and transmission, and the type of subjects suitable for telemonitoring must be well defined. To analyze differences in patients with PD and healthy controls (HC) with the wearable inertial device SensHands–SensFeet (SH–SF), adopting a standardized acquisition mode, to verify if motor measures provided by SH–SF have a high discriminating capacity and high intraclass correlation coefficient (ICC). Altogether, 64 patients with mild‐to‐moderate PD and 50 HC performed 14 standardized motor activities for assessing bradykinesia, postural and resting tremors, and gait parameters. SH–SF inertial devices were used to acquire movements and calculate objective motor measures of movement (total: 75). For each motor task, five or more biomechanical parameters were measured twice. The results were compared between patients with PD and HC. Fifty‐eight objective motor measures significantly differed between patients with PD and HC; among these, 32 demonstrated relevant discrimination power (Cohen's d > 0.8). The test–retest reliability was excellent in patients with PD (median ICC = 0.85 right limbs, 0.91 left limbs) and HC (median ICC = 0.78 right limbs, 0.82 left limbs). In a supervised environment, the SH–SF device provides motor measures with good results in terms of reliability and discriminant ability. The reliability of SH–SF measurements should be evaluated in an unsupervised home setting in future studies.

Myasthenia gravis (MG) is an autoimmune disorder primarily caused by antibodies targeting neuromuscular junction proteins, particularly the acetylcholine receptor and the muscle-specific tyrosine kinase. However, 10%-20% of patients with MG are double-seronegative (dsMG). Antibodies against low-density lipoprotein receptor-related protein 4 (LRP4-IgG) have been found in a variable proportion of dsMG cases, but their frequency and clinical relevance remain unclear because of differences in assay methodologies and study populations. In this study, we assessed the frequency of LRP4-IgG in patients with suspected MG using different cell-based assay (CBA) protocols. In this multicenter observational study, we enrolled consecutive patients presenting with symptoms suggestive of MG. LRP4-IgG was tested by 2 centers using 3 different CBAs: live (l-CBA), methanol-fixed (mf-CBA), and paraformaldehyde-fixed (pf-CBA). Patients were classified as having MG or other disorders (ODs). Positive samples were cross-tested between centers. Among 684 patients (302 with MG, 382 with ODs), LRP4-IgG was detected by mf-CBA in 2% (6/302) of MG cases and in 0.52% (2/382) of OD cases. Among patients with MG, 3.9% (4/102) of dsMG and 1% (2/200) of seropositive patients tested positive. Only 50% of mf-CBA-positive cases were confirmed by pf-CBA, and none were detected by l-CBA. Cross-center testing showed partial reproducibility. LRP4-IgG detection in suspected MG is rare and inconsistent across assays, suggesting that routine testing is not currently warranted and that these antibodies are at present of limited diagnostic value. These findings highlight the need for standardized, validated LRP4-IgG assays. Future studies should focus on direct comparison and harmonization of testing protocols to clarify the clinical utility of LRP4-IgG testing.