We previously documented that idebenone treatment in OPA1‐Dominant Optic Atrophy (OPA1‐DOA) led to some degrees of visual improvement in seven patients. We here present the results of a cohort study, which investigated the effect of off‐label idebenone administration in a larger OPA1‐DOA group compared with untreated patients. Inclusion criteria were: OPA1‐DOA clinical and molecular diagnosis, baseline visual acuity (VA) greater than/equal to counting fingers and treatment duration greater than 7 months. We found a significant difference between the last visit and baseline VA in favor of stabilization/recovery in idebenone‐treated as compared to untreated patients. This effect was retained after controlling for confounders.

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.

Summary: The aim of this study was to assess work productivity and activity impairments and to explore their association with excessive daytime sleepiness, body mass index (BMI), depression, and anxiety in patients with narcolepsy type 1. We carried out a cross‐sectional study in which patients with narcolepsy type 1 and matched controls for sex, age, and education were assessed for occupational features, EDS (Epworth Sleepiness Scale), BMI, depression (Beck Depression Inventory), anxiety (State–Trait Anxiety Inventory), and Work Productivity and Activity Impairment (WPAI). Different statistical approaches were used to investigate differences between groups and correlations between WPAI scores and clinical features. The 127 patients with narcolepsy type 1 (mean age 38.2 ± 15.5, 91.3% taking drugs for narcolepsy) and 131 controls (mean age of 37.4 ± 14.3) included did not differ in terms of occupational features, except for hours worked/week (29.9 in patients vs. 34.9 in controls) and officially recognised disability (30.7% vs. 5.3%). Impairment in all WPAI scores was approximately three times greater in patients. Narcolepsy was associated with work time missed in 27.4% of patients, while 93.2% to 95.5% of them had some impairment while working or during daily activities (vs. 37.5–46.8% of controls). Correlations with WPAI scores were found for excessive daytime sleepiness only in patients, and for both depression and anxiety in patients and controls, with a stronger correlation for activity impairment in patients. These results suggest that, despite treatment, narcolepsy type 1 was associated with extensive impairment especially regarding job effectiveness and daily activities. Future studies should investigate risk factors and effects of interventions on these outcomes.

Summary: To investigate potential sex‐related differences in patients with narcolepsy type 1, we carried out an analysis of baseline data from 93 women and 89 men with narcolepsy type 1 who participated in the TElemedicine for NARcolepsy (TENAR) trial. The following data were considered: sociodemographics; diagnostic (disease history, polysomnography, orexin, human leukocyte antigen) and clinical features, including sleepiness (Epworth Sleepiness Scale), cataplexy and other narcolepsy symptoms; disease severity (Narcolepsy Severity Scale); pharmacological treatment; depressive symptoms (Beck Depression Inventory); and self‐reported relevance of eight narcolepsy‐related issues. We found that, compared with men, significantly more women reported automatic behaviours (55.4% versus 40%) and had higher Epworth Sleepiness Scale (median 10 versus 9) and Beck Depression Inventory scores (median 10.5 versus 5), and there was a trend for a higher Narcolepsy Severity Scale total score in women (median 19 versus 18, p = 0.057). More women than men were officially recognized as having a disability (38% versus 22.5%) and considered 5/8 narcolepsy‐related issues investigated as a relevant problem. More severe sleepiness and a greater narcolepsy‐related burden in women could mirror sex differences present in the general population, or may be related to suboptimal management of narcolepsy type 1 or to more severe depressive symptoms in women. Future studies and guidelines should address these aspects.