Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors.

BACKGROUND: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. OBJECTIVE: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). METHODS: Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. RESULTS: SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. CONCLUSION: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.

Associations of High-Sensitivity C-Reactive Protein and Interleukin-6 with Depression in a Sample of Italian Adolescents During COVID-19 Pandemic.

Introduction: Many studies highlighted the role of inflammation in the pathogenesis of depression, although not for every patient nor for every symptom. It is widely shared that stressors can increase inflammation and lead to depressive symptoms. Little is known about the symptom-specificity of the inflammation-depression link in adolescence, which we aimed to explore. The single symptom analysis is a core feature of the recent network approach to depression, supposing that psychiatric disorders consist of co-occurring symptoms and their tendency to cause each other. Patients and Methods: We recruited 52 adolescents diagnosed with a Depressive Disorder during the COVID-19 stressful period. We used regression analysis to measure associations between high sensitivity C-Reactive Protein (hs-CRP) and Interleukin-6 (IL-6) and depressive symptoms assessed by the Children's Depression Inventory 2 (CDI 2). For the study of symptom specificity, we selected 13 items from the CDI 2 Self Report corresponding with the DSM-5 diagnostic criteria for Major Depressive Disorder and we coded them as dichotomous variables to perform a regression analysis. Results: We found that a higher CDI 2-Parent Version total score was significantly predicted by higher hs-CRP (coefficient 3.393; p 0.0128) and IL-6 (coefficient 3.128; p 0.0398). The endorsement of the symptom self-hatred, measuring the DSM-5 symptom "feelings of worthlessness", was significantly predicted by hs-CRP (OR 10.97; 95% CI 1.29-93.08; p 0.0282). Conclusion: A novel symptom-specificity emerged, with hs-CRP significantly predicting the endorsement of the symptom self-hatred, recognized as a core feature of adolescent depression, following the network theory. We considered it a possible phenotypic expression of one depression endophenotype previously causally linked to inflammation. Due to the limited sample size, these preliminary findings require confirmation with future research focusing on the relationship between inflammation and self-hatred and other central nodes of the depression network, representing an opportunity for targeting interventions on crucial symptoms.

Assessing Clinical Features of Adolescents Suffering from Depression Who Engage in Non-Suicidal Self-Injury.

Depressive disorders (DDs) and non-suicidal self-injury (NSSI) are important juvenile mental health issues, showing alarming increasing rates. They frequently co-occur, mainly among adolescents, increasing the suicide risk. We aimed to compare the clinical features of two groups of adolescents with DDs, differed by their engagement or not in NSSI ("DD + NSSI" and "DD"). We hypothesized that NSSI would characterize particularly severe forms of DDs suitable for becoming specific phenotypes of adolescent depression. We enrolled 56 adolescents (11-17 years) diagnosed with a DD according to the DSM-5 criteria. They were assessed for NSSI endorsement (Ottawa Self-Injury Inventory), depressive symptoms (Children's Depression Inventory 2), emotional dysregulation (Difficulties in Emotional Regulation Scale), and anxiety symptoms (Screen for Child Anxiety-Related Emotional Disorders). The two groups accounted for 31 ("DD + NSSI") and 25 ("DD") individuals. The "DD + NSSI" group had significantly higher suicidal ideation (p 0.0039), emotional dysregulation (p 0.0092), depressive symptoms (p 0.0138), and anxiety symptoms (p 0.0153) than the "DD" group. NSSI seemed to characterize more severe phenotypes of adolescent depression, applying for a potential role as a "specifier" of DDs, describing relevant information for their management. Further studies are needed to support this hypothesis and its potential opportunities for prevention and treatment.

Pediatric Optic Neuritis: Description of Four Cases and Review of the Literature.

Pediatric optic neuritis (PON) may be a clinically isolated and self-limiting event or may present in the context of underlying neurologic, infective, or systemic disease. PON has a high impact on the quality of life as it may or may not evolve into other acquired demyelinating syndromes (ADSs), such as multiple sclerosis (MS), neuromyelitis optica (NMO), or other syndromes related to the myelin oligodendrocyte glycoprotein IgG antibodies (MOG-IgG). These different PON phenotypes present variable clinical and radiological features, plasma and liquor biomarkers, and prognosis. We describe four pediatric cases presenting clinically with ON, with different etiopathogenetic pictures: one case had a probable infective etiology, while the others were associated with different demyelinating disorders (MS, NMO, syndrome related to MOG-IgG). We discuss the possible evolution of presenting ON in other ADSs, based on recent literature. A careful evaluation of the clinical and investigation findings and the natural course of PON is necessary to define its pathogenic pathway and evolution. Further prolonged follow-up studies are needed to highlight the predictors of PON evolution, its potential sequelae, and the best treatment options.