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Background: A latent period of variable length elapses between multiple sclerosis (MS) biological onset and the occurrence of the first clinical episode reflecting a central nervous system (CNS) demyelinating event. Factors affecting the duration of such interval are unknown. Objective: To explore whether brain reserve, which moderates the impact of structural damage along MS course, could also affect the timing of MS clinical onset. Methods: We conducted a time-to-event analysis in 326 relapsing-onset multiple sclerosis patients to ascertain the effect of brain reserve, that is, larger maximal lifetime brain growth (MLBG) estimated as intracranial volume, on the risk of an earlier disease onset. For this purpose, we carried out a Cox proportional hazards regression model stratified by sex and adjusted by site and pre-morbid MS risk factors. All patients reached the event (i.e. the disease onset) with no censored case; the age (years) at disease onset was set as the main time variable. Results: We identified a protective effect of brain reserve on the time to disease onset (HR = 0.11, 95% CI = 0.02–0.83, p = 0.032), unchanged when accounting for MS risk factors. Conclusion: Brain reserve might counteract the pathological mechanisms ongoing after biological initiation, thus delaying the disease overt clinical manifestation. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and type 1 diabetes (T1D) are chronic conditions that result from dysfunction of the immune system. Their common root in autoimmunity stimulates interest in the exploration of similarities and differences between the two diseases. Genetic susceptibility is relevant, creating a substrate, on which environmental factors act as a trigger of an aberrant immune response. Despite being both T‐cell mediated disorders with a strong involvement of the humoral arm, immunomodulation is a mainstay of MS management, whereas hormone replacement therapy remains the principal approach for T1D. T1D is usually diagnosed in children and adolescents, while MS is typical of young adults. This difference has implications for disease progression and treatment. The SARS‐CoV‐2 pandemic and its effect on immunity may affect the prevalence of these conditions, as well as their clinical manifestation. [ABSTRACT FROM AUTHOR]

Background: Primary headache disorders are common and burdensome conditions. They are associated to several comorbidities, such as cardiovascular or psychiatric ones, which, in turn, contribute to the global burden of headache. The aim of this study is to provide a comprehensive description of the pooled prevalence of comorbidities of primary headache disorders using a meta-analytical approach based on studies published between 2000 and 2020. Methods: Scopus was searched for primary research (clinical and population studies) in which medical comorbidities were described in adults with primary headache disorders. Comorbidities were extracted using a taxonomy derived from the Global Burden of Disease (GBD) study. We compared prevalence of comorbidities among headache sufferers against general population using GBD-2019 estimates, and compared comorbidities' proportions in clinical vs. population studies, and by age and gender. Results: A total of 139 studies reporting information on 4.19 million subjects with primary headaches were included: in total 2.75 million comorbidities were reported (median per subject 0.64, interquartile range 0.32–1.07). The most frequently addressed comorbidities were: depressive disorders, addressed in 51 studies (pooled proportion 23 %, 95 % CI 20–26 %); hypertension, addressed in 48 studies (pooled proportion 24 %, 95 % CI 22–26 %); anxiety disorders addressed in 40 studies (pooled proportion 25 %, 95 % CI 22–28 %). For conditions such as anxiety, depression and back pain, prevalence among headache sufferers was higher than in GBD-2109 estimates. Associations with average age and female prevalence within studies showed that hypertension was more frequent in studies with higher age and less females, whereas fibromyalgia, restless leg syndrome, and depressive disorders were more frequent in studies with younger age and more female. Conclusions: Some of the most relevant comorbidities of primary headache disorders – back pain, anxiety and depression, diabetes, ischemic heart disease and stroke – are among the most burdensome conditions, together with headache themselves, according to the GBD study. A joint treatment of headaches and of these comorbidities may positively impact on headache sufferers' health status and contribute to reduce the impact of a group of highly burdensome diseases. [ABSTRACT FROM AUTHOR]

Background: A latent period of variable length elapses between multiple sclerosis (MS) biological onset and the occurrence of the first clinical episode reflecting a central nervous system (CNS) demyelinating event. Factors affecting the duration of such interval are unknown., Objective: To explore whether brain reserve, which moderates the impact of structural damage along MS course, could also affect the timing of MS clinical onset., Methods: We conducted a time-to-event analysis in 326 relapsing-onset multiple sclerosis patients to ascertain the effect of brain reserve, that is, larger maximal lifetime brain growth (MLBG) estimated as intracranial volume, on the risk of an earlier disease onset. For this purpose, we carried out a Cox proportional hazards regression model stratified by sex and adjusted by site and pre-morbid MS risk factors. All patients reached the event (i.e. the disease onset) with no censored case; the age (years) at disease onset was set as the main time variable., Results: We identified a protective effect of brain reserve on the time to disease onset (HR = 0.11, 95% CI = 0.02-0.83, p = 0.032), unchanged when accounting for MS risk factors., Conclusion: Brain reserve might counteract the pathological mechanisms ongoing after biological initiation, thus delaying the disease overt clinical manifestation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Transverse myelitis is a noncompressive myelopathy of inflammatory origin. The causes are broad, ranging from infective or toxic to immuno-mediated etiology. They can be manifestations of systemic diseases, such as sarcoidosis and systemic lupus erythematous, or phenotypes of neuroinflammation; in a portion of cases, the etiology remains unknown, leading to the designation idiopathic. The clinical presentation of transverse myelitis depends on the level of spinal cord damage and may include sensorimotor deficits and autonomic dysfunction. The age of onset of the disorder can impact the symptoms and outcomes of affected patients, with differences in manifestation and prognosis between children and adults. Spinal cord magnetic resonance imaging and cerebrospinal fluid examination are the main diagnostic tools that can guide clinicians in the diagnostic process, even though the search for antibodies that target the structural components of the neural tissue (anti-aquaporin4 antibodies and anti-myelin-oligodendrocyte antibodies) helps in the distinction among the immune-mediated phenotypes. Management and outcomes depend on the underlying cause, with different probabilities of relapse according to the phenotypes. Hence, immunosuppression is often recommended for the immune-mediated diseases that may have a higher risk of recurrence. Age at onset has implications for the choice of treatment., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The improved understanding of multiple sclerosis (MS) neurobiology alongside the development of novel markers of disease will allow precision medicine to be applied to MS patients, bringing the promise of improved care. Combinations of clinical and paraclinical data are currently used for diagnosis and prognosis. The addition of advanced magnetic resonance imaging and biofluid markers has been strongly encouraged, since classifying patients according to the underlying biology will improve monitoring and treatment strategies. For example, silent progression seems to contribute significantly more than relapses to overall disability accumulation, but currently approved treatments for MS act mainly on neuroinflammation and offer only a partial protection against neurodegeneration. Further research, involving traditional and adaptive trial designs, should strive to halt, repair or protect against central nervous system damage. To personalize new treatments, their selectivity, tolerability, ease of administration, and safety must be considered, while to personalize treatment approaches, patient preferences, risk-aversion, and lifestyle must be factored in, and patient feedback used to indicate real-world treatment efficacy. The use of biosensors and machine-learning approaches to integrate biological, anatomical, and physiological parameters will take personalized medicine a step closer toward the patient's virtual twin, in which treatments can be tried before they are applied., (Copyright © 2023 Elsevier B.V. All rights reserved.)