Degenerative neurological and neuromuscular disease最新文献

Background: Microglia are closely linked to Alzheimer's disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice.

Objective: In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia.

Methods: We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice.

Results: In all leptin treatment group, the brain Aβ levels were decrease. We found increased levels of IL-1β, IL-6 and microglial activation in the hippocampus of adult mice. Using aged mice as an experimental model for chronic neuroinflammation and leptin resistance, the number of Iba-1+ microglia and the levels of IL-1β/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference.

Conclusion: Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.

Background: Today, living well with multiple sclerosis (MS) is often measured by a person's overall quality of life rather than being limited to the more traditional metrics of reduced frequency of relapses or progression of disability. This change in focus, to a more holistic view of health, such as overall quality of life, has shifted the views of what both providers and people with multiple sclerosis view as essential for living well with MS.

Purpose: This narrative review aims to examine the relevant literature on existing and emerging non-pharmacological interventions shown to improve the quality of life for people with multiple sclerosis across all health domains.

Methods: A literature search was conducted on MEDLINE, CINAHL, and Scopus electronic databases using the following search terms: quality of life, health-related quality of life, life quality, life satisfaction, non-pharmacological intervention, non-drug, and intervention. After screening the abstracts, 24 were selected for this review.

Results: Common non-pharmacological interventions were used for fatigue and sleep, mental and emotional health, cognition, physical health, and chronic pain. Several non-pharmacological interventions included in this review positively improved the overall quality of life for people with multiple sclerosis. These interventions included exercise, cognitive behavior therapy, and cognitive rehabilitation.

Conclusion: Non-pharmacological interventions such as exercise and cognitive behavioral therapy improve the quality of life for people with MS. These interventions should be prescribed more during routine medical care. Translating this research into standard clinical practice should be one area of focus. In addition, higher quality studies, such as randomized control trials, need to be conducted on emerging nonpharmacological interventions to assess effectiveness.

Sphingosine 1-phosphate (S1P) receptors are bioactive lipid metabolites that bind five different types of receptors expressed ubiquitously in human body and mediate a broad range of biological functions. Targeting S1P receptors is nowadays a well-established pharmacological strategy to treat multiple sclerosis (MS). However, the adverse events associated with the ancestor (fingolimod), especially in terms of heart conduction and slow reversibility of its pharmacodynamics effect on lymphocytes, have stimulated a search for a S1P modulator with greater selectivity for S1P₁ (the most important immune mechanism to prevent MS-related neuroinflammation). Ponesimod is a second-generation, orally active, directly bioavailable, highly selective, and rapidly reversible modulator of the S1P₁ receptor. Gradual 14-day up-titration of ponesimod mitigates its first-dose effects on heart rate and facilitates its use over fingolimod, as it does not require first-dose cardiac monitoring. Ponesimod is rapidly eliminated within 1 week of discontinuation, thereby representing a more manageable approach in case of vaccination, pregnancy, or adverse events. However, the fast reversibility of ponesimod may also raise concerns about the possibility of a rapid reactivation of disease activity following its discontinuation. Ponesimod was recently approved for the treatment of relapsing MS forms on the basis of a Phase III, double-blind, double-dummy, randomized clinical trial (OPTIMUM) that demonstrated the superiority of ponesimod over teriflunomide on disease activity markers, without unexpected safety concerns. This review summarizes the pharmacodynamic and pharmacokinetic characteristics of ponesimod, and the main Phase II and III studies that led to its approval. Comparisons of ponesimod with other S1P receptor modulators currently available for MS (fingolimod, ozanimod, siponimod) are also provided.

Cases of PML should be evaluated according to predisposing factors, as these subgroups differ by incidence rate, clinical course, and prognosis. The three most significant groups at risk of PML are patients with hematological malignancies mostly previously treated with immunotherapies but also untreated, patients with HIV infection, and patients using monoclonal antibody (mAb) treatments. Epidemiological data is scarce and partly conflicting, but the distribution of the subgroups appears to have changed. While there is no specific anti-JCPyV treatment, restoration of the immune function is the most effective approach to PML treatment. Research is warranted to determine whether immune checkpoint inhibitors could benefit certain PML subgroups. There are no systematic national or international records of PML diagnoses or a risk stratification algorithm, except for MS patients receiving natalizumab (NTZ). These are needed to improve PML risk assessment and to tailor better prevention strategies.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by dysfunction at multiple levels of the neuraxis. It remains a clinical diagnosis without a definitive diagnostic investigation. Electrodiagnostic testing provides supportive information and, along with imaging and biochemical markers, can help exclude mimicking conditions. Neuromuscular ultrasound has a valuable role in the diagnosis and monitoring of ALS and provides complementary information to clinical assessment and electrodiagnostic testing as well as insights into the underlying pathophysiology of this disease. This review highlights the evidence for ultrasound in the evaluation of bulbar, limb and respiratory musculature and peripheral nerves in ALS. Further research in this evolving area is required.