The gut‐brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.

Introduction: Multiple sclerosis (MS) is a chronic central nervous system immune-mediated disease with an important inflammatory component associated with focal demyelination and widespread neurodegeneration. In most cases, the clinical presentation is relapsing-remitting, followed by a secondary progressive phase, characterized by disability accrual unrelated to relapses. In a minority, the phenotype is progressive from the beginning. Major therapeutic achievements have been made concerning the relapsing phase but modifying the evolution of progressive MS remains an unmet need. Areas covered: This review covers siponimod (BAF312), a new sphingosine 1-phosphate receptor modulator, and its role in the treatment of secondary progressive MS. The authors reviewed PubMed English literature using the keywords ‘siponimod’ or ‘BAF312’ and ‘multiple sclerosis.’ They also present the pharmacological profile of siponimod, as well as clinical efficacy and safety, with emphasis on the recently published results of a Phase III trial. Phase II data in relapsing MS are also summarized. Expert opinion: Siponimod may reduce the activity of the disease and has a modest effect on the gradual disability accrual. If approved, it may become one of the few available therapy options for secondary progressive MS.

Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut–brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson’s disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.

Multiple sclerosis (MS) is a chronic and disabling immune-mediated disease of the central nervous system. Beta-interferons are the first approved and still the most widely used first-line disease-modifying treatment in MS. Here we focus on recent developments in pharmacology and delivery systems of beta-interferons, and discuss their place within current state of the art therapeutic approaches. We briefly review the clinical trials for classical and PEGylated formulations, emphasizing effectiveness, safety concerns, and tolerability. The mechanisms of action of IFN-β in view of MS pathogenesis are also debated Though only modestly efficient in reducing the annualized relapse rate, beta-interferons remain a valid first-line option due to their good long-term safety profile and cost-efficacy. Moreover, they are endogenous class II cytokines essential for mounting an effective antiviral response, and they may interact with putative MS triggering factors such as Epstein-Barr virus infection and human endogenous retroviruses. Recent improvements in formulations, delivery devices and drug regimens tackle the tolerability and adherence issues frequently seen with these drugs, and scientific advances may offer means for a better selection of patients. Although a well-established immunomodulatory treatment, beta-interferons have not said their last word in the management of MS.

Background and Objectives: Parkinson’s disease (PD) is a prevalent neurodegenerative condition responsible for progressive motor and non-motor symptoms. Currently, no prophylactic or disease-modifying interventions are available. Uric acid (UA) is a potent endogenous antioxidant, resulting from purine metabolism. It is responsible for about half of the antioxidant capacity of the plasma. Increasing evidence suggests that lower serum UA levels are associated with an increased risk of developing PD and with faster disease progression. Materials and Methods: We conducted an electronic medical record database study to investigate the associations between UA levels and different characteristics of PD. Results: Out of 274 datasets from distinct patients with PD, 49 complied with the predefined inclusion and exclusion criteria. Lower UA levels were significantly associated with the severity of parkinsonism according to the Hoehn and Yahr stage (rs = 0.488, p = 0.002), with the motor complications of long-term dopaminergic treatment (r = 0.333, p = 0.027), and with the presence of neurocognitive impairment (r = 0.346, p = 0.021). Conclusions: Oxidative stress is considered a key player in the etiopathogenesis of PD, therefore the involvement of lower UA levels in the development and progression of PD is plausible. Data on the potential therapeutic roles of elevating serum UA (e.g., by precursor administration or diet manipulation) are scarce, but considering the accumulating epidemiological evidence, the topic warrants further research.

Background/Objectives: Parkinson’s disease (PD) and hypertension are often coexistent conditions that interact in entwined ways at various levels. Cardiovascular autonomic dysfunction (CAD), a non-motor feature of PD occurring across all stages, alters blood pressure (BP) regulation. Methods: We conducted a cross-sectional study enrolling patients with PD and primary hypertension, without diabetes mellitus or other causes of secondary CAD, aiming to characterize BP profiles/patterns by ambulatory BP monitoring. We also sought associations between different CAD phenotypes and PD characteristics, disability, and cardiovascular comorbidities. Results: We included 47 patients with a median age of 71 years, PD duration of 9 years, and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score of 40. Diurnal and nocturnal BP values were within the reference range, but BP load was excessive. Almost one-third had neurogenic orthostatic hypotension (OH) and 80% were non-dippers. The overall burden of non-motor symptoms was significant in these phenotypes. Patients with neurogenic OH were more prone to constipation, anxiety, and urinary problems, whereas gustatory dysfunction, loss of libido, and erectile dysfunction were more frequently reported by non-dippers. No significant differences with regard to cognitive decline were identified in subjects with and without neurogenic OH. Neurogenic OH was symptomatic in 78% of the cases, whereas 56% of those with orthostatic symptoms did not have OH at repeated measurements. Conclusions: Neurogenic OH is an independent predictor of disability in patients with PD and hypertension, after adjusting for PD duration, Hoehn and Yahr stage, levodopa equivalent daily dose (LEDD), and Montreal Cognitive Assessment (MoCA) score.