Bulbar Symptoms as an Unusual Presentation of Multiple Sclerosis: A Case Report.

Multiple sclerosis (MS) is a complex multifactorial disease with different clinical manifestations. Bulbar symptoms such as dysarthria and dysphagia are common in MS patients with advanced secondary progressive disease. However, they are not common at disease onset. We present the case of a 17-year-old male who initially presented with vomiting, dysarthria, and dysphagia. The investigations led to the diagnosis of MS, with an active lesion in the brainstem, more specifically in the area postrema region. Differential diagnoses were eliminated. The patient received intravenous methylprednisolone resulting in amelioration of symptoms. Treatment with fingolimod was started after discharge. The recognition of MS with atypical onsets is important to make an early accurate diagnosis and prescribe appropriate treatment for a disease known to be one of the most common causes of neurologic disability in young adults. LEARNING POINTS: Multiple sclerosis can have atypical presentations.Bulbar symptoms such as dysarthria and dysphagia can be initial symptoms of multiple sclerosis, although uncommon.Clinicians should be able to recognize multiple sclerosis with atypical onsets in order to make an early accurate diagnosis.

Clinical Evaluation of Siponimod for the Treatment of Secondary Progressive Multiple Sclerosis: Pathophysiology, Efficacy, Safety, Patient Acceptability and Adherence.

Introduction: A number of disease-modifying therapies have been approved for use in relapsing-remitting multiple sclerosis (MS) in the past two decades. However, only few treatment options are available for patients with secondary progressive multiple sclerosis (SPMS). Siponimod has recently been approved for use in patients with active forms of SPMS (who experience clinical relapses or new lesions on MRI superimposed on secondary progression independent of relapse activity). Objective: The aim of this article is to provide a comprehensive review on the mechanism of action, efficacy, safety, cost effectiveness and patient adherence with siponimod. Methods: We performed a PubMed search using the search terms: "siponimod", "secondary progressive multiple sclerosis", "sphingosine 1-phosphate modulators". Titles and abstract were screened and selected for relevance to the key section of this article. Findings: Siponimod is an oral sphingosine-1-phosphate receptor (S1PR) modulator with selectivity to S1PR-1 and 5. Modulation of this receptor on lymphocytes causes its internalization and degradation, preventing their egress from lymphoid tissues to the blood. In the pivotal Phase 3 randomized controlled trial EXPAND, siponimod was superior to placebo in reducing the risk of disability progression confirmed at 3 and 6 months, as well as the development of new MRI lesions and the rate of brain volume loss. Secondary analysis also showed a benefit on measures of cognitive functioning. The risk of lymphopenia and first-dose bradycardia appears to be lower with siponimod compared to non-selective S1P1R modulators. Different CYP2C9 genotypes affect the metabolism of siponimod; hence, genetic testing is required to adapt the titration and final dose accordingly. Conclusion: Long-term extension and real-world studies will allow further evaluation of efficacy and safety in this population. Future research should focus on better defining SPMS, and identifying biomarkers of progression and outcome measures of treatment response in this category of patients.

Safety of Newer Disease Modifying Therapies in Multiple Sclerosis.

In the past decade, the therapeutic arsenal for multiple sclerosis has expanded greatly. Newer more potent disease modifying therapies (DMTs) with varying mechanisms of actions are increasingly used early in the disease course. These newer DMTs include oral therapies (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab), and are associated with better control of disease activity and long-term outcomes in patients with MS compared to older injectable therapies (interferon beta and glatiramer acetate). However, they are associated with safety concerns and subsequent monitoring requirements. Adverse events are initially observed in phase 2 and 3 clinical trials, and further long-term data are collected in phase 3 extension studies, case series, and post-marketing reports, which highlight the need to periodically re-evaluate and adjust monitoring strategies to optimize treatment safety in an individualized approach.

The use of mirabegron in neurogenic bladder: a systematic review.

PURPOSE: To evaluate the use of mirabegron in patients with neurogenic bladder. METHODS: A systematic review of the literature was conducted using four databases (Medline via PubMed, Scopus, Cochrane, and EMBASE). Articles evaluating mirabegron in neurogenic bladder patients were collected, and assessment of the drug's efficacy was reviewed according to clinical and urodynamic parameters. RESULTS: Seven studies were selected and a total of 302 patients with NB were evaluated, ranging from 15 to 66 patients per study. All of the patients had received antimuscarinics as a previous treatment modality. Mirabegron was used as a second-line treatment after antimuscarinics lacked efficacy or caused adverse effects. The duration of the treatments ranged from 4 to 12 weeks. Reported in two studies each, bladder compliance and maximal cystometric capacity were the most commonly improved urodynamic parameters. In the majority of the studies, positive outcomes were reported for clinical scores. Additionally, analysis of the IPSS subscores revealed an improvement of storage symptoms as opposed to voiding symptoms. In all of the studies, mirabegron was well tolerated. CONCLUSION: Mirabegron appears to be an effective treatment in the management of neurogenic bladder unresponsive to antimuscarinics, particularly in patients presenting with storage symptoms. There is still no evidence concerning the use of mirabegron as a first-line therapy for neurogenic bladder.