Addition of quantitative MRI to the routine clinical care of patients with multiple sclerosis-Results from the MAGNON project.

BACKGROUND: The revised Lublin classification offers a framework for categorizing multiple sclerosis (MS) according to the clinical course and imaging results. Diagnosis of secondary progressive MS (SPMS) is often delayed by a period of uncertainty. Several quantitative magnetic resonance imaging (qMRI) markers are associated with progressive disease states, but they are not usually available in clinical practice. METHODS: The MAGNON project enrolled 629 patients (early relapsing-remitting MS (RRMS), n = 51; RRMS with suspected SPMS, n = 386; SPMS, n = 192) at 55 centers in Germany. Routine magnetic resonance imaging (MRI) scans at baseline and after 12 months were analyzed using a centralized automatic processing pipeline to quantify lesions and normalized brain and thalamic volume. Clinical measures included relapse activity, disability, and MS phenotyping. Neurologists completed questionnaires before and after receiving the qMRI reports. RESULTS: According to the physicians' reports, qMRI results changed their assessment of the patient in 31.8% (baseline scan) and 27.6% (follow-up scan). For ∼50% of patients with RRMS with suspected SPMS, reports provided additional information that the patient was transitioning to SPMS. In >25% of all patients, this information influenced the physicians' assessment of the patient's current phenotype. However, actual changes of treatment were reported only in a minority of these patients. CONCLUSIONS: The MAGNON results suggest that standardized qMRI reports may be integrated into the routine clinical care of MS patients and support the application of the Lublin classification as well as treatment decisions. The highest impact was reported in patients with suspected SPMS, indicating a potential to reduce diagnostic uncertainty.

[Aspects of nutrition for prevention and treatment of chronic neurological diseases]. / Aspekte der Ernährung zur Prävention und Therapie chronisch neurologischer Erkrankungen.

Chronic neurodegenerative and neuroinflammatory diseases, such as idiopathic Parkinson's syndrome, amyotrophic lateral sclerosis and multiple sclerosis, represent a therapeutic challenge. Their pathophysiology is not well understood and a cure for any of these diseases is not possible. Over the past decades lifestyle and nutritional habits in modern industrial nations have changed and evidence is increasing that the prevalence of chronic diseases as well their clinical presentation are also changing. Epidemiological investigations indicate that nutritional components might have an impact on the pathogenesis of chronic neurological diseases. A profound understanding of these correlations could foster a better prevention as well as treatment of such chronic disabling diseases. This continuing medical education article summarizes the current understanding of selected nutritional components and their effect on the development and clinical course of chronic neurological disorders.

Restoring Axonal Function with 4-Aminopyridine: Clinical Efficacy in Multiple Sclerosis and Beyond.

The oral potassium channel blocker 4-aminopyridine has been used in various neurological conditions for decades. Numerous case reports and studies have supported its clinical efficacy in ameliorating the clinical presentation of certain neurological disorders. However, its short half-life, erratic drug levels, and safety-related dose restrictions limited its use as a self-compounded drug in clinical practice. This changed with the introduction of a prolonged-release formulation, which was successfully tested in patients with multiple sclerosis. It was fully approved by the US FDA in January 2010 but initially received only conditional approval from the European Medicines Agency (EMA) in July 2011. After additional clinical studies, this conditional approval was changed to unrestricted approval in August 2017. This article reviews and discusses these recent studies and places aminopyridines and their clinical utility into the context of a broader spectrum of neurological disorders, where clinical efficacy has been suggested. In 2010, prolonged-release 4-aminopyridine became the first drug specifically licensed to improve walking in patients with multiple sclerosis. About one-third of patients across disease courses benefit from this treatment. In addition, various reports indicate clinical efficacy beyond multiple sclerosis, which may broaden its use in clinical practice.

Fampridine-PR (prolonged released 4-aminopyridine) is not effective in patients with inflammatory demyelination of the peripheral nervous system.

Fampridine-PR is a voltage-gated potassium channel inhibitor potentially improving nerve conduction in demyelinated axons. Based on its established clinical efficacy in patients with demyelination in the central nervous system, we assessed if fampridine-PR is also effective in patients with inflammatory demyelination of the peripheral nerve. In this small open-label study, 10 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were treated with fampridine-PR 10 mg BID for 28 days and assessed clinically as well as by nerve conduction studies. In this study, Fampridine-PR failed to improve CIDP based on clinical measures and nerve conduction studies. Our findings suggest that Fampridine-PR appears to be ineffective in demyelinating polyneuropathies. These observations may indicate a more complex mode of action beyond improving action potential conduction in demyelinated axons.

Symptomatic therapy in multiple sclerosis: the role of cannabinoids in treating spasticity.

A large proportion of patients with multiple sclerosis (MS) have spasticity, which has a marked impact on their quality of life. Anecdotal evidence suggests a beneficial effect of cannabis on spasticity as well as pain. Recently, randomized, double-blind, placebo-controlled studies have confirmed the clinical efficacy of cannabinoids for the treatment of spasticity in patients with MS. Based on these data, nabiximols (Sativex), a 1:1 mix of Δ-9-tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, received approval for treating MS-related spasticity in various countries around the globe. In this article we review the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option addressing spasticity in patients with MS.

Risks and benefits of multiple sclerosis therapies: need for continual assessment?

PURPOSE OF REVIEW: The aim is to describe and discuss the ongoing debate on how to balance an increase in clinical efficacy against a heightened risk of developing serious side-effects, as has surfaced recently with some novel therapies for relapsing forms of multiple sclerosis. RECENT FINDINGS: New therapies are emerging that differ with regard to their mechanism of action, their mode of administration, their side-effect profile and the clinical benefits that they offer to patients in comparison with established therapeutic modalities in multiple sclerosis. Treating physicians will need to make choices on the best treatments for their patients on the basis of limited experience. This process requires optimal assessment of risks and benefits. SUMMARY: Careful assessment of the risk-benefit profile of the various options may allow treatment choices and perhaps ensure that patients obtain the most benefit from treatment without being exposed to unnecessary risk.