Neurology and Therapy 

About: Neurology and Therapy is an academic journal published by Adis, Springer Healthcare. The journal publishes majorly in the area(s): Medicine & Internal medicine. It has an ISSN identifier of 2193-6536. It is also open access. Over the lifetime, 504 publications have been published receiving 5442 citations.

Vitamin D and Multiple Sclerosis: A Comprehensive Review

Abstract: Numerous observational studies have suggested that there is a correlation between the level of serum vitamin D and MS risk and disease activity. To explore this hypothesis, a literature search of large, prospective, observation studies, epidemiological studies, and studies using new approaches such as Mendelian randomization was conducted. Available data and ongoing research included in this review suggest that the level of serum vitamin D affects the risk of developing MS and also modifies disease activity in MS patients. Newer Mendelian randomization analyses suggest there is a causal relationship between low vitamin D level and the risk of MS. Post-hoc evaluations from two phase 3 studies, BENEFIT and BEYOND, support the findings of observational trials. Study limitations identified in this review recognize the need for larger controlled clinical trials to establish vitamin D supplementation as the standard of care for MS patients. Though there is increasing evidence indicating that lower vitamin D levels are associated with increased risk of MS and with greater clinical and brain MRI activity in established MS, the impact of vitamin D supplementation on MS activity remains inadequately investigated.

A Review of Fluid Biomarkers for Alzheimer’s Disease: Moving from CSF to Blood

Abstract: A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal degeneration, tau phosphorylation with tangle formation, and Aβ aggregation with deposition of the peptide into plaques. The core AD CSF biomarkers have been validated clinically in numerous studies, and found to have a very high diagnostic performance to identify AD, both in the dementia and in the mild cognitive impairment stages of the disease. CSF Aβ42 has also been found to show very high concordance with amyloid PET to identify brain amyloid deposition. The synaptic protein neurogranin is a novel candidate CSF biomarker for AD and prodromal AD. High CSF neurogranin predicts future cognitive decline and seems to be more specific for AD than, for example, T-tau. Importantly, technical developments have given ultrasensitive measurement techniques that allow measurement of brain-specific proteins such as tau and neurofilament light (NFL) in blood samples. Both plasma tau and NFL are increased in AD, and a recent study showed that plasma NFL has a diagnostic performance comparable to the core AD CSF biomarkers, and predicted future cognitive decline. Future large longitudinal clinical studies are warranted to determine the potential for plasma tau and NFL to serve as first-in-line screening tools for neurodegeneration in primary care.

Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis

Abstract: Transthyretin (TTR) transports the retinol-binding protein-vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR-related amyloidoses are rare, fatal, protein-misfolding disorders, characterized by formation of soluble aggregates of variable structure and tissue deposition of amyloid. The TTR amyloidoses present with a spectrum of manifestations, encompassing progressive neuropathy and/or cardiomyopathy. Until recently, the only accepted treatment to halt progression of hereditary TTR amyloidosis was liver transplantation, which replaces the hepatic source of mutant TTR with the less amyloidogenic wild-type TTR. Tafamidis meglumine is a rationally designed, non-NSAID benzoxazole derivative that binds with high affinity and selectivity to TTR and kinetically stabilizes the tetramer, slowing monomer formation, misfolding, and amyloidogenesis. Tafamidis is the first pharmacotherapy approved to slow the progression of peripheral neurologic impairment in TTR familial amyloid polyneuropathy. Here we describe the mechanism of action of tafamidis and review the clinical data, demonstrating that tafamidis treatment slows neurologic deterioration and preserves nutritional status, as well as quality of life in patients with early-stage Val30Met amyloidosis.

Pregnancy outcomes following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis.

Abstract: Introduction Teriflunomide, indicated for the treatment of relapsing–remitting multiple sclerosis, is contraindicated in pregnancy based on signs of developmental toxicity in the offspring of rats and rabbits; developmental toxicity has also been observed in preclinical studies of other disease-modifying therapies. Despite the requirement to use reliable contraception in clinical trials evaluating the safety and efficacy of teriflunomide, a number of pregnancies have been reported. This work reports pregnancy outcomes in teriflunomide clinical trials.

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations.

Abstract: Because the treatment of multiple sclerosis (MS) may span decades, the need often arises to make changes to the treatment plan in order to accommodate changing circumstances. Switching drugs, or the discontinuation of immunomodulatory agents altogether, may leave patients vulnerable to relapse or disease progression. In some cases, severe MS disease activity is noted clinically and on MRI after treatment withdrawal. When this disease activity is disproportionate to the pattern observed prior to treatment initiation, patients are said to have experienced rebound. Of the US Food and Drug Administration (FDA)-approved agents to treat MS, the drugs most commonly implicated in rebound are natalizumab and fingolimod. In this review based on the reported cases and data from clinical trials, we characterize disease rebound after fingolimod cessation. We also outline fingolimod rebound management considerations, summarizing what evidence is available to help clinicians mitigate the risk of rebound, switch therapies, and treat rebound events when they occur. The commonly encountered situation of fingolimod discontinuation prior to pregnancy is also discussed.