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1.
Fatty Acids and Antioxidants in Multiple Sclerosis: Therapeutic Role of GEMSP.
Ahumada-Pascual, P, Gañán, DG, Montero, YEB, Velasco, A
Current pharmaceutical design. 2019;(4):376-380
Abstract
Multiple sclerosis is a high-frequency neurological disorder in young adults. Although there are some genetic and environmental factors that have been related to the onset of the disease, these are still not completely understood and nowadays multiple sclerosis can neither be prevented, nor its symptom effectively treated due to disease heterogeneity. For this reason, the search of prognostic factors and new therapeutic compounds for MS has long aroused among clinicians and researchers. Among these therapeutic compounds, GEMSP, which consists of a mixture of functional constituents as fatty acids, antioxidants, free radical scavengers and amino acids linked individually to poly-L-Lysine (PL), is emerging as a promising drug for MS treatment. Pre-clinical studies using GEMSP have demonstrated that this drug strongly inhibits brain leukocyte infiltration and completely abolishes experimental autoimmune encephalomyelitis. In addition, in an open clinical trial in humans treated with GEMSP, in 72% of the cases, a positive evolution of the state of the MS patients treated with GMSP was observed. In this review a biochemical characterization of main constituents of GEMSP, which include fatty acids as oleic acid, linoleic acid or azelaic acid and the antioxidants alpha-tocopherol or ascorbic acid, will be provided in order to understand their proved therapeutic effects in MS.
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2.
Effects of Fampridine in People with Multiple Sclerosis: A Systematic Review and Meta-analysis.
Valet, M, Quoilin, M, Lejeune, T, Stoquart, G, Van Pesch, V, El Sankari, S, Detrembleur, C, Warlop, T
CNS drugs. 2019;(11):1087-1099
Abstract
BACKGROUND Prolonged-release (PR) fampridine is a potassium channel blocker used as a symptomatic treatment for walking disability in patients with multiple sclerosis (MS). Its clinical effects in such patients have not been systematically reviewed, and may be more wide-ranging than expected. OBJECTIVES To summarize the evidence on the effects of PR fampridine in patients with MS. METHODS A systematic search of Pubmed, Scopus (including EMBASE), and PsycINFO (completed in 01/2019) was carried out to identify randomized controlled trials (RCT) that compared PR fampridine to placebo. When appropriate, data were pooled using a random-effects model, and standardized mean differences (SMD) were computed. Study quality was assessed using the Downs and Black checklist. PRISMA guidelines were followed. All retrieved functional outcomes were categorized according to the International Classification of Functioning, Disability and Health (ICF). RESULTS A total of 706 articles were screened for inclusion. Twenty RCTs involving 2616 patients met the eligibility criteria. Most studies were of good-to-excellent quality. PR fampridine administration resulted in significant benefits in relation to walking short distances (SMD: 1.23 (95% IC 0.65-1.81)) and perceived walking capacity (0.64 (0.27-1.02)). Its effects on muscle strength and middle-distance walking were not significant (0.53 (- 0.04 to 1.10) and 0.31 (- 0.18 to 0.80), respectively). No effect on higher-level cognitive functions (- 0.07 (- 0.58 to 0.45)) or hand and arm use (0.16 (- 0.33 to 0.64)) was observed. Individual studies reported effects on other outcomes across the ICF domains. CONCLUSIONS There is strong evidence that PR fampridine exerts strong effects on the ability to walk short distances and on perceived walking capacity. Other effects of PR fampridine according to the ICF are possible but still unclear.
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3.
Implications of Vitamin D in Multiple Sclerosis and Other Neurodegenerative Processes: Bibliometric Analysis and Systematic Review.
Caballero-Villarraso, J, Jiménez-Jiménez, MJ, Escribano, BM, Agüera, E, Santamaría, A, Túnez, I
CNS & neurological disorders drug targets. 2019;(6):478-490
Abstract
In recent years, numerous investigations focused on the pleiotropic actions of vitamin D have been carried out. These actions include the participation of this molecule in neurophysiological and neuropathological processes. As a consequence, abundant scientific literature on the role of this vitamin in neurodegenerative entities has emerged, even concerning clinical studies. To identify the level of scientific evidence concerning the relation between vitamin D and neurodegenerative diseases, from a quantitative and qualitative perspective. To describe, by means of a bibliometric analysis, the scientific production and its evolution through time in quantitative terms, regarding the implications of vitamin D in neurodegeneration. To analyse and present the degree of evidence in the aforementioned field of study, a systematic review of the literature focused on the most prevalent neurodegenerative diseases was carried out. We retrieved 848 articles in the bibliometric analysis, the majority of which were dated between the years 2010-2017. The most studied metabolite was the 25(OH)D3 and the most cited disease was multiple sclerosis. In the systematic review, we found studies about Alzheimer's and Parkinson's diseases and again, about multiple sclerosis prominently (in number and quality), with 12 randomised double-blind clinical trials. The research about vitamin D and its relations with neurodegenerative diseases shows a growing evolution over the last decade. More studies are needed to find correlations between the clinical severity of these diseases and the specific status of vitamin D and the genotypes related with them, which seems to be a future trend.
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4.
Achillea millefolium is beneficial as an add-on therapy in patients with multiple sclerosis: A randomized placebo-controlled clinical trial.
Ayoobi, F, Moghadam-Ahmadi, A, Amiri, H, Vakilian, A, Heidari, M, Farahmand, H, Fathollahi, MS, Fatemi, I, Shafiei, SA, Alahtavakoli, M, et al
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019;:89-97
Abstract
BACKGROUND Multiple sclerosis (MS) is a neurological disease for which to date there is no cure and the existing disease-modifying drugs just slow down the disease progression. PURPOSE In this clinical trial we evaluated the efficacy of Achillea millefolium (A. millefolium) aqueous extract in MS patients. METHODS A triple-blind randomized placebo-controlled parallel group trial was conducted on 75 MS patients. The patients were randomized into three groups including placebo and two groups receiving A. millefolium with two different doses, i.e. 250 mg/day and 500 mg/day, for 1 year. The primary outcome was the annualized relapse rate. Also, number and volume of lesions were obtained from magnetic resonance imaging (MRI) scans. Furthermore, we performed a comprehensive neurological and cognitive tests as follows: changes in the expanded disability status scale (EDSS), the multiple sclerosis functional composite (MSFC), fatigue severity scale (FSS), Ashworth spasticity assessment, Beck depression test, State-trait anxiety inventory (STAI), mini-mental status examination (MMSE), Wisconsin card sorting test (WCST), tower of London test (TOL), word-pair learning, paced auditory serial addition task (PASAT) and standard laboratory tests. RESULTS This study showed one year administration of A. millefolium (both doses) decreased the annual relapse rate in MS patients. The mean volume change of lesions significantly decreased in the 500 mg A. millefolium group. The add-on therapy also increased time to first relapse and the MSFC z-score; it decreased the EDSS score and improved performance in word-pair learning, PASAT, and WCST. CONCLUSION We found beneficial effects of A. millefolium aqueous extract as an add-on therapy in MS patients.
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5.
Family planning, antenatal and post partum care in multiple sclerosis: a review and update.
Van Der Walt, A, Nguyen, AL, Jokubaitis, V
The Medical journal of Australia. 2019;(5):230-236
Abstract
Multiple sclerosis is more prevalent in women of childbearing age than in any other group. As a result, the impact of multiple sclerosis and its treatment on fertility, planned and unplanned pregnancies, post partum care and breastfeeding presents unique challenges that need to be addressed in everyday clinical practice. Given the increasing number of disease-modifying agents now available in Australia for the treatment of multiple sclerosis, there is a growing need for clinicians to provide their patients with appropriate counselling on family planning. Providing better evidence regarding the relative risks and benefits of continuing therapy before, during and after pregnancy is an important research priority. International pregnancy registries are essential in developing better evidence-based practice guidelines, and neurologists should be encouraged to contribute to these when possible. The management of women with multiple sclerosis, especially when they are taking disease-modifying agents, requires careful assessment of fertility and disease characteristics as well as a multidisciplinary approach to ensure positive outcomes in both mothers and their children.
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6.
Predicting responsiveness to fampridine in gait-impaired patients with multiple sclerosis.
Filli, L, Werner, J, Beyer, G, Reuter, K, Petersen, JA, Weller, M, Zörner, B, Linnebank, M
European journal of neurology. 2019;(2):281-289
Abstract
BACKGROUND AND PURPOSE Fampridine leads to significant improvements in walking in many people with multiple sclerosis (PwMS). However, a relevant proportion of PwMS does not respond to fampridine and predictors of initial drug responsiveness are unknown. METHODS Drug response to prolonged-release (PR)-fampridine was assessed in 55 PwMS using the timed 25-foot walk (T25FW), 6-min walk test (6MWT) and 12-item multiple sclerosis walking scale as outcome parameters. Patients were treated with PR-fampridine and placebo for 6 weeks each in a randomized, double-blind, placebo-controlled trial with crossover design (NCT01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed the drug responses of 32 patients treated with PR-fampridine over 3 years to identify potential predictors of long-term drug responsiveness. RESULTS Severity of walking disability was positively correlated with enhanced responses to PR-fampridine. The strongest single predictor of drug responsiveness was poor 6MWT performance at baseline, which was positively correlated with enhanced drug response in the 6MWT (R = -0.541; P < 0.001). A multivariable logistic regression model including 6MWT and T25FW baseline performances predicted PR-fampridine responder status with an accuracy of 85.5% (specificity, 90.0%; sensitivity, 73.3%), with a threshold of 211 m in the 6MWT best separating responders from non-responders. Enhanced drug responsiveness after 3 years correlated with decline in walking endurance during this period (R = -0.634; P = 0.001). CONCLUSIONS Initial walking impairment is a good predictor of therapeutic responsiveness to PR-fampridine. Valid predictors of patients' responsiveness to PR-fampridine are essential for patient stratification and optimization of multiple slcerosis treatment.
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7.
Trigeminal neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options.
Di Stefano, G, Maarbjerg, S, Truini, A
The journal of headache and pain. 2019;(1):20
Abstract
BACKGROUND Trigeminal neuralgia is one of the most characteristic and difficult to treat neuropathic pain conditions in patients with multiple sclerosis. The present narrative review addresses the current evidence on diagnostic tests and treatment of trigeminal neuralgia secondary to multiple sclerosis. METHODS We searched for relevant papers within PubMed, EMBASE and the Cochrane Database of Systematic Reviews, taking into account publications up to December 2018. RESULTS Trigeminal neuralgia secondary to multiple sclerosis manifests with facial paroxysmal pain triggered by typical manoeuvres; neurophysiological investigations and MRI support the diagnosis, providing the definite evidence of trigeminal pathway damage. A dedicated MRI is required to identify pontine demyelinating plaques. In many patients with multiple sclerosis, neuroimaging and surgical evidence suggests that neurovascular compression might act in concert with the pontine plaque through a double-crush mechanism. Although no placebo-controlled trials have been conducted in these patients, according to expert opinion the first-line therapy for trigeminal neuralgia secondary to multiple sclerosis relies on sodium-channel blockers, i.e. carbamazepine and oxcarbazepine. The sedative and motor side effects of these drugs frequently warrant an early consideration for neurosurgery. Surgical procedures include Gasserian ganglion percutaneous techniques, gamma knife radiosurgery and microvascular decompression in the posterior fossa. CONCLUSIONS The relatively poor tolerability of the centrally-acting drugs carbamazepine and oxcarbazepine highlights the need to develop new selective and better-tolerated sodium-channel blockers. Prospective studies based on more advanced neuroimaging techniques should focus on how trigeminal anatomical abnormalities may be able to predict the efficacy of microvascular decompression.
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8.
Vitamin D and the nervous system.
Bivona, G, Gambino, CM, Iacolino, G, Ciaccio, M
Neurological research. 2019;(9):827-835
Abstract
Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.
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9.
Association of Vitamin D Receptor Gene Polymorphisms and the Risk of Multiple Sclerosis: A Meta Analysis.
Zhang, D, Wang, L, Zhang, R, Li, S
Archives of medical research. 2019;(6):350-361
Abstract
BACKGROUND Previous studies have reported vitamin D receptor (VDR) polymorphisms in multiple sclerosis (MS); however, the results remain contradictory. This study aimed to investigate the association between VDR polymorphisms and the risk of MS. METHODS PubMed and Embase databases were searched to obtain eligible studies. Data were calculated by odds ratios (OR) with 95% confidence intervals (CI). RESULTS Twenty seven case-control studies with 4879 MS patients and 5402 controls were included. There was no significant association between ApaI polymorphisms and MS in the overall population. In Asians, no association was found between ApaI polymorphism and MS in the recessive, dominant, Codominant (OR1), Codominant (OR2), Codominant (OR3) models and allele contrast. Similar results were obtained between BsmI polymorphisms and MS. The association between TaqI polymorphism and MS showed significance in the recessive, homozygous, codominant (OR3) models in the overall population and Caucasians. The dominant model showed no association of Taq I polymorphism with MS risk in HLA-DRB1*15-positive and HLA-DRB1*15-negative groups. FokI polymorphism with MS was found in Codominant (OR3) model in the overall population. In Asians, FokI polymorphism showed association with MS in recessive, dominant, Codominant (OR1), Codominant (OR3) models and allele contrast. Subgroup analysis of sex showed no associations between TaqI or FokI polymorphism and MS risk in males or females in all models or allele contrast. CONCLUSIONS The VDR TaqI polymorphisms showed association with MS risk, especially in Caucasians. In Asians, ApaI and FokI polymorphisms correlated with MS risk, while BsmI polymorphisms showed no association with MS.
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10.
Vitamin D deficiency is an etiological factor for MS - No.
Langer-Gould, A, Lucas, RM
Multiple sclerosis (Houndmills, Basingstoke, England). 2019;(5):639-641