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1.
Role of diet in regulating the gut microbiota and multiple sclerosis.
Sanchez, JMS, DePaula-Silva, AB, Libbey, JE, Fujinami, RS
Clinical immunology (Orlando, Fla.). 2022;:108379
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αB-crystallin as a promising target in pathological conditions - A review.
Maksimiuk, M, Sobiborowicz, A, Tuzimek, A, Deptała, A, Czerw, A, Badowska-Kozakiewicz, AM
Annals of agricultural and environmental medicine : AAEM. 2020;(3):326-334
Abstract
INTRODUCTION AND OBJECTIVE αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. STATE OF KNOWLEDGE α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. CONCLUSIONS Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.
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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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A guide to treating gait impairment with prolonged-release fampridine (Fampyra®) in patients with multiple sclerosis.
Ramió-Torrentà, L, Álvarez-Cermeño, JC, Arroyo, R, Casanova-Estruch, B, Fernández, O, García-Merino, JA, Hernández, MA, Izquierdo, G, Martínez-Yélamos, S, Meca, J, et al
Neurologia. 2018;(5):327-337
Abstract
INTRODUCTION Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. DEVELOPMENT PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. CONCLUSIONS These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS.
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Vitamin D for the management of multiple sclerosis.
Jagannath, VA, Filippini, G, Di Pietrantonj, C, Asokan, GV, Robak, EW, Whamond, L, Robinson, SA
The Cochrane database of systematic reviews. 2018;(9):CD008422
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Abstract
BACKGROUND This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12). Multiple sclerosis (MS) is characterised by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system (CNS), which can result in varying levels of disability. Some studies have provided evidence showing an association of MS with low levels of vitamin D and benefit derived from its supplementation. OBJECTIVES To evaluate the benefit and safety of vitamin D supplementation for reducing disease activity in people with MS. SEARCH METHODS We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Specialized Register up to 2 October 2017 through contact with the Information Specialist with search terms relevant to this review. We included references identified from comprehensive electronic database searches and from handsearches of relevant journals and abstract books from conferences. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs that compared vitamin D versus placebo, routine care, or low doses of vitamin D in patients with MS. Vitamin D was administered as monotherapy or in combination with calcium. Concomitant interventions were allowed if they were used equally in all trial intervention groups. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the methodological quality of studies, while another review author sorted any disagreements. We expressed treatment effects as mean differences (MDs) for continuous outcomes (Expanded Disability Status Scale and number of magnetic resonance imaging (MRI) gadolinium-enhancing T1 lesions), as standardised MDs for health-related quality of life, as rate differences for annualised relapse rates, and as risk differences (RDs) for serious adverse events and minor adverse events, together with 95% confidence intervals (CIs). MAIN RESULTS We identified 12 RCTs enrolling 933 participants with MS; 464 were randomised to the vitamin D group, and 469 to the comparator group. Eleven trials tested vitamin D₃, and one trial tested vitamin D₂. Vitamin D₃ had no effect on the annualised relapse rate at 52 weeks' follow-up (rate difference -0.05, 95% CI -0.17 to 0.07; I² = 38%; five trials; 417 participants; very low-quality evidence according to the GRADE instrument); on the Expanded Disability Status Scale at 52 weeks' follow-up (MD -0.25, 95% CI -0.61 to 0.10; I² = 35%; five trials; 221 participants; very low-quality evidence according to GRADE); and on MRI gadolinium-enhancing T1 lesions at 52 weeks' follow-up (MD 0.02, 95% CI -0.45 to 0.48; I² = 12%; two trials; 256 participants; very low-quality evidence according to GRADE). Vitamin D₃ did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I² = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I² = 20%; eight trials; 701 participants; low-quality evidence according to GRADE). Three studies reported health-related quality of life (HRQOL) using different HRQOL scales. One study reported that vitamin D improved ratings on the psychological and social components of the HRQOL scale but had no effects on the physical components. The other two studies found no effect of vitamin D on HRQOL. Two studies reported fatigue using different scales. One study (158 participants) reported that vitamin D₃ reduced fatigue compared with placebo at 26 weeks' follow-up. The other study (71 participants) found no effect on fatigue at 96 weeks' follow-up. Seven studies reported on cytokine levels, four on T-lymphocyte proliferation, and one on matrix metalloproteinase levels, with no consistent pattern of change in these immunological outcomes. The randomised trials included in this review provided no data on time to first treated relapse, number of participants requiring hospitalisation owing to progression of the disease, proportion of participants who remained relapse-free, cognitive function, or psychological symptoms. AUTHORS' CONCLUSIONS To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D₃ at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review.
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High intensity interval training for people with multiple sclerosis: A systematic review.
Campbell, E, Coulter, EH, Paul, L
Multiple sclerosis and related disorders. 2018;:55-63
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Abstract
BACKGROUND Aerobic high intensity interval training (HIIT) is safe in the general population and more efficient in improving fitness than continuous moderate intensity training. The body of literature examining HIIT in multiple sclerosis (MS) is expanding but to date a systematic review has not been conducted. The aim of this review was to investigate the efficacy and safety of HIIT in people with MS. METHODS A systematic search was carried out in September 2017 in EMBASE, MEDline, PEDro, CENTRAL and Web of Science Core collections using appropriate keywords and MeSH descriptors. Reference lists of relevant articles were also searched. Articles were eligible for inclusion if they were published in English, used HIIT, and included participants with MS. Quality was assessed using the PEDro scale. The following data were extracted using a standardised form: study design and characteristics, outcome measures, significant results, drop-outs, and adverse events. RESULTS Seven studies (described by 11 articles) were identified: four randomised controlled trials, one randomised cross-over trial and two cohort studies. PEDro scores ranged from 3 to 8. Included participants (n = 249) were predominantly mildly disabled; one study included only people with progressive MS. Six studies used cycle ergometry and one used arm ergometry to deliver HIIT. One study reported six adverse events, four which could be attributed to the intervention. The other six reported that there were no adverse events. Six studies reported improvements in at least one outcome measure, however there were 60 different outcome measures in the seven studies. The most commonly measured domain was fitness, which improved in five of the six studies measuring aspects of fitness. The only trial not to report positive results included people with progressive and a more severe level of disability (Extended Disability Status Scale 6.0-8.0). CONCLUSION HIIT appears to be safe and effective in increasing fitness in people with MS and low levels of disability. Further research is required to explore the effectiveness of HIIT in people with progressive MS and in those with higher levels of disability.
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From Disease to Health: Physical Therapy Health Promotion Practices for Secondary Prevention in Adult and Pediatric Neurologic Populations.
Quinn, L, Morgan, D
Journal of neurologic physical therapy : JNPT. 2017;(Suppl 3 IV STEP Spec Iss):S46-S54
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Abstract
BACKGROUND AND PURPOSE Over the last decade there has been a substantial increase in efforts to better understand how targeted physical activity and exercise interventions can be used to minimize secondary consequences arising from neurological damage in both adult and pediatric populations. This article offers an overview of contemporary research that addresses mediators of functional and neuroplastic adaptations associated with physical activity and exercise. We emphasize the important role that physical therapists can play to increase participation and improve well-being in adults and children with neurological disorders. We further highlight potential strategies to foster translation of evidence-based findings for use by clinicians and consumers. SUMMARY OF KEY POINTS Engagement in physical activity can serve as a powerful promoter of health and well-being in adults and youth with neurologic disease, and has the potential to alter the course of disease processes. Physical therapists can play a key role in promoting fitness and wellness by encouraging active living, providing early diagnosis of disease and prescribing targeted activity interventions to improve fitness and participation, and helping individuals overcome personal and environmental barriers to an active lifestyle. RECOMMENDATIONS FOR CLINICAL PRACTICE Physical therapists must adopt a model of rehabilitation that emphasizes secondary prevention in adults and youth with neurologic diseases. Physical therapists have a unique role in developing forward-thinking approaches in using innovative health and wellness strategies to promote positive changes in activity and exercise behaviors.
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Multiple Sclerosis and Clinical Gait Analysis before and after Fampridine: A Systematic Review.
Lecat, M, Decavel, P, Magnin, E, Lucas, B, Gremeaux, V, Sagawa, Y
European neurology. 2017;(5-6):272-286
Abstract
BACKGROUND Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS. SUMMARY This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long-term studies are needed on related gait and functional parameters.
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Zinc in Multiple Sclerosis: A Systematic Review and Meta-Analysis.
Bredholt, M, Frederiksen, JL
ASN neuro. 2016;(3)
Abstract
In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS. Searching the databases PubMed and EMBASE as well as going through reference lists in included articles 24 studies were found measuring Zn in patients with MS. Of these, 13 met inclusion criteria and were included in the meta-analysis. The result of the meta-analysis shows a reduction in serum or plasma Zn levels in patients with MS with a 95% CI of [-3.66, -0.93] and a p value of .001 for the difference in Zn concentration in μM. One of six studies measuring cerebrospinal fluid, Zn levels found a significant increase in patients with MS with controls. The studies measuring whole blood and erythrocyte Zn levels found up to several times higher levels of Zn in patients with MS compared with healthy controls with decreasing levels during attacks in relapsing-remitting MS patients. Future studies measuring serum or plasma Zn are encouraged to analyze their data through homogenous MS patient subgroups on especially age, sex, and disease subtype since the difference in serum or plasma Zn in these subgroups have been found to be significantly different. It is hypothesized that local alterations of Zn may be actively involved in the pathogenesis of MS.
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Sodium MRI of multiple sclerosis.
Petracca, M, Fleysher, L, Oesingmann, N, Inglese, M
NMR in biomedicine. 2016;(2):153-61
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Multiple sclerosis (MS) is the most common cause of non-traumatic disability in young adults. The mechanisms underlying neurodegeneration and disease progression are poorly understood, in part as a result of the lack of non-invasive methods to measure and monitor neurodegeneration in vivo. Sodium MRI is a topic of increasing interest in MS research as it allows the metabolic characterization of brain tissue in vivo, and integration with the structural information provided by (1)H MRI, helping in the exploration of pathogenetic mechanisms and possibly offering insights into disease progression and monitoring of treatment outcomes. We present an up-to-date review of the sodium MRI application in MS organized into four main sections: (i) biological and pathogenetic role of sodium; (ii) brief overview of sodium imaging techniques; (iii) results of sodium MRI application in clinical studies; and (iv) future perspectives.