Abstract Background Balance and gait deficits are common in people with multiple sclerosis (MS). Physical interventions directed at improving balance and walking abilities have been implemented using ...various approaches. Nonetheless, no mode of training has been universally agreed upon. Objectives To determine whether textured insoles have immediate effects on postural control and spatiotemporal parameters of gait and plantar sensation in people with people with MS and to explore effects 4 weeks after insole wear as to whether any immediate effects are maintained over time. Design Within-subject experimental study with a 4-week intervention phase. Settings Multiple Sclerosis Center, Center of Advanced Technologies in Rehabilitation, Sheba Medical Center, Tel-Hashomer, Israel. Participants Twenty-five relapsing-remitting patients diagnosed with MS, 16 women and 9 men, aged 49.6 years (standard deviation = 6.5 years). Intervention Textured insoles customized according to foot size and adapted to the participant's casual shoes. Main outcome measures Spatiotemporal parameters of gait and center of pressure (CoP) excursions during static postural control were studied using the Zebris FDM-T Treadmill. Light-touch and pressure-sensation thresholds were determined using the Semmes-Weinstein monofilaments test. Results Textured insoles did not alter static postural control parameters when examined with eyes open. Examination during the eyes-closed task demonstrated an immediate reduction in the CoP path length (298.4 mm, standard error = 49.7 mm, versus 369.9 mm, SE = 56.3 mm; P = .04) and sway rate (12.0 mm/s, standard error = 1.4 mm/s, versus 15.1 mm/s, standard error = 1.6 mm/s; P = .03) after insertion of the textured insoles compared to casual shoes alone. These findings were maintained at termination of the insole 4-week intervention period. In terms of spatiotemporal parameters of gait, differences were not observed between casual shoes and shoes with textured insoles at baseline. Likewise, no differences were observed between initial and concluding gait trials. Significant differences in plantar sensitivity measures were not observed after the insole 4-week intervention phase. Conclusions Although there were improvements in some aspects of balance, the efficacy of textured insoles in the MS population remains unclear.
Highlights • Fear of falling is related to spatial and temporal gait parameters in people with MS. • Fearful patients demonstrated a larger variability of the CoP trajectory during gait. • CoP ...variability in the lateral plane was significantly correlated to fear of falling.
•Pro-inflammatory cytokines were enormously elevated in patients with COVID19.•IL6 and TNFα were higher in patients that did not survive.•IL6 expression predicted 30-day mortality with high ...sensitivity and specificity.
Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1β (IL1β), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA.
Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7–39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%.
Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.
The ability to predict the spatial frequency of relapses in multiple sclerosis (MS) would enable physicians to decide when to intervene more aggressively and to plan clinical trials more accurately.
...In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS). The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray.
We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p < 0.001). If the predicted relapse was to occur in less than 500 days, a second stage predictor based on an additional different set of 9 genes was used to give a more accurate estimation of the time till the next relapse (in resolution of 50 days). The error rate of the second stage predictor was 2.3 fold lower than the error rate of random predictions (error rate = 0.35, p < 0.001). The predictors were further evaluated and found effective both for untreated MS patients and for MS patients that subsequently received immunomodulatory treatments after the initial testing (the error rate of the first level predictor was < 0.18 with p < 0.001 for all the patient groups).
We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature.
Late-Onset Multiple Sclerosis Polliack, Michael Leon; Barak, Yoram; Achiron, Anat
Journal of the American Geriatrics Society (JAGS),
Febuary 2001, Letnik:
49, Številka:
2
Journal Article
Recenzirano
OBJECTIVE: The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and ...clinical characteristics of late‐onset MS.
DESIGN: A retrospective chart review.
SETTING: The Multiple Sclerosis Center at Sheba Medical Center, Israel.
PARTICIPANTS: 640 patients with a definite diagnosis of MS.
MEASUREMENTS: Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late‐onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM‐IV, SCID‐lifetime Hebrew version.
RESULTS: Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late‐onset MS. Mean age at onset was 53.5 ± 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing‐remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration.
CONCLUSIONS: Late‐onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent.
Abstract Low expression of NR4A gene family members (NR4A1, NR4A3) and 1-alpha, 25-dihydroxyvitamin D3 receptor (VDR) genes was demonstrated in peripheral blood mononuclear cells (PBMC) of subjects ...evaluated during the pre-disease state of multiple sclerosis (MS-to-be, MS2b), in patients with clinically isolated syndrome (CIS) during the very early presentation of neurological symptomatology and in relapsing-remitting MS (RRMS) patients. Both NR4A1 and NR4A3 are known to be involved in T-cell receptor-induced apoptosis and are regulated by VDR. We further evaluated the precise implications of apoptosis signaling regulators in relation to MS pathogenesis at the cellular level by studying the effects of 1-alpha, 25-dihydroxyvitamin D3 (Vit D3 ) upon NR4A1 expression. We demonstrated that the low apoptotic level in MS patients was repaired by Vit D3 mainly through NR4A1 and to a lesser extent thorough BCL2-associated X protein (BAX). These findings prove a role for Vit D3 as a possible therapeutic intervention in MS patients aimed to activate the repressed apoptosis and enhance better control of the disease.
Multiple sclerosis (MS) is a multi-focal progressive disorder of the central nervous system often resulting in diverse clinical manifestations. Imbalance appears in most people with multiple ...sclerosis (PwMS). A popular balance training tool is virtual reality (VR) with several advantages including increased compliance and user satisfaction. Therefore, the aim of this pilot RCT (Trial registration number, date: ISRCTN14425615, 21/01/2016) was to examine the efficacy of a 6-week VR balance training program using the computer assisted rehabilitation environment (CAREN) system (Motek Medical BV, Amsterdam, Netherlands) on balance measures in PwMS. Results were compared with those of a conventional balance exercise group. Secondary aims included the impact of this program on the fear of falling.
Thirty-two PwMS were equally randomized into the VR intervention group or the control group. Each group received balance training sessions for 6 consecutive weeks, two sessions per week, 30 min sessions. Clinical balance tests and instrumented posturography outcome measures were collected upon initiation of the intervention programs and at termination.
Final analysis included 30 patients (19 females, 11 males; mean age, (S.D.) = 45.2 (11.6) years; mean EDSS (S.D.) = 4.1 (1.3), mean disease duration (S.D.) = 11.0 (8.9) years). Both groups showed a main effect of time on the center of pressure (CoP) path length with eyes open (F = 5.278, P = .024), sway rate with eyes open (F = 5.852, P = .035), Functional Reach Test (F = 20.841, P = .001), Four Square Step Test (F = 9.011, P = .031) and the Fear of Falls self-reported questionnaire (F = 17.815, P = .023). In addition, significant differences in favor of the VR program were observed for the group x time interactions of the Functional Reach Test (F = 10.173, P = .009) and fear of falling (F = 6.710, P = .021).
We demonstrated that balance training based on the CAREN device is an effective method of balance training for PwMS.
Objective:
Evaluate the effects of a Pilates exercise programme on walking and balance in people with multiple sclerosis and compare this exercise approach to conventional physical therapy sessions.
...Design:
Randomized controlled trial.
Setting:
Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel.
Subjects:
Forty-five people with multiple sclerosis, 29 females, mean age (SD) was 43.2 (11.6) years; mean Expanded Disability Status Scale (S.D) was 4.3 (1.3).
Interventions:
Participants received 12 weekly training sessions of either Pilates (n=22) or standardized physical therapy (n=23) in an outpatient basis.
Main measures:
Spatio-temporal parameters of walking and posturography parameters during static stance. Functional tests included the Time Up and Go Test, 2 and 6-minute walk test, Functional Reach Test, Berg Balance Scale and the Four Square Step Test. In addition, the following self-report forms included the Multiple Sclerosis Walking Scale and Modified Fatigue Impact Scale.
Results:
At the termination, both groups had significantly increased their walking speed (P=0.021) and mean step length (P=0.023). According to the 2-minute and 6-minute walking tests, both groups at the end of the intervention program had increased their walking speed. Mean (SD) increase in the Pilates and physical therapy groups were 39.1 (78.3) and 25.3 (67.2) meters, respectively. There was no effect of group X time in all instrumented and clinical balance and gait measures.
Conclusions:
Pilates is a possible treatment option for people with multiple sclerosis in order to improve their walking and balance capabilities. However, this approach does not have any significant advantage over standardized physical therapy.
Central neuropathic pain (CNP) and musculoskeletal pain (MSP) are often comorbid with multiple sclerosis (MS), yet data on the emotional burden entailed by this comorbidity are very limited. We ...studied whether MS patients with CNP exhibited greater emotional burden and pain severity than those with MSP and whether this emotional burden was attributed to the MS, the chronic pain, or both. Participants were 125 MS patients (55 with CNP; 30 with MSP; 40 MS pain-free) and 30 healthy controls (HCs). Participants completed questionnaires assessing pain interference, pain catastrophizing, depression, anxiety, stress, hypervigilance, and chronic pain. Group comparisons and a two-step cluster analysis were performed, and the association between cluster membership and clinical group membership was evaluated. Chronic pain was stronger and more widespread in the CNP group than in the MSP group. Both pain groups had higher pain interference, pain catastrophizing, and stress compared to MS pain-free and HC groups. All MS groups had greater depression levels compared to HCs, and the CNP group had the highest anxiety level. The “high psychological distress” cluster comprised mainly participants with CNP (57%), and the “minimal psychological distress” cluster comprised mainly the MS pain-free and HC groups. In conclusion, CNP seems to induce greater emotional burden and pain severity than does MSP. Whereas depression may be attributed to MS, and anxiety to CNP, enhanced pain interference, catastrophizing, and stress may be attributed to the comorbidity of MS and chronic pain. Identifying these traits among MS patients and targeting them in management programs may contribute to more effective, individually based care.
Glatiramer acetate (GA, Copaxone) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only ...partially understood.
To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC).
Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS.
GA induced a specific gene expression molecular signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation.
Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as molecular markers of GA activity.
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