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Background: Inpatient multidisciplinary rehabilitation (MDR) can improve health-related quality of life (HRQoL) in multiple sclerosis (MS) patients. However, the evidence of a long-term benefit is limited. Objectives: To investigate the long-term effectiveness of inpatient MDR on HRQoL in MS patients. Methods: We conducted a randomized controlled partial crossover trial with 427 MS patients. Results: Statistical significant long-term improvements in HRQoL were found in three of the six outcome measures at 12-month follow-up. Three in four suggested minimal clinically important differences (MCIDs) were unmet. Conclusion: These results indicate that the administration of inpatient MDR may lead to long-lasting improvements in HRQoL in MS patients.

Background: Cytokines have been found to play a role in the disease activity of multiple sclerosis (MS). Previous studies indicate that acupuncture can affect cytokine levels in persons with other inflammatory diseases. Objectives: The aim of this study is to investigate the effect of acupuncture on cytokine levels and health-related quality of life (HRQoL) in persons with MS. Materials and Methods: A single-blind, randomized controlled trial was performed. Participants (n = 66) were randomized into three groups (real acupuncture, sham acupuncture, and reference). Participants in the real acupuncture and sham groups received six treatments during a period of 4 weeks. The serum levels of 11 pro- and anti-inflammatory cytokines (IFNγ, IL-1β, IL-6, IL-8, IL-12p70, IL-13, TNFα, IL-10, IL-4, IL-2, and IL-17A) were assessed at baseline, after 2 and 4 weeks of treatment, and 4 weeks after the final treatment. Changes in HRQoL were assessed using the Functional Assessment of Multiple Sclerosis questionnaire. Results: No statistically significant differences in plasma levels between the three groups were seen for either of the cytokines, nor were there any differences between the groups for HRQoL. Conclusions: In this study, the authors could not demonstrate that a 4-week acupuncture treatment had a measurable effect on the plasma levels of seven selected cytokines or on HRQoL among people with MS. The trial was registered with the ISRCTN registry as ISRCTN34352011.

Purpose: Increasing knowledge suggests that nutrition and lifestyle factors affect multiple sclerosis. This study explores how people with multiple sclerosis experience daily multiple sclerosis disease activity and the influence of nutrition and lifestyle factors (e.g., stress, sleep, and environmental temperature).Methods: Four phases mix qualitative and quantitative elements in an exploratory study. The initial two phases consisted of an exploratory study with 14 participants followed by 15 semi-structured interviews. Results from the two first phases were substantiated in a survey completed by 425 respondents (response rate: 42.5%). Finally, findings and inconsistencies were elaborated in three focus group interviews.Results: In the initial exploratory study, several of the participants linked nutrition and lifestyle factors to disease activity. Results from the semi-structured interviews showed that particularly stress, meat, fatty foods, and processed sugar were perceived to have a negative impact on disease activity, and some participants had experienced immediate effects of these factors on their disease activity. The survey supported these findings that were further elaborated in focus groups.Conclusion: People with multiple sclerosis perceive nutrition and lifestyle to affect daily disease activity. Individuals who have experienced links between their multiple sclerosis, and nutrition and lifestyle attribute some of these changes to e.g., stress, and the consumption of sugar, meat, and fatty food.Implications for rehabilitationA majority of the participants in this study perceived nutrition and lifestyle factors to have an effect on their multiple sclerosis, particularly stress, meat, fatty foods, and processed sugar.Some participants with multiple sclerosis experienced that nutrition, stress, environmental temperature, and physical activity had a direct effect on the severity of daily symptom manifestations.Nutrition and lifestyle factors that potentially influence multiple sclerosis disease activity should be considered when organizing rehabilitation and care to better meet the needs of the individual with multiple sclerosis.

Background: The lack of medical treatment options to reduce fatigue in patients with multiple sclerosis (MS) emphasize the importance of identifying potential non-pharmacological modifiable factors, as this may help advance current treatment strategies. The aim of this study was to identify potential modifiable lifestyle factors as well as patient- and disease-related characteristics, that are associated with fatigue in a large sample of clinically well-characterized patients with MS. Methods: This study was a secondary analysis of a pragmatic randomized controlled trial of inpatient multidisciplinary rehabilitation in Denmark. MS patients aged 18 to 65 years and with a disease severity score ≤ 7.5 according to the Expanded Disability Status Scale participated. Data on patient- and disease-related characteristics, fatigue impact (Modified Fatigue Impact Scale (MFIS)), and on lifestyle factors (tobacco smoking, alcohol intake, and physical activity), were collected at baseline. A linear mixed model was used to compare MFIS total, physical, cognitive, and psychosocial scores across subgroups of selected characteristics. Regression analyses were used to examine associations between lifestyle factors and MFIS total, physical, cognitive, and psychosocial scores. Results: In the sample of 417 MS patients, median age was 51 years, 69% were female, median time since diagnosis was 8 years, with 41% having relapsing remitting MS. Higher MFIS total scores were observed in MS patients with shorter time since diagnosis, being a tobacco smoker, and not undertaking regular physical activity. Somewhat similar findings were observed for MFIS subscores (physical, cognitive, psychosocial), especially MFIS physical scores. In the multivariate analyses, physical activity was significantly associated with fatigue impact on total, physical and psychosocial functioning. Tobacco smoking was significantly associated with fatigue impact on psychosocial functioning. Alcohol intake was not associated with fatigue impact. None of the lifestyle factors were associated with fatigue impact on cognitive functioning. In the adjusted models time since diagnosis was significantly associated with fatigue impact on total, physical and cognitive functioning, as was disease severity with fatigue impact on physical and cognitive functioning. Conclusion: Physical activity showed the most pronounced associations with fatigue impact on physical and psychosocial functioning, while the impact on cognitive functioning showed a trend. Tobacco smoking contributed significantly to impact on psychosocial functioning, while alcohol intake did not contribute to fatigue impact. Introducing or supporting maintenance of physical activity/exercise and cessation of tobacco smoking seems to be a useful approach for rehabilitation services to help patients with MS manage fatigue.

Purpose Evidence of the effects of inpatient multidisciplinary rehabilitation (MDR) on physical function in patients with multiple sclerosis (MS) is limited, particularly whether clinically relevant improvements can be achieved. The aim of this study, therefore, was to investigate the effects of personalised inpatient MDR on the physical function of MS patients. Methods Embedded in the Danish MS Hospitals Rehabilitation Study, a pragmatic study was performed in MS patients undergoing four weeks of inpatient MDR specifically targeting physical function. Outcomes were assessed at baseline (n = 142), at discharge (n = 137) and at six months follow-up (n = 126) using the six-minute walk test (6MWT), six-spot step test (SSST), five times sit to stand test (5STS), nine-hole peg test (NHPT), dynamic gait index (DGI) and 12-item MS walking scale (MSWS). Results From Baseline-to-Discharge, significant and clinically relevant improvements were found in all measures of walking capacity (6MWT, SSST, 5STS, DGI and MSWS; p 2.5–5.5] vs. severe [EDSS6.0–7.5]) and age (young/middle-aged [Age24–59] vs. old [Age60–65]), an attenuated adaptation was nevertheless observed for 6MWT in the most affected and vulnerable subgroups (i.e. SP + PP, EDSS6.0–7.5 and Age60–65). The significant improvements in walking capacity and upper extremity function persisted at six months follow-up but did not exceed anymore the thresholds regarded as clinically relevant. Conclusion The results provide novel evidence that personalised inpatient MDR targeting physical function in MS patients elicits significant and clinically relevant improvements in physical function.

Background: In multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) reflects disease severity. Although parts of the EDSS are dependent on actual walking distance, self-reported statements are often applied. Objectives: The purpose of the present study was, therefore, to compare self-reported walking distance to actual walking distance to outline how this influences EDSS scoring. Methods: MS patients with EDSS 4.0–7.5 ( n = 273) were included from the Danish MS hospitals rehabilitation study ( n = 427). All patients subjectively classified their maximal walking distance according to one of seven categories (>500; 300–499; 200–299; 100–199; 20–99; 5–19; 0–4 m). Subsequently, actual maximal walking distance was assessed and EDSS was determined from both self-reported walking distance (EDSSself-report) and actual walking distance (EDSSactual). Results: In 145 patients (53%), self-reported walking distance was misclassified when compared to the actual walking distance. Misclassification was more frequent in patients using walking aids (64% vs. 44%, p self-report vs EDSSactual) of ⩾0.5 point in 24%. Conclusion: In MS patients with EDSS 4.0–7.5, 53% misclassified their walking distance yielding incorrect EDSS scores in 24%. Therefore, correct EDSS determination must be based on measurement of actual walking distance.

Background: There is insufficient evidence to support the effectiveness of multidisciplinary rehabilitation on the health-related quality of life (HRQoL) of MS patients. Objectives: To evaluate the longer term effectiveness of inpatient multidisciplinary rehabilitation on the HRQoL of MS patients. Methods: The study was a two-hospital, pragmatic, randomized controlled trial with a 6-month follow-up. Patients aged 18–65 years with MS and Expanded Disability Status Scale scores ≤7.5 were randomly assigned (1:1) to 4 weeks of inpatient multidisciplinary rehabilitation (20 days of scheduled rehabilitation) or 6 months on a wait list. The outcome measures were Functional Assessment in Multiple Sclerosis (FAMS), Multiple Sclerosis Impact Scale-29 (MSIS-29), EQ-5D-5L and 15D. Results: We randomized 213 patients to the wait-list control group and 214 patients to the treatment group. Trends in favour of the treatment group were observed across all measures. However, the difference was significant in only two of the six measures. The treatment effect was −2.7 (95% CI: −5.6 to (−0.1)), p = 0.046) for the MSIS-29 Psychological and 0.017 (95% CI: 0.005–0.030, p = 0.008) for the 15D. FAMS, which we used to calculate the sample size, was not significant. Conclusion: The results indicated that inpatient multidisciplinary rehabilitation is effective in improving the HRQoL of MS patients after 6 months.

Objective The present study evaluated ankle stiffness in adults with and without neurological disorders and investigated the accuracy and reproducibility of a clinically applicable method using a dynamometer. Methods Measurements were obtained from 8 healthy subjects (age 39.3), 9 subjects with spastic cerebral palsy (CP) (age 39.8) and 8 subjects with multiple sclerosis (MS) (age 49.9). Slow and fast dorsiflexion stretches of the ankle joint were performed to evaluate passive muscle-tendon-joint stiffness, reflex mediated stiffness and range of movement (ROM), respectively. Intra/inter-rater reliability for passive and reflex mediated ankle muscle stiffness was assessed for all groups. Results Subjects with CP and MS showed significantly larger values of passive stiffness in the triceps surae muscle tendon complex and smaller ROM compared to healthy individuals, while no significant difference in reflex mediated stiffness. Measurements of passive muscle-tendon-joint stiffness and reflex mediated stiffness showed good to excellent inter- and intra-rater reliability (ICC: 0.62–0.91) in all groups. Conclusion Increased stiffness was found in subjects with CP and MS with a clinically applicable method that provides valid and reproducible measurement of passive ankle muscle-tendon-joint stiffness and reflex mediated stiffness. Significance The present technique may provide important supplementary information for the clinician.

Valproate (VPA)-induced hepatic affection is a rare complication. 2 such cases are described in the present study, the first a 24-year-old woman developing liver lesion due to VPA treatment, and the second a 73-year-old woman developing liver affection most probably due to VPA treatment. Both cases were reversible. The latter represents the oldest patient ever reported to suffer VPA-induced reversible liver lesion. Liver biopsy showed liver tissue with drug-induced changes. In order to prevent the development of irreversible liver toxicity, it is important to instruct the patient about the sympoms of VPA-induced liver toxicity and stop the treatment if necessary.

Globally, the number of people suffering from multiple sclerosis (MS) is more than two million, and MS is characterized by increasing symptom development over time. The socio-economic costs are enormous. Therefore, effective management of MS is of great importance. Multidisciplinary rehabilitation (MR) seeks to prevent and stop loss of function and trains the patients to deal with symptoms and challenges that will arise in the future. Because there is a need for high-quality evidence of the effectiveness of MR, the MS hospitals in Denmark have initiated the largest study of its kind on MR.

The transcranial Doppler (TCD) and cardiovascular responses to established tests of autonomic function were studied in 50 migraineurs (23 of whom experienced aura and 27 who did not) and 30 healthy control subjects. In addition to the measurements outside attacks, 10 migraineurs were also tested during unilateral attacks of migraine without aura. Transcranial Doppler examinations of middle cerebral artery (MCA) blood velocity showed no differences between migraineurs and healthy subjects and no difference between migraineurs experiencing an attack and outside an attack when examined in response to a head-up tilt test, a cold-pressor test and a Valsalva manoeuvre. The cardiovascular reflexes in response to the Valsalva manoeuvre suggested a mild parasympathetic hypofunction in migraineurs, both those with and those without aura. On the basis of the present results and previous findings by others, we conclude that mild parasympathetic hypofunctioning with preserved sympathetic functioning is an established finding in migraine both with and without aura.

Background Multiple sclerosis (MS) is a complex, chronic and progressive disease and rehabilitation services can provide important support to patients. Few MS rehabilitation programs have been shown to provide health improvements to patients in a cost-effective manner. The objective of this study is to assess the effects in terms of changes measured by a variety of standardized quality of life, mastery, coping, compliance and individual goal-related endpoints. This combination provides the basis for analyzing the complexity of MS and outcomes of a personalized rehabilitation. Methods/Design Patients with MS referred to hospital rehabilitation services will be randomized to either early admission (within two months) or usual admission (after an average waiting time of eight months). They will complete a battery of standardized health outcome instruments prior to randomization, and again six and twelve months after randomization, and a battery of goal-related outcome measures at admission and discharge, and again one, six and twelve months after randomization. Discussion The results of the study are expected to contribute to further development of MS rehabilitation services and to discussions about the design and content of such services. The results will also provide additional information to health authorities responsible for providing and financing rehabilitation services. Trial registration Current Controlled Trials (ISRCTN05245917)

Background The Danish Multiple Sclerosis Society initiated a large-scale bridge building and integrative treatment project to take place from 2004–2010 at a specialized Multiple Sclerosis (MS) hospital. In this project, a team of five conventional health care practitioners and five alternative practitioners was set up to work together in developing and offering individualized treatments to 200 people with MS. The purpose of this paper is to present results from the six year treatment collaboration process regarding the development of an integrative treatment model. Discussion The collaborative work towards an integrative treatment model for people with MS, involved six steps: 1) Working with an initial model 2) Unfolding the different treatment philosophies 3) Discussing the elements of the Intervention-Mechanism-Context-Outcome-scheme (the IMCO-scheme) 4) Phrasing the common assumptions for an integrative MS program theory 5) Developing the integrative MS program theory 6) Building the integrative MS treatment model. The model includes important elements of the different treatment philosophies represented in the team and thereby describes a common understanding of the complexity of the courses of treatment. Summary An integrative team of practitioners has developed an integrative model for combined treatments of People with Multiple Sclerosis. The model unites different treatment philosophies and focuses on process-oriented factors and the strengthening of the patients’ resources and competences on a physical, an emotional and a cognitive level.

The functional assessment of multiple sclerosis (FAMS) is a disease-specific instrument that describes functional status of individuals with multiple sclerosis. The instrument was originally developed in the US and has been adapted to different languages including Danish. This study is a validation of the Danish version of FAMS in a sample of individuals referred to a four-week rehabilitation program at either of the two Multiple Sclerosis Rehabilitation centers in Denmark. FAMS data were obtained through self-completed questionnaires from 190 individuals who attended the rehabilitation centers after referral by their general practitioner or specialist neurologist. The validation of the FAMS included assessment of data quality, scale assumptions, acceptability, construct validity, and reliability. Responsiveness was assessed by comparing individual FAMS scores at admission with the discharge score for groups of respondents who reported no change, improvement, or deterioration in their ability to cope with their illness. The Danish version of FAMS appears to be an acceptable, valid, and reliable measure of current health and functional status of individuals with multiple sclerosis.

Whether cerebral blood flow (CBF) autoregulation is maintained in autonomic dysfunction has been debated for a long time, and the rather sparse data available are equivocal. The relationship between CBF and mean arterial blood pressure (MABP) was therefore tested in eight patients with symptoms and signs of severe cardiovascular autonomic dysfunction.Eight patients were included, three of whom had Parkinson's disease, three diabetes, one pure autonomic failure and the last one had multiple system atrophy. By the use of two techniques, the arteriovenous oxygen [(a-v)O2] method and xenon-inhalation with single photon emission tomography, 15 measurements (range 10-20) and three to four CBF measurements, respectively, were obtained in each patient. Following CBF measurements during baseline, MABP was raised gradually using intravenous noradrenaline infusion, and then lowered by application of lower body negative pressure. From the (a-v)O2 samples the CBF response to changes in MABP was evaluated using a computer program fitting one or two regression lines through the plot.Preserved autoregulation was observed in three patients, while the remaining five patients showed a linear relationship between CBF and MABP. Comparison of the results of the tomographic CBF measurements to the (a-v)O2 data demonstrated that it is not possible to assess whether CBF is autoregulated or not with only three to four pairs of data.

1. Relative changes in blood flow and vascular resistance in arm and leg muscle during head-up tilt at 45° were studied in eight patients with complete cervical spinal cord transection and in 13 healthy volunteers. 2. Muscle blood flow was measured by the local 133Xe washout method. 3. In forearm muscle kept at heart level blood flow remained constant in the tetraplegic patients during head-up tilt, in contrast to that seen in the normal subjects, where blood flow decreased by 30%. In the dependent leg muscle, head-up tilt caused a decrease in blood flow of 46% and 40% in the patients and normals, respectively. Abolition of the local veno-arteriolar axon reflex, by inducing local counter-pressure to prevent venous distension in the dependent leg muscle, reduced the decrease in blood flow to 24% and 23%, respectively. Thus, the vascular response to head-up tilt differed significantly in forearm muscle between the two groups, whereas no difference was seen in the leg muscle. 4. The absence of the vasoconstrictor response in forearm muscle indicates that postural sympathetic reflexes to this region depend on sympathetic reflexes integrated in centres located rostrally to the spinal cord. The results further suggest that local veno-arteriolar axon reflexes as well as spinal reflexes contribute to the observed vasoconstriction in the leg muscle.