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1.
  • Longinetti, E., et al. (author)
  • Physical and cognitive fitness in young adulthood and risk of amyotrophic lateral sclerosis at an early age
  • 2017
  • In: European Journal of Neurology. - Stockholm : Wiley-Blackwell. - 1351-5101 .- 1468-1331. ; 24:1, s. 137-142
  • Journal article (peer-reviewed)abstract
    • Background and purpose: There is a clinical impression that patients with amyotrophic lateral sclerosis (ALS) have a higher level of physical fitness and lower body mass index (BMI) than average. However, there is a lack of literature examining the relationship between cognitive fitness and ALS risk. In this study we explored the associations of both physical and cognitive fitness with future risk of ALS.Methods: Data on physical fitness, BMI, intelligence quotient (IQ) and stress resilience were collected from 1 838 376 Swedish men aged 17-20 years at conscription during 1968-2010. Their subsequent ALS diagnoses were identified through the Swedish Patient Register. Hazard ratios (HRs) and 95% CIs from flexible parametric models were used to assess age-specific associations of physical fitness, BMI, IQ and stress resilience with ALS.Results: We identified 439 incident ALS cases during follow-up (mean age at diagnosis: 48 years). Individuals with physical fitness above the highest tertile tended to have a higher risk of ALS before the age of 45 years (range of HRs: 1.42-1.75; statistically significant associations at age 41-43 years) compared with others. Individuals with BMI ≥ 25 tended to have a lower risk of ALS at all ages (range of HRs: 0.42-0.80; statistically significant associations at age 42-48 years) compared with those with BMI < 25. Individuals with IQ above the highest tertile had a statistically significantly increased risk of ALS at an age of 56 years and above (range of HRs: 1.33-1.81), whereas individuals with stress resilience above the highest tertile had a lower risk of ALS at an age of 55 years and below (range of HRs: 0.47-0.73).Conclusions: Physical fitness, BMI, IQ and stress resilience in young adulthood might be associated with the development of ALS at an early age.
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  • Aked, Joseph, et al. (author)
  • Survival, causes of death and recurrence up to 3 years after stroke : A population-based study
  • 2021
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:12, s. 4060-4068
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Up-to-date population-based information about long-term survival, causes of death and recurrence after stroke is needed. Methods: Four hundred consecutive individuals in a population-based cohort of first-ever stroke between 2015 and 2016 in Lund, Sweden, were followed up to 3 years regarding (i) survival (Swedish Population Register); (ii) causes of death (Swedish Causes of Death Register); and (iii) stroke recurrence (interview and medical chart review). Index and recurrent ischaemic stroke cases were classified using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and Oxfordshire Community Stroke Project; and comorbidities were classified using the Charlson Comorbidity Index. Cox regression was used to determine predictors for 3-year mortality. Survival rates were compared with three local studies over a 30-year timespan. Results: Amongst 400 first-ever stroke patients, 265 (66%) survived 3 years post-stroke. Age (hazard ratio [HR] 1.09; 95% confidence interval [CI] 1.06–1.11), stroke severity (HR 1.11; 95% CI 1.08–1.13) and comorbidities (HR 1.36; 95% CI 1.22–1.53) were independently related to 3-year mortality. Amongst index ischaemic stroke patients, survival was lowest amongst those with cardio-aortic embolism (51/91; 56%). Cerebrovascular disease (54/135; 40%) and ischaemic heart disease (25/135; 19%) were the most common causes of death. Within 3 years, 30 (8%) had recurrent stroke. Amongst patients with index ischaemic stroke, 16/29 (55%) had a different TOAST pathogenetic mechanism or hemorrhagic stroke upon recurrence. Stroke survival improved between 1983–1985 and 2015–2016 (p = 0.002), but no significant change was observed between 2001–2002 and 2015–2016 (p = 0.48). Conclusions: Stroke survival rates are relatively high, but their improvement over recent decades may be slowing down, possibly due to the composition of the first-ever stroke population. The common occurrence of changed pathogenetic mechanisms between first-ever and recurrent stroke highlights the value of reassessment in recurrent stroke.
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  • Amirkhani, Ardeshir, et al. (author)
  • Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients
  • 2005
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 12:8, s. 625-631
  • Journal article (peer-reviewed)abstract
    • Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing-remitting MS patients receiving long-term and acute interferon-beta (IFN-beta) treatment. Twenty-four hours post-administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long-term IFN MS, P = 0.036) were found. The long-term IFN MS group had higher K/T ratios at 4 and 12 h post-administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine-2,3-dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.
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  • Andersen, Peter M., et al. (author)
  • EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) : revised report of an EFNS task force
  • 2012
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 19:3, s. 360-E24
  • Journal article (peer-reviewed)abstract
    • Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. Objectives: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel. Methods: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus. Recommendations: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background.
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  • Andlin-Sobcki, P, et al. (author)
  • Cost of anxiety disorders in Europe
  • 2005
  • In: European journal of neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 1212 Suppl 1, s. 39-44
  • Journal article (peer-reviewed)
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  • Andlin-Sobocki, P, et al. (author)
  • Cost of addiction in Europe
  • 2005
  • In: European journal of neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 1212 Suppl 1, s. 28-33
  • Journal article (peer-reviewed)
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  • Andlin-Sobocki, P, et al. (author)
  • Cost of affective disorders in Europe
  • 2005
  • In: European journal of neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 1212 Suppl 1, s. 34-38
  • Journal article (peer-reviewed)
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  • Andlin-Sobocki, P, et al. (author)
  • Cost of disorders of the brain in Europe
  • 2005
  • In: European journal of neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 1212 Suppl 1, s. 1-
  • Journal article (peer-reviewed)
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  • Andlin-Sobocki, P, et al. (author)
  • Cost of psychotic disorders in Europe
  • 2005
  • In: European journal of neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 1212 Suppl 1, s. 74-77
  • Journal article (peer-reviewed)
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  • Andrén, Kerstin, 1980, et al. (author)
  • Early shunt surgery improves survival in idiopathic normal pressure hydrocephalus
  • 2021
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:4, s. 1153-1159
  • Journal article (peer-reviewed)abstract
    • Background and purpose To examine the effect of delayed compared to early planning of shunt surgery on survival, in patients with idiopathic normal pressure hydrocephalus (iNPH), a long-term follow-up case-control study of patients exposed to a severe delay of treatment was performed. Methods In 2010-2011 our university hospital was affected by an administrative and economic failure that led to postponement of several elective neurosurgical procedures. This resulted in an unintentional delay of planning of treatment for a group of iNPH patients, referred to as iNPH(Delayed) (n = 33, waiting time for shunt surgery 6-24 months). These were compared to patients treated within 3 months, iNPH(Early) (n = 69). Primary outcome was mortality. Dates and underlying causes of death were provided by the Cause of Death Registry. Survival was analysed by Kaplan-Meier plots and a Cox proportional hazard model adjusted for potential confounders. Results Median follow-up time was 6.0 years. Crude 4-year mortality was 39.4% in iNPH(Delayed) compared to 10.1% in iNPH(Early) (p = 0.001). The adjusted hazard ratio in iNPH(Delayed) was 2.57; 95% confidence interval 1.13-5.83, p = 0.024. Causes of death were equally distributed between the groups except for death due to malignancy which was not seen in iNPH(Delayed) but in 4/16 cases in iNPH(Early) (p = 0.044). Conclusions The present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.
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  • Anjemark, Linnea, et al. (author)
  • Car accidents in drivers with Parkinson's disease or multiple sclerosis: A Swedish nationwide study
  • 2023
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 30:6, s. 1631-1638
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Parkinson's disease (PD) and multiple sclerosis (MS) can impair driving. However, we lack evidence on car accidents associated with these diseases. The aims of this study were to examine what types of car accident were associated with drivers with PD and MS, compared to individuals with ulcerative colitis (UC; the comparison group), and to evaluate the occurrence of car accidents in relation to years since diagnosis.Methods: This retrospective nationwide, registry-based study included drivers involved in car accidents between 2010 and 2019, based on the Swedish Traffic Accident Data Acquisition database. Data on pre-existing diagnoses were retrieved retrospectively from the National Patient Registry. Data analyses included group comparisons, time-to-event analysis, and binary logistic regression.Results: In total, 1491 drivers, including 199 with PD, 385 with MS, and 907 with UC, were registered to have been involved in a car accident. The mean time from diagnosis to the car accident was 5.6 years for PD, 8.0 years for MS, and 9.4 years for UC. Time to car accident since diagnosis differed significantly (p < 0.001) among groups (adjusted for age). Drivers with PD had more than twice the odds of a single-car accident than drivers with MS or UC, but no differences were observed between MS and UC.Conclusions: Drivers with PD were older and experienced the car accident within a shorter timeframe after disease diagnosis. Although several factors may cause a car accident, fitness to drive could be more thoroughly evaluated for patients with PD by physicians, even early after the diagnosis.
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  • Appelros, P, et al. (author)
  • A national stroke quality register : 12 years experience from a participating hospital
  • 2007
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 14:8, s. 890-894
  • Journal article (peer-reviewed)abstract
    • Registration of all hospitalized stroke patients is practiced in Sweden in order to assess care quality. Data in this register, Riks-Stroke (RS), may be biased due to incomplete registration. The purpose of this paper was to report changes in stroke outcome in relation to fluctuations in registration. Patients registered in RS at a hospital during the period 1994-2005 were analyzed. Case fatality at 28 days, living conditions, and activities of daily living (ADL) performance at 3 months were correlated to the number of patients registered and follow-up frequency. A total of 4994 stroke cases were registered during the period. A high annual registration rate was significantly correlated to a high case fatality ratio. A low annual follow-up rate was associated with a low proportion of patients living in their own home without any need of help. Quality parameters are sensible for selection bias, which make them difficult to compare over time and between hospitals. We suggest that by weighing outcome data against stroke severity, safer conclusions may be drawn. Additionally, hospitals considering setting up quality registers should make every effort to attain complete case ascertainment at all times, including patients managed outside the hospital, in order to avoid selection bias.
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  • Appelros, Peter, et al. (author)
  • Changes in mini mental state examination score after stroke : lacunar infarction predicts cognitive decline
  • 2006
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 13:5, s. 491-495
  • Journal article (peer-reviewed)abstract
    • Stroke and cognitive impairment are inter-related. The purpose of this study was to show the natural evolution of cognitive performance during the first year after a stroke, and to show which factors that predict cognitive decline. Subjects were patients with a first-ever stroke who were treated in a stroke unit. A total of 160 patients were included. At baseline patients were evaluated with regard to stroke type, stroke severity, pre-stroke dementia and other risk factors. Mini Mental State Examinations (MMSE) were performed after 1 week and after 1 year. Patients had a median increase of 1 point (range -8 to +9) on the MMSE. Thirty-two pre cent of the patients deteriorated, 13% were unchanged, and 55% improved. Lacunar infarction (LI) and left-sided stroke were associated with a failure to exhibit improvement. Patients with LI had an average decline of 1.7 points, whilst patients with other stroke types had an average increase of 1.8 points. Most stroke survivors improve cognitively during the first year after the event. The outcome for LI patients is worse, which suggests that LI may serve as a marker for concomitant processes that cause cognitive decline.
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  • Askmark, Håkan, et al. (author)
  • Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3 : a pilot study
  • 2012
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 19:12, s. 1554-1560
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Vitamin D has important roles both in the autoimmune response and in skeletal muscles. We determined the levels of 25-hydroxy vitamin D [25(OH)D] in patients with MG and in healthy subjects to determine whether vitamin D deficiency is present in MG and whether vitamin D supplementation has beneficial effects on fatigue. METHODS: Plasma levels of 25(OH)D were analyzed in 33 patients with MG (22 males; mean age, 58 years) and in 50 healthy age- and sex-matched blood donors, without vitamin D3 medication. MG composite score (MGC) assessed fatigue. 13 patients with MG without previous vitamin D3 supplementation were started on vitamin D3 supplementation (cholecalciferol) 800 IU/day, with a follow-up examination after 2.5-10 months (mean, 6 months). RESULTS: Patients with MG without pre-existing vitamin D3 supplementation (N = 16) had a mean MGC of 4.5 and lower plasma 25(OH)D levels (mean, 51 ± 19 nM) than healthy controls (69 ± 21 nM) (P = 0.017). Seventeen patients had pre-existing vitamin D3 supplementation, because of corticosteroid treatment, and their mean 25(OH)D was 79 ± 22 nM and mean MGC was 5.5. In the 13 patients who received cholecalciferol, 25(OH)D was overall increased at follow-up with 22% (P = 0.033) and MGC score improved with 38% (P = 0.05). CONCLUSIONS: Plasma 25(OH)D levels are significantly lower in patients with MG compared with healthy controls. As vitamin D has beneficial effects on the autoimmune response and on fatigue score in patients with MG, we suggest monitoring this parameter in patients with MG and supplementation with vitamin D3 when 25(OH)D levels are low.
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  • Asplund Högelin, K., et al. (author)
  • B-cell repopulation dynamics and drug pharmacokinetics impact SARS-CoV-2 vaccine efficacy in anti-CD20-treated multiple sclerosis patients
  • 2022
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:11, s. 3317-3328
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Recent findings document a blunted humoral response to SARS-CoV-2 vaccination in patients on anti-CD20 treatment. Although most patients develop a cellular response, it is still important to identify predictors of seroconversion to optimize vaccine responses. Methods: We determined antibody responses after SARS-CoV-2 vaccination in a real-world cohort of multiple sclerosis patients (n = 94) treated with anti-CD20, mainly rituximab, with variable treatment duration (median = 2.9, range = 0.4–9.6 years) and time from last anti-CD20 infusion to vaccination (median = 190, range = 60–1032 days). Results: We find that presence of B cells and/or rituximab in blood predict seroconversion better than time since last infusion. Using multiple logistic regression, presence of >0.5% B cells increased probability of seroconversion with an odds ratio (OR) of 5.0 (95% confidence interval [CI] = 1.0–28.1, p = 0.055), whereas the corresponding OR for ≥6 months since last infusion was 1.45 (95% CI = 0.20–10.15, p = 0.705). In contrast, detectable rituximab levels were negatively associated with seroconversion (OR = 0.05, 95% CI = 0.002–0.392, p = 0.012). Furthermore, naïve and memory IgG+ B cells correlated with antibody levels. Although retreatment with rituximab at 4 weeks or more after booster depleted spike-specific B cells, it did not noticeably affect the rate of decline in antibody titers. Interferon-γ and/or interleukin-13 T-cell responses to the spike S1 domain were observed in most patients, but with no correlation to spike antibody levels. Conclusions: These findings are relevant for providing individualized guidance to patients and planning of vaccination schemes, in turn optimizing benefit–risk with anti-CD20. 
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  • Becker, C, et al. (author)
  • Risk of incident depression in patients with Parkinson disease in the UK
  • 2011
  • In: European Journal of Neurology. - 1351-5101. ; 18:3, s. 448-453
  • Journal article (peer-reviewed)abstract
    • Background: Non-motor symptoms are not widely recognized in patients with Parkinson disease (PD). We sought to assess the incidence rate as well as the risk of depression in newly diagnosed patients with PD and to compare it to PD-free controls. Methods: We conducted a population-based follow-up study with a nested case–control analysis based on data from the UK-based General Practice Research Database (GPRD). We included PD patients ≥ aged 40 years with a first PD diagnosis between 1994 and 2005, and a matched comparison group free of PD. We assessed incidence rates (IRs) and relative risk estimates (odds ratios [ORs] with 95% confidence intervals [CI]). Results: The IR of depression in newly diagnosed PD in the UK community was 26.0 (95% CI 22.9–29.5) per 1000 person-years. The risk of developing depression was increased almost twofold in patients with PD when compared to patients without PD (adj. OR 1.89; 95% CI 1.49–2.40). The increased relative risk was most pronounced in women and in individuals 40–69 years of age. Long-term users of levodopa had an increased depression risk when compared to short-term users. Conclusions: Patients with PD are at an approximately twofold increased risk of being diagnosed with depression compared to the PD-free population.
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  • Ben-Menachem, Elinor, 1945, et al. (author)
  • Surgically implanted and non-invasive vagus nerve stimulation: areview of efficacy, safety and tolerability
  • 2015
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 22:9, s. 1260-1268
  • Journal article (peer-reviewed)abstract
    • Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.
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  • Biström, Martin, et al. (author)
  • Epstein-Barr virus infection after adolescence and Human herpesvirus 6A as risk factors for multiple sclerosis
  • 2021
  • In: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:2, s. 579-586
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Infections with human herpesvirus 6A (HHV-6A) and Epstein–Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV-6A associated risks of developing MS.Methods: In this nested case–control study, Swedish biobanks were accessed to find pre-symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead-based multiplex assay was used to determine serological response against EBV and HHV-6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.Results: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20–29 and 30–39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV-6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6–2.7).Conclusions: This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.
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  • Bohlen, S, et al. (author)
  • Physical therapy in Huntington's disease : towards objective assessments?
  • 2013
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 20:2, s. 389-393
  • Journal article (peer-reviewed)abstract
    • Background and purposePhysical therapy is recommended for the treatment of Huntington's disease, but reliable studies investigating its efficacy are almost non-existent. This may in part be due to the lack of suitable outcome measures. Therefore, we investigated the applicability of novel quantitative and objective assessments of motor dysfunction in the evaluation of physical therapy interventions aimed at improving gait and posture.MethodsTwelve patients with Huntington disease received a predefined twice-weekly intervention focusing on posture and gait over 6 weeks. The GAITRite mat and a force plate were used for objective and quantitative assessments. The Unified Huntingtons Disease Rating Scale Total Motor Score, the timed Up &Go test, and the Berg Balance Scale were used as clinical outcome measures.ResultsSignificant improvements were seen in GAITRite measures after therapy. Improvements were also seen in the Up & Go test and Berg Balance Scale, whereas force plate measures and Total Motor Scores did not change.ConclusionsThe results suggest that physical therapy has a positive effect on gait in Huntington's disease. The study shows that objective and quantitative measures of gait and posture may serve as endpoints in trials assessing the efficacy of physical therapy. They should be explored further in larger trials applying a randomized controlled setting.
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