Profiling cognitive-motor interference in a large sample of persons with progressive multiple sclerosis and impaired processing speed: results from the CogEx study.

BACKGROUND: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown. OBJECTIVE: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level. METHODS: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTCmotor with clinical measures. Adjusted significance level was 0.01. RESULTS: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTCmotor of 15.8% and DTCcognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTCmotor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTCcognitive did not differ from zero for any of the groups (p ≥ 0.039). CONCLUSION: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups.

Polarimetric Thomson scattering measurements in Joint European Torus high temperature plasmas.

Thomson scattered light is polarized in the same orientation as the incident laser beam at low electron temperatures (Te). At high Te, part of the spectrum begins to become randomly polarized due to relativistic reasons. First measurements of the depolarized Thomson scattering spectrum were obtained from Joint European Torus (JET) pulses in 2016. This paper builds upon these initial measurements with the data obtained during 2021. These new measurements improve upon first results, in particular, by obtaining spectral measurements of the depolarized spectrum. The recent JET campaign was well suited to these measurements with long and hot plasmas. The resulting data are averaged over many plasmas and laser pulses to obtain a measurement of the amount of "p" and "s" scattered light as a function of Te. This experimentally obtained d(p/s)/dTe is then fitted and found to show reasonable agreement with the theoretically predicted depolarized fraction. Error estimates on the measured "p/s" have been obtained and show that the measurements are meaningful. This is good news for ITER for which the intention is to use this measurement as a check on Te determined by the core plasma Thomson scattering diagnostic by using conventional spectral measurement techniques.

Electronic visual analogue scales for pain, fatigue, anxiety and quality of life in people with multiple sclerosis using smartphone and tablet: a reliability and feasibility study.

OBJECTIVE: To explore the reliability and feasibility of electronic visual analogue scales in people with multiple sclerosis (MS) and healthy individuals. DESIGN: Cross-sectional observational study Setting: Clinical setting Subjects: Convenience sample of 52 people with MS and 52 matched healthy controls Interventions: NA Main measures: Participants scored 15 statements assessing fatigue, pain, anxiety and quality of life on an electronic visual analogue scale (eVAS), either using a smartphone or a tablet (randomly allocated). To check for test-retest reliability, statements were administered in two separate randomly ordered groups. Subjects completed a feasibility questionnaire. RESULTS: Mean (SD) eVAS scores ranged from 35 (28.1) to 80 (22.1) in MS group, and from 57 (28.0) to 86 (13.2) in controls. Intra Class Correlations ranged from 0.73 to 0.95 in MS sample; 0.61 to 0.92 in controls. For most statements, Bland-Altman plots indicated no systematic error, but relatively large random error of the eVAS scores (exceeding 20mm). Considerable ceiling effects (i.e. better health) were found in healthy controls. Similar reliability was found among smartphone or tablet, different demographic groups and the experience-groups. CONCLUSION: Electronic visual analogue scales are reliable and useful for people with MS to register fatigue, pain, anxiety and quality of life.

Assessment of anterior subcutaneous hypersignal on proton-density-weighted MR imaging of the knee and relationship with anterior knee pain.

PURPOSE: The purpose of this study was to evaluate the prevalence of anterior subcutaneous hypersignal indicating edema on proton-density (PD)-weighted MRI of the knee and to determine whether reporting anterior edema is clinically relevant. MATERIALS AND METHODS: One hundred and ninety-one knee MRIs from 162 patients were reviewed for anterior subcutaneous edema. There were 92 men and 70 women with a mean age of 41.72years±13.92 (SD) (range, 15-80years) years and a mean body weight of 75.94kg±12.54 (SD) (range, 50-130kg). The MRI findings were compared with patient age, gender, body weight, history of repetitive microtrauma and clinical findings. Patellar and trochlear chondropathy, medial plica, joint effusion, synovitis, infrapatellar fat-pad signal intensity, suprapatellar fat-pad signal intensity with mass effect, quadriceps and patellar tendon abnormalities were also reviewed. RESULTS: An anterior hypersignal on PD-weighted MRI was detected in 158/191 MR examinations (82.7%) and 104 (84.6%) of these cases had histories of anterior knee pain. No correlation between anterior pain and anterior edema was found (P=0.42). Age (P<0.0001), weight (P<0.0001), and repetitive microtrauma (P=0.001) were identified as significant variables associated with anterior edema. CONCLUSION: Anterior edema may be a physiological phenomenon or degenerative change related to patient age, weight, and knee movement or mechanics. It should not be reported as a pathological finding on MRI unless clinical findings support regional infection or inflammation.

Regulation of myoglobin in hypertrophied rat cardiomyocytes in experimental pulmonary hypertension.

A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) concentration. We explored how cardiac hypertrophy, oxidative capacity, and Mb expression in right ventricular cardiomyocytes are regulated at the transcriptional and translational levels in an early stage of experimental pulmonary hypertension, in order to identify targets to improve the oxygen supply/demand ratio. Male Wistar rats were injected with monocrotaline to induce pulmonary hypertension (PH) and right ventricular heart failure. The messenger RNA (mRNA) expression levels per nucleus of growth factors insulin-like growth factor-1Ea (IGF-1Ea) and mechano growth factor (MGF) were higher in PH than in healthy controls, consistent with a doubling in cardiomyocyte cross-sectional area (CSA). Succinate dehydrogenase (SDH) activity was unaltered, indicating that oxidative capacity per cell increased. Although the Mb protein concentration was unchanged, Mb mRNA concentration was reduced. However, total RNA per nucleus was about threefold higher in PH rats versus controls, and Mb mRNA content expressed per nucleus was similar in the two groups. The increase in oxidative capacity without an increase in oxygen supply via Mb-facilitated diffusion caused a doubling of the critical extracellular oxygen tension required to prevent hypoxia (PO2crit). We conclude that Mb mRNA expression is not increased during pressure overload-induced right ventricular hypertrophy and that the increase in myoglobin content per myocyte is likely due to increased translation. We conclude that increasing Mb mRNA expression may be beneficial in the treatment of experimental PH.

Origin of fatigue in multiple sclerosis: review of the literature.

Fatigue is one of the most common and most disabling symptoms of multiple sclerosis (MS). Although numerous studies have tried to reveal it, no definite pathogenesis factor behind this fatigue has been identified. Fatigue may be directly related to the disease mechanisms (primary fatigue) or may be secondary to non-disease-specific factors. Primary fatigue may be the result of inflammation, demyelination, or axonal loss. A suggested functional cortical reorganization may result in a higher energy demand in certain brain areas, culminating in an increase of fatigue perception. Higher levels of some immune markers were found in patients with MS-related fatigue, whereas other studies rejected this hypothesis. There may be a disturbance in the neuroendocrine system related to fatigue, but it is not clear whether this is either the result of the interaction with immune activation or the trigger of this process. Fatigue may be secondary to sleep problems, which are frequently present in MS and in their turn result from urinary problems, spasms, pain, or anxiety. Pharmacologic treatment of MS (symptoms) may also provoke fatigue. The evidence for reduced activity as a cause of secondary fatigue in MS is inconsistent. Psychological functioning may at least play a role in the persistence of fatigue. Research did not reach consensus about the association of fatigue with clinical or demographic variables, such as age, gender, disability, type of MS, education level, and disease duration. In conclusion, it is more likely to explain fatigue from a multifactor perspective than to ascribe it to one mechanism. The current evidence on the pathogenesis of primary and secondary fatigue in MS is limited by inconsistency in defining specific aspects of the concept fatigue, by the lack of appropriate assessment tools, and by the use of heterogeneous samples. Future research should overcome these limitations and also include longitudinal designs.

Within-session practice effect on paced auditory serial addition test in multiple sclerosis.

The paced auditory serial addition test (PASAT) is increasingly used in multiple sclerosis (MS) studies. Since these studies rely on repeated assessments with relatively short inter-test intervals, practice effects can be a confounding factor. We examined intra-session PASAT practice effects in 70 relapsing remitting (RR) and 40 secondary progressive (SP) patients. The average number of correct answers increased from 39.6+/-11.7 in the first PASAT run to 43.8+/-11.4 in the second run for the RR group, and from 39.1+/-11.6 to 41.8+/-13.3 in the SP group. PASAT scores showed a consistent decrease when comparing the second half of each test to the first half for both patient groups, and for both runs. Items for which the answer was a number greater than 9 had the same discrimination ability as other test items, but were significantly more difficult. A simulation of ;single-button' responses supported the use of the simplified scoring method which is currently used in fMRI studies. Our results demonstrate a within-session PASAT practice effect in MS, as well as a fatigability effect for both patient groups.

Multidisciplinary fatigue management programme in multiple sclerosis: a randomized clinical trial.

OBJECTIVE: To establish the efficacy of a multidisciplinary fatigue management programme (MFMP) in MS. Method Fifty-one subjects with MS were randomly allocated to group A, who only received the four weeks MFMP, or group B receiving a placebo intervention programme first and the MFMP after 6 months. In both groups, assessment was performed at baseline, 3 weeks and 6 months after the programmes and included Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), MS Self-Efficacy scale (MSSE), Mental Health Inventory (MHI) and Impact on Participation and Autonomy (IPA). RESULTS: The MFIS showed a significant change over time (F(4,152) = 3.346, P = 0.012), which was similar in both groups (time*group interaction: F(4,152) = 1.094, P = 0.361). A clinically relevant reduction of MFIS score of 10 points or more was found in 17% of individuals following the MFMP, compared to 44% after the placebo intervention programme (P = 0.06). Compared to no intervention, a significant effect of the MFMP after 6 months (P = 0.003) was found in five participants (31%). No significant changes in FSS, MSSE, MHI and IPA, in both groups, were found. CONCLUSION: Although an additional effect was found, the multidisciplinary fatigue management programme showed no efficacy in reducing the impact of fatigue compared to a placebo intervention programme.

P300 and treatment effect of modafinil on fatigue in multiple sclerosis.

To evaluate the value of visual and auditory P300 for predicting the response of multiple sclerosis-related fatigue to modafinil treatment, 33 patients were treated with 100 mg modafinil once daily for 4 weeks, following a 4-week baseline phase and an optional 8-week extension phase. The main clinical outcome parameter was a decrease in the fatigue visual analogue score (VAS) before and after 4 weeks of treatment. Patients with shorter auditory P300 latency at baseline were more likely to benefit from modafinil treatment. Auditory P300 latency predicted treatment response with a specificity of 76% and a sensitivity of 75% at a cut-off latency of 350 ms. Visual P300 latency could not be used to predict treatment response. Baseline auditory P300 latency predicted treatment response, whereas visual P300 latency did not. Clinical improvement did not correlate with changes in either visual or auditory P300.

Evaluation of the Modified Fatigue Impact Scale in four different European countries.

OBJECTIVE: To evaluate the psychometric properties of the Modified Fatigue Impact Scale (MFIS) in four different European countries. METHODS: Individuals with definite multiple sclerosis (MS) were selected from centres in Italy (n =50), Spain (n =30), Slovenia (n =50) and Belgium (n =51) and completed the MFIS and the Fatigue Severity Scale (FSS) twice (interval < or =3 days). RESULTS: In all four samples, the MFIS demonstrated a good reproducibility (intraclass correlation coefficient > or = 0.84), with no significant differences between countries (P =0.77). Moderate correlations were found between the MFIS and FSS. No significant correlations were found between the MFIS and age, gender, type of MS, duration of the disease or EDSS score. Factor analysis of all samples (n = 181) could not completely confirm the original assumptions concerning the physical, cognitive and psychosocial component The total score, the physical and the cognitive subscale of the scale were homogeneous (Cronbach's alpha 0.92, 0.88 and 0.92, respectively), but the psychosocial subscale had a Cronbach's alpha of 0.65. CONCLUSIONS: No cultural or linguistic differences were found in the psychometric properties of the Belgian, Italian, Slovenian or Spanish version of the MFIS. We recommend this scale for research purposes and in clinical practice. Due to the limited value of the psychosocial subscale, we recommend interpreting this subscale with caution.

Validity of the TEMPA for the measurement of upper limb function in multiple sclerosis.

OBJECTIVE: To investigate concurrent and construct validity of the TEMPA (Test d'Evaluation de la performance des Membres Supérieurs des Personnes Agées) in patients with upper limb dysfunction due to multiple sclerosis. SUBJECTS: Forty-three patients with upper limb dysfunction due to multiple sclerosis. DESIGN: Patients performed upper limb tests and were assessed on measures of functional independence. SETTING: National Multiple Sclerosis Centre, Melsbroek, Belgium. MAIN OUTCOME MEASURES: TEMPA, Jebsen Handfunction Test, Nine Hole Peg Test, Functional Independence Measure (FIM) and activities of daily living (ADL) self-questionnaire. RESULTS: The correlation between TEMPA and Jebsen Handfunction and the Nine Hole Peg test respectively is good (0.56-0.87) and high (0.79-0.9). The correlation between TEMPA and the FIM and ADL self-questionnaire was moderate (0.44-0.61) although mostly higher than the correlation between the Jebsen Handfunction and the Nine Hole Peg test respectively and the measures of functionality (0.22-0.55/0.1-0.47). CONCLUSIONS: This study provides data supporting the concurrent validity of the TEMPA with the Jebsen Handfunction and the Nine Hole Peg Test in patients with multiple sclerosis. The results suggest construct validity of the TEMPA for the measurement of functionality during activities of daily life in patients with upper limb dysfunction due to multiple sclerosis.

Safe and effective fluid management by automated gravitation during hysteroscopy.

OBJECTIVE: The automated gravitational Vario Flow system with weighing-based electronic fluid deficit indicator was used in order to reduce the risk of fluid intravasation during continuous flow hysteroscopic procedures. Early experiences are reported. METHODS: Between August 1996 and July 1997, the Vario Flow with fluid deficit indicator and alarm system was used in 203 hysteroscopic operations. Between January 1994 and August 1996 the Vario Flow without fluid deficit indicator was used in 240 hysteroscopic operations. In all, there were 443 hysteroscopic operations: 301 metroplasties, 20 endometrial ablations, 10 cases of lysis of synechiae, 58 myomectomies and 54 polypectomies. The data on fluid deficit before and after the introduction of the electronic fluid deficit indicator were similar. RESULTS: Fluid deficit indicator was proved highly efficient in 203 operations. It provided the information on fluid deficit at any moment during hysteroscopic operations. Besides intrauterine pressure, the actual fluid deficit has become one of the leading parameters during our continuous flow hysteroscopic procedures. CONCLUSIONS: We therefore conclude that by using an automated gravitational system with fluid deficit indicator and alarm system, the safety for patients during hysteroscopic procedures has been increased.