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Authors

 Nikos Evangelou, DPhil, C floor, South Block, Queen's Medical Centre, Nottingham, NG7 2UH, UK; 

PANORAMA: A 2021 Clinician Survey of Treatment Approaches for People With New Diagnoses of Relapsing-Remitting Multiple Sclerosis in the United Kingdom

The quality of life (QOL) of people with multiple sclerosis (MS) is considerably poorer than the QOL of people with other chronic diseases. QOL management should not be restricted to only clinical aspects but also factors modifying QOL. The aim of this study was to identify the sociodemographic and clinical determinants of QOL in people with MS.

A cross-sectional study conducted from 2022 to 2023 included 200 participants aged 18 and over recruited from the Hassan II University Medical Hospital in Fez, Morocco. QOL assessment was performed using the Arabic version of the Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaire. Univariate analysis using Student 

 test, analysis of variance, and Pearson correlation was performed, followed by multiple linear regression analysis to determine the main factors associated with QOL.

QOL was impaired in the physical health (PH) (48.51±22.08) and mental health (MH) (48.69±17.18) components of the MSQOL-54. Male sex, unemployment, and high scores on the Expanded Disability Status Scale (EDSS) were factors significantly associated with lower scores on both the PH and MH components. In contrast, later age at MS diagnosis and older age were significantly associated with worse PH and MH, respectively. EDSS score was a strong predictor of QOL (PH: β = −34.983; 95% CI, −39.64 to −30.31; MH: β = −23.383; 95% CI, −27.62 to −19.14).

The results highlight the importance of sociodemographic and clinical determinants of QOL. Clinicians need to integrate a biopsychosocial approach into therapeutic education programs, considering the risk factors and specific needs of people with MS to optimize their QOL.

From the Laboratory of Epidemiology and Health Sciences Research (IR, FN, MFB) and the Laboratory of Epidemiology, Clinical Research and Community Health (HB), Faculty of Medicine, Pharmacy and Dentistry, Sidi Mohammed Ben Abdallah University, Fez, Morocco); Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco; Department of Biology and Geology, Teachers Training College (École Normale Supérieure), Sidi Mohamed Ben Abdellah University, Fez, Morocco (MAR); Department of Neurology, Hassan II University Hospital Center, Fez, Morocco (MFB).

Ilham Raji, MS, Laboratory of Epidemiology and Health Sciences Research, Faculty of Medicine, Pharmacy and Dentistry, Sidi Mohammed Ben Abdallah University, 30070, Fez, Morocco; 

We are grateful to all researchers whose articles were reviewed in the study.

 The authors have declared no conflicts of interest.

Multiple sclerosis (MS) is a neurodegenerative, demyelinating disease of the central nervous system,

 arising from the interplay between genetic predisposition and environmental factors.

 According to a report by the Multiple Sclerosis International Federation, approximately 2.8 million individuals worldwide are impacted by the disease.

 It is diagnosed in young people, typically between the ages of 20 and 40 years, with a higher prevalence in women. However, the diagnosis sometimes occurs later in life, even if initial symptoms may have appeared earlier.

 MS causes severe neurological disability.

 The unpredictability and variability of MS symptoms give it a complex pathology, including ataxia, cognitive disorders, visual and sensory impairments, fatigue, sexual dysfunction, and bladder and bowel dysfunction.

 Psychological well-being is also impacted by a high prevalence of depressive disorders and anxiety.

 As the disease progresses, worsening episodes may leave persistent symptoms, leading to increased physical limitations and significant repercussions. These include psychological impacts such as reduced self-esteem,

 economic challenges like higher medical expenses and job loss,

 and social difficulties such as trouble maintaining personal relationships and participating in daily activities.

 As a result, the quality of life (QOL) of people with MS is significantly affected, even at early stages.

 Moreover, it is perceived to be worse than that observed in other chronic pathologies such as inflammatory bowel disease, rheumatoid arthritis,

 Research has therefore recently focused on QOL as a key outcome indicator

 as a benchmark in the evaluation of treatment efficacy and the planning and management of MS care.

QOL is a comprehensive concept consisting of physical, social, psychological, and functional aspects.

 Many tools are used to measure QOL, but, due to its multidimensional and hybrid nature, the Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaire is one of the instruments most commonly used to measure MS-specific QOL.

 MS-specific instruments provide more comprehensive and accurate assessment of the impact MS has on health and QOL than generic instruments.

Deterioration in QOL can be interpreted as a marker of disease progression,

 but may ultimately be hard to discern given that its many individual factors make it more difficult to measure, altering the reliability of QOL results.

 As sociodemographic and clinical components affect QOL for people with MS, we can anticipate variations in its determinants in different countries due to social, cultural, economic, and health care system divergences.

 Thus, understanding the factors that influence MS QOL will uncover certain associations between individual patient characteristics and its various aspects. This will help health care professionals optimize the decision-making process when choosing effective interventions by assessing whether further action is required,

 thereby improving their management of MS.

 The aim of this study was to identify the sociodemographic and clinical determinants of QOL in Moroccan people with MS.

This cross-sectional study was conducted over a 6-month period from October 2022 to April 2023. Recruited patients were followed by the neurology department of the University Medical Hospital Hassan II in Fez, Morocco, and were contacted either during their outpatient hospitalization or in consultation. Via consecutive sampling, we included a total of 200 patients who fulfilled the following inclusion criteria: (1) aged 18 years or older, (2) confirmed diagnosis of MS based on the revised McDonald criteria (2011),

 (3) an Expanded Disability Status Scale (EDSS)

 score between 0 and 8, and (4) no exacerbations recorded in at least the previous 4 weeks. Exclusion criteria included patients with a questionable diagnosis of MS, with pronounced cognitive and psychiatric disorders, and with concomitant diseases likely to interfere with QOL.

After obtaining approval from the Ethics Committee of the Faculty of Medicine, Pharmacy and Dentistry at Sidi Mohamed Ben Abdellah University in Fez (Registration No. 31/22), all participants were provided with pertinent details regarding the study and willingly provided their written informed consent, in accordance with the Declaration of Helsinki.

Data were obtained through the use of a preestablished questionnaire, including sociodemographic and clinical data. Sociodemographic variables included sex, age (categorized as ≥40 and < 40), area of residence (categorized as urban or rural), occupational status (grouped as active or inactive), level of education (illiterate, primary, secondary, or university), and marital status (single, married, widowed, or divorced). Clinical variables included associated comorbidities, family history of MS, age at diagnosis, duration of disease course, form of MS (relapsing-remitting [RR], secondary progressive, or primary progressive),

 current treatment (first-line treatment [ie, interferon beta, teriflunomide, azathioprine] second-line treatment [ie, natalizumab, fingolimod, ocrelizumab, rituximab], or third-line treatment

), and EDSS score (low [≤ 3.5] or moderate to high [≥ 4]). All these data were collected via self-report and the medical record of each participant.

Data on QOL were collected using the validated Arabic version of the MSQOL-54 questionnaire, specifically adapted for the Moroccan context.

 The Cronbach coefficient for this version varied between 0.69 and 0.92, with 100% success in both convergence and divergent validity.

 This is a commonly used and standardized questionnaire

 of 54 items, with 18 items designed specifically for MS. It contains 12 subscales, 2 single-item measures related to satisfaction with sexual function and change in health status, and 2 composite scores related to physical health (PH) and mental health (MH).

 The subscales are physical function, pain, role-physical limitations, health perception, energy/fatigue, cognitive function, sexual function, role-emotional limitations, health-related distress, social function, emotional well-being, and global QOL.

 Each question is scored from 0 to 100, and a score was assigned for each subscale. Scores closer to 100 indicate higher QOL.

To describe and synthesize the sociodemographic and clinical variables, as well as the MSQOL-54 scores, a descriptive statistical analysis was conducted of mean and SD for quantitative variables and frequency and percentage for categorical variables. A univariate analysis was performed to study the association between variables and PH and MH MSQOL-54 scores, including a Student 

 test and analysis of variance for the independent variables (ie, age, sex, marital status, area of residence, level of education, occupational status, associated comorbidities, family history of MS, form of disease, and type of current treatment), and a Pearson test for quantitative variables (eg, EDSS score, age at diagnosis, duration of disease). For all conducted tests, a 

 value less than .05 was considered significant. Multivariate analysis using multiple linear regression (with a stepwise procedure) was performed to determine the determinants of QOL in Moroccan people with MS. Factors with a 

 value less than or equal to .25 in the univariate analysis were considered for inclusion in the models. Significant associations were indicated through the adjusted β coefficient and 95% CI. Independent variables with a higher absolute value of β are those with a more marked influence on QOL. All statistical analyses were conducted utilizing IBM’s SPSS version 26.0.

Sociodemographic and clinical characteristics are presented in 

. Of the total of 200 patients, 74.0% were women, 71.5% were under 40 years of age, 56.5% were married, and 79.0% lived in an urban area. The majority of patients (63%) were unemployed, and 33% had attended university. In terms of clinical data, the RR form of MS was the most frequent subtype (90.5%). The mean age at diagnosis was 33.28 ± 10.71 years (range, 13-67 years). Mean disease duration in months was 67.62 ± 64.87; 77.5% had an EDSS less than or equal to 3.5; 84% were receiving second-line treatment. Mean PH and MH scores were 48.51 ± 22.08 and 48.69 ± 17.18, respectively. Of all MSQOL-54 dimensions, participants had the highest mean scores for physical function (58.33 ± 34.60) and the lowest mean scores for sexual function (36.02 ± 31.93) (

The results of the analysis indicate that low PH and MH scores were significantly associated with certain sociodemographic variables, including advanced age (

 = .013 for MH), absence of a professional activity (

 = .012 for MH). Decreases in PH and MH scores were negatively associated with certain clinical factors, including a higher EDSS score (

 = .001) and advanced age at MS diagnosis (PH: 

 = .0001). Increased disease duration was negatively correlated with low PH (

 = .05); however, its influence on MH was not statistically significant. First-line treatment appeared to have a significant influence on PH compared with second-line treatment (

 = .002), but there was no significant difference in MH. Form of MS also showed a significant association for both PH and MH (

 = .0001), with higher results noted for RR, indicating better QOL. Finally, marital status, comorbid conditions, and family history of MS were not significantly associated with QOL (

Multivariate Multiple Regression Analyses 

Final models were established after performing a manual multiple linear regression analysis, carefully integrating relevant sociodemographic and clinical factors. Results indicated that the factors negatively associated with PH and MH were: male gender (PH: β = −9.969; 95% CI, −14.43 to −5.50/MH: β= −5.760; 95% CI, −9.80 to −1.71), unemployment (PH: β = −8.515; 95% CI, −12.79 to −4.23/MH: β= −8.236; 95% CI, −12.09 to −4.37), and as high EDSS scores (PH: β = −34.983; 95% CI, −39.64 to −30.31/MH: β = −23.383;95% CI, −27.62 to −19.14). Moreover, advanced age was associated with low MH (β = −4.924; 95% CI, −8.79 to −1.05), whereas late age at diagnosis contributed to worsened PH (β = −0.317; 95% CI, −0.496 to −0.137). EDSS score was found to be the strongest predictor of QOL for people with MS in our study (

The main aim of this study was to identify the sociodemographic and clinical determinants of QOL in Moroccan people with MS. Our results revealed that the QOL was impaired for PH and MH, aligning with the results of several previous studies.

 Furthermore, significant impairments in both PH and MH were associated with male gender, unemployment, and a high EDSS score. Late age at diagnosis and advanced age were also significantly associated with lower PH and MH scores, respectively. Finally, EDSS score was found to be a strong predictor of QOL.

After a univariate analysis, the factors influencing PH are multiple. Indeed, an exclusively negative correlation was demonstrated between disease duration and PH, with no significant impact on MH. Some studies have also noted that the longer the duration of illness, the more physical QOL decreases,

 making disease duration a risk factor for decreasing QOL.

 In general, although physical function may decline with the progression of chronic diseases, MH may still remain favorable.

 For current treatment, a significant association was observed with PH, indicating higher scores for first-line treatment. Other studies have shown that first-line treatment of MS was linked to improved QOL in patients with both pediatric and adult onset.

 In contrast, receiving treatment for MS was associated with a lower PH score.

 Although it is widely accepted that disease-modifying drugs impact QOL,

 the variations in study findings may be attributed to specific adverse effects associated with the range of drugs available.

 Furthermore, it is plausible that patients on first-line treatment experience a higher QOL, possibly due to reduced disease activity,

 compared with those receiving other treatments. In Morocco, between 70.4% and 89.6% of people with MS do not have access to disease-modifying treatments due to their high cost and the limitations of the health care system, which negatively impacts the management of their disease.

 our results showed that mean age at MS onset was in the 30s. After multivariate analysis, a later age at diagnosis was negatively correlated with deterioration in PH.

 However, few studies take this variable into account when assessing QOL. Our results could be linked, in part, to late diagnosis, which holds the opportunity for disease progression with a likelihood of increased disability over a shorter period. Late diagnosis could also limit the effectiveness of available treatment options.

 Those diagnosed at a younger age tend to have good PH and impaired MH

 and to display significantly more favorable scores in the domain of health status perception.

 Older age at disease onset in adults is also associated with lower QOL scores

Our results surprisingly indicate that advanced age had a significant negative impact, specifically on MH. However, the literature presents divergent findings, with some authors claiming that older age is associated with good MH,

 whereas others have confirmed that, unlike mental health, PH is generally marked by deterioration with age.

 Previous research also indicated that older people with MS have lower PH and MH scores than younger people with MS.

 Our results highlight the challenges in self-perceived acceptance that people with MS face as they age,

 where coping strategies and resilience act as significant mediators between mental QOL and sense of coherence.

After univariate analysis, several factors influence both PH and MH. People living in urban areas had significantly higher PH and MH scores than those living in rural areas, which is supported by previous studies.

 This may be due to their greater access to specialists and other therapies. As a result, they are more likely to receive the assistance they need to overcome difficulties.

 In addition, higher levels of education were significantly associated with better PH and MH. More educated people with MS experience greater confidence and an enhanced ability to initiate treatment early, contributing to more effective management and strong adaptation to the physical and mental challenges involved.

 A higher level of education therefore acts as a protective factor against QOL deterioration, as it promotes a better understanding of the disease.

 Some studies indicate that patients with RRMS have better PH and MH scores.

 However, other studies have indicated that the type of MS has no bearing on QOL.

 One possible explanation is that the disease develops more rapidly in patients with progressive MS, leading to severe symptoms that may have a negative impact on QOL.

Our results after adjustment highlighted that, as in other studies,

 a high EDSS score was a strong predictor of worse PH and MH in people with MS. QOL appeared to be strongly influenced by the number and severity of symptoms, as well as by associated impairments.

 A higher EDSS score is associated with high vulnerability, high dependence on others, role restrictions in daily life, and decreases in self-efficacy and mental health.

 The results of a study conducted in Morocco showed a notable association between the level of disability and PH and MH, and that incorporating psychological support into care programs was essential.

After a multivariate analysis, male sex remained negatively associated with deterioration in PH and MH. This finding aligns with prior studies confirming that male sex was associated with unfavorable QOL in people with MS.

 Compared with women with MS, men with MS have poorer physical QOL

 and are generally faced with a worse prognosis than women.

 The impact of disability on QOL is more powerful in men than women, especially on physical function, social and mental health, and vitality.

 This may be explained by a finding that women are better able to develop coping mechanisms and capacities to adjust to MS-related disability, thus helping to reduce the impact on their QOL.

 Unemployment was also highlighted as a risk factor for deterioration in PH and MH, consistent with previous studies that have confirmed that unemployed people with MS generally have low QOL

 and tend to develop psychosocial problems.

 Participation in meaningful activities, including work, acts as a protective element against depression and QOL decline.

 Thus, employment is associated with positive mental well-being in people with MS

 and also with an increase in self-efficacy and self-esteem.

 Other authors, however, have highlighted that feelings of inadequacy can lead to withdrawal from employment. Even in the absence of a significant influence of the disease on functional status, people with MS may feel a functional incapacity when they compare their present state of health and function with what they had before the onset of the disease.

 In the Moroccan context, unemployed individuals face greater difficulties accessing appropriate care, which can exacerbate disease symptoms and affect their QOL.

This study has a few limitations. First, caution should be exercised in interpreting our results due to the study’s cross-sectional design and the establishment of a causal relationship between QOL and the various identified factors. Second, we did not have the opportunity to involve additional participants due to the limited recruitment within the neurology department and issues related to access to disease-modifying therapies. These factors constrained our ability to establish significant associations with certain variables as well as to assess QOL based on this disease sub-type, particularly among people with RRMS, which was the most prevalent group in our sample. However, to our knowledge, this is the first study to cover a wide range of determinants of QOL in Moroccan people with MS, paving the way for a deeper understanding of the impacts on QOL in this population and for more in-depth future research to inform clinical management.

We found that MS had a negative impact on the physical and mental dimensions of QOL. The present study contributes to a deeper understanding of the interaction between sociodemographic and clinical determinants of QOL of people with MS in Morocco. Significant impairment of both PH and MH was associated with male sex, unemployment, and higher EDSS scores. In addition, late age at MS diagnosis and advanced age were significantly associated with low PH and low MH, respectively. EDSS score was found to be a powerful predictor of QOL. Recognition of these factors offers opportunities to organize healthcare proactively, enabling integrated management of MS. However, it also raises the importance of taking into account nonmodifiable factors and the specific needs of people with MS with a biopsychosocial approach and personalized therapeutic education programs. This includes psychological support, rehabilitation, and integration of QOL assessment into care protocols. The challenge is to guide patients, families, and clinicians toward optimal disease management.

Sociodemographic and Clinical Determinants of the Quality of Life of Moroccan People With Multiple Sclerosis

People with multiple sclerosis (MS) have an increased risk of falls, which are often associated with changes in movement direction and preceded by head rotation (HR). We aimed to investigate the effects of HR on postural control and gait temporal parameters in people with MS compared with controls (Cs) and to quantify the number of strides required to correct gait after HR.

Eighteen people with MS (44.4 ± 9.9 years; 3.1 ± 1.5 Expanded Disability Scale Score) and 10 Cs (43.6 ± 10.3 years) participated. Postural control during a standing task on a force plate was assessed and quantified by center of pressure displacement. Gait was assessed by 2D sagittal video analysis and analyzed with Kinovea. After30 seconds of unperturbed walking on a treadmill, participants were instructed to turn their head to the left and walk on, followed by a right HR. The 10 strides after the HR were compared with the mean of normal walking strides. Inter- and intragroup comparisons were performed using a mixed model for repeated measurements. Hierarchical testing was used for stride analysis.

While standing, people with MS performed worse in all conditions and increased center of pressure displacement after HR in comparison with Cs (

 ≤ .05). While walking, both groups increased the relative stance phase after HR (

 ≤ .05); however, people with MS reduced stride times (

 ≤ .05), and Cs maintained them. After HR, people with MS needed 3 strides to normalize stride times back to baseline, versus 1 to none for Cs.

People with MS have higher transient imbalance while walking and standing after an HR compared with Cs.

From the Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gemeinnützige GmbH, Berg, Germany (MR, IK); the Department for Clinical Neurosciences and Preventive Medicine, Danube University, Krems an der Donau, Austria (MR); University MS Center, Hasselt Pelt, Belgium (CR, LM, PF); REVAL Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt University, Belgium (CR, LM, PF); freelance instructor in Biomechanics, Kinetae, Barcelona, Spain (JVV-R); Institute of Psychoacoustics and Electronic Music, Faculty of Arts and Philosophy, Ghent University, Ghent, Belgium (LM); Department of Neurology, Ruhr University Bochum, Bochum, Germany (IK). 

 Marianne Rösner, Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gemeinnützige GmbH, Milchberg 21, 82335 Berg, Germany; 

We would like to thank all our colleagues from the diagnostics and medical teams of the Marianne-Strauß-Klinik, especially the physiotherapy team, for their engagement during the patient recruitment period. In particular, we would like to thank M. R. for technical support during the development phase of the study.

This material was previously a poster presentation at the all-virtual Rehabilitation in Multiple Sclerosis conference, November 27-28, 2021.

Peter Feys, PhD, PT, is on the editorial boards of 

. He has been a consultant to Biogen and Neuro-Compass. Ingo Kleiter, MD, has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Almirall, Bayer, Biogen, GSK, Hexal, Horizon, Merck, Neuraxpharm, Roche/Chugai, and Sanofi. He is an editorial board member of 

. All other authors have declared no relevant conflicts of interest.

Multiple sclerosis (MS) is an inflammatory demyelinating disease with the pathological hallmark of an accumulation of lesions in the white and gray matter of the brain and spinal cord that lead to a wide range of symptoms.

 A frequent complaint among people diagnosed with MS is loss of dynamic and static balance control.

 Approximately half of people with MS report at least 1 fall in a period of 3 months, and 35% report regular falls during a 6-month period.

 Eighty percent of falls can be associated with mobility tasks, and 60% of them occur during walking.

 Furthermore, people with MS usually report falls during activities of daily living, which are preceded by slips, stumbling, or changes in movement directions.

Head rotation (HR) represents a pivotal component in the modification of movement direction, thereby presenting 2 significant challenges that must be surmounted. First, there is the shift of attention from the current to the new situation, which can be interpreted as a dual-task in real-life scenarios. It is well documented that situations that engender such interference can have a detrimental effect on gait and postural control in people with MS.

 Second, the maintenance of movement over time while ensuring balance control is a process governed by brain regions and networks associated with cognition, motor control, and sensory integration, which are frequently impaired in individuals with MS.

 Reweighting processes between sensory systems for intersensory integration is highly related to the reliability of sensory input via the proprioceptive system, the most sensitive and fastest responding system to balance perturbations over time.

 Nevertheless, it has been suggested that people with MS rely more on visual than on proprioceptive sensory input to control balance.

Although studies in the past have concentrated on disease-related changes during unperturbed walking and balance tasks,

 along with the repercussions of assorted extrinsic disturbances on balance maintenance,

 the current study sought to shift the focus to the function of head rotation as a form of self-induced perturbation, discernible in routine activities. We hypothesized that, due to the accumulation of neurological deficits, people with MS would demonstrate an inadequate ability to cope with and/or modulate the perturbation induced by head rotation. We further hypothesized that people with MS would manifest a transitory decline in performance during standing and walking when compared with controls (Cs).

The objectives of this study were to investigate the role of HR on postural control during semistatic balance tasks and on gait temporal parameters during treadmill walking in people with MS compared with Cs. We further aimed to identify the number of strides to adapt and correct walking after the HR in people with MS compared with Cs.

People were recruited from an inpatient MS clinic and had to fulfill the following inclusion criteria: neurologist-confirmed diagnosis of MS according to 2017 McDonald criteria

; 18 years or older; Expanded Disability Status Scale (EDSS) score 1.0 to 5.5; disturbed balance while walking and standing as a main clinical problem stated by the patient and not primarily explained by muscle weakness, ataxia, or spasticity (as assessed by a clinical examination by an experienced physiotherapist); the ability to walk without assistive device for at least 150 m in 3 minutes; and the ability to perform barefoot, free, open-eye quiet standing for 30 seconds. Exclusion criteria were relapse or corticosteroid therapy in the past 3 months, newly prescribed medication with dizziness as a potential adverse effect in the 4 weeks prior to participation, cognitive deficits interfering with direct communication, and the presence of other pathology causing alterations in the locomotor system or balance. Age- and sex-matched healthy controls were recruited from the hospital staff. Written informed consent was obtained from all participants.

Clinical and demographic data of people with MS were obtained from their electronic medical records. All patients were examined following standardized protocols during the first 2 days after hospital admission by a multidisciplinary team, including physicians, physiotherapists, and occupational therapists. All people involved in the conduct and analysis of the study had long-term experience in the diagnosis and treatment of people with MS.

The study was conducted at the Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gemeinnützige GmbH (Germany) in accordance with the Declaration of Helsinki and all applicable regulations. The protocol was approved by the ethics commission of the Bayerische Landesärztekammer (Bavarian Medical Association) in December 2019, and the study was registered at the German Clinical Trials Register (file number DRKS00018076).

Participants with MS had a familiarization session the day before testing to prevent fatigue, to ensure that they would be able to walk safely on the treadmill, and to set a comfortable walking speed. For Cs, familiarization was performed on the day of testing, half an hour before the experimental procedures. The experimental setup is described in 

The Stability Easy force plate (TechnoBody) was used to assess balance control. This rehabilitation training and testing device combines a highly sensitive force plate with an advanced software system for interpretation. Participants were instructed to fix their gaze on a black screen with a white cross, placed in front of them at eye level, while standing along the lines drawn on the plate in a V shape (malleolus medialis is always placed along the central line, coinciding with the axis of movement of the plate). They were asked to perform the standing task in 3 conditions: (1) quiet, standing with eyes open (30 seconds); (2) quiet, standing with eyes open combined with a left head turn at the fifth second and back to the center 3 seconds later until the end of the test (total time: 30 seconds), and (3) same parameters as condition (2), except with a right head turn. Signals were given acoustically (Figure 1B).

Participants were asked to walk on a treadmill (quasar med 50; h/p/cosmos) while secured with a harness and attached to a secure strap. All participants walked at a self-selected comfortable walking speed.

A motion capture system was used for 2-dimensional video recordings. Cameras were placed on the lateral left (Sony Alpha a6400 camera, 120 frames, ISO 100) and dorsal (Nikon 1 J5 camera; 60 frames; ISO 160) while LED-markers (LED-M, Kinetae) were placed on anatomical landmarks of the lower limb (metatarsi-V distal, malleolus lateralis, dorsal calcaneus, lateral knee [interarticular space], lateral thigh [under trochanter major in the line with knee and trunk], second thoracic vertebra [Th2], first sacral vertebra [S1]).

Walking speed was assessed the day before in a training session for people with MS to prevent fatigue, and on the test day, half an hour before testing, for Cs. Individual walking speed remained consistent throughout the trial. Before the video recording, a short warm-up was done for a maximum of 2 minutes until participants said they felt balanced and secure while walking. The experimental procedure consisted of a walking period (unperturbed) followed by walking after head rotations. Participants heard an audio signal, a beep, which instructed them to turn their head. The beep was verbally supported with 

. The first turn was left, and the second turn was right (Figure 1).

Each participant performed the complete standing task 2 times, of which the first execution was analyzed and the second served as a backup in case of inadequate adherence or technical errors.

Balance parameters from the force plate were calculated by the force plate software (ProKin 252 Stability E, TechnoBody, Italy) using the Romberg test application. The displacement of the center of pressure (COP) was used such that COP velocity (mm/s) and area 95% (mm

) provided mean values and a maximum and minimum for each condition for the full length of 30 seconds. The parameters COP displacement (COPd), antero-posterior velocity, and medio-lateral velocity were subjected to statistical analysis.

Raw temporal data from the 3-foot-LEDs were obtained from the video recordings and analyzed using the open-source software Kinovea version 0.9.1 and Microsoft Excel. The LED profiles from the forefoot and the heel were superimposed, so that the time span between maximum and minimum (points of movement inversion) could be read, showing the different gait phases. The initial swing was provided by the forefoot and the initial contact and midswing by the heel, resulting in a stance and a swing phase. The swing phase was further divided into 2 periods, early and late, identified by the turning point at maximal heel speed. A gait cycle was defined as the time span between 2 consecutive initial contacts of the heel of 1 leg, referred to as stride time, and was calculated in milliseconds. Gait phases were given in percentages.

Stride time was the primary outcome measurement, on the assumption that small perturbations could be overcome by adapting phases without the need to change stride time periodicity. The relation between stride times and gait phases provided an idea of the degree of imbalance experienced; the use of adaptive strategies was a secondary outcome. Only the first trial for each HR was analyzed.

For the standing condition, a nonparametric test was used, since values were not normally distributed. A 2-factor analysis of variance with Friedman ranks was used for intragroup analysis, and the Wilcoxon-Mann-Whitney U test was used for intergroup analysis using a pairwise comparison. SPSS (IBM) was used for statistical analysis, as the SPSS Friedman test permitted the analysis of more than 2 time points simultaneously.

For the walking condition, a mixed model for repeated measurements was run via the JMP Pro 15 (SAS Institute) software, with a random effect of subjects in the model. The fixed variables were baseline values given in means and the 10 strides after HR, starting from the first initial contact after completion of the HR.

People with MS and Cs were analyzed separately for the comparison between baseline and perturbed conditions and time points. Afterward, an intergroup comparison of the overall means was done. The mean of the strides from 20 seconds of unperturbed walking was compared with: (1) each one of the 10 following strides (10-fSt) after left and right head rotation (post HRL/post HRR); (2) the mean of the 10-fSt; and (3) between the 10-fSt for the intragroup analysis.

Hypotheses were tested using a hierarchical testing model based on the work of Bauer et al.

 Three test levels were given. For detailed information about the hierarchical testing model, see 

 values for stance and gait parameters were corrected with the Bonferroni correction where applicable. Group-level data are presented as means, SDs, and 95% CIs at a significance level of a less than or equal to .05.

Demographic and clinical data for the 10 Cs and 18 people with MS included in the experimental procedures are shown in 

. Two people with MS were unable to adapt to the treadmill and were excluded after the familiarization session.

Comparison of Balance Tasks at Baseline and After Head Rotation

Intergroup analysis showed that people with MS and Cs differed in baseline values. During still stance, people with MS showed significantly larger COPd and increased anteroposterior velocities than Cs. Furthermore, people with MS performed worse than Cs for all test parameters during the conditions with HR.

Intragroup analysis of people with MS showed a significantly increased COPd and mediolateral velocity for the turn with right HR and a trend toward an increased COPd during the standing condition with the turn with HR left compared with baseline, whereas Cs showed no significant decline in performance. See 

Comparison of Gait at Baseline and After Head Rotation

Compared with Cs, people with MS showed significantly longer stride times while walking normally, with proportionally longer support and shorter swinging phases by a reduction in the relative time span between initial swing and mid swing. This was maintained post HRL and post HRR. Intragroup analysis revealed that people with MS shortened their stride times post HRL, whereas Cs maintained them. Both groups showed an increase in relative time of stance phase post HRL and post HRR, which was more pronounced for Cs (

 .0001) and less so for people with MS, reaching significance post HRL (

Stride-to-Stride Analysis After Head Rotation While Walking

A 1-to-1 stride analysis showed significantly shorter stride times for the first 3 strides post HRL (for stride 1 

 .02) in people with MS compared with baseline values. In contrast, the shortening of strides after HR was much less pronounced, and only the first stride post HRL was significantly shorter in Cs (

In people with MS, stride-1 post HR differed from all other strides, with the shortest stride time. The first stride post HRL differed from all other strides (

≤.02), and the first stride post HRR differed from baseline and strides 4 to 10 (

Left strides 2 and 3 showed no difference in stride time to the following strides after Bonferroni correction (significant value, 

≤ .005), while rightstride-2 had a shorter stride time compared with stride 6 (

.0001), and right stride-3 to stride-10 (

In addition, in people with MS, stride 2 and stride 3 post HRL had relatively longer stance phases in relation to baseline (

.005) and a relatively longer stance phase and shorter swing phase compared with stride-1 (

In Cs, a 1-to-1 stride analysis showed that the first step post HRL was the only step to differ significantly from baseline with a shortened stride time (

 .0031) and increased relative swing time (

 .033). No other differences could be seen.

Nikos Evangelou, DPhil

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