Assessment of patients with multiple sclerosis according to tests of the Multiple Sclerosis Functional Composite

Introduction: The Multiple Sclerosis Functional Composite (MSFC) is a scale that evaluates the functional and cognitive aspects of patients with multiple sclerosis (MS). Objective: To compare the performance of individuals with the relapsing-remitting form of MS (RRMS) with a group of healthy subjects using the MSFC. Methods: Twenty subjects were investigated in this study, consisting of 10 patients with clinical diagnosis of RRMS and 10 controls with similar gender and age to the group with the disease. The three tests that comprise the MSFC were used for the evaluation of gait, upper limb motor function and cognition (memory and processing speed). Student's t-test was used to assess data with normal distribution and data with skewed distribution were evaluated using the Mann-Whitney test. Results: The results showed that the patients with RRMS took longer to perform the locomotion test (6.91 ± 2.35) compared to the control group (5.16 ± 1.28). The MS group (22.06 ± 5.44) also showed greater dif iculty in performing a task with the dominant upper limb compared to the healthy subjects (17.79 ± 2.96). No statistically signi icant difference was found between the groups in the performance of cognitive tasks (p = .65). Conclusion: The use of the MSFC tests proved valuable for measuring possible motor and cognitive impairments in patients with RRMS. Thus, it is *AIF: MS, e-mail: aneliseif@gmail.com CRNP: Doctoral Student, e-mail: carlinha_polachini@hotmail.com ALCP: PhD, e-mail: analucia459@hotmail.com


Introduction
Multiple sclerosis (MS) is an in lammatory autoimmune disease characterized by demyelinating lesions in the central nervous system (CNS), which has a slow and progressive course with periods of remission and exacerbation of the neurologic symptoms (1,2).It can affect motor, sensory, cerebellar, cognitive, sphincter and spinal cord areas (3).
Multiple sclerosis predominates in young adults, affecting them in the productive phase of their professional life, with the incidence being higher in females and it often being a disabling disease (4,5).Studies show that in Brazil, the prevalence is 15 cases per 100 thousand inhabitants, being more frequent in the south and southeast of the country (6,7).
According to the symptomatology and clinical indings, there are four subtypes of MS: relapsing-remitting, secondary-progressive, primary-progressive and progressive-relapsing (8).The relapsing-remitting form is present in about 80% of cases, characterized by relapses with new or worsening of symptoms, interspersed with periods of complete or partial remission of symptoms between the relapses (9).
Normally, this disease starts as a relapsing-remitting process and evolves into a secondary-progressive phase with the accumulation of disabilities (10).In the remaining cases, it assumes a progressive form from the beginning, with these patients presenting a progressive course of disabilities (11).
Although the etiology of MS remains unknown, currently, it is believed there is an in luence from immune, genetic and environmental factors (12).Due to the diffuse character of the formation of the demyelinating plaques, the clinical manifestations are determined by the location of the lesions and are highly variable, including gait and sensory disturbances, spasticity, visual de icits, fatigue, bladder disorders, motor incoordination, and cognitive changes, such as slower information processing (13).Thus, these changes may limit people with MS in the performance of their daily activities, as well as remove them from social life (14,15).
The therapy used is individualized, with this having different objectives, dependent upon the clinical signs presented by each patient.Pharmacological treatment is accomplished through the use of anti-in lammatory, immunomodulatory and immunosuppressive medications (16).In addition, multidisciplinary rehabilitation programs also represent an important non-pharmacological approach used with these patients (17).This multidisciplinary treatment aims to improve the performance of people with MS in their activities of daily living (ADLs), to maximize functional abilities, as well as to prevent the onset of disability, thus improving their quality of life (18).
The instruments available to conduct clinical evaluations present a constant challenge due to the large variability between periods of disability and improvement of the symptoms that this disease causes, making it dif icult to quantify them in the neurology practice (19).Thus, some neurological scales, such as: the Expanded Disability Status Scale (EDSS) and the Ambulatory Index (AI) have been used to verify the changes that MS patients present.However, these scales have many problems and limitations, including: the fact that they are long for clinical application, have ordinal and not interval measures and the areas evaluated emphasize aspects related to physical disabilities, ignoring cognitive functioning (20).
In an attempt to accompany the evolution of the clinical condition in a simpli ied and standardized way, the National Multiple Sclerosis Society (NMSS) of the USA developed a scale known as: the Multiple Sclerosis Functional Composite (MSFC) which measures the main disabilities found in patients with MS in a multidimensional way (21).The MSFC evaluates ambulation, upper limb function and cognitive aspects through tests encompassing the three main domains affections by this disease (22,23).Thus, this scale has been considered superior to others, due to its ease of application and the reliability of the results obtained (24).
In the search for alternatives to assess the main de icits and the evolution of the condition of patients with MS, this study aimed to compare the performance of individuals with the relapsing-remitting form of multiple sclerosis with healthy subjects in the functional and cognitive tasks required by the MSFC, seeking, through these tests, to ind the main neurological compromises of MS patients in the remission phase.

-Study design
This study was characterized as a prospective, cross-sectional study, with quantitative data analysis.

-Ethical aspects
The evaluation methods and intervention protocols used in this study are in accordance with the requirements of Resolution No. 196/96 of the National Health Council on research involving human subjects and were approved by the Research Ethics Committee of the Federal University of Santa Maria under authorization No. 00731012.5.0000.5346.All participants voluntarily signed the Informed Consent form prior to performing the tests, with it being clear that they could withdraw from participation at any time, without prejudice.

-Subjects
The sample consisted of 20 individuals.The initial group consisted of 15 patients with MS, however, 5 were excluded because they did not meet the inclusion criteria.Individuals who were clinically diagnosed as being in the progressive phase of the disease were excluded from the study.The subjects with the disease included in the study had to be able to move around by walking, have comprehensive language and have no visual impairment that would prevent the tests, all patients had to be in the remission phase.Thus, 10 patients with clinical diagnosis of relapsingremitting type Multiple Sclerosis from the rehabilitation program of the University Hospital of Santa Maria/RS Physiotherapy Service, in the period June to September 2012, and 10 healthy volunteers, as the control group, were selected for this study.
Participants were divided into two groups: the MS Group: composed of patients with the relapsingremitting form of the disease, of both genders, aged 12 to 50 and the Control Group: composed of healthy volunteers, with genders and ages the same or similar to the MS group.
-Experimental procedure Prior to testing, the participants answered some questions regarding: the stage of the disease, its onset, frequency of relapses, main symptoms, use of pharmacological therapy and of other forms of treatment therapies.Next, the Multiple Sclerosis Functional Composite Measure (MSFC) was applied, which consists of three tests: Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Task (25,26,19).median and interquartile range (p 25 -75).Data with normal distribution were analyzed using the paired Student's t-test and those with asymmetric distribution were analyzed using the Mann-Whitney test.All results were considered signi icant when p < .05

Results
Table 1 presents the general characteristics of the subjects with MS.It was observed that MS predominantly affected females between the aged of 13 and 50 years.The majority of the patients had a mean of 3 relapses per year, had the diagnosis for a mean of 6.2 ± 4.0 years, with the use of glatiramer acetate being prevalent for the treatment in this population.The results of the gait assessment test revealed that the MS group presented signi icant impairment in locomotion (6.91 ± 2.35, p < .05)compared to the control group (5.16 ± 1.28, p < .05)(Figure 1).Importantly, there was no signi icant difference for the people with MS when comparing the locomotion times of the irst and the second attempt (p = .73).
For the evaluation of the gait, the Timed 25-Foot Walk was used, a test that consists of a mark at a distance of 7.62 meters (25 feet), each 1 foot = 30.48cm, with the individual being encouraged to walk as fast as he/she could without running, over two attempts.A stopwatch is used to measure the time, which is expressed in tenths of a second, this task was carried out in the corridor of the University Hospital of Santa Maria (HUSM) Physiotherapy Service.
Subsequently, the 9-Hole Peg Test was applied, which assesses the motor function of the upper limbs.For the performance of this test a wooden kit was made in the carpentry workshop of the UFSM Arts Center, which consists of a board with nine holes in which nine pins can be inserted, one by one.On the side of the board there is a space to store all the pins at the beginning and end of the evaluation.The place where the pins are stored faces the hand that will be tested, with the row of holes facing the hand that is not being tested.Primarily, two evaluations are performed with the dominant hand and then two evaluations with the non-dominant hand.The participant is encouraged to put the pins in the holes as fast as possible, with the timer being started when the irst pin is taken.Each pin should be placed in a hole in any order and then each pin is returned, one by one, to the place where they are stored, whereupon the clock is stopped.
Finally, the Paced Auditory Serial Addition Task (PASAT) was applied, which veri ies the cognitive impairment and involves memory and processing speed tasks.In this scale, this test is applied twice, irst with intervals of 3 seconds between the stimuli and secondly with intervals of 2 seconds.The stimuli were given by the researcher in a loud and clear voice.Numbers from one to nine are presented in a random and pre-determined sequence.The task is to sum the numbers presented, in pairs, disregarding the result of the calculation, therefore, if the string is "4, 3, 6, 2 and 1" the correct answer is "7, 9, 8 and 3".The test was administered in a quiet room without visual or auditory stimuli, with only the subject and the examiner present in the room.At irst a version with 10 items for training was presented.When the participant demonstrated dif iculty in understanding, a demonstration in writing was performed with the series of number.

-Statistical analysis
The GraphPad Prism software was used.Data are expressed as mean ± standard deviation (SD) or it is important to note that some patients were only able to carry out the irst stage of the test, in which an interval of 3 seconds is given between the stimuli.When summing of the number of correct responses in the 3" and 2" tests, no signi icant difference was detected between the study participants (p = .65)(3c).3a.Regarding the upper limbs test, a signi icant decline in function was observed in the MS group, as these patients took longer to perform the task with the dominant upper limb (22.06 ± 5.44) compared to the control group (17.79 ± 2.96) (Figure 2). Figure 3 shows the results of the test that assessed the memory and cognition of the participants.As can be observed, there was no signi icant difference after a 3 second interval (p = .75)(3a), nor in the performance of the test after 2 seconds (p = .23)(3b), between the MS patients and the healthy individuals.Furthermore,

Discussion
This study aimed to investigate the functionality and cognitive performance of MS patients, through the MSFC test, and to compare their performance with a group of healthy subjects.Even though the sample to which the tests of this scale were applied was small, it was found that the patients with RRMS presented de icits in gait and upper limb motor function when compared to the control group.However, both groups showed the same performance in the cognitive function test.
In this study 80% of the sample consisted of women with a mean age of 40 years.These data corroborate the reports in the literature that show multiple sclerosis presents in higher proportions among women (27,28), at around 40 years of age (29).In addition, there are a large number of studies showing that the relapsing-remitting form is the most prevalent form (30), consequently, all the patients in this study were in this phase, characterized by complete recovery of symptoms, however, in some cases leaving residual sequelae (31).
Among the key indings, it should be noted that the MS group needed more time to perform the walking test, Timed 25-Foot Walk, when compared with the control group.This behavior shows that, even in a symptom remission phase, patients present impairment in the gait.This dif iculty in the individuals with MS may have been due to fatigue, muscle weakness and/or spasticity, or a combination of these factors.It is suggested that being slower to complete the proposed test might be due to some post-relapse residual de icit.
Fatigue may have been the main cause of the decline in the function of the lower limbs, considering that it is one of the most common and disabling symptoms in MS, affecting about 50 to 60% of patients (32).It is regarded as the most disabling symptom, when compared to spasticity and muscle weakness (33).According to Mendes et al. (34) in patients with neurological diseases, fatigue is different from that reported in other diseases, because in these cases it leads to greater impairment of the quality of life, causing dif iculty in the performance of work activities and eventually leading to social isolation, with this symptom being very relevant to the general condition of the patients.These authors also claim that, in MS this feeling of fatigue is often associated with a degree of persistent disability and, although it is chronic, the fatigue luctuates in intensity, being more intense in the late afternoon and at elevated temperatures (34).
Importantly, in patients with MS the fatigue that arises is possibly of multifactorial origin (central and/or peripheral) and is related to immune and central changes, inability to maintain a central impulse for spinal motor neurons due to demyelination, lack of physical conditioning and changes in the neuromuscular plate (35).In addition, in studies conducted by Solari et al. (36) it was observed that people with MS presented dif iculties in the learning process to carry out the task required in the Timed 25-Foot Walk, therefore, this may be an effective test to monitor the progress of patients, since the results of the present study show that in the relapsing-remitting phase there is already a signi icant reduction in the walking speed of MS patients when compared with healthy subjects.
In this study it was also observed that MS patients required a longer time to perform the upper limb functional test compared to the control group.This result may be due to the presence of demyelinating plaques in the cerebellum, which leads to a decrease in motor function resulting in dif iculty to perform tasks that require more manual dexterity.The motor de icit may impair the performance of movements of the upper members and hinder the execution of ine motor skills (37).
Regarding cognition, the results of this study showed no signi icant difference between the groups in the test that evaluated this parameter.The failure to ind a signi icant difference between the groups may suggest that the scale used is sensitive to the location of the demyelinating plaques, and that the evaluated subjects had greater impairment at the spinal cord level.Corroborating this hypothesis, Moreira et al. (38) found in their study that the most common evolutionary symptoms in the relapsing-remitting form were spinal cord symptoms (75.9%).In addition, many MS patients tend to present more cognitive deterioration when they are in the progressive phase of the disease (39).

Conclusion
Based on the results obtained in this study, it was concluded that MSFC was sensitive to evaluate the functional performance in subjects with the relapsing-remitting form of MS when compared with healthy subjects.Regarding the cognitive aspect, in addition to the tasks involving memory and processing speed, it is believed that other tests should be added to better assess this parameter.However, the MSFC, due to its ease of application, can be replicated and used in the clinic to monitor the progress of the disease, thus prioritizing the individual needs of each patient and optimizing the treatment proposals.

Figure 1 -
Figure 1 -Timed 25-Foot Walk for the MS and control groups.Values represented in median with interquartile range (P25-P75).*represents a significant difference from the control group (Mann-Whitney test, p < .05n = 10).

Table 1 -
General characteristics of the study participants