Nedeljkovic et al. 2016

Multidisciplinary rehabilitation and steroids in the management of multiple sclerosis relapses: a randomized controlled trial

Serbia

RCT

PEDro=5

N_Initial=49, N_Final=37

Population: Intervention Group (IG; n=17): Mean age=41.3yr; Gender: males=6, females=11; Disease course: RRMS; Mean EDSS=4.5; Mean disease duration=104.5mo. Control Group (CG; n=20): Mean age=39.4yr; Gender: males=5, females=15; Disease course=RRMS; Mean EDSS=4.0; Mean disease duration=80.6mo.

Intervention: Subjects were randomized to a multidisciplinary inpatient rehabilitation program (IG) or standard care (CG) after receiving intravenous methylprednisolone (1g/d, 5d). Rehabilitation was comprised of physiotherapy (1h/d, 5d/wk) and occupational therapy (30min/d, 3d/wk) for a total of 3wks. Outcomes were assessed at baseline, 1mo, and 3mo.
 Primary Outcome Measures: Not specified.

Quality of Life Outcome Measures: Multiple Sclerosis Quality of Life-54 (MSQoL-54).

Other Outcome Measures: Functional Independence Measure (FIM); EDSS; Beck Depression Inventory (BDI). 

1. On the MSQoL-54 at 1mo, the intervention group showed significantly greater improvement on the ‘physical role limitations’ subscale than the control group (p=0.015).
2. On the MSQoL-54 at 3mo, the intervention group showed significantly greater improvement on the ‘physical role limitations’ (p=0.016), ‘emotional role limitations’ (p=0.010), and ‘mental health composite’ (p=0.017) subscales than the control group.

Rietberg et al. 2014

Effects of multidisciplinary rehabilitation on chronic fatigue in multiple sclerosis: a randomized controlled trial

The Netherlands

RCT

PEDro=7

N_Initial=48, N_Final=44

Population: Multidisciplinary outpatient rehabilitation (MDR) group (n=23): Mean age=45yr; Gender: males=9, females=14; Disease course: RRMS=16, PPMS=2, SPMS=5; Median EDSS=3; Mean disease duration=7yr. Nurse consultation (NC) group (n=25): Mean age=47yr; Gender: males=8, females=17; Disease course: RRMS=12, PPMS=6, SPMS=7; Median EDSS=4; Mean disease duration=8yr.

Intervention: MS patients with chronic fatigue were randomized to MDR or to MS-NC groups. Assessments were performed at baseline and after intervention.
 Primary Outcome Measures: Checklist Individual Strength (CIS-20R).

Quality of Life Outcome Measures: Disability and Impact Profile (DIP).

Other Outcome Measures: Functional Independence Measure (FIM); MS Impact Scale (MSIS-29); Impact on Participation and Autonomy (IPA); Modified Fatigue Impact Scale (MFIS); Fatigue Severity Scale (FSS).

1. At 12–24wks, the DIP subscale “symptoms” showed a significant difference in favour of the MDR group (p=0.03). 
2. No significant within-group effects were found for multidisciplinary rehabilitation or nurse consultation with respect to the primary and secondary outcome measures from baseline to 12 or 24wks.

Salhofer-Polanyi et al. 2013

Benefits of inpatient multidisciplinary rehabilitation in multiple sclerosis

Austria

RCT

PEDro=5

N_Initial=21, N_Final=19

Population: Intervention Group (n=10): Mean age=53.8yr; Gender: males=5, females=5; Disease course: RRMS=2, PPMS=2, SPMS=6; Median EDSS=6; Mean disease duration=17.6yr. Control Group (n=9): Mean age=52.9yr; Gender: males=3, females=6; Disease course: RRMS=2, SPMS=7; Median EDSS=5.5; Mean disease duration=15.9yr.

Intervention: Subjects were randomized to a multidisciplinary inpatient rehabilitation program (intervention) or a waiting list (control). Rehabilitation was provided 5d/wk with 4-5 sessions/d, for a total of 3wks. Outcomes were assessed at baseline and after 15wks.
 Primary Outcome Measures: Timed 50m Walk (T50MW); 2-min Walk Test (2MW); 6-min Walk Test (6MW); Walking Speed.

Quality of Life Outcome Measures: Functional Assessment in Multiple Sclerosis (FAMS).

Other Outcome Measures: EDSS; Rivermead Mobility Index (RMI); Berg Balance Scale (BBS); Tinetti Test (TT); MS Functional Composite: 9 Hole Peg Test (9HPT), Timed 25ft Walk (T25FW), Paced Auditory Serial Addition Test (PASAT); MS Self-Efficacy Scale (MSSE); Global Clinical Impression Scale (GCIS).

1. There was no significant difference between the intervention group and the control group in mean improvement on the FAMS (+7.5 vs. +3.5, p=0.372) after treatment.

Khan et al. 2010

A randomised controlled trial: outcomes of bladder rehabilitation in persons with multiple sclerosis

Australia

RCT

PEDro=9

N_Initial=74, N_Final=58

Population: Treatment group (n=24): Mean age=49.9yr; Gender: males=9, females=15; Disease course: RRMS=6; PPMS=4; SPMS=14; EDSS: 0-3=5, 3.5-6.0=9, 6.5 or greater=10; Mean disease duration=12.2yr. Control group (n=34): Mean age=51.1yr; Gender: males=5, females=29; Disease course: RRMS=14, PPMS=4, SPMS=16; EDSS: 0-3=9, 3.5-6.0=21, 6.5 or greater=4; Mean disease duration=10.0yr.

Intervention: Patients were randomized to either the intervention group where they received a multifaceted, individualized, bladder rehabilitation programme, or to the control group (no intervention). Ten participants randomized to control group required some treatment during the study.

Primary Outcome Measures: Urogenital distress inventory (UDI6); Incontinence impact questionnaire (IIQ7).

Quality of Life Outcome Measures: Incontinence impact questionnaire (IIQ7); AUA Symptom Index.

Other Outcome Measures: Guy’s Neurological Disability Scale (GNDS – bladder subscale only). 

1. In comparison to the control group, the treatment group showed statistically significant within-group differences in IIQ7 (p<0.001) change scores before-and-after treatment. The effect size was large (0.5 or greater), as per Cohen’s criteria.
2. In the control group, a larger proportion of patients deteriorated compared to the treatment group as measured by the IIQ7 (ϰ²=14.47, df=2, p=0.001) scores.
3. There were statistically significant differences in change scores between the treatment and control groups with respect to the AUA total and AUA Quality of Life scores (all p<0.001). The effect sizes of these differences in change scores were large (0.5 or greater), as per Cohen’s criteria.
4. In the treatment group, within-group differences in AUA total scores from baseline to post-treatment were statistically significant (p=0.03); this was indicated by higher symptom levels at baseline compared to post-treatment. 

Khan et al. 2008

Effectiveness of rehabilitation intervention in persons with multiple sclerosis: a randomised controlled trial

Australia

RCT

PEDro=8

N_Initial=101, N_Final=98

Population: Treatment Group (n=49): Mean age=49.5yr; Gender: males=18, females=31; Disease course: RRMS=13, PPMS=7, SPMS=29; EDSS: 0-3=7, 3.5-6.0=27, 6.5+=15; Mean disease duration=10.69yr. Control Group (n=52): Mean age=51.1yr; Gender: males=11, females=41; Disease course: RRMS=18, PPMS=7, SPMS=27; EDSS: 0-3=12, 3.5-6.0=32, 6.5+=8; Mean disease duration=9.73yr.

Intervention: The treatment group underwent multidisciplinary rehabilitation and received either individualized patient (IP) or outpatient (OP) rehabilitation. IP rehabilitation: 3-6wks, 3 or more times/wk, 3h therapy/d, 2 blocks of 45min physiotherapy and occupational therapy with other blocks comprised of speech pathology, neuropsychology and social work. OP rehabilitation: Up to 6wks, 2-3times/wk, 30min sessions for physiotherapy, occupational therapy, social work and speech pathology in addition to doing stretching home exercises. The control group received no intervention, only an 8 weekly monitoring phone call for information about medical hospital visits in the previous month and received no other information.
 Primary Outcome Measures: Functional Independence Measure (FIM) motor subscale.

Quality of Life Outcome Measures: General Health Questionnaire (GHQ-28).

Other Outcome Measures: Multiple Sclerosis Impact Scale (MSIS-29).

1. There were no differences between the treatment and control group scores on the GHQ-28.

Storr et al. 2006

The efficacy of multidisciplinary rehabilitation in stable multiple sclerosis patients 

Denmark

RCT

PEDro=8

N_Initial=106, N_Final=90

Population: Control group (n=52): Mean age=50.1yr; Gender: males=16, females=36; Disease course: RRMS=12 (23%), PPMS=11 (21%), SPMS=29 (56%); Median EDSS=6.5; Median disease duration=9.0yr. Intervention group (n=38): Mean age=53.0yr; Gender: males=16, females=22, Disease course: RRMS=5 (13%), PPMS=9 (24%), SPMS=24 (63%); Median EDSS=6.5; Median disease duration=9.0yr.

Intervention: Individuals were randomized either to the control group and received no rehabilitation treatment, or to the intervention group and received rehabilitation treatment from the MS rehabilitation hospital in Haslev Denmark.

Primary Outcome Measures: Functional Assessment in Multiple Sclerosis (FAMS). 

Quality of Life Outcome Measures: FAMS; Life Appreciation and Satisfaction Questionnaire (LASQ).  

Other Outcome Measures: Guy’s Neurological Disability Scale (GNDS); Multiple Sclerosis Impairment Scale (MSIS); EDSS; Visual Analog Scale for symptoms (VAS); 10 meter walk test (TW10); Nine-Hole Peg Test (9HPT). 

1. No significant difference was found between the control and the intervention groups on any of the outcome measures.

Craig et al. 2003

A randomised controlled trial comparing rehabilitation against standard therapy in multiple sclerosis patients receiving intravenous steroid treatment

UK

RCT

PEDro=5

N_Initial=41, N_Final=40

Population: Control group (n=20): Mean age=42yr; Gender: males=4, females=16; Disease course: active relapsing; Mean EDSS=5.1; Mean disease duration=5.69yr. Intervention group (n=20): Mean age=38yr; Gender: males=9, females=11, Disease course: active relapsing; Mean EDSS=5.4; Mean disease duration=7.42yr.

Intervention: All MS participants were randomized to either the control group and received standard ward routine care and 3d of intravenous methylprednisolone (IVMP), or to the intervention group and received planned coordinated multidisciplinary team treatment and 3d of IVMP. Participants were assessed at baseline upon receiving IVMP treatment, at 1mo and at 3mo after the first day of IVMP.

Primary Outcome Measures: Guy’s Neurological Disability Scale (GNDS); Amended Motor Club Assessment (AMCA).

Quality of Life Outcome Measures: 36-Item Short Form Health Survey (SF-36). 

Other Outcome Measures: Barthel Index (BI); Human Activity Profile (HAP).

1. Changes in SF-36 scores did not differ between groups from baseline to 3mo.

Patti et al. 2002

The impact of outpatient rehabilitation on quality of life in multiple sclerosis 

Italy

RCT

PEDro=8

N_Initial=111, N_Final=111

Population: Outpatient rehabilitation (n=58): Mean age=45.2yr; Gender: males=24, females=34; Disease course: PPMS or SPMS; Mean EDSS=6.2; Mean disease duration=17.2yr. Home exercise (n=53): Mean age=46.1yr; Gender: males=23, females=30; Disease course: PPMS or SPMS; Mean EDSS=6.1; Mean disease duration=17.2yr.

Intervention: Patients were randomized to a comprehensive rehabilitation program and a home exercise group. The patients in the comprehensive rehabilitation group received an individualized, goal-oriented program involving an interdisciplinary team, addressing a wide range of areas for 6wks (6x/wk) and a home exercise program for a further 6wks. The home exercise group received the home exercise program for 12wks. Both groups were assessed at baseline and at 12wks.

Primary Outcome Measures: 36-Item Short Form Health Survey (SF-36); EDSS. 

Quality of Life Outcome Measures: SF-36.

Other Outcome Measures: Fatigue Impact Scale (FIS); Social Experience Tempelaar Checklist (SET); Beck Depression Inventory (BDI).  

1. All health related quality of life domains of the SF-36 improved significantly in the rehabilitation group (p<0.001 in physical functioning, role physical, bodily pain, general health, social functioning; p<0.05 in vitality, role emotional, mental health).

Pozzilli et al. 2002

Home based management in multiple sclerosis: results of a randomised controlled trial

Italy

RCT

PEDro=5

N_Initial=201, N_Final=188

Population: Intervention group (n=133): Mean age=47yr; Gender: males=47, females=86; Disease course: RRMS=26, PPMS=27, SPMS=80; Mean EDSS=6.0; Mean disease duration=18.4yr. Control group (n=68): Mean age=46.7yr; Gender: males=21, females=47; Disease course: RRMS=14, PPMS=14, SPMS=40; Mean EDSS=6.0; Mean disease duration=18.6yr.

Intervention: MS patients were randomized to receive either individually tailored multidisciplinary home-based medical care with regular phone support available 5d/wk (intervention group) or routine care involving multidisciplinary care coordinated through a hospital-based MS centre (control group). Assessments were performed at baseline and at 12mo.
 Primary Outcome Measures: Not specified.

Quality of Life Outcome Measures: 36 item short form health survey questionnaire (SF-36). 

Other Outcome Measures: Functional Independence Measure (FIM); EDSS; Mini-Mental State Examination (MMSE); Fatigue Severity Scale (FSS); State Trait Anger Expression Inventory (STAXI); State Trait Anxiety Inventory (STAI); Clinical Depression Questionnaire (CDQ); cost resource assessment. 

1. The intervention group had a significant improvement in bodily pain (p=0.0001), general health (p=0.0001), social functioning (p=0.001), and role, emotional (p=0.0001) compared to the control group.
2. The intervention group showed more favourable changes than the control group in terms of both physical component score (p=0.0001) and mental component score (p=0.0001) of the SF-36. 
3. The intervention group displayed an improvement in eight SF-36 scales, while the control group had increased scores on four SF-36 scales.  However, the improvement was less consistent than in the intervention group.

Guagenti-Tax et al. 2000

Impact of a comprehensive long-term care program on caregivers and persons with multiple sclerosis

US

RCT

PEDro=5

N_Initial=73, N_Final=59 (patient-caregiver units)

Population: 

Patients (n=59):

Experimental: Mean age=44.0yr; Gender: males=8 (13.3%), females=51 (86.7%); Disease course: CPMS=39 (66.7%); Mean EDSS=7.06; Mean disease duration=8.9yr.

Control: Mean age=49.0yr; Gender: males=18 (31.0%), females=41 (69.0%); Disease course: CPMS=51 (86.2%); Mean EDSS=7.24; Mean disease duration=14.2yr.

Caregivers (n=59):

Experimental: Mean age=44.9yr; Gender: males=43.3%, females=56.7%.

Control: Mean age=51.8yr; Gender: males=48.3%, females=51.7%.

Intervention: Patient-caregiver units were randomized to a comprehensive rehabilitation program or a standard care group. The comprehensive rehabilitation program consisted of 4 coordinated components: 1) twice-monthly medical day-care program, 2) a series of semi-annual workshops for persons with MS and family caregivers, 3) monthly home visits by social workers, nurses, and volunteers, 4) case management and liaison services. Patients and caregivers were assessed at baseline, 12 and 24mo.

Primary Outcome Measures: Not specified.

Quality of Life Outcome Measures: 36-Item Short Form Health Survey (SF-36).

Other Outcome Measures: EDSS; Incapacity Status Scale (ISS); Number of acute hospital admissions; Perceived deficits questionnaire (PDQ); Hopkins Verbal Learning Test (HVLT); Mental Health Inventory (MHI); Sickness Impact Profile (SIP); Revised UCLA Loneliness-Companionship Scale; Questionnaire on Resource and Stress (QRS); Satisfaction with care; Length of stay.

1. A significant interaction was found on the SF-36 general health subscale, with the control patient group and their caregivers reporting significantly greater decline in perceived health compared to the rehabilitation group (p=0.039, p=0.01).
2. Control patients reported significantly greater satisfaction with getting help with their daily routine compared to the rehabilitation patients (p=0.004).

Pappalardo et al. 2016

Inpatient versus outpatient rehabilitation for multiple sclerosis patients: Effects on disability and quality of life

Italy

RCT – Pre-Post for Quality of Life analyses

PEDro=6

N_Initial=146, N_Final=146

Population: Group A outpatient (n=49): Mean age=48.0yr; Gender: males=18, females=31; Disease course: PPMS=18, SPMS=31; Mean EDSS=6.5; Disease duration: unspecified. Group B inpatient (n=49): Mean age=46.0yr; Gender: males=17, females=32; Disease course: PPMS=17, SPMS=32; Mean EDSS=6.5; Disease duration: unspecified. Group C control (n=48): Mean age=45.0yr; Gender: males=18, females=30; Disease course: PPMS=18, SPMS=30; Mean EDSS=6.4; Disease duration: unspecified.

Intervention: MS patients were randomized to three groups: the outpatient treatment group (Group A), the inpatient treatment group (Group B) and the control waiting list (Group C). Assessments were performed at baseline (T0) and at 6mo follow-up (T1).
Primary Outcome Measures: Functional Independence Measure (FIM).

Quality of Life Outcome Measures: 36-Health Survey Questionnaire (SF-36).

Other Outcome Measures: None.

1. Significant intragroup differences in SF-36 were observed at T1 compared to T0 only in Group A. In particular, the most significant change was found in physical role functioning (p<0.0001), vitality (p<0.0001), social role functioning (p<0.0001) and mental health (p<0.0001).
2. The authors did not conduct inter-group analyses for the SF-36.

Bjerre et al. 2011

Self-reported changes in quality of life among people with multiple sclerosis who have participated in treatments based on collaboration between conventional healthcare providers and CAM practitioners

Denmark

PCT

N_Initial=173, N_Final=142

Population: Intervention group (n=142): Mean age=51.1yr; Gender: males=46, females=96; Disease course: RRMS=47, PPMS=21, SPMS=65; Mean EDSS=5.5; Mean disease duration=16.2yr. Comparison group (n=142): Mean age=52.1yr; Gender: males=54, females=88; Disease course: RRMS=52, PPMS=13, SPMS=72; Mean EDSS=5.2; Mean disease duration=17.1yr.

Intervention: MS patients were treated with combined interventions by a team of 5 healthcare practitioners and 5 complementary and alternative medicine practitioners for 18mo. A comparison group treated with conventional therapy was included as a control. Assessments were performed before and after the intervention. 
 Primary Outcome Measures: Functional Assessment of Multiple Sclerosis (FAMS).

Quality of Life Outcome Measures: FAMS.

Other Outcome Measures: None. 

1. The average change in FAMS total score was significantly different in the intervention group compared to the comparison group (p<0.01). People with MS in the intervention group experienced an increase in quality of life whereas patients in the comparison group experienced a decrease in quality of life.
2. The intervention group and the comparison group differed in terms of change scores for the following FAMS subscales, when measured over the period of 18mo: emotional well-being, thinking/fatigue.
3. No significant difference was found in terms of change scores on the other FAMS subscales: mobility, symptoms, general contentment, family/social well-being.
4. Treatment group allocation was significant in all analyses when confounding factors were accounted for (gender, age, EDSS, diagnosis).

Vikman et al. 2008

Effects of inpatient rehabilitation in multiple sclerosis patients with moderate disability

Sweden

Pre-Post

N_Initial=58, N_Final=58

Population: Cohort A (n=40): Mean age=56.3yr; Gender: males=8, females=32; Disease course: RRMS=2, PPMS=15, SPMS=21, unclassified=2; Mean EDSS=5.8; Mean disease duration=20.4yr. Cohort B (n=18): Mean age=54.7yr; Gender: males=4, females=14; Disease course: PPMS=4, SPMS=14; Mean EDSS=5.6; Mean disease duration=17.0yr.

Intervention: MS patients with moderate disability received 3wks of inpatient neurorehabilitation in two cohorts, A and B. Rehabilitation consisted of physiotherapy, occupational therapy, and consultation by speech therapist, social worker, and psychologist. Cohort A was assessed on admission and discharge during a rehabilitation period. Cohort B was assessed 3wks before admission, on admission and at discharge.
 Primary Outcome Measures: Not specified.

Quality of Life Outcome Measures: 36 Item Short-Form questionnaire (SF-36); Functional Assessment of Multiple Sclerosis (FAMS).

Other Outcome Measures: Barthel Index (BI); Fatigue Severity Scale (FSS); Beck Depression Inventory (BDI); Multiple Sclerosis Functional Composite (MSFC); Grippit; Box and Block Test (B&B); Nine Hole Peg Test (9HPT); Clinical Outcome Variables (COVS); Berg Balance Scale (BBS); Timed 25-Foot Walk Test (T25FWT).

1. Cohort A improved significantly in the SF-36 domains of general health (p<0.05), vitality (p<0.05) and mental health (p<0.05) between admission and discharge.
2. Cohort B improved significantly in the FAMS domain emotional well-being between the first assessment (3wks before admission) and the second assessment at admission (mean score 19.2 to 21.6, p<0.05), but not between admission and discharge.

Freeman et al. 1999

Inpatient rehabilitation in multiple sclerosis: Do the benefits carry over into the community?

UK

Pre-Post

N_Initial=50, N_Final=44

Population: Mean age=44.8yr; Gender: males=21, females=29; Disease course: PPMS=7, SPMS=42; Mean EDSS=6.7; Mean disease duration=11.6yr.

Intervention: Patients with progressive MS undergoing inpatient rehabilitation were followed for 12mo after discharge. Assessments were undertaken on admission (A), at discharge, and subsequently at 3mo intervals for 1yr (1Y).
 Primary Outcome Measures: Functional Independence Measure (FIM); London Handicap Scale (LHS). 

Quality of Life Outcome Measures: 36-item Short Form Health Survey Questionnaire (SF-36); 28-item General Health Questionnaire (GHQ). 

Other Outcome Measures: EDSS; Kurtzke's Functional Systems.

1. Improvement was seen across all measures during the inpatient stay. These gains declined in varying patterns after discharge. 
2. Improvements in emotional well-being (GHQ) were maintained, on average, for 7mo. Improvements in SF-36 physical scores were maintained for nearly 10mo and SF-36 mental scores for nearly 6mo. However, there was considerable variability.
3. No tests of statistical significance were reported in this study.

Sitzia et al. 1998

Evaluation of a nurse-led multidisciplinary neurological rehabilitation programme using the Nottingham Health Profile 

UK

Pre-Post

N_Initial=42, N_Final=33

Population: MS participants (n=33): Mean age=49.0yr; Gender: males=11, females=31; Disease course: unspecified; Disease severity: unspecified; Disease duration: unspecified.

Intervention: MS patients received an individually adapted, multidisciplinary rehabilitation programme. The programmes lasted from 5-10d. Assessments were performed at baseline and after rehabilitation.
 Primary Outcome Measures: Nottingham Health Profile Part 1 (NHP-1). 

Quality of Life Outcome Measures: NHP-1.

Other Outcome Measures: None.  

1. The multiple sclerosis group showed a significant improvement in the dimensions ‘emotional reactions’ (p<0.01), ‘pain’ (p<0.01), and ‘physical mobility’ (p<0.05), and in the total NHP-1 score (p<0.01).
2. Overall improvement was not significantly associated with either gender or age.

Di Fabio et al. 1997

Health-related quality of life for patients with progressive multiple sclerosis: influence of rehabilitation 

US

PCT

N_Initial=44, N_Final=31

Population: Treatment group (n=12): Mean age=44.5yr; Gender: males=2, females=10; Disease course: PPMS or SPMS; EDSS range: 5-8; Mean disease duration=17.6yr. Waitlist group (n=19): Mean age=49.2yr; Gender: males=4, females=15; Disease course: PPMS or SPMS; EDSS range: 5-8; Mean disease duration=14.2yr.

Intervention: MS patients received either outpatient care for 1yr or did not receive rehabilitation (waitlist control). 

Primary Outcome Measures: Rand 36-Item Health Survey 1.0 (SF-36).

Quality of Life Outcome Measures: SF-36; MS Quality of Life 54 Item (MSQoL-54).

Other Outcome Measures: Rehabilitation Institute of Chicago Functional Assessment Scale (RIC-FAS) version 2.

1. The treatment group showed improvements in 6 health status measures on the SF-36 that were not improved in the wait-listed group: physical health, bodily pain, energy/fatigue, social support, cognitive ability, and overall positive change in general health from the previous year.
2. No significant effect of treatment on the MSQoL-54 was observed in either group. 
3. Health status improved for both groups in the areas of role limitations due to physical problems, general health, emotional wellness, and health distress.