Motor and non-motor outcomes after a rehabilitation program for patients with Functional Motor Disorders: A prospective,observational cohort study

Abstract

BACKGROUND:

Rehabilitation has proven effective in improving motor symptoms (i.e., weakness, tremor, gait and balance disorders) in patients with Functional Motor Disorders (FMDs). Its effects on non-motor symptoms (NMSs) such as fatigue, pain, depression, anxiety and alexithymia, have not been explored yet.

OBJECTIVE:

To explore the effects of a validated inpatient 5-day rehabilitation program, followed by a home-based self-management plan on functional motor symptoms, NMSs, self-rated perception of change, and quality of life (QoL).

METHODS:

33 FMD patients were enrolled. Measures for motor symptoms and NMSs were primary outcomes. Secondary outcomes included measures of self-perception of change and QoL. Patients were evaluated pre-treatment (T0), post-treatment (T1), and 3-month follow-up (T2).

RESULTS:

There was an overall significant decrease in functional motor symptoms, general, physical, and reduced-activity fatigue (for all, p < 0.001). Post hoc comparison showed significant improvements at T1, whereas effects remained significant at T2 for motor symptoms and physical fatigue. Gait and balance, alexithymia, and physical functioning (QoL) significantly improved at T2. More than 50% of patients reported marked improvement at T1 and T2.

CONCLUSIONS:

Our study suggests the benefits of rehabilitation and self-management plan on functional motor symptoms and physical fatigue in the medium-term. More actions are needed for the management of pain and other distressing NMSs in FMDs.

Keywords

Functional motor disorders fatigue pain non-motor symptoms physiotherapy rehabilitation

1 Introduction

Functional Motor Disorders (FMDs) come under the broader category of Functional Neurological Disorders (FNDs), frequently encountered in clinical practice (Stone et al., 2010). They are characterized by abnormal movements (e.g., weakness, tremor, dystonia, gait and balance disorders) that are clinically incongruent with those caused by neurological diseases and are altered by distraction or nonphysiological maneuvers (Pringsheim & Edwards, 2017; Carson & Lehn, 2016).

Patients suffering from FMDs experience disability and distress similar to patients with movement disorders (Gendre et al., 2019). In addition to motor complaints, non-motor symptoms (NMSs) such as fatigue, pain, anxiety, depression, and alexithymia have been increasingly recognized as important contributors to poor quality of life (QoL), producing levels of disability over and above those caused by the abnormal movement (Espay et al., 2018; Gelauff et al., 2014; Věchetová et al., 2018; Pick et al. 2019). Fatigue, pain, and depression are among the most relevant clinical features of FMDs, associated with poor QoL, poor self-rated health, and poor outcome after treatment (Věchetová et al., 2018; Gelauff et al., 2018; Czarnecki et al., 2012). Despite the clinical burden, the exact pathophysiological mechanisms underlying FMDs have not been elucidated. Emerging neurobiological evidence has implicated dysfunction in attentional focus, sense of agency, and beliefs/expectations as the key pathogenetic processes (Edwards, 2017; Marotta et al., 2017). Rehabilitation protocols based on this pathophysiological model have proven beneficial in improving functional motor symptoms (Nielsen et al., 2015a; Nielsen et al., 2015b; Nielsen et al., 2017a) and have been widely accepted as an essential tool in FMDs management (Nielsen et al., 2015b; Nielsen et al., 2017a; Gilmour et al. 2020). An intensive 5-day physiotherapy program has been demonstrated to improve the self-rated perception of change, balance, gait speed, and physical domains of QoL in patients with FMDs (Nielsen et al., 2015a). A randomized feasibility trial comparing specialist intensive physical rehabilitation and usual care in FMDs showed moderate-to-large effect sizes for both physical and social functioning outcomes, in the absence of improvement of mental health symptoms (Nielsen et al., 2017a). There are limited data on the efficacy of rehabilitation for NMSs such as fatigue and pain, despite their central role in precipitating and prolonging disability (Gilmour et al., 2020). Patients with excessive fatigue and pain have been generally excluded from rehabilitation protocols because they were considered unsuitable or unable to engage in high-intensity and short-duration treatment (Czarnecki et al., 2012; Nielsen et al., 2015a; Nielsen et al., 2017a). When such patients were included, fatigue and pain were not evaluated with specific measures (Jacob et al., 2018; Jordbru et al., 2014) or not reassessed after baseline (Maggio et al., 2020). In contrast, they have been included in the interdisciplinary FNDs treatment framework, thus underscoring the need for a holistic approach to FNDs patient care (Gilmour et al., 2020).

With this study, we explored the effects of a validated inpatient rehabilitation program followed by a tailored home-based self-management plan on functional motor symptoms, NMSs, self-rated perception of change, and quality of life (QoL) in patients with FMDs, regardless of the presence and severity of fatigue and pain in the short (5-days) and medium-term (3 months). To do this, we employed a validated rehabilitation protocol which has been demonstrated to be effective in improving motor symptoms by Nielsen and colleagues (Nielsen et al., 2015a; Nielsen et al., 2017a) and we assessed NMSs in terms of fatigue, pain, depression, anxiety and alexithymia.

2 Methods

2.1 Study design

Patients were admitted for 5 days to the Neurology Unit B (AOUI Verona, Italy) through referral by a consultant neurologist who had diagnosed the FMDs (MT). Patients underwent baseline assessment before starting rehabilitation at admission (T0), and then at discharge, after the end of the 5-day inpatient rehabilitation program (T1), and at 3-month follow-up (T2). Assessments were carried out by the same clinicians (MG, MR). Two neurophysiotherapists delivered the rehabilitation, both trained in FMDs (FB, CG).

2.2 Participants

The study population consisted of 33 patients recruited at an FMDs clinic in the Parkinson’s Disease and Movement Disorders Unit –AOUI Verona (Italy). Inclusion criteria were a clinical definite diagnosis of FMDs according to the Gupta & Lang criteria (Gupta & Lang, 2009) and age≥18 years. Exclusion criteria were prominent dissociative seizures; prominent cognitive and/or physical impairment that precluded signing the informed consent form for participation in the study, based on a clinical judgement (MT, MR). All participants gave their written, informed consent to participate in the study, which was carried out under the Helsinki Declaration tenets (2013). Approval was obtained from the Institutional Ethics Committee (Project Number. 1757CESC).

2.3 Intervention

The rehabilitation treatment consisted of a 5-day program (2 h/day) to re-establish normal movement patterns within a multidisciplinary etiological framework, according to a validated rehabilitation protocol for FMDs (Nielsen et al., 2015b; Nielsen et al., 2017a). A self-help website (www.neurosymptoms.org) was used to guide patients in taking an active part in the care process and understanding their symptoms through video consultation and experience sharing. Treatment was tailored to the needs of each patient, following general treatment principles in physiotherapy for FMDs: (1) education; (2) exploration of how symptoms affect movement and posture; (3) retraining movement using strategies based on redirection of attention; and (4) development of a self-management plan (Nielsen et al., 2015b). Non-specific graded exercises were part of the rehabilitation program to address reduced exercise tolerance and chronic fatigue and pain (Nielsen et al. 2015b; Larun et al. 2017).

2.4 Education

As mentioned by the program developers, the purpose of education is to reinforce information about diagnosis and explain symptoms according to the pathophysiological model of FMDs (Nielsen et al., 2015b; Edwards et al., 2012; Edwards et al., 2013).

2.5 Exploration of how symptoms affect movement and posture

Exploring how symptoms affect movement and posture and the demonstration of positive signs, such as Hoover’s sign for weakness or entrainment for tremor, can aid patients in developing strategies to overcome abnormal movement patterns. This powerful tool engages patients in diagnosis and treatment to regain normal movement.

2.6 Retraining movement using strategies based on redirection of attention

The goal of retraining movement is to reduce self-focused attention while increasing external-focused attention, which is achieved by diverting attention with the use of cognitive (counting or arithmetic) or physical (finger tapping or hand prono-supination) exercises performed during concurrent meaningful tasks (i.e., walking). Graded exercises, visualization techniques with mirrors and video observation and distraction maneuvers were employed. Example of exercises were: sit-to-stand, transfers, forward and backward walking or, weigth bearing progressively reducing the upper limb support, upper and lower limb coordination exercises in static (quiet stance) and dynamic (during gait) conditions by using ball, treadmill walking and with visual feedbacks by using mirror. Mirrors and video were helpful to document strategies that appear to normalize movements, reinforce the patients’ unserstanding of the diagnosis, provide feedbacks on the mismatch between the patient’s belief and the movement performed and to reinforce achievements (Nielsen et al. 2017a). Positive gains were verbally reinforced, and task repetition was used to lock-in improvements. Walking aids, splints, and orthoses were preferably avoided to prevent interference from adaptive behaviors.

2.7 Development of a self-management plan

The purpose of the home-based self-management plan is to facilitate the acquisition of the program’s educational components and to promote the engagement of patients in the treatment after discharge. Treatment was implemented during the inpatient rehabilitation with tailored exercises to the patient’s need and condition, which were reported in a paper log and video recorded. The paper log is part of the educational component of the program, aimed at supporting patients in the self-management. It includes goals, activity plans and strategies to be used for retraining movements and redirect attention. Videos included exercises demonstration and execution and startegies to retrain movements. At discharge, the self-management plan and videos were explained and discussed with the patients and their caregivers (Demartini et al., 2020). Patients were encouraged to perform the self-management plan at home (1 h/day, 3 days/week) on their own or with their caregivers’ help.

2.8 Measures

Patient demographics (i.e., age, gender) and clinical data (i.e., duration of symptoms, phenotype, presence of facial, voice and swallowing disorders, and gait impairments) and a detailed clinical history of motor symptoms and NMSs, disease duration, neurological, psychiatric or medical comorbidities, and previous organic diagnoses were collected at admission. Measures for motor symptoms and NMSs were primary outcomes. Measures for self-perception of change after rehabilitation and Health-related QoL and were secondary outcomes. Information on adherence to the home-based exercise program were also collected.

2.9 Motor symptoms severity assessment

Duration and severity of functional motor symptoms were measured with the objective-rated Sim-plified Functional Movement Disorders Rating Scale (S-FMDRS) (Nielsen et al., 2017b) (range: 0–54; higher = worse). The GAITRite walkway system (CIR Systems Inc, Havertown, PA, USA) and electronic monoaxial stabilometric platform (Technobody ^©, Dalmine, Italy) were used to evaluate gait and postural control in quiet stance, respectively. The main outcomes for gait were gait speed (cm/s), cadence (step/min), and stride length (cm). The main outcomes for postural control were the length of the center of pressure (CoP) trajectory (mm) and sway area (mm²) measured in the eyes open (EO) and the eyes closed (EC) condition. Each condition lasted 30 s. The EO condition refers to integrating visual, proprioceptive, and vestibular contributions to postural stability. In contrast, the EC condition refers to the proprioceptive contribution to and the visual dependency on postural control.

2.10 NMSs severity assessment

Fatigue was assessed with the Multidimensional Fatigue Inventory Scale (MFI-20) (Smets et al., 1995), which differentiates general, physical, reduced-activity, reduced-motivation, and mental fatigue (subscale range: 4–20; higher = worse). Pain, depression, anxiety, and alexithymia were assessed with the self-rated Brief Pain Inventory (BPI) (Caraceni et al., 1996) divided into intensity (range: 0–40; higher = worse) and interference (range: 0–70; higher = worse), the Beck Depression Inventory (BDI-II) (Beck et al., 1996) (range: 0–63; higher =worse), the Beck Anxiety Inventory (BAI) (Beck & Steer, 1993) (range: 0–63; higher = worse), the Toronto Alexithymia Scale (TAS-20) (Taylor et al., 1992) (range: 20–100; higher = worse), respectively.

2.11 QoL, self-perception of changes, and adherence to the home-based exercises program

The Health-Related QoL was evaluated by the Mental Health and Physical functioning of the 12-item Short-Form Health Survey (SF-12) (range: 0–120; higher = better) (Ware et al., 1996). Self-rated perception of change after treatment was assessed with the 7-point Clinical Global Impression (CGI) scale with scores from 1 (very much improved) to 7 (very much worse) (Guy, 1976). The Exercise Adherence Rating Scale (EARS) (Newmann-Beinart et al., 2017) measured adherence to the home-based exercise program. The EARS-B sub-item evaluates the adherence to exercise (range: 0–24; higher = better) The EARS-C subitem evaluates the adherence to promote/impede exercise (range: 0–40; higher = better). The total score is obtained from the sum of the EARS B and C (range: 0–64 higher = better).

The S-FMDRS, MFI-20, BPI, and CGI were completed at T0, T1, and T2. The BDI-II, BAI, TAS, the SF-12, and gait and balance assessment were evaluated at T0 and T2. EARS were collected at T2 to determine whether the patients had done their prescribed exercises at home between T1 and T2.

2.12 Data analysis

Descriptive statistics included frequency tables for categorical variables and mean and standard deviation for continuous variables. Data about CGI changes at discharge and follow-up were transformed in percentage. Normality of data distribution was checked with the Shapiro-Wilk test; since it was violated for most of the variables (p < 0.05), non-parametric analyses were performed. Two-way non-parametric Friedman’s test was used to analyze factor timing to compare the means for the three-time points: admission, discharge, and follow-up (T0, T1, T2). Post hoc analysis was performed using the Wilcoxon signed-rank test; p < 0.0167 was considered statistically significant with three comparisons (admission vs. discharge vs. follow-up); p < 0.025 was considered statistically significant with two comparisons (discharge vs. follow-up). The effect size (Pearson’s correlation, r) was calculated (Rosenthal, 1991), and the effects were interpreted as small (r < 0.3), medium (0.3≤r < 0.5), and large (r≥0.5) (Cohen, 1988). Negative values indicate that values reported at T1 or T2 are higher than those reported at T0. All analyses were performed with SPSS 26 software for Mac (IBM-SPSS, Armonk, NY, USA).

3 Results

Demographical and main clinical features of the 33 patients are reported in Table 1. All patients reported fatigue, while n = 26 (78.8%) reported chronic pain. All patients completed the scheduled assessments at various timepoints. Of the 28 patients with gait impairment, those able to complete the instrumental assessment (n = 21) underwent additional gait and stabilometric instrumental evaluations.

Table 1
Main demographic and clinical characteristics of FMDs patients, n = 33

Demographic characteristics

Mean age, years (±SD) 40.64 (16.85)

Female, no. (%) 26 (78.8)

Mean duration symptoms, years (±SD) 4.58 (16.85)

Clinical characteristics

Motor symptoms No. (%)

Weakness 33 (100)

Tremor 26 (78.8)

Dystonia 13 (39.3)

Myoclonus 5 (15.1)

Gait impairment 28 (84.8)

Facial disorder 4 (12.1)

Voice disorder 10 (30.3)

Swallowing disorder 7 (21.2)

FMDs phenotype

Isolated 1 (3.1)

Combined 32 (96.9)

NMSs

Reporting fatigue 33 (100)

Report chronic pain 26 (78.8)

Previous organic disease/comorbidities^*

Neurological disease 9 (27.3)

Psychiatric disease 9 (27.3)

Medical comorbidities 18 (54.5)

no., number; SD, standard deviation; NMSs, non-motor symptoms; FMDs, functional motor disorders; ^*patients can have 1 or more organic/comorbidities.

3.1 Motor symptoms severity

A significant overall improvement in motor symptoms (χ² = 23.55, df = 2, p < 0.001) as measured on the S-FMDRS was noted (Table 2). Post-hoc comparisons revealed a significant improvement between T0 and T1 (Z = –4.480, p < 0.001), which was maintained between T0 and T2 (Z = –2.648, p = .006). A non-significant increase was reported between T1 and T2. A significant increase in gait speed (Z = –3.980, p < .001), cadence (Z = –3.875, p < .001), and stride length (Z = –3.980, p < .001) was found at T2 in the subgroup of 21 patients. There was a significant reduction in sway area in the EO condition (Z = –2.091, p = 0.037) but not in the EC condition. In contrast, there was a significant reduction of the length of the CoP in the EO (Z = –2.003, p = 0.042) and the EC condition (Z = –2.294, p = 0.022) (see Table 3 for all p values). The data for the 21 patients are representative of the entire sample of 33 patients since they replicate the same effects.

Table 2
Outcome measures at three time points: admission, discharge (end of the 5-day in-hospital rehabilitation) and at 3-month follow-up, n = 33

Clinical scale/Subscale Admission 5-days discharge 3-month follow-up Friedman’s Test Post hoc comparisons

T0 T1 T2 T0-T2 T0 vs T1 T0 vs T2 T1 vs T2

Mean±SD Mean±SD Mean±SD X² statistic, P value P value^, r P value^, r P value^, r

S-FMDRS (0–54) 22.96±10.70 12.60±9.59 17.54±11.75 X²(2) = 23.55, p < 0.001 p < 0.001,* p = 0.006, p = 0.065

r = –0.78 r = –0.54

MFI –20

General fatigue (4–20) 16.61±2.67 12.03±4.02 14.94±4.62 X²(2) = 25.10, p < 0.001 p < 0.001 , p = 0.058 p < 0.001,

r = –0.75 r = –0.63

Physical fatigue (4–20) 16.67±3.29 11.45±4.25 13.88±4.79 X²(2) = 21.65, p < 0.001 p < 0.001, p = 0.006, p = 0.006,

r = –0.75 r = –0.48 r = –0.48

Reduced-activity (4–20) 14.39±4.35 11.18±4.47 12.30±5 X²(2) = 18.17, p < 0.001 p < 0.001, p = 0.053 p = 0.108

r = –0.64

Reduced-motivation (4–20) 10.21±3.63 9.21±3.03 10.52±3.52 X²(2) = 2.56, p = 0.278

Mental-fatigue (4–20) 13.06±3.68 11.39±3.58 13.06±3.99 X²(2) = 5.33, p = 0.070

BPI

Intensity (0–40) 19.21±11.92 17.61±11.89 20.15±12.01 X²(2) = 0.91, p = 0.636

Interference (0–70) 33.58±24.89 27.70±24.16 33.61±23.16 X²(2) = 2.34, p = 0.310

Clinical scale/Subscale	Admission	5-days discharge	3-month follow-up	Friedman’s Test	Post hoc comparisons
S-FMDRS (0–54)	22.96±10.70	12.60±9.59	17.54±11.75	X²(2) = 23.55, p < 0.001	p < 0.001,	p = 0.006,	p = 0.065
					r = –0.78	r = –0.54
MFI –20
General fatigue (4–20)	16.61±2.67	12.03±4.02	14.94±4.62	X²(2) = 25.10, p < 0.001	p < 0.001 ,	p = 0.058	p < 0.001,
					r = –0.75		r = –0.63
Physical fatigue (4–20)	16.67±3.29	11.45±4.25	13.88±4.79	X²(2) = 21.65, p < 0.001	p < 0.001,	p = 0.006,	p = 0.006,
					r = –0.75	r = –0.48	r = –0.48
Reduced-activity (4–20)	14.39±4.35	11.18±4.47	12.30±5	X²(2) = 18.17, p < 0.001	p < 0.001,	p = 0.053	p = 0.108
					r = –0.64
Reduced-motivation (4–20)	10.21±3.63	9.21±3.03	10.52±3.52	X²(2) = 2.56, p = 0.278
Mental-fatigue (4–20)	13.06±3.68	11.39±3.58	13.06±3.99	X²(2) = 5.33, p = 0.070
BPI
Intensity (0–40)	19.21±11.92	17.61±11.89	20.15±12.01	X²(2) = 0.91, p = 0.636
Interference (0–70)	33.58±24.89	27.70±24.16	33.61±23.16	X²(2) = 2.34, p = 0.310

S-FMDRS, Simplified Functional Movement Disorders Rating Scale; MFI-20, Multidimentional Fatigue Inventory-20; BPI, Brief Pain Inventory. ^*P value was adjusted for multiple comparisons, p≤0.0167 was considered statistically significant. Statistically significant results are given in bold. r, effect size.

Table 3

Gait and stabilometric performance at two time points: admission and at 3-months follow-up, n = 21

Assessment /outcomes	Admission	3-month follow-up	Wilcoxon signed-rank test
	T0	T2
	Mean±SD	Mean±SD	Z score	P value^*, r
Gait analysis
Gait speed (cm/s)	58.77±5.2	82.52±5.3	z = –3.980	p < 0.001, r = –0.69
Cadence (step/min)	82.56±4.6	97.46±4.04	z = –3.875	p < 0.001, r = –0.67
Stride length (cm)	81.21±4.43	99.64±4.17	z = –3.980	p < 0.001, r = –0.69
Stabilometric assessment
Sway area (mm2)
Eyes open	295.85±84.91	114.57±22.53	z = –2.091	p = 0.037 , r = –0.45
Eyes closed	649.57±160.12	588.33±357.79	z = –1.680	p = 0.093,
CoP displacement (mm)
Eyes open	254.23±40.04	169.47±18.89	z = –2.003	p = 0.042 , r = –0.44
Eyes closed	395.14±55.85	295.52±49.08	z = –2.294	p = 0.022 , r = –0.50

^*Statistically significant results are given in bold, p < 0.05; r, effect size.

3.2 NMSs severity

A significant overall effect of the general (χ² ==25.107, df = 2, p < 0.001), physical (χ² = 21.658, df = 2, p < 0.001), and reduced activity (χ² = 18.171, df = 2, p < 0.001) subscales of the MFI-20 scale was observed (Table 2). Post-hoc comparison revealed between T0 and T1 a significant effect of general fatigue (Z = –4.349, p < .001), physical fatigue (Z = –4.340, p < .001) and reduced activity (Z =–3.687, p < .001). General fatigue significantly increased between T1 and T2 (Z = –3.617, p < 0.001) and values at T2 returned comparable to baseline (Z = –1.896, p = .058). Physical fatigue significantly increased between T1 and T2 (Z = –2.770, p < 0.006), but an overall improvement remained significant at T2 (Z = –2.756, p = .006). Non-significant changes were reported in reduced activity fatigue between T1 and T2 and between T0 and T2.

No significant overall effects were found for the reduced motivation and mental fatigue as assessed with the MFI-20, nor for pain intensity and interference, as evaluated by the BPI scale (Table 2). No significant changes were found for the BDI-II and BAI. The TAS-20 showed a significant decrease in alexithymia symptoms (Z = –2.796, p = .005), though the final score was still above the cut-off (>51) for possible alexithymia (Table 4).

Table 4
Outcome measures at two time points: admission and at 3-months follow-up, n = 33

Clinical scales/subscale Admission 3-month follow-up Wilcoxon signed-rank test

T0 T2

Mean±SD Mean±SD Z score P value^, r

BDI-II (0–63) 13.76±7.90 11.24±8.99 z =* –1.742 p = 0.081

BAI (0–63) 21.33±9.38 18.39±9.61 z = –0.932 p = 0.351

TAS-20 (20–100) 57.12±12.06 54.06±12.67 z = –2.796 p = 0.005, r = –0.48

SF-12 (0–120)

Physical functioning 28.86±8.97 34.89±9.43 z = –3.507 p < 0.001, r = –0.61

Mental Health 37.98±10.3 39.46±14.11 z = –0.504 p = 0.614,

Clinical scales/subscale	Admission	3-month follow-up	Wilcoxon signed-rank test
BDI-II (0–63)	13.76±7.90	11.24±8.99	z = –1.742	p = 0.081
BAI (0–63)	21.33±9.38	18.39±9.61	z = –0.932	p = 0.351
TAS-20 (20–100)	57.12±12.06	54.06±12.67	z = –2.796	p = 0.005, r = –0.48
SF-12 (0–120)
Physical functioning	28.86±8.97	34.89±9.43	z = –3.507	p < 0.001, r = –0.61
Mental Health	37.98±10.3	39.46±14.11	z = –0.504	p = 0.614,

BDI-II, Beck Depression Inventory; BAI, Beck Anxiety Inventory; TAS-20, Toronto Alexithymia Scale; SF-12, 12-item Short-Form Health Survey (SF-12); r, effect size. ^*P value was corrected for multiple comparisons, p≤0.025 was considered statistically significant. Statistically significant results are given in bold.

3.3 QoL, self-perception of changes, and ad-herence to the home-based exercises program

There was a significant improvement on the physical subscale of the SF-12 between T0 and T2 (Z = –3.507, p < .001) (Table 4), whereas no significant changes for the mental health subscale were measured.

A marked improvement (corresponding to the CGI scale scores “very much improved = 1” & “much improved = 2”) was reported by 51% (n = 17) and 54% (n = 18) of patients at T1 and T2, respectively (Table 5).

Table 5
Patient-rated perception of change at discharge and follow-up, n = 33

CGI Change End of treatment 3-month follow-up

T1 T2

No. (%) No. (%)

Very much improved 8 (24) 9 (27)

Much improved 9 (27) 9 (27)

Minimally improved 12 (36) 8 (24)

No change 2 (6) 1 (3)

Minimally worse 1 (3) 2 (6)

Much worse 1 (3) 4 (12)

Very much worse 0 (0) 0 (0)

CGI Change	End of treatment	3-month follow-up
Very much improved	8	(24)	9	(27)
Much improved	9	(27)	9	(27)
Minimally improved	12	(36)	8	(24)
No change	2	(6)	1	(3)
Minimally worse	1	(3)	2	(6)
Much worse	1	(3)	4	(12)
Very much worse	0	(0)	0	(0)

No, number; CGI, Clinical Global Impression scale.

Only 2 (6%) at T1 and 6 (18%) at T2 reported their symptoms were “minimally worse or much worse”. The Total EARS mean score was 44.44 (± 9.88), with higher scores indicating better treatment adherence. The mean score for the subscale EARS-B adherence to exercise was 17.39 (±4.93), whereas the mean score for the subscale EARS-C measuring factors that promote or impede adherence to exercises was 27.06 (±6.31).

A reference value found in literature for the EARS-B adherence to exercise subscale considered 17/24 as a score of high adherences (de Lira et al., 2020).

4 Discussion

With this study, we explored the effects of a validated inpatient 5-day rehabilitation program, followed by a home-based self-management plan on motor symptoms, NMSs, self-rated perception of change, and QoL in patients with FMDs in the short (5-days) and medium-term (3 months) outcomes, regardless of the presence and severity of fatigue and pain.

We found that motor symptoms, assessed by the S-FMDRS, significanty improved after rehabilitation, and improvements were still present three months later (T2). The subgroup of patients who underwent instrumental assessment for gait and balance disturbances achieved a significant improvement in spatio-temporal gait and stabilometric parameters at follow-up. Significant improvement in the dimensions of general, physical and reduced-activity fatigue, as assessed by the MFI-20, were found in the short term (5-days), with a decline over time except for the improvement in physical fatigue, still significant at T2. Additional significant benefits on physical functioning domain of Health-Related QoL (SF-12) and alexithymia (TAS-20) were noticed at T2, even though the mean score of the latter was still above the cut-off for possible alexithymia. More than 50% of patients reported marked improvement (CGI 1-2) at T1 and T2. Overall, between admission and follow-up patients remained minimally depressive, moderately anxious and self-perceived mental health did not change.

Our study further supports the crucial role of in-tensive rehabilitation in the management of functional motor symptoms, as showed by the significant improvement of the S-FMDRS immediately after treatment. Moreover, a tailored self-management exercise plan may help sustain these changes in the medium-term. When assessed at 3-month follow-up, we found a significant improvement in instrumental measures of gait and balance. Indeed, we found an increase in gait speed, cadence, and stride length and a decrease in CoP length and sway area. Nonetheless, the improvement of postural control in the EC sensory condition suggested a decrease in reliance on visual inputs and a better integration of the proprioceptive information from lower limbs in quiet stance, which might have fostered the gait improvement. Given the lack of data on gait and balance at T1, it is not possible to determine the relative contribution of the inpatient or the home-based exercise program. However, previous findings showing a significant improvement on the Berg Balance Scale and the 10 Metre Walk Test at T2, without a significant improvement between T1 and T2 (Nielsen et al., 2015a), might allow the assumption that the inpatient rehabilitation was relatively more effective on gait and balance also in our sample.

Here, we provide preliminary evidence for im-provement of the inpatient rehabilitation on some aspects of fatigue: short-term improvement in general and reduced-activity fatigue and short-to-medium-term improvement in physical fatigue. These findings are promising as they show that fatigue, particularly in its physical component, may respond to intensive rehabilitation, alongside functional motor symptoms, thus raising the crucial question, which we seek to answer in future work, of whether these symptoms might share some common pathophysiological mechanisms. Moreover, the lack of improvement in mental health measures suggests that the observed changes in fatigue are independent from the burden of depression and anxiety, which variably contribute to fatigue occurrence in neurological illnesses (Kluger et al., 2013). However, the decline between T1 and T2 in the general and physical aspects of fatigue could indicate that the self-management plan is not effective in managing this distressing NMSs. Moreover, no significant benefits in mental fatigue and reduced motivation were noted. Likewise, pain intensity and interference with everyday life did not improve in our study. This might rely on the fact that we did not target pain separately and in isolation, indeed no specific exercises addressing it were used. Future trials specifically designed to target pain in FMDs might shed more lights on the management strategies for this disabling symptom. Nevertheless, the lack of worsening of pain might suggest that pain does not necessarily contraindicate rehabilitation.

In line with previous studies, most patients re-ported amelioration of their general condition after treatment. Indeed, more than half of patients reported a marked improvement at T1 and T2: n = 17 (51%) and n = 18 (54%) respectively, according to the patient-rated CGI scale (Table 5). Our results are partially shared by the study of Nielsen and collaborators who reported good outcomes at discharge in 63% and 55% at follow-up (Nielsen et al, 2015a) even in patients with disease duration longer than 1 year (Nielsen et al., 2015a), who are generally considered at risk for poor outcome (Sharpe et al., 2010). For our study, we enrolled patients with a history FMDs of 4.58 years on average. These findings, however, report a lower percentage of improvement compared to the study of Jacob and colleagues (2018) who reported an improvement of 86.7% of patients at discharge, maintained in 69.2% at 6-months follow-up after a multidisciplinary 1-week inpatient rehabilitation program. Arguably, the multidisciplinary nature of the used intervention with psychological training sessions (Jacob et al., 2018) and the high rate of distressing NMSs such as fatigue and pain (Table 1) in our sample, might partially account for this difference.

In keeping with the study by Jordbru and colleagues (Jordbru et al., 2014), we found a carry-over effect in the physical score of the SF-12 scale at follow-up. Similarly, Nielsen et al. (2017a) reported the benefit of intensive rehabilitation program on QoL.

Our study shows a meaningful decrease in motor symptoms, aspects of general, physical and reduced-activity fatigue levels (MFI-20) and physical score of the SF-12 scale, further supporting the importance of a specialist rehabilitation program in improving clinical features and health condition in patients with FMDs. However, in keeping with previous findings (Jacob et al., 2018, Nielsen et al., 2015a, Gelauff et al., 2014), a decline in many motor and NMSs outcomes was observed between discharge and follow-up, thus allowing us to speculate that the 5-day rehabilitation program, consisting of graded exercises with a progressive increase in exercise intensity, may result in a more dynamic, engaging, and challenging program compared to the home-based one, despite a good adherence. Moreover, the attention and care of trained physiotherapists in a specialized in-hospital rehabilitative setting could also have fostered the observed improvement in motor and NMSs outcomes. We found a good adherence to self-management plan. However, several intrinsic and extrinsic factors, namely motivation, symptoms severity, and the presence of pain and/or fatigue might affect it. In this scenario, telemedicine with a trained physiotherapist could improve adherence to home-based self-management plan, and suggesting to dynamically grade exercises, based on the patient’s condition.

We acknowledge several limitations of our study. They are: a) the lack of long-term follow-up assessment; b) the small sample; c) the lack of a control group; d) a heterogenic cohort with a variety of neurological, psychiatric, and medical comorbidities; e) some measures were collected only at T0 and T2, not allowing a precise recognition of the relative contribution of rehabilitation or self-management plan f) the lack of gait and balance assessment in patients with no obvious gait or balance disorders g) motor symptoms were assessed only by the S-FMDRS h) no specific exercises were performed to target independently NMSs i) results were based mainly on explorative analysis, which allows only a preliminary exploration of data collected. Besides, the patients who agreed to participate in the study were probably more motivated to achieve functional recovery.

The strengths of our study are the use of a) a validated rehabilitation protocol; b) a comprehensive assessment battery to capture clinical features, comorbidities, and contributing illness factors, such as patient-rated outcome measures that are particularly important when assessing outcomes in the FMDs population (Pick et al., 2020); c) the use of the recommended clinician-rated scale (S-FMDRS) and d) instrumental assessment of gait and balance for patients with prominent gait and balance disorders to obtain quantitative data of performance; and e) an acceptable parameter of adherence to a home-based exercise program.

5 Conclusion

In conclusion, a rehabilitation program based on the validated protocol by Nielsen and colleagues (2015a) followed by a tailored home-based self-management plan were found to improve gait, balance, other motor symptoms, as well as physical QoL dimensions and functional fatigue, primarily in its physical expression. Evidence for how best to structure an FMDs rehabilitation program for NMSs lacks in the literature. Based on our findings, it seems reasonable to consider reducing fatigue as a good outcome of a rehabilitation protocol. Further studies need to be conducted to seek ways to improve distressing NMSs such as mental health symptoms, pain, other dimensions of fatigue and of QoL, optimizing care of FMDs patients so that they can gain greater daily functionality.

Footnotes

Acknowledgments

We thank the medical doctor A. Botticelli for her help in collecting data on instrumental assessments of patients.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declare that they have no competing interests.

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Demographic characteristics
Mean age, years (±SD)	40.64	(16.85)
Female, no. (%)	26	(78.8)
Mean duration symptoms, years (±SD)	4.58	(16.85)
Clinical characteristics
Motor symptoms	No.	(%)
Weakness	33	(100)
Tremor	26	(78.8)
Dystonia	13	(39.3)
Myoclonus	5	(15.1)
Gait impairment	28	(84.8)
Facial disorder	4	(12.1)
Voice disorder	10	(30.3)
Swallowing disorder	7	(21.2)
FMDs phenotype
Isolated	1	(3.1)
Combined	32	(96.9)
NMSs
Reporting fatigue	33	(100)
Report chronic pain	26	(78.8)
Previous organic disease/comorbidities^*
Neurological disease	9	(27.3)
Psychiatric disease	9	(27.3)
Medical comorbidities	18	(54.5)