Walking function determinants in parkinson patients undergoing rehabilitation

Abstract

BACKGROUND:

To date little is known about factors affecting walking rehabilitation in Parkinson’s disease (PD) patients.

OBJECTIVE:

This prospective observational cohort study evaluated the walking distance covered in 6 minutes (6 MWD) before and after conventional rehabilitation and verified which among PD motor disorders was the most important determinant of walking distance in PD patients undergoing rehabilitation.

METHODS:

Data were collected from 55 PD patients, performing a conventional outpatient motor rehabilitation program. The 6MWD at the end of rehabilitation and gain in 6MWD were the outcome measures. The Unified Parkinson’s Disease Rating Scale, Hoehn and Yahr scale, Nine Hole Peg Test, Grip and Pinch test, ROM wrist motility, and Berg Balance Scale (BBS) were used to assess PD patients at admission and were considered as dependent variables. Backward multiple regression analyses identified the determinants of 6MWD outcomes.

RESULTS:

The 6MWD was 246.58±115 meters at admission and 286.90±116 at the end of rehabilitation. At end of rehabilitation, the 6MWD was 42.32±47 meters greater than admission (p < 0.001), corresponding to an increase of +17.16%. At the end of rehabilitation, the 6MWD was significantly longer in PD patients with stages 1–3 of the Hoehn and Yahr scale. Berg Balance Scale (β= 0.47, p < 0.001) and right Grip and Pinch at admission (β= 0.36, p = 0.001) were the only determinants of final 6MWD. The R² value of the model was 0.47 (R² adjusted 0.45). No variable was a determinant of gain in 6MWD.

CONCLUSIONS:

The study indicates that balance and generalized muscle strength are important determinants of walking rehabilitation in PD patients, in whom it is essential to maintain high levels of balance and muscle strength for a time as long as possible. These findings suggest planning more intensive rehabilitation treatments in PD patients with low levels of balance and muscle strength.

Keywords

Balance conventional rehabilitation motor coordination muscle strength passive range of motion

1 Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, after Alzheimer’s disease. It affects 1% of the population over 60 years of age, and the risk increases proportionally with age (Reeve 2014). The primary motor symptoms of PD include slowness of movements (bradykinesia), tremors, muscle stiffness (rigidity), and disorders of balance and coordination (postural instability) (Magrinelli 2016). As a consequence of such symptoms, walking function disorders can appear in Parkinson’s disease patients, including reduction of lower limb joints excursion, irregular and asymmetric timing of steps, decrease and absence of arm swing, and abnormal reduction of walking speed and stride length (Borrione 2014).

Reduction of walking speed is one of the clinical hallmarks of Parkinson’s disease (PD) and a frequent cause of disability (Atrsaei 2021) and impairment of quality of life (Hariz 2011).

Complementary to pharmacotherapy and neurosurgical treatments, rehabilitation is a commonly prescribed intervention for people with Parkinson’s disease (Radder 2020). Rehabilitation consists of many different treatment modalities (Radder 2020), and conventional rehabilitation, based on physiotherapy exercises, is one of the most common methods used in PD patients (Radder 2020; Papamichael 2021).

Many studies demonstrated that conventional rehabilitation treatments can be effective in increasing motor function, gait ability, and patient autonomy in PD patients (Keus 2007; van der Kolk 2013).

However, despite the studies executed (Radder 2020; Papamichael 2021; Keus 2007; van der Kolk 2013; Üğüt 2022), to date, it is not known which among the most common specific motor disorders of PD have the highest impact on walking rehabilitation in PD patients. Identification of factors that contribute to walking function impairments in PD patients undergoing standard rehabilitation may help physicians to better manage these patients by planning a more appropriate rehabilitation program.

This prospective observational cohort study evaluated the walking distance covered in 6 minutes (6 MWD) before and after a conventional rehabilitation program and verified which, among specific motor disorders of PD, is the most important determinant of 6MWD in PD patients undergoing standard rehabilitation.

2 Materials and Methods

2.1 Patients

This retrospective cohort study was conducted at the Rehabilitation Unit of the Istituti Clinici Scientifici Maugeri IRCCS (in two different centers: Lumezzane and Castel Goffredo).

Data were collected in outpatients with PD diagnosed by a neurologist and admitted to our Rehabilitation Institute between May 2017 and December 2020. From this database (152 patients), we selected patients with disability related to PD who were aged≥55 years, and demonstrated adequate language comprehension after administration of cognitive tests (Ramaker 2002; Folstein 1975) and gave their written informed consent to use their clinical data for scientific research.

We excluded patients who had acute medical diseases, other concomitant neurological pathologies, orthopedic/surgical conditions causing per se a locomotor impairment, and missing data.

The study was conducted in accordance with the principles of the Declaration of Helsinki.

2.2 Mode of Assessment

Clinical evaluation of all patients was performed at admission and at the end of rehabilitation by a qualified team of physiatrists, physiotherapists, and occupational therapists. Patient demographic characteristics and comprehensive clinical data including body mass index (BMI), disease duration, dominant hand, and medication intake were recorded. PD patients were tested during a clinical “on” status.

Moreover, the following scales were used for the assessment:

Unified Parkinson’s Disease Rating Scale (UPDRS) was used to assess the severity of disease in PD patients (Ramaker 2002; Antonini 2013). In the study, the third segment (motor examination) of the UPDRS was considered (range 0–108).

Cumulative Illness Rating Scale (CIRS) was used to evaluate comorbidities (Salvi 2008). In this study, we considered the average severity of all comorbidities (severity index).

Mini-Mental State Examination (MMSE) was used to evaluate cognitive impairment (Folstein 1975). The MMSE was corrected for age and educational level.

Modified Hoehn and Yahr Scale was used to establish the stage of PD, which ranges from stage I (unilateral involvement) to stage V (confinement to bed or wheelchair, unless aided) (Goetz 2004).

Berg Balance Scale (BBS) was used to measure balance among PD patients (Berg 1989; Ottonello 2003). The BBS consists of 14 items that require subjects to maintain positions of varying difficulty and perform specific tasks. Each item is scored on a 5-point ordinal scale ranging from 0 (unable to perform) to 4 (normal performance) so that the aggregate score ranges from 0 to 56.

Nine Hole Peg Test was utilized for measuring the motor coordination of upper limbs. (Poole 2005). The test material consists of nine small bars made in standard size and a nine-hole board on which to place them. NHPT is applied in a sitting position. The patient is asked to string the nine bars inside the box resting on the table into the holes of the other box as quickly as possible and remove them immediately after finishing. Time is measured with a stopwatch and is started when the hand touches the first bar and is finished when the last bar is placed in the box (Poole 2005).

Grip and Pinch Test was utilized for measuring the isometric handgrip strength of patients (Werle 2009), which is an adequate measurement for generalized muscle strength (Buckley 2018). A Sammons Jamar Hydraulic Hand Dynamometer was used. Participants were asked to perform the task three times with each hand. The best result obtained with each hand was used for the present analyses. The device measured strength in kilograms.

Passive range of motion (ROM) of the wrist was utilized to assess rigidity and was measured by a manual goniometer with the patient relaxed in a sitting position. The sum of ROM in flexion (0–80°) and extension (0–70°) of the right and left wrist was considered in the study (Cipriano 1997).

6 Minutes Walking Test (6MWT) was used to measure the maximal distance that the patient could walk on a flat surface, as fast as possible, for 6 minutes (6 MWD). The participants were asked to walk for 6 minutes along a 30-meter corridor, covering as much ground as possible. Participants were allowed to use an assistive device and could stop to rest if necessary, but they were asked to resume walking as soon as possible (Falvo 2009).

2.3 Outcome measures

The 6MWD at the end of rehabilitation and gain in 6MWD were the outcome measures.

2.4 Rehabilitation program

The outpatient rehabilitation program consisted of an average of 300 min/week of conventional motor rehabilitation (5 days/week) for 4 weeks. Each patient’s needs, specific rehabilitation goals, and progress/outcomes were discussed at admission and after 2 weeks by the rehabilitation team composed of physicians, physiotherapists, and an occupational therapist.

Rehabilitation commenced the day after admission and was conducted by physiotherapists (3-year professional qualification) with more than 5 years of experience in the rehabilitation of neurologic diseases. Motor rehabilitation was based on gradual and full-range passive mobilization exercises of the trunk and limbs, active head and trunk extension exercises, muscle activation exercises of upper limbs and lower limbs, and stretching exercises.

Moreover, it included trunk rotation exercises, sit-to-stand and vice-versa exercises, balance exercises in sitting and standing positions, gait activities (with parallel bars, walker, crutches) on a flat surface, and on an uneven surface and with obstacles. The rehabilitation program was tailored to each patient’s needs.

2.5 Statistical analysis

Statistical analysis was performed using descriptive statistic tests (mean±SD), Shapiro-Wilk test, and paired Student’s t-test for comparison of pre-to-post data. To evaluate effect size, Cohen’s d test was applied and, according to the threshold proposed by Cohen, values for effect size 0.2–0.4 indicated small effect, 0.5 –0.7 medium effect, and 0.8 –≥1 large effect (Cohen 1988).

Moreover, Pearson’s correlation coefficient was used to assess correlations between variables, and backward stepwise multiple regression analyses were performed to identify determinants of outcome measures.

All independent variables significantly correlated with outcome measures at Pearson’s correlation were submitted to the backward stepwise multiple regression. The independent variables were the UPDRS, Hoehn Yahr (HN) scale, Nine Hole Peg, Grip and Pinch test, ROM wrist motility, and BBS at admission. The dependent variables were the 6MWD score at the end of rehabilitation and gain in 6MWT. These latter variables had a Gaussian distribution and, therefore, multiple regression analyses were performed on 6MWD outcomes and residual distribution and homoscedasticity were checked.

All statistical analyses were performed with the software application Statistica version 6 (StatSoft, Tulsa, OK, 2001). P values of less than 0.05 were considered statistically significant.

3 Results

During the study period, out of 152 with PD who were consecutively admitted to our Rehabilitation Unit, 55 patients had complete pre-to-post data for 6MWT and specific symptoms of PD.

Table 1 reports the demographic and clinical characteristics of the study population at admission. Table 2 describes profiles of motor disorders in PD patients, showing that BBS score (p = 0.001), right wrist ROM (p = 0.001), Grip and Pinch Test for right and left hand (p = 0.001, for both), and nine-hole peg for right hand (p = 0.018) and 6MWD (p < 0.001) significantly improved at the end of rehabilitation.

Table 1
Demographic and clinical characteristics of PD patients (n = 55)

Mean±sd Number

Age (years) 74.67±7.96

Male/Female (n) 30/25

Dominant hand: right/left (n) 55/0

Duration of disease (years) 7.66±4.25

CIRS severity (score) 1.76±0.42

Body Mass Index, Kg/m² 26.43±4.65

Medication intake: Levodopa/Dopamine Agonists/ MAO-B and COMT inhibitors (n) 41/27/20

Levodopa intake (mg/die) 480.14±295.52

MMSE* (score) 23.78±4.72

Hoehn and Yahr: levels 1/1.5/2/2.5/3/4 4/2/13/8/18/10

	Mean±sd	Number
Age (years)	74.67±7.96
Male/Female (n)		30/25
Dominant hand: right/left (n)		55/0
Duration of disease (years)	7.66±4.25
CIRS severity (score)	1.76±0.42
Body Mass Index, Kg/m²	26.43±4.65
Medication intake: Levodopa/Dopamine Agonists/ MAO-B and COMT inhibitors (n)		41/27/20
Levodopa intake (mg/die)	480.14±295.52
MMSE* (score)	23.78±4.72
Hoehn and Yahr: levels 1/1.5/2/2.5/3/4		4/2/13/8/18/10

Data are expressed as mean and SD, absolute numbers; CIRS = Cumulative Illness Rating Scale Geriatrics; MMSE = Mini-Mental State Examination. *Data were available in 46 patients.

Table 2

Profile of motor disorders in PD patients (n = 55)

	ADMISSION	Minimum/Maximum	DISCHARGE	Minimum/Maximum	P value	EFFECT SIZE
						Cohen’s d	Confidence interval
Hoehn and Yahr Scale (score)	2.67±0.85	1.0/4.0	–		–	–	–
UPDRS III (score)	35.60±24.48	3.0/94.0	–		–	–	–
Berg Balance Scale (score)	39.18±10.68	15.0/56.0	45.41±12.57	18.0/56.0	0.001	0.534	CI: 0.152 –0.913
Nine Hole Test of the right hand (sec)	26.30±.11.01	12.0/50.0	24.27±.9.51	12.0/50.0	0.018	0.197	CI: –1.178 –0.571
Nine Hole Test of the left hand (sec)	26.35±10.01	11.2/50.0	25.31±9.75	14.0/50.0	0.119	0.105	CI: –0.269 –0.479
ROM of the right wrist (°)	112.40±24.66	57.0/174.0	118.69±23.58	68.0/180.0	0.001	0.261	CI: –0.115 –0.635
ROM of the left wrist (°)	112.41±26.51	50.0/180.0	117.45±24.20	62.0/200	0.059	0.199	CI: –0.177 –0.573
Grip and Pinch of the right hand (kg)	23.25±10.39	2.9/50.7	26.12±10.54	9.6/58.0	0.001	0.274	CI: –0.102 –0.649
Grip and Pinch of the left hand (kg)	21.89±9.58	5.5/54.7	24.25±10.27	8.0/59.7	0.001	0.238	CI: –0.138 –0.612
6MWD	246.58±115.11	32.0/460.0	286.90±116.01	31.0/540.0	<0.001	0.349	CI: –0.028 –0.725

Data are expressed as mean and SD. Unified Parkinson’s Disease Rating Scale = UPDRS, ROM = Passive Range of Motion, 6MWD = 6 Minutes Walking Distance. Comparisons pre-post rehabilitation were performed by paired Student’s t-test. A p < 0.05 was considered statistically significant.

In PD patients the 6MWD at end of rehabilitation was 42.32±47 meters longer than admission (p < 0.001), corresponding to +17.16 % of admission. Figure 1 describes pre to post changes of 6MWD in PD patients classified according to the HN scale. Patients in stages 1–3 of the HN scale walked significantly ampler distances at the end of rehabilitation (for all, p < 0.05). The effect size of the 6MWD was small in HN stage 3 (Cohens’d = 0.26), while a medium effect was shown in stages HN 1 and 2 (Cohens’d = 0.45 and Cohens’d = 0.57, respectively). No significant improvement was observed in patients in stage HN 4. The 6MWD did not differ between male and female before (p = 0.165) and after rehabilitation (p = 0.067), while was larger in patients aged≤75 years before (p = 0.042) and after rehabilitation (p = 0.015).

Fig. 1

Pre (T0) to post (T1) changes in 6MWD according to the Hoen &Yahr stage. Legend: HN stage 1 includes patients from stages HN 1 (n = 4) and HN 1.5 (n = 2); HN stage 2 includes patients from stages HN 2 (n = 13) and HN 2.5 (n = 8). ° for p < 0.05; * for p = 0.001.

Table 3 reports the correlations between motor disorders of PD and 6MWD outcomes, as assessed by Pearson’s correlation. Table 4 describes the results of backward regression analyses performed on data from PD patients and shows that the BBS (p < 0.001) and right Grip and Pinch at admission (p = 0.001) were the only determinants of final 6MWD. Conversely, no variable was a determinant of gain in 6MWD.

Table 3

Relationships between outcome measures and motor aspects of PD patients (n = 55)

	6 MWD
Admission	At the end of rehabilitation	Gain
Hoehn and Yahr Scale (score)	–0.48**	–0.27*
UPDRS III (score)	–0.40**	–0.27*
Berg Balance Scale (score)	0.60**	–0.10
Nine Hole Test of the right hand (sec)	–0.51**	–0.03
Nine Hole Test of the left hand (sec)	–0.41**	–0.12
ROM of the right wrist (°)	0.34*	–0.06
ROM of the left wrist (°)	0.18	0.03
Grip and Pinch of the right hand (kg)	0.54**	0.02
Grip and Pinch of the left hand (kg)	0.40**	0.18

Relationships were evaluated by Pearson’s correlation coefficient (r). 6MWD = 6 Minutes Walking Distance, Unified Parkinson’s Disease Rating Scale = UPDRS, ROM = Passive Range of Motion. *p < 0.05 and **p < 0.01.

Table 4

Backward stepwise regression analyses performed in PD patients (n = 55)

Dependent variable	Independent variables	β	B	p-value	Adjusted R²
6MWD at the end of rehabilitation				<0.001	0.45
	Berg Balance Scale	0.47	5.083	<0.001
	Grip and Pinch of the right hand	0.36	3.976	0.001

All independent variables are admission scores. β indicates standardized regression coefficient, B = unstandardized regression coefficient, 6MWD = 6 Minutes Walking Distance.

4 Discussion

This study aimed to evaluate 6MWD before and after a conventional rehabilitation program and to identify determinants of 6MWD in PD patients undergoing rehabilitation. At the end of rehabilitation, 6MWD, Grip and Pinch for right and left hand, right wrist ROM, and BBS were significantly improved with respect to admission.

During the study period, the patients continued to maintain their pharmacological treatments, therefore the improvement in 6MWD, Balance, Grip and Pinch, wrist ROM and BBS was not influenced by drug therapy. At end of rehabilitation, in PD patients the improvement in 6MWD was +17.16% of admission and was significantly higher in PD patients with Hoehn and Yahr stage≤3. These findings are in line with Frazzitta et al. (Frazzitta 2010), who demonstrated that 6MWD increased by 17% after rehabilitation in PD patients, and with other studies showing conventional motor rehabilitation increases the 6MWD in PD patients with unilateral or mild-moderate bilateral disease and some postural instability (Bloem 2015; Nadeau 2017).

The study used a backward multiple regression to identify determinants of the 6 minutes walking distance at the end of rehabilitation and considered as independent variables the specific motor disorders of PD. Qualified physiotherapists and occupational therapists evaluated coordination, muscle strength, and rigidity with Nine Hole Peg, Grip and Pinch test, and wrist ROM, which have already been used in PD studies and allow an accurate quantitative measurement of PD symptoms (Picelli 2014; Toktas 2016; Cano-de-la-Cuerda 2020). Multiple regression found that BBS and Grip and Pinch test of the right hand were important determinants of the 6MWD at the end of rehabilitation.

These findings are not confirmed by the literature, which is poor in studies analyzing determinants of walking distance in PD patients undergoing rehabilitation. Up to date, in the literature, there are studies evaluating only walking distance in baseline conditions (Üğüt 2022; Falvo 2009; Christofoletti 2016; Ivey 2012; Carvalho 2020) showing that balance (Christofoletti 2016) and muscle strength (Allen 2010) were essential requirements to walk longer distances in PD patients.

In our study balance was strongly associated with walking distance covered in 6 minutes at the end of rehabilitation and the relationship between 6MWD and BBS was positive. This indicates that balance is an important determinant of gait rehabilitation in patients with PD and suggests that patients with higher balance levels before rehabilitation have a higher probability to walk longer distances after rehabilitation. Appropriate levels of balance are essential to maintain adaptable bodily functions for the full execution of gait (Christofoletti 2016; Takakusaki 2008).

Moreover, right Grip and Pinch was a determinant of 6MWD after rehabilitation, as well.

Associations between Grip and Pinch and 6MWD were positive showing that the walking distance was longer when the handgrip strength was higher. The Grip and Pinch Test measures the maximum isometric strength produced by muscles responsible for forearm extension, flexion of the metacarpals and phalanges, flexion of the fingers, and adduction of the thumb (Hogrel 2015). The handgrip strength measured by Grip and Pinch Test is closely related to total muscle strength (Wind 2010) and, therefore, is an adequate measurement for generalized muscle strength (Buckley 2018).

In PD patients muscle strength is reduced and muscle weakness increases with performance velocity (Nogaki 1999), repeated contractions, and muscle fatigue (Stevens-Lapsley 2012)]. Muscle weakness decreases postural stability and mobility and has a negative impact on the activities that require strength and speed as walking function, so explaining the findings of the study (Allen 2010; Nocera 2010; Paul 2012).

The study also analyzed rigidity, coordination, and UPDRS as determinants, but multiple regression analysis did not demonstrate associations between these variables and 6MWD.

UPDRS III was not a determinant of 6MWD at the end of rehabilitation, although UPRDS is considered an important requirement for this outcome in baseline conditions in PD patients (Ivey 2012). The reason is that the association between UPRDS III and 6MWD after rehabilitation is weaker than others once included in the regression model evaluating specific motor disorders of PD.

6 Strengths

The study shows that balance and generalized muscle strength are important determinants of the improvement in 6MWD in patients undergoing rehabilitation. These findings add knowledge on the role of balance and muscle strength on walking function in PD patients, indicating that they are not only essential requirements to walk longer distances in basal conditions, as reported in the literature (Christofoletti 2016; Ivey F 2012; Carvalho 2020), but also factors affecting gait rehabilitation. Moreover, the use of instrumental tests in assessing rigidity, muscle strength, and coordination, giving a higher level of accuracy and reliability with respect to manual ones was a strength of the study.

Muscle strength as assessed by the Grip and Pinch test is a determinant of the outcome, as well. The current data suggest that the Grip and Pinch test can be a useful tool for assessing a quantitative evaluation of the generalized muscle strength (Buckley 2018; Win 2010) in PD patients and an option with respect to tools evaluating segmental muscle strength.

7 Limitations

Despite these considerations, the current study has some limitations. The study was performed on a population admitted to a Rehabilitation Institute for physical rehabilitation needs. Therefore, our population does not reflect the actual functional disability of every PD patient: those with slight impairment did not require inpatient rehabilitation, while extremely disabled patients would have been transferred directly to skilled nursing facilities after acute care. Patients were admitted to a conventional rehabilitation program and therefore the results may not apply to other programs with different entry criteria. The study did not analyze all motor disorders of PD, that may affect the 6MWD, like tremors and bradykinesia. Execution of the Nine Hole Peg and Grip and Pinch test, used in the study, may have been affected by compliance and capacity of patients to maintain attention for a fairly long time. Due to the retrospective nature of the study, we cannot exclude that, despite good statistical significance, some variables can need a greater sample size to reach an appropriate statistical power.

8 Conclusion

A conventional rehabilitation program improves the 6MWD in PD patients, and balance and generalized muscle strength are important determinants of walking rehabilitation in PD patients. High levels of balance and muscle strength have to be maintained for as long as possible, as well. Therefore, PD patients should be educated to perform continuous physical activity and exercises at home (Keus 2007; van der Kolk 2013). Furthermore, the findings of the study suggest a tailored, planned, and more intensive rehabilitation treatment for these patients with low levels of balance and muscle strength because of their higher risk of achieving low walking levels.

Footnotes

Acknowledgments

The authors would like to thank the health professional Iacopo Orfano for the data collection.

Conflict of interest

The authors have no conflict of interest to declare.

Funding

This work was supported by the “Ricerca Corrente” funding scheme of the Ministry of Health, Italy.

Ethics statement

The study was conducted in accordance with the principles of the Declaration of Helsinki.

Informed consent

Informed consent to the use of personal clinical data for scientific research was obtained from all participants at the time of admission to the hospital.

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