Does Pisa syndrome affect upper limb function in patients with Parkinson’s disease? An observational cross-sectional study

Abstract

BACKGROUND:

Trunk alignment is thought to contribute to upper limb (UL) function. However, this common assumption is not clear in patients with Parkinson’s Disease (PD) suffering from Pisa syndrome (PS). PS is a postural abnormality, characterized by revisable lateral trunk flexion more than 10 degrees.

OBJECTIVE:

To investigate the UL functioning and activities of daily living in PD patients with PS.

METHODS:

Forty-five participants distributed equally in three groups PD patients with PS, PD patients without PS and age/sex matched healthy controls (HC). The function and disability of UL was assessed by Arm Shoulder and Hand (DASH) questionnaire for all groups. PD groups then completed clinical assessments by the Unified Parkinson’s Disease Rating Scale (UPDRS) part II-III, Modified Hoenh & Yahr (mH&Y) staging and the Levodopa Equivalent Daily Dose (LEDD).

RESULTS:

Three groups showed significant differences in DASH questionnaire (p < 0.001) with higher scores for PS group, intermediate for PD group and lower for HC group. PS group also showed higher score in UPDRS-II and mH&Y (p = 0.019), while no differences emerged between PD and PS in UPDRS-III score and LEDD.

CONCLUSION:

Our results demonstrated that PS is associated with major impairment of both UL functioning and activities of daily living in PD patients.

Keywords

Parkinson’s disease Pisa syndrome dystonia lateral trunk flexion upper limb function rehabilitation axial bending

1 Introduction

Pisa syndrome (PS) is considered a rare subtype of axial dystonia, characterized by a lateral trunk flexion of more than 10 degrees and resolution by passive mobilization or lying in supine position (Doherty, van de Warrenburg, Peralta, Silveira-Moriyama, Azulay, Gershanik, & Bloem et al., 2011). In addition to being a drug reaction (Tinazzi, Geroin, Gandolfi, Smania, Tamburin, Morgante, & Fasano 2016), PS often complicates advanced phases of Parkinson’s disease (PD) (Tassorelli, Furnari, Buscone, Alfonsi, Pacchetti, Zangaglia, & Bolla, 2012; Geroin, Smania, Schena, Dimitrova, Verzini, Bombieri,... & Gandolfi, 2015; Tinazzi, Fasano, Geroin, Morgante, Ceravolo, Rossi,... & Cossu, 2015).

The pathophysiological mechanisms of PS in PD are emphasized on either central or peripheral mechanisms (Tinazzi et al., 2016). The central mechanisms refer to basal ganglia dysfunction and abnormal sensorimotor integration (Geroin et al., 2015; Vitale et al., 2016). The peripheral mechanism based on the alterations of the musculoskeletal system such as myopathy and degenerative spinal and soft tissue changes. Both mechanisms may lead to muscle imbalance, weakness, and compensatory posture (Doherty et al., 2011).

PD patients with PS show higher PD asymmetry, back pain, balance and posture disorders and poorer quality of life compared to PD patients without PS (Tassorelli et al., 2012; Geroin et al., 2015; Tinazzi et al., 2015). However, the optimal alignment of bone structures is functionally important in the musculoskeletal system, and the complex interaction of the neuromuscular system is necessary for ergonomic balance and deliberate displacement of the human body (Schwab et al., 2010). Previous studies have shown a direct relationship between trunk alignments and UL function, including manipulative activities (Gillen, Boiangiu, Neuman, Reinstein, & Schaap, 2007; Wee, Hughes, Warner, & Burridge, 2014).

Gillen et al. (2007) found that the neutral trunk alignment provide the most efficient postural alignment for UL functional performance in healthy adults. Moreover, Wee et al. (2014) discovered that trunk restraint has a moderate effect on reduction of UL impairment in chronic stroke patients. In addition, more studies reported a reduction in UL activities result of trunk dysfunction in patients with neurological diseases (Poizner et al. 2000; Reft & Hasan 2002; Ustinovak et al., 2004).

Despite, this robust evidence on the fundamental importance of trunk alignment, no studies to date have investigated the effects of PS, a condition of lateral trunk deviation, on UL function and activates of daily living in patients with PD.

The aim of this study is to investigate the effect of PS on UL function in patients with PD and PS, patients with PD without PS, age- and sex-matched healthy controls.

2 Methods

2.1 Participants

This observational cross-sectional study involved 15 patients with PD and PS (age range 77-50 years, mean 67.87±7.14 SD), 15 patients with PD but without PS (age range 76-55 years, mean 65.07±5.62), and 15 sex- and-age-matched healthy controls (age range 80-57 years, mean 65.80±6.07). The sample size estimated depends on the PD patients with PS with a prevalence of 1.9% (Bonanni et al., 2007).

The controls were recruited from among the patients’ family members who showed no signs of neurological disease at assessment, and UL orthopedic problems during enrollment into the study. All patients were attending the outpatient clinic of the Movement Disorders Division from January 2017 to April 2017, Neurology Unit of Policlinico Tor Vergata (Rome, Italy).

Demographic and clinical characteristics are reported in Table 1. All patients underwent neurological evaluation before enrollment. Inclusion criteria were: a medical diagnosis of PD confirmed according to the United Kingdom Parkinson’s Disease Society Brain Bank criteria (Gelb et al., 1999) and/or PS defined as at least 10 degrees of lateral trunk flexion that can be reduced by passive mobilization or supine positioning (PS≥10) (Doherty et al., 2011). Exclusion criteria were: severe dyskinesia or “on-off” fluctuations; modified Hoehn & Yahr (mH&Y) stage >3 in “ON” medication phase, cognitive impairment; Mini-Mental status Examination (MMSE) <24, PD medication modification in the 3 months preceding enrollment into the study; need for assistive devices to rise from a chair or bed; other neurological, orthopedic or cardiovascular co-morbidities. All patients gave their informed consent to participate in the study. The study was carried out according to the Declaration of Helsinki and was approved by the Local Ethics Committee.

Table 1
Demographic and clinical features of the three groups

PD (Mean±SD) N = 15 PS (Mean±SD) N = 15 HC (Mean±SD) N = 15 P-Values

Gender (Male/Female) 6/9 6/9 6/9 ns

Age (yrs) 65.07±5.62 67.87±7.14 65.80±6.07 ns

BMI (Kg/M²) 27.43±2.90 27.79±6.45 27.75±4.10 ns

Weight (Kg) 77.73±12.42 75.60±14.03 79.07±11.88 ns

Height (Cm) 167.73±9.18 166.67±8.19 169.40±6.90 ns

PD duration (yrs) 3.80±2.96 6.20±3.78 NT ns

UPDRS II score 7.87±3.76 11.47±3.42 NT p = 0.009

UPDRS III score 22.67±7.13 29.73±10.90 NT ns

H &Y stage Modified 1.77±0.68 2.54±0.61 NT p = 0.009

DASH score 17.83±4.42 49.85±13.87 8.50±4.91 p < 0.001

LEDD (mg/day) 468.00±225.14 595.93±247.03 NT ns

Levodopa and Dopamine Agonist 8 7 NT ns

Levodopa 8 7 NT ns

PD onset symptoms (Right/left) 8/7 7/8 NT ns

PS Direction (Right/left) NT 8/7 NT _

	PD (Mean±SD) N = 15	PS (Mean±SD) N = 15	HC (Mean±SD) N = 15	P-Values
Gender (Male/Female)	6/9	6/9	6/9	ns
Age (yrs)	65.07±5.62	67.87±7.14	65.80±6.07	ns
BMI (Kg/M²)	27.43±2.90	27.79±6.45	27.75±4.10	ns
Weight (Kg)	77.73±12.42	75.60±14.03	79.07±11.88	ns
Height (Cm)	167.73±9.18	166.67±8.19	169.40±6.90	ns
PD duration (yrs)	3.80±2.96	6.20±3.78	NT	ns
UPDRS II score	7.87±3.76	11.47±3.42	NT	p = 0.009
UPDRS III score	22.67±7.13	29.73±10.90	NT	ns
H &Y stage Modified	1.77±0.68	2.54±0.61	NT	p = 0.009
DASH score	17.83±4.42	49.85±13.87	8.50±4.91	p < 0.001
LEDD (mg/day)	468.00±225.14	595.93±247.03	NT	ns
Levodopa and Dopamine Agonist	8	7	NT	ns
Levodopa	8	7	NT	ns
PD onset symptoms (Right/left)	8/7	7/8	NT	ns
PS Direction (Right/left)	NT	8/7	NT	_

Abbreviations: PS: denotes patients with Parkinson’s disease and Pisa Syndrome, PD: patients with Parkinson’s Disease (without PS), HC: aged-matched and sex-matched healthy controls, SD: standard deviation, yrs: years, BMI: Body mass index, UPDRS: Unified Parkinson Disease Rating Scale, H&Y: Modified Hoehn and Yahr scale, DASH: Disabilities of the Arm Shoulder and Hand questionnaire, LEDD: Levodopa Equivalent Daily Dose, NT: not tested, ns: non-significant, p significant if <0.05.

2.2 Procedures

Assessments were made in a single session with the patients on their usual drug treatment, during the ON medication phase; all PD patients were on best medical treatment. The diagnostic and neurological evaluations were performed by a specialist in movement disorders. Clinical and demographic variables were recorded: gender, age, weight, height and body mass index (BMI). Patients were assessed using Unified Parkinson’s Disease Rating Scale (UPDRS) part II (activities of daily living) and part III (motor performance) (Fahn et al., 1987) and Modified Hoehn and Yahr staging scale (mH & Y) (Hoehn & Yahr 1967); Levodopa equivalent daily dose (LEDD) was calculated using standardized conversion formulas (Tomlinson et al., 2010). Also, we used the MMSE to eliminate potential cognitive impairment (Folstein et al., 1975).

Further information was gathered for the PD and PS patients: PD duration, affected side, direction of leaning at the thoracolumbar level for PS which measured by wall goniometer to confirm the PS diagnosis. The primary outcome measure was the “disability and symptoms” of the UL assessed by “Disabilities of the Arm Shoulder and Hand questionnaire” (DASH) (Padua et al., 2003; Institute for Work and Health, 2006). It is a 30-item questionnaire (21 physical function items, 6 symptom items, and 3 social/role function items) with 2 optional 4-item modules. The DASH is easy to use and takes less than 13 minutes to complete (Bot et al., 2004). A 5-point scale is used for each item with 1 = no difficulty and 5 = extremely difficult. A disability/symptom score is easily determined, which is converted to a score out of 100, with higher scores representing greater disability.

2.3 Statistical analysis

Chi-square test was used to examine differences between groups in categorical variables. Nonnormality of continuous variables was checked by visual inspection of distribution and confirmed by Kolmogorov-Smirnov test. Since continuous variables were not normally distributed, values were expressed as means±SDs. We used nonparametric Mann–Whitney U test and Kruskall-Wallis test to assess differences among groups. Statistical significance was set at p < 0.05. Statistical analysis was performed by using IBM-SPSS-22.

3 Results

All PD patients were receiving chronic therapy with a dopaminergic drug and showed good motor compensation in appendicular function. Both PD groups received the same medication: 16 patients took (Levodopa and Dopamine Agonist) and 14 patients took Levodopa. None had psychiatric disturbances or cognitive impairments. There were no significant differences among the groups in gender, age and biometrical data distribution (Table 1).

Groups showed differences in DASH score: PS group showed the highest score (mean 49.85±13.87, SD), HC group had the lowest DASH score (8.50±4.91) and PD group had intermediate values (17.83±4.42). The differences were statistically significant among the three groups (p < 0.001) and also between PS and PD group (p < 0.001) and PD and control group (p < 0.001) (Fig. 1).

Fig.1

The differences and average of the Disabilities of the Arm Shoulder and Hand questionnaire (DASH) scores, represent as (Mean±SD) in PD: patients with Parkinson’s Disease (without PS), PS: patients with Parkinson’s disease and Pisa Syndrome and HC: aged-matched and sex-matched healthy control groups. The significance values are reported (_* = P < 0.05).

There were no differences between PD and PS group in UPDRS-III score and LEDD. Contrariwise the two groups showed differences in UPDRS-II score (p = 0.019) and mH&Y staging (p = 0.019) (Fig. 2).

Fig.2

The differences and average of UPDRS: Unified Parkinson Disease Rating Scale second and third parts, H&Y: Modified Hoehn and Yahr scale, LEDD: Levodopa Equivalent Daily Dose represent as (Mean±SD) in PD: patients with Parkinson’s Disease (without PS), and PS: patients with Parkinson’s disease and Pisa Syndrome groups. The significance values are reported (_* = P < 0.05).

4 Discussion

The present study is the first to investigate the effect of PS on UL functioning. Our findings showed worse DASH score in PS group, indeed revealed that PS affects negatively UL functioning and physical performances. Interestingly, these results support the hypothesis of a relationship between trunk alignment and UL functions (Bobath 1990; Fisher 1987; Gillen 2004a; Gillen 2004b). In consistent with a previous study (Gillen et al., 2007) which demonstrated slower UL performance in forward or lateral flexed trunk positions, compared with neutral trunk position in healthy subjects.

Moreover, we noticed that PD patients without PS exhibit an impaired UL function, with intermediate score between PS and HC that could be an obvious consequence of PD motor disturbances, as previously described in other works (Harrington & Haaland 1991; Peto et al., 1995; Negrotti et al., 2005; Ghbhardt et al., 2008; Proud & Morris 2010). DASH results and UPDRS-II scores (evaluating activity of daily living) were significantly worse in PS group.

PS group showed a higher mH&Y staging result of the postural abnormality. Contrariwise, the non significant differences in UPDRS-III score and LEDD suggests that the UL limitations in PS patients were not related to severe motor phenotype but it may indeed depend on the lateral deviation of the trunk. However, it should be mentioned that in PS there is a higher prevalence of cognitive disturbances than in PD patient without this postural abnormality (Vitale et al., 2016) that could be affect the manual abilities. Therefore, we excluded patients with severe cognitive impairment to limit this bias.

The relationship between the UL and trunk has been elegantly modeled by Tyler and Hasan 1995, which divided movements in focal and nonfocal. The focal movements are the movements of the UL and the muscles directly involved in producing the movement, while the Nonfocal movements are the movements and muscle activity that support the focal movement (Tyler & Hasan 1995). The trunk musculature performs nonfocal movements in anticipation of the focal movements of the UL. Before the focal UL movement occurrence, postural muscles are activated to allow focal movements of the UL to occur more smoothly and to prevent destabilization of the postural system (Tyler & Hasan, 1995).

The peripheral mechanism of PS demonstrated abnormal tonic activation and muscular atrophy with fatty degeneration in non focal movement muscles such as: paraspinal, abdominal oblique, rectus femoris, rectus abdominis, external oblique, and quadratus lumborum muscles and lumbar paraspinal muscles (Di Matteo, Fasano, Squintani, Ricciardi, Bovi, Fiaschi, & Tinazzi et al., 2011; Tassorelli et al., 2012; Tinazzi, Juergenson, Squintani, Vattemi, Montemezzi, Censi, & Fasano, 2013). The relationship between the UL function, trunk alignment (Tyler & Hasan, 1995) and peripheral mechanism of PS (Di Matteo et al., 2011; Tassorelli et al., 2012; Tinazzi et al., 2013) suggests that the nonfocal movements (trunk musculature) deteriorated in PD patients with PS and make the focal movements (UL muscles) of UL more difficult and limited.

Based on the current study findings, we recommended for the rehabilitation programs to pay attention for UL function in PD patients, abnormal muscular activation and lack of trunk misalignment awareness. Moreover, the functional exercise intervention should be scheduled according to individual characteristics of patients such as level of function and physical capacity.

This study has several limitations firstly we defined PS as a lateral flextion >10 because the absence of definite diagnostic criteria of PS (Tinazzi et al., 2016). We used the MMSE to test the cognitive function, but we did not use more specific cognitive evaluation batteries. Finally, we did not assess the UL muscles activity and trunk muscles activity by electromyogram (EMG). Future studies assess the UL muscles activity and trunk muscles activity in PD with PS using the EMG during the activity of daily living. However, the results are clear in indicating the role of lateral trunk deviation in provoking an impairment of UL functions.

5 Conclusion

This pilot observational cross sectional study suggests that the lateral bending in PS is associated with significantly reduction in UL functioning and activates of daily living. Our results contribute to understanding much of the literature on this subject by complementing some of extant data. Collectively, we recommended rehabilitation specialist to consider improving UL movements and functions as well as improving lateral trunk flexion or other postural deformities in PD patients.

Conflict of interest

None to report.

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