The Role of Muscle Strength in the Sit-to-Stand Task in Parkinson's Disease

Background Rising from a chair or the sit-to-stand (STS) task is frequently impaired in individuals with Parkinson's disease (PD). These patients commonly attribute such difficulties to weakness in the lower extremities. However, the role of muscle strength in the STS transfer task has not been fully elucidated. Objective We aim at determining the role of muscle strength in the STS task. Methods We studied 90 consecutive patients with PD and 52 sex- and age-matched controls. Lower limb strength was determined in both legs by clinical examination using the Medical Research Council Scale, dynamometric (leg flexion) and weighting machine (leg pressure) measures. Patients were interrogated regarding the presence of subjective lower limb weakness or allied sensations. Results There were 20 patients (22.2%) with abnormal STS task (item 3.9 of the MDS-UPDRS-III ≥2 points). These patients had higher modified Hoehn and Yahr stage (P  <  0.001) and higher total motor scores of the MDS-UPDRS(P  <  0.001), compared with 70 PD patients with normal STS task. Patients with abnormal STS task endorsed lower limb weakness more frequently and had lower muscle strength in the proximal lower extremities, compared to PD patients with normal STS task and normal controls. The presence of perceived lower limb weakness increased the risk of an abnormal STS task, OR: 11.93 (95% C.I. 1.51–94.32), whereas a hip extension strength ≤9 kg/pressure also increased the risk of abnormal STS task, OR: 4.45 (95% C.I. 1.49–13.23). In the multivariate regression analysis, bradykinesia and decreased hip strength were related to abnormal STS task. Conclusions Patients with PD and abnormal STS task complain more commonly of lower limb weakness and have decreased proximal lower limb strength compared to patients with PD and normal STS task, likely contributing to abnormalities in performing the STS task.


Introduction
Parkinson's disease (PD) is a neurological disorder characterized by degeneration of dopaminergic cells in the substantia nigra [1].Patients with PD develop diverse motor and nonmotor manifestations during the course of the disease.Bradykinesia, muscle rigidity, and tremor are the most commonly recognized motor manifestations; however, other symptoms, such as difculty in rising from a chair or performing the sit-to-stand (STS) task are frequently reported by these patients [2].Te STS task plays an important role in general mobility determining functional independence and infuencing the quality of life [2,3].It is estimated that about 44% of patients with PD have some degree of difculty to perform this task [2].
Abnormalities in kinematics, joint torques, and postural instability have been deemed important in the pathogenesis of abnormal STS task in patients with PD [4][5][6].Patients with PD frequently complain of decreased muscle strength in the lower limbs and attribute their difculties for rising to the chair to such perceived weakness [7,8].Clinicians frequently face the clinical paradox of fnding normal muscle strength in the lower limbs of patients with PD during the neurological examination, while observing prominent abnormalities in the STS task attributed to weakness in a proportion of cases.
A number of studies have shown decreased muscle strength in patients with PD by means of reproducible, quantitative methods [9][10][11].Tis includes studies reporting decreased lower limb muscle strength, mainly at the hip level, associated with difculties for STS task [5,12].Contrasting research studies have not found diferences in muscle strength during the STS task in PD patients compared with healthy controls [13].However, the number of individuals enrolled in these studies is relatively small, for that reason, we studied muscle strength in patients with PD and matched healthy controls by clinical and dynamometric methods and correlated with the STS task in these patients.

Materials and Methods
We enrolled consecutive patients diagnosed with PD from a tertiary-care center for movement disorders.Inclusion criteria considered patients of both sexes, age equal or older than 18 years and with a diagnosis of Parkinson's disease, according to the Queen Square Brain Bank Criteria [14].Exclusion/elimination criteria considered patients with Parkinsonism who would not fulfll diagnostic criteria for PD and the presence of musculoskeletal or neurological abnormalities that may result in decreased motor strength in the lower limbs independently of PD.
Te clinical evaluation was performed by the Movement Disorders Society Unifed Parkinson's Disease Rating Scale part III or motor score (MDS-UPDRS-III).We assessed for signs of severe neuropathy and spasticity, including abnormal muscle refexes and the Babinski sign in all patients.Item 3.9 "arising from chair" was used to assess for the STS task.Te item has fve subcategories as follows: (0) no problems, patient is able to arise quickly without hesitation; (1) slight: patient is slower than normal and may need more than one attempt or move forward in the chair to arise; (2) mild: patient pushes him/herself up from the arms of the chair without difculty; (3) moderate: patient needs to push of, but tends to fall back, or may have to try more than once using the arms of the chair, but can get up without help; and (4) severe: patient is unable to arise without help.For the purpose of this study, we defned an "abnormal" item 3.9 "arising from chair" as a score equal or higher than 2, as a score of 1 may just refect hesitation or poor preparation to stand up from the chair, and it is uncertain if this represents a clear abnormality.We calculated composite scores for leg tremor, rigidity, and bradykinesia by totaling items of each leg and dividing them between two.
Te disease stage was determined by the modifed Hoehn and Yahr scale [15].Te total levodopa equivalent daily dose (LEDD) at the time of the clinical evaluations was also assessed [16].We recorded the presence of dyskinesia during the neurological examination.We also evaluated the presence of orthostatic hypotension (OH) while seated and 3 minutes after standing and defned OH as sitting-tostanding systolic blood pressure drop ≥20 mmHg or a diastolic blood pressure drop ≥10 mmHg [17].
We assessed the frequency of perceived lower limb weakness in all patients and matched controls.Abnormal lower limb sensations, such as "heavy" or "fatigued" legs, were considered within the spectrum of lower limb weakness.Tese sensations were rated by each patient from 1 (very mild) to 10 (very severe).Patients also rated the functional impact of weakness and allied sensations as "mild": limitation only for long hikes, i.e., more than 5 blocks; "moderate": limitation to walk between 1 and 5 blocks; and "severe": limitation to walk few meters or to walk at all.In addition, we enrolled 52 sex-and age-matched healthy controls.We assessed lower limb strength, perceived weakness, and allied sensations in these controls.
Te strengths of iliopsoas, rectus femoris, and sartorius and pectineus muscles were assessed by manual muscle testing using the Medical Research Council (MRC) Scale [18]] and by dynamometric calculation (ZP-500, Digital Force Gauge, Alipo, China).Te rectus femoris, vastus lateralis, vastus medialis, and vastus intermedius were assessed during manual test of leg (knee) extension.Te hamstrings (biceps femoris, semitendinosus, and semimembranosus), gracilis, sartorius, gastrocnemius, and popliteus muscles strength were individually assessed in each leg during sequential leg pressure over the foor using a calibrated weighing machine (BF-679W, Tanita, Arlington Heights, Illinois, USA).Reproducibility for these tests has been previously determined [8].Leg pressure requires maximal muscle strength (force) generated by rapid muscle contractions (velocity).Muscle power (force × velocity) has been found decreased in PD and such defcit becomes more evident at increasing velocities of isokinetic muscle contractions [19].Te study was approved by the local committee of ethics at the Sante Medical Tower (number: 20220501) and patients and controls provided written informed consent to participate in the study.

Statistics
We summarized data in means and standard deviations and percentages.Te X 2 and Fisher's exact test were used to compare nominal or ordinal data.Te paired t-test was used to compare means between patients and age-matched controls.Risks were calculated with odd ratios (ORs) and 95% confdence intervals (C.Is).Statistical evaluations were performed using SPSS version 22; a P value <0.05 was considered signifcant.We ran two multivariate logistic regression analyses.In model 1, we tested the efect of signifcant variables obtained in the bivariate analysis on the dependent variable: abnormal STS; in model 2, we tested variables with a plausible causal efect on the abnormal STS task.An estimated weight of the independent variables was assessed with exponentiation of B (Exp B) coefcient.Goodness of ft of the regression model was evaluated with the Hosmer-Lemeshow test, and a P value <0.05 was considered as poor ft.

PD Patients with and without Abnormal STS Task.
We studied 92 consecutive patients with PD.Two patients were excluded, one had lumbar stenosis, resulting in lower limb weakness, and one had a glioma presenting initially 2 Parkinson's Disease with Parkinsonism.We analyzed 90 patients with PD.Tere were 20 (22.2%) patients with abnormal STS task (item 3.9, ≥2 points).Tere were no diferences in age and sex distribution between PD patients with and without abnormal STS task.Te evolution time of PD did not difer between groups.However, patients with abnormal STS task had a higher modifed HY stage (P < 0.001) and MDS-UPDRS-III total score (P < 0.001) and were taking higher doses of LEDD, although this variable did not reach statistical signifcance (P � 0.174) (Table 1).No diference in OH was observed between groups.A higher proportion of perceived lower limbs weakness and allied sensations (P � 0.004) was observed among patients with abnormal STS task, and they rated these abnormal sensations greater than PD patients with normal STS task (P < 0.001) (Table 1).Te presence of perceived lower limb weakness greatly increased the risk of an abnormal STS task, OR: 11.93 (95% C.I. 1.51-94.32).
Patients with PD and abnormal STS task had a signifcantly higher composite score for leg bradykinesia (P < 0.001) (Table 1).Leg tremor did not show signifcance between groups (P � 0.405), whereas leg rigidity showed a statistically signifcant trend (P � 0.053).Items for gait, "freezing," and postural instability were higher in patients with abnormal STS task (P < 0.001, for all variables).A hip extension strength ≤9 kg increased the risk of an abnormal STS task, OR: 4.45 (95% C.I. 1.49-13.23).Te lower muscle strength at the hip level was observed in patients with abnormal STS task (Table 1).
In the multivariate analysis, including statistically signifcant variables from the bivariate analysis as independent (model 1), gait and leg strength (≤9 kg) were included in the fnal model.In model 2, we included composite leg tremor, leg rigidity, and leg bradykinesia scores as well as leg strength for hip extension (≤9 kg); only the latter two variables showed signifcance in the fnal regression model (Table 2).When variables that may explain an abnormal STS task were included as independent (model 2) such as leg bradykinesia, leg rigidity, leg tremor, and muscle strength for hip extension, age, sex, and evolution time of PD; only leg bradykinesia and leg strength (≤9 kg) were included in the fnal regression model (Table 2).

PD Patients with Abnormal STS Task vs. Controls.
We compared 20 patients with PD and abnormal STS task with sex-and age-matched controls.Patients with PD and abnormal STS task endorsed lower limb weakness much more frequently than controls: 95 vs. 21% (P<0.001) and rated their abnormal lower limb sensations as more severe than controls(P < 0.001) (Table 3).Decreased muscle strength at the hip level was detected in patients compared with controls by MRC or quantitative assessment (Table 3).

Discussion
In this study, we found that patients with PD and moderateto-severe abnormal STS task (≥2 points in item 3.9 of the MDS-UPDRS-III) have increased complains related to the lower limb weakness and rated such weakness as more severe compared with PD patients with normal STS task.Te presence of perceived lower limb weakness increased the risk of an abnormal STS task by 11.93.
Patients with PD and moderate-to-severe abnormal STS task also had higher scores in the Hoehn and Yahr and MDS-UPDRS part III, suggesting that central motor abnormalities, particularly the lower limb bradykinesia and rigidity, may play a role in difculties rising from a chair.Tese patients had decreased muscle strength in the lower extremities compared with PD patients with normal STS task and normal controls.Tis weakness was detected at the hip level by assessing isokinetic muscle contractions, suggesting that decreased torque at the coxofemoral joint may infuence the dynamics of the STS task.We found that decreased muscle torque for hip extension (≤9 kg) signifcantly increased the risk for having an abnormal STS task.However, this diference was not found with hip fexion assessed by dynamometric measures.
Te relatively small diference in muscle strength between PD patients with normal or abnormal STS task or normal controls suggests that such decreased muscle strength only partially explains the difculties in the STS task in most patients with PD and is difcult to detect in routine clinical examination.
Body kinematics have shown that this technique is useful to classify individuals with and without PD after assessing the STS task [20,21].Patients with PD use greater preparative strategies compared to normal subjects to stand up by means of increased preparatory hip or trunk fexion with greater forward displacement of the center-of-mass (COM) (Figures 1(a) and 1(b)) [4,22].It has been postulated that such preparatory movements are related to decreased muscle strength in the lower extremities, particularly at the hip level [22].Indeed, decreased hip and knee extensor strength was observed in 10 patients with PD, compared with 10 sex-and age-matched controls in one study [5].Our study supports this observation.Te greater forward body inclination observed in patients with PD as a strategy to achieve the STS task may result in greater backward stability at the expense of increased risk of forward balance loss at the time of movement termination [23].
Usually, patients with PD have shown prolonged STS total times compared with healthy controls [24].Tis difference has been attributed to inappropriate peak hip fexion and ankle dorsifexion torques, prolonged torque production, and difculty to shift from the fexion to extension direction during the STS task [24].Patients with PD may take longer to generate the force to achieve the STS task, and they dedicate a larger proportion of time to complete the fexion momentum phase compared with controls [2].
Previous studies have shown that maximal velocity of the COM and limb support determined by the hip height at the instant of peak velocity were predictors of success in the STS task (Figures 1(c) and 1(d)), whereas dynamic stability does not seem to predict such success [6,25].Patients with PD redistribute their joint torques in the lower extremities when performing the STS task; this phenomenon seems related to compensation in order to try to gain postural stability [26].

Parkinson's Disease
Patients with PD may show increased angular velocity of the trunk in the sagittal plane to complete the STS task, even at the early stages of the disease compared to healthy individuals supporting the notion that appropriate acceleration while performing the STS task is key to achieve it successfully.Patients with PD sufering more postural instability and gait difculty had shown a slower anteroposterior COM velocity displacement, while performing the STS task by biomechanical analysis [25].We confrmed those fndings as in our study patients with PD, and abnormal STS task had signifcantly greater scores (worse) in gait, freezing, and postural instability than patients with PD and unaltered STS task.
Te pathophysiology of decreased muscle strength in PD is not fully understood.A central mechanism has been postulated as the Parkinsonian features does not fully explain the reduced muscle strength [5].In our study, we found that bradykinesia and decreased muscle strength were

4
Parkinson's Disease independently related with abnormal STS task; however, the coefcient of correlation (R 2 ) was low in the fnal regression model, suggesting that these two variables explain less than 25% of the STS task abnormality, indicating that other mechanisms may play an important role.Intrinsic abnormalities in skeletal muscles have been detected in patients with PD, as there is higher distribution and larger cross-sectional area of type I muscle fbers, which is considered a compensatory mechanism for heterogenic changes of type II fbers [27].However, mitochondrial dysfunction with decreased β-oxidation in muscles and decreased 12-14 long-chain acylcarnitines during the early stages of PD patients have been reported [28,29].
Our study has a number of limitations; we were not able to compare males with females.Moreover, we did not carry computed kinematics that would help to determine which aspects of the STS task correlate better with the hip torque.In our study, we did not determine the efect of therapy in the muscle strength and STS task.Tere is evidence that task-specifc training using preparatory audiovisual cues may improve overall dynamic stability in forward and backward balance loss [23].Audiovisual cues increase hip fexion and knee extension torques, decrease time to complete the STS task, and decrease the time to peak joint torques with increase in peak horizontal and vertical velocities of COM [30].Another limitation is that we did not  Parkinson's Disease assess the presence of recent falls that may be related to abnormal; however, no patient had a history of recent bone fractures or surgery for joint prothesis.

Concluding Remarks
Abnormalities in the STS task have an important role in mobility in patients with PD.Te pathogenesis of such abnormalities is not fully understood; but it seems to implicate dynamic muscle adjustments to control displacement of the COM and appropriate torque transmission to the joints of the lower extremities.Patients with abnormal STS task frequently complain of the lower limb weakness and allied sensation and have decreased muscle strength particularly around the hips.Muscle strength ≤9 kg for hip extension and leg bradykinesia were independently associated with an abnormal STS task; this suggests a role of peripheral and central mechanisms for abnormal chair rising in patients with PD.

Figure 1 :
Figure 1: Te STS task in Parkinson's disease.(a, b) Increased compensatory trunk fexion, patients tend to sit down near the border of a chair.(c, d) Patients show increased velocity during the rising stage, increasing the forward instability but decreasing backward instability.

Table 1 :
Clinical and demographic features between patients with abnormal and normal sit-to-stand tasks.OH is defned as drop in the systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg. *

Table 2 :
Multivariate analysis to assess the efect of muscle strength and Parkinsonian variables on the sit-to-stand task.

Table 3 :
Clinical and demographic features between patients with PD and controls.
MDS-UPDRS-III, Movement Disorders Society Unifed Parkinson's Disease Rating Scale part III; MRC, Medical Research Council; VAS, visual analog scale.