Screening cut-off scores for clinically significant fatigue in early Parkinson's disease.

Background: Fatigue is one of the most disabling non-motor symptoms in PD. Researchers have previously used cut-offs validated in non-PD conditions when using the Fatigue Severity Scale (FSS) or the Multidimensional Fatigue Inventory (MFI) scores to evaluate fatigue in PD. Objective: We used a set of criteria for diagnosing clinically significant fatigue in PD to identify the proper cut-offs of the FSS and MFI. Methods: One hundred thirty-one PD patients (59F; age 67.3 ± 7.6 y; H&Y 1.6 ± 0.7) were assessed for clinically significant fatigue, followed by the FSS, MFI, Center for Epidemiologic Studies Depression Scale (CES-D), and Montreal Cognitive Assessment (MOCA). Mean scores were compared between 17 patients who met diagnostic criteria (significant fatigue group, SFG) and 114 who did not (non-significant fatigue group, NSFG). Results: The SFG had significantly higher scores in the 9-item FSS (p <.0001), total MFI score (p <.0001), and every MFI dimension except reduced motivation (p =.1) than the NSFG. Using area under the curve (AUC) of receiver operating characteristic (ROC) analyses, we recommend the following cut-offs: 9-item FSS 37; total MFI 60; general fatigue 11; reduced activity 10; physical fatigue 9; mental fatigue 9; and reduced motivation 9. Conclusions: The recommended cut-offs for clinically significant fatigue in the FSS, MFI, and MFI dimensions will be valuable for diagnosing clinically significant fatigue and for future studies in investigating pathophysiology and potential treatments of fatigue in PD.

The Effect of Skeletal Muscle-Pump on Blood Pressure and Postural Control in Parkinson's Disease.

PURPOSE: Activation of the calf (gastrocnemius and soleus) and tibialis anterior muscles play an important role in blood pressure regulation (via muscle-pump mechanism) and postural control. Parkinson's disease is associated with calf (and tibialis anterior muscles weakness and stiffness, which contribute to postural instability and associated falls. In this work, we studied the role of the medial and lateral gastrocnemius, tibialis anterior, and soleus muscle contractions in maintaining blood pressure and postural stability in Parkinson's patients and healthy controls during standing. In addition, we investigated whether the activation of the calf and tibialis anterior muscles is baroreflex dependent or postural-mediated. METHODS: We recorded electrocardiogram, blood pressure, center of pressure as a measure of postural sway, and muscle activity from the medial and lateral gastrocnemius, tibialis anterior, and soleus muscles from twenty-six Parkinson's patients and eighteen sex and age-matched healthy controls during standing and with eyes open. The interaction and bidirectional causalities between the cardiovascular, musculoskeletal, and postural variables were studied using wavelet transform coherence and convergent cross-mapping techniques, respectively. RESULTS: Parkinson's patients experienced a higher postural sway and demonstrated mechanical muscle-pump dysfunction of all individual leg muscles, all of which contribute to postural instability. Moreover, our results showed that coupling between the cardiovascular, musculoskeletal, and postural variables is affected by Parkinson's disease while the contribution of the calf and tibialis anterior muscles is greater for blood pressure regulation than postural sway. CONCLUSION: The outcomes of this study could assist in the development of appropriate physical exercise programs that target lower limb muscles to improve the muscle-pump function and reduce postural instability in Parkinson's disease.

Effect of Parkinson's Disease on Cardio-postural Coupling During Orthostatic Challenge.

Cardiac baroreflex and leg muscles activation are two important mechanisms for blood pressure regulation, failure of which could result in syncope and falls. Parkinson's disease is known to be associated with cardiac baroreflex impairment and skeletal muscle dysfunction contributing to falls. However, the mechanical effect of leg muscles contractions on blood pressure (muscle-pump) and the baroreflex-like responses of leg muscles to blood pressure changes is yet to be comprehensively investigated. In this study, we examined the involvement of the cardiac baroreflex and this hypothesized reflex muscle-pump function (cardio-postural coupling) to maintain blood pressure in Parkinson's patients and healthy controls during an orthostatic challenge induced via a head-up tilt test. We also studied the mechanical effect of the heart and leg muscles contractions on blood pressure. We recorded electrocardiogram, blood pressure and electromyogram from 21 patients with Parkinson's disease and 18 age-matched healthy controls during supine, head-up tilt at 70°, and standing positions with eyes open. The interaction and bidirectional causalities between the cardiovascular and musculoskeletal signals were studied using wavelet transform coherence and convergent cross mapping techniques, respectively. Parkinson's patients displayed an impaired cardiac baroreflex and a reduced mechanical effect of the heart on blood pressure during supine, tilt and standing positions. However, the effectiveness of the cardiac baroreflex decreased in both Parkinson's patients and healthy controls during standing as compared to supine. In addition, Parkinson's patients demonstrated cardio-postural coupling impairment along with a mechanical muscle pump dysfunction which both could lead to dizziness and falls. Moreover, the cardiac baroreflex had a limited effect on blood pressure during standing while lower limb muscles continued to contract and maintain blood pressure via the muscle-pump mechanism. The study findings highlighted altered bidirectional coupling between heart rate and blood pressure, as well as between muscle activity and blood pressure in Parkinson's disease. The outcomes of this study could assist in the development of appropriate physical exercise programs to reduce falls in Parkinson's disease by monitoring the cardiac baroreflex and cardio-postural coupling effect on maintaining blood pressure.

Early Detection of Parkinson's Disease Using Center of Pressure Data and Machine Learning.

Parkinson's disease (PD) is a progressive neurodegenerative disorder resulting in abnormal body movements. Postural instability is one of the primary motor symptoms of PD and contributes to falls. Measurement of postural sway through center of pressure (COP) data might be an objective indicator of Parkinson's disease. The goal of this work is to use machine learning to evaluate if different features of postural sway can differentiate PD patients from healthy controls. Time domain, frequency domain, time-frequency, and structural features were extracted from COP data collected from 19 PD patients and 13 healthy controls (HC). The calculated parameters were input to various machine-learning models to classify PD and HC. Random Forest outperformed the rest of the classifiers in terms of accuracy, false negative rate, F1-score, and precision. Time domain features had the best performance in differentiating PD from HC compared to other feature groups.

Placebo responses in Parkinson's disease.

Parkinson's disease (PD) patients exhibit strong placebo responses in clinical trials. Patient characteristics that affect placebo include patients' expectations of good outcomes, genetic variants, and personality. The presence of motor fluctuation and high baseline UPDRS motor scores predicted placebo response. However, gender, age, duration of PD, religion, or level of education do not correlate with placebo response. PD patients who are preconditioned with active treatment such as apomorphine have more robust placebo effects. Studies that focused on patients with motor fluctuations, surgical intervention, or higher probability of placebo assignment had higher rates of placebo response. Patients view participating in placebo-controlled trials positively. Placebo effect can be measured objectively using neuroimaging and neurophysiological techniques. PET studies show that placebo-induced improvement is associated with dopamine release in the dorsal striatum and that the expectation of receiving the reward, not the reward itself, increased dopamine release in the ventral striatum. Expectations of benefitting from repetitive transcranial magnetic stimulation also induced dopamine release. Expectations of receiving a dopaminergic drug induced changes in fMRI in a reward-learning task. Single cell recordings demonstrate that placebo response is associated with changes of single neuronal activities in the basal ganglia circuit. These studies demonstrate that placebo effects are genuine biological responses to the administration of placebo. In clinical trials, we can use several approaches to minimize placebo responses. In clinical practice, we can use approaches to harness the power of placebo and minimize nocebo effects to improve patients' outcome.

Relationship between Ischemic Stroke and Pulse Rate Variability as a Surrogate of Heart Rate Variability.

Autonomic reflex ascertains cardiovascular homeostasis during standing. Impaired autonomic reflex could lead to dizziness and falls while standing; this is prevalent in stroke survivors. Pulse rate variability (PRV) has been utilized in the literature in lieu of heart rate variability (HRV) for ambulatory and portable monitoring of autonomic reflex predominantly in young, healthy individuals. Here, we compared the PRV with gold standard HRV for monitoring autonomic reflex in ischemic stroke survivors. Continuous blood pressure and electrocardiography were acquired from ischemic stroke survivors (64 ± 1 years) and age-matched controls (65 ± 2 years) during a 10-minute sit-to-stand test. Beat-by-beat heart period (represented by RR and peak-to-peak (PP) intervals), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse arrival time (PAT), an indicator of arterial stiffness, were derived. Time and frequency domain HRV (from RR intervals) and PRV (from PP intervals) metrics were extracted. PAT was lower (248 ± 7 ms vs. 270 ± 8 ms, p < 0.05) suggesting higher arterial stiffness in stroke survivors compared to controls during standing. Further, compared to controls, the agreement between HRV and PRV was impaired in stroke survivors while standing. The study outcomes suggest that caution should be exercised when considering PRV as a surrogate of HRV for monitoring autonomic cardiovascular control while standing in stroke survivors.

3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia.

INTRODUCTION: 3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. METHODS: We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). RESULTS: Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had > 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P < 0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (P < 0.0001). Requirement for rescue and adverse events were more common in the placebo group. DISCUSSION: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM. Muscle Nerve 57: 561-568, 2018.

Centella asiatica triterpenes for diabetic neuropathy: a randomized, double-blind, placebo-controlled, pilot clinical study.

BACKGROUND: Diabetic neuropathy (DN), a common complication of diabetes mellitus, results from hyperglycemia, poor microcirculation and attendant nerve damage. Currently available treatments relieve symptoms, but do not modify the neurodegeneration underlying DN. Centella asiatica (CA) triterpenes improved microcirculation in earlier clinical studies, and showed neurotropic effects in preclinical models suggesting a potential disease modifying effect in DN. This 52-week, randomized, double-blind, placebo-controlled trial examined the effects of CAST, a standardized CA extract containing triterpenes, on neuropathy symptoms in Type II diabetic subjects. PATIENTS AND METHODS: The study enrolled patients with a history of Type II diabetes, with evidence of symptomatic symmetrical DN with total symptom score (TSS) ≥4, and stable HbA1c level <8. The primary outcome measure was TSS, which assessed intensity and frequency of parasthesia, numbness, pain and burning symptoms self-reported by patients. Secondary measures were nerve conduction, neurological impairment score, and quantitative sensory testing. RESULTS: Comparing CAST (n=21) and Placebo (n=22) groups, significant reductions from baseline for TSS (p<0.01) and paresthesia (p<0.01) were seen only in CAST treated groups. Numbness increased from baseline only in the Placebo group (p<0.05) and was significantly higher than for the CAST group (p<0.001). Burning sensation was reduced in both groups (p<0.01). Plasma triterpene levels in patients treated with CAST mirrored neurotropic concentrations in vitro. CONCLUSIONS: CAST is a potential oral treatment for diabetic neuropathy, as it is well tolerated and effective in reducing the severity of DN symptoms in patients with Type II diabetes.

Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.

OBJECTIVE: To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD). METHODS: Patients with PD and depression were enrolled in this multicenter, double-blind, sham-controlled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex [DLPFC]), DLPFC ( + sham M1), M1 + DLPFC, or double sham. The TMS course consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000 stimuli for each M1 (50 × 4-second trains of 40 stimuli at 10 Hz). Patients were evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Primary endpoints were changes in motor function assessed with the Unified Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression Rating Scale at 1 month. RESULTS: Of the 160 patients planned for recruitment, 85 were screened, 61 were randomized, and 50 completed all study visits. Real M1 rTMS resulted in greater improvement in motor function than sham at the primary endpoint (p < 0.05). There was no improvement in mood in the DLPFC group compared to the double-sham group, as well as no benefit to combining M1 and DLPFC stimulation for either motor or mood symptoms. CONCLUSIONS: In patients with PD with depression, M1 rTMS is an effective treatment of motor symptoms, while mood benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1 and DLPFC in each rTMS session showed no evidence of synergistic effects. CLINICALTRIALSGOV IDENTIFIER: NCT01080794. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with PD with depression, M1 rTMS leads to improvement in motor function while DLPFC rTMS does not lead to improvement in depression compared to sham rTMS.

Parkinson's disease-related fatigue: A case definition and recommendations for clinical research.

Fatigue is one of the most common and disabling symptoms in Parkinson's disease (PD). Since fatigue was first described as a common feature of PD 20 years ago, little progress has been made in understanding its causes or treatment. Importantly, PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. In response, the Parkinson Disease Foundation and ProjectSpark assembled an international team of experts to create recommendations for clinical research to advance this field. The working group identified several areas in which shared standards would improve research quality and foster progress including terminology, diagnostic criteria, and measurement. Terminology needs to (1) clearly distinguish fatigue from related phenomena (eg, sleepiness, apathy, depression); (2) differentiate subjective fatigue complaints from objective performance fatigability; and (3) specify domains affected by fatigue and causal factors. We propose diagnostic criteria for PD-related fatigue to guide participant selection for clinical trials and add rigor to mechanistic studies. Recommendations are made for measurement of subjective fatigue complaints, performance fatigability, and neurophysiologic changes. We also suggest areas in which future research is needed to address methodological issues and validate or optimize current practices. Many limitations in current PD-related fatigue research may be addressed by improving methodological standards, many of which are already being successfully applied in clinical fatigue research in other medical conditions (eg, cancer, multiple sclerosis). © 2016 International Parkinson and Movement Disorder Society.

Fatigue in Parkinson's disease and potential interventions.

BACKGROUND: Fatigue is common in patients with Parkinson's disease (PD). It occurs at every stage of PD and affects quality of life. Fatigue severity worsens over time as PD progresses, and it is associated with other non-motor symptoms such as apathy, depression, sleep disorder, and cognitive dysfunction. PURPOSE: In this literature review, I discuss the measurement and pathophysiology of fatigue and fatigability. There are no evidence-based treatments for fatigue and fatigability available. I review several pilot studies on the effects of pharmacological agents and exercise on fatigue and fatigability. These studies provide some insights on the design of future larger clinical trials. CONCLUSION: Fatigue inventories including The Fatigue Severity Scale, the Multidimensional Fatigue Inventory, or theParkinson Fatigue Scale are used to assess the severity of fatigue. Finger tapping and force generation are useful in quantifying physical fatigability. A reaction time paradigm such as the Attention Network Test can be used to measure cognitive fatigability. Physical fatigability is associated with the change in cortical excitability in PD measured by Transcranial Magnetic Stimulation. Cognitive fatigability is most likely associated with the neurotransmitter abnormalities (dopaminergic, cholinergic and noradrenergic) in PD. Levodopa, modafanil, methylphenidate, and rasagiline may be effective in treating fatigue and fatigability. Exercise programs may also be effective.

Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition. METHODS: In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983. FINDINGS: Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0.06; HC/HC vs control, p=0.06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0.0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0.03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group. INTERPRETATION: Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease. FUNDING: Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.

Treatment of severe hand impairment following stroke by combining assisted movement, muscle vibration, and biofeedback.

BACKGROUND AND PURPOSE: Few studies have addressed the rehabilitation of hand function in persons with severe impairment following stroke, and few therapeutic options are available for treatment. We investigated whether an intervention of robot-assisted movement and muscle vibration could reduce impairment and enable hand-opening to a greater extent when combined with torque biofeedback or electromyographic (EMG) biofeedback. METHODS: Forty-three participants with severe hand impairment due to chronic stroke (≥1 year poststroke) were randomized to 1 of 2 treatment groups receiving assisted movement and muscle vibration combined with either torque or EMG biofeedback. Each participant received 30 sessions (30 minutes duration per session) directed at the impaired hand over 10 to 12 weeks. Outcomes were assessed using the Upper Extremity Fugl-Meyer Assessment (UE-FMA), Stroke Impact Scale, and Box-and-Block Test scores. RESULTS: Twenty-eight of 43 participants had no baseline finger extension; the remainder had an average of 23 ± 26 mm extension in the most active finger. Assisted movement and muscle vibration were associated with a significant increase in all outcome measures across both treatment groups, and for the UE-FMA and Stroke Impact Scale within treatment groups, with no significant difference between groups. Based on the Box-and-Block Test scores, the assisted movement and muscle vibration intervention did not restore functional hand-opening to participants with baseline UE-FMA scores less than 17/66, regardless of the form of biofeedback. DISCUSSION AND CONCLUSIONS: Assisted movement and muscle vibration, combined with either EMG or torque biofeedback, appears to reduce upper limb impairment, improve volitional activation of the hand muscles, and restore a modicum of hand function in some persons with severe hand impairment due to chronic stroke.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A64) for more insights from the authors.

Effect of expectancy and personality on cortical excitability in Parkinson's disease.

Our previous studies in Parkinson's disease have shown that both levodopa and expectancy of receiving levodopa reduce cortical excitability. We designed this study to evaluate how degree of expectancy and other individual factors modulate placebo response in Parkinson's patients. Twenty-six Parkinson's patients were randomized to 1 of 3 groups: 0%, 50%, and 100% expectancy of receiving levodopa. All subjects received placebo regardless of expectancy group. Subjects completed the NEO-Five Factor Inventory, General Perceived Self-Efficacy Scale, and Perceived Stress Scale. Cortical excitability was measured by the amplitude of motor-evoked potential (MEP) evoked by transcranial magnetic stimulation. Objective physical fatigue of extensor carpi radialis before and after placebo levodopa was also measured. Responders were defined as subjects who responded to the placebo levodopa with a decrease in MEP. Degree of expectancy had a significant effect on MEP response (P < .05). Subjects in the 50% and 100% expectancy groups responded with a decrease in MEP, whereas those in the 0% expectancy group responded with an increase in MEP (P < .05). Responders tended to be more open to experience than nonresponders. There were no significant changes in objective physical fatigue between the expectancy groups or between responders and nonresponders. Expectancy is associated with changes in cortical excitability. Further studies are needed to examine the relationship between personality and placebo effect in Parkinson's patients. © 2013 Movement Disorder Society.

Techniques in assessing fatigue in neuromuscular diseases.

Fatigue is common in neuromuscular disease and it may affect quality of life; however, it has not been adequately studied. We can approach fatigue in neuromuscular diseases systematically. Questionnaires are used to assess subjective or experienced fatigue, and with the wide availability of the Internet, many patients can fill out questionnaires through Web-based surveys. Researchers can use force-generation protocols to evaluate physical fatigability and attention protocols to evaluate mental fatigability. Using these techniques to further understand the mechanisms of subjective and physiologic fatigue will help physicians to develop more effective treatments for fatigue and improve patients' quality of life.

Management of amyotrophic lateral sclerosis (ALS) by the family nurse practitioner: a timeline for anticipated referrals.

PURPOSE: This article reviews characteristics of amyotrophic lateral sclerosis (ALS) and appropriate timing of referrals by the nurse practitioner (NP). DATA SOURCES: Selected research and clinical articles. CONCLUSION: Management of patients with ALS by the NP requires anticipation of needed referrals based on symptom assessment and knowledge of the common timeline of ALS progression. Close collaboration with specialists such as neurologists, pulmonologists, and a palliative care team provides patients and families with much needed support and improves outcomes. IMPLICATIONS FOR PRACTICE: Anticipating and initiating appropriate and timely referrals for patients with ALS may improve quality of life for patients with this devastating condition.

Concentric Needle Quantitative EMG of Pubovisceralis Muscle Group: Normative Data from Asymptomatic Nulliparous Women.

OBJECTIVES: The muscles of the pelvic floor closest to the vaginal opening are subject to the greatest degree of stretch during vaginal childbirth. We aim to define normative quantitative EMG (QEMG) parameters for the pubovisceralis (PV) muscle in nulliparous women, and compare them to the external anal sphincter (EAS). METHODS: In 31 asymptomatic nulliparous women, concentric Needle EMG of the PV and the EAS was performed. Multi-motor unit action potential (Multi-MUAP) and interference pattern (IP) algorithms were utilized to obtain QEMG parameters. We used paired t-tests to compare PV and EAS parameters. RESULTS: The motor units for the PV were of greater duration (p < 0.002) and had more turns (p = 0.03) than the paired motor units in the EAS. The EAS demonstrated more turns/second (p = 0.02), greater activity (p = 0.01), and more short segments (p = 0.009) than the PV. CONCLUSIONS: The PV has longer and more complex motor units than the EAS. This knowledge continues to improve our ability to detect neuropathic changes in this vulnerable muscle area following childbirth or in women with pelvic floor dysfunction. In addition, the PV muscle group appears less responsive to requests for increased neuromuscular activity than the EAS. This needs to be further evaluated, as it may be associated with understanding which portion of the muscle functionally shortens to maintain the closure of the levator hiatus.