Reduced muscle strength is the major determinant of reduced leg muscle power in Parkinson's disease

BackgroundReduced muscle power (speed × strength) is associated with increased fall risk and reduced walking speed in people with Parkinson's disease (PD) as well as in the general older population. This study aimed to determine the relative contribution of motor impairments (bradykinesia, tremor, rigidity and weakness) to reduced leg muscle power in people with PD.MethodsEighty-two people with PD were tested while “on” medication. Leg extensor muscle strength and muscle power were measured using pneumatic variable resistance equipment. Lower limb bradykinesia, rigidity and tremor were measured using the Movement Disorders Society-sponsored Unified Parkinson's Disease Rating Scale. Associations between motor impairments and leg muscle power were examined using linear regression.ResultsUnivariate models revealed that muscle strength (R² = 0.84), bradykinesia (R² = 0.05) and rigidity (R² = 0.05) were significantly associated with leg muscle power, while tremor was not. A multivariate model including bradykinesia, tremor, rigidity, muscle strength, age and gender explained 89% of the variance in leg muscle power. This model revealed reduced muscle strength to be the major determinant of reduced muscle power (β = 0.7), while bradykinesia was a minor contributor to reduced muscle power (β = ?0.1), even when accounting for age and gender.ConclusionsThe findings that reduced strength and bradykinesia contribute to reduced muscle power in people with PD tested “on” medication suggest that these impairments are potential targets for physical interventions.     

Reduced muscle power is associated with slower walking velocity and falls in people with Parkinson's disease

PurposeMuscle strength (force) and power (force × velocity) are reduced in Parkinson's disease (PD). Reduced muscle power is associated with slower walking velocity and falls in the older population, but these associations in people with PD have not previously been investigated. This study investigated the relationships between leg extensor muscle power and strength with walking speed and past falls in people with PD.Participants and MethodsForty people with mild to moderate PD were assessed. Walking velocity was measured over 10 m and the number of falls the participant reported having in the past 12 months was recorded. Leg extensor muscle power and strength were measured using a Keiser leg press machine.ResultsMuscle power explained more than half of the variance (R² = 0.54) in walking velocity and remained significantly (p < 0.05) associated with walking velocity in models which included Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. Participants with low muscle power were 6 times more likely to report multiple falls in the past year than those with high muscle power (OR = 6.0, 95% CI 1.1 to 33.3), though this association between falls and power was no longer significant in models which included UPDRS motor scores (p = 0.09).ConclusionMuscle power is a significant determinant of walking velocity in PD even after adjusting for UPDRS motor score. Muscle power training warrants investigation in people with PD.     

High-intensity resistance training amplifies muscle hypertrophy and functional gains in persons with Parkinson's disease.

Strength deficits in persons with Parkinson's disease (PD) have been identified as a contributor to bradykinesia. However, there is little research that examines the effect of resistance training on muscle size, muscle force production, and mobility in persons with PD. The purpose of this exploratory study was to examine, in persons with PD, the changes in quadriceps muscle volume, muscle force production, and mobility as a result of a 12-week high-force eccentric resistance training program and to compare the effects to a standard-care control. Nineteen individuals with idiopathic PD were recruited and consented to participate. Matched assignment for age and disease severity resulted in 10 participants in the eccentric group and 9 participants in the control group. All participants were tested prior to and following a 12-week intervention period with testing and training conducted at standardized times in their medication cycle. The eccentric group performed high-force quadriceps contractions on an eccentric ergometer 3 days a week for 12 weeks. The standard-care group exercise program encompassed standard exercise management of PD. The outcome variables were quadriceps muscle volume, muscle force, and mobility measures (6-minute walk, stair ascent/descent time). Each outcome variable was tested using separate one-way analyses of covariance on the difference scores. Muscle volume, muscle force, and functional status improvements occurred in persons with PD as a result of high-force eccentric resistance training. The eccentric group demonstrated significantly greater difference scores for muscle structure, stair descent, and 6-minute walk (P < 0.05). Magnitude of effect size estimators for the eccentric group consistently exceeded those in the standard-care group for all variables. To our knowledge, this is the first clinical trial to investigate and demonstrate the effects of eccentric resistance training on muscle hypertrophy, strength, and mobility in persons with PD. Additional research is needed to determine the anatomical and neurological mechanisms of the observed strength gains and mobility improvements.     

Distal and proximal prehension is differentially affected by Parkinson‘s disease

Prehension movements consist of distal (grasp) and proximal (reach, lift) components. The proximal lifting movements (achieved at the wrist) of patients with Parkinson’s disease (PD) are characterized by bradykinesia. With respect to the distal component, PD patients show pathologically high grip forces (generated by the fingers) and slowing of force development indicative of disturbed sensorimotor adjustments during prehension. Combining kinematic and force analyses of prehension movements, we investigated whether PD differentially affects the adjustments of the distal or proximal prehension components to current load conditions. First, PD patients (n = 12) and healthy, age-matched control subjects grasped and lifted light and heavy objects without any load cues. Then, they were presented with cues that indicated changes in object load. These load cues were either consciously perceived or rendered subconscious through use of the technique of metacontrast masking. Consistent with the functional organization of the basal ganglia, patients with PD could adapt distal prehension components (grip force) to current load conditions using both types of cues. However, they were impaired in adjusting proximal prehension components (lift velocity). While controls were able to normalize lift velocity with the help of both conscious and subconscious load cues, the PD patients could use neither form of cue, and retained a pathological overshoot in lift velocity. Our results demonstrate that visuomotor integration during prehension movements differs at distal and more proximal joints and that deficits in this integration are pronounced for the latter in Parkinson’s disease.     

Cross-bridge mechanisms of muscle weakness in multiple sclerosis

Vastus lateralis muscle biopsies were obtained from six individuals with multiple sclerosis (MS) having an Expanded Disability Status Score of 4.75 +/- 0.28, and from six age- and gender-matched individuals without MS. Biopsies from the MS group showed fewer fibers (31 +/- 4 vs. 46 +/- 4%) containing the type IIa myosin heavy chain (MHC) isoform exclusively. However, the percentage of fibers coexpressing type IIa and IIx MHC increased in direct proportion with MS disability status. The average unloaded shortening velocity of skinned fibers containing type I or IIa MHC did not differ between subject groups. Peak Ca(2+)-activated force was 11-13% lower in fibers from the MS group due to atrophy (type I and IIa fibers) and reduced specific force (type I fibers). Increasing intracellular inorganic phosphate (0-30 mM) or hydrogen ion (pH 7.0-6.2) reduced Ca(2+)-activated force in a manner that was independent of MS status. Thus, fibers from the MS group showed a subtle shift in fast MHC isoform coexpression and a modest reduction in cross-bridge number, density, or average force, with no change in maximal cross-bridge cycling rate or susceptibility to intracellular metabolites. These changes explain part of the muscle weakness and fatigue experienced by individuals with MS.     

Changes in characteristics of rat skeletal muscle after experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE) serves as an animal model for certain neuroinflammatory diseases of the central nervous system, in particular multiple sclerosis (MS). EAE is accompanied by transient weakness or paralysis of hind limbs. We have investigated the effect of partial and transient conduction failure in the central nervous system on skeletal muscle function. At approximately 2.5 days after development of maximal clinical signs, body and medial gastrocnemius muscle mass were lower (by approximately 21 and 33%, respectively; P < 0.05) in EAE rats compared with controls. Fiber cross-sectional area was lower by 40-50% in all fiber types. Maximal force and power were substantially lower (by 58% and 73%) in EAE rats, as was the force normalized for muscle mass (35%). However, no such weakness was found when lower stimulation frequencies were used. Generation of similar submaximal forces was attributable to a slower relaxation in EAE muscles. This advantage for the EAE muscles was lost during repeated exercise. While fatigability was similar, the difference in relaxation rate between EAE and control disappeared in fatigue. Our data suggest that, as a result of central neuroinflammatory diseases, maximal performance of skeletal muscle is impaired but submaximal performance is relatively well maintained.     

Voluntary muscle activation, contractile properties, and fatigability in children with and without cerebral palsy

Cerebral palsy (CP) may lead to profound weakness in affected portions of the extremities and trunk. Knowing the mechanisms underlying muscle weakness will help to better design interventions for increasing force production in children with CP. This study quantified voluntary muscle activation, contractile properties, and fatigability of the quadriceps femoris and triceps surae in children with and without CP. Twelve children with CP (7-13 years) and 10 unaffected children (controls, 8-12 years) were assessed for (1) voluntary muscle activation during maximum voluntary isometric contractions (MVICs); (2) antagonist coactivation during agonist MVICs; (3) contractile properties, and (4) fatigability using electrically elicited tests. Children with CP were significantly weaker, had lower agonist voluntary muscle activation, and greater antagonist coactivation. In children with CP, the quadriceps normalized force-frequency relationship (FFR) was shifted upward at low frequencies and was less fatigable than controls. No differences were seen between groups in the normalized FFR and fatigability of the triceps surae. In addition, no differences were seen in the sum of the time to peak tension and half-relaxation times between groups for either muscle. Because children with CP demonstrated large deficits in voluntary muscle activation, using voluntary contractions for strength training may not produce forces sufficient to induce muscle hypertrophy. Techniques such as enhanced feedback and neuromuscular electrical stimulation may be helpful for strengthening muscles that cannot be sufficiently recruited with voluntary effort.     

帕金森病的眼球跟踪运动特点

目的 定量分析帕金森病(PD)患者眼球跟踪运动的特点,为评价PD患者的前庭功能提供依据.方法 选取30名健康人(对照组)和55例PD患者(PD组)作为受试者,PD组包括静止件震颤起病者31例(静止性震颤组),运动减少起病者23例(运动减少组),混合起病1例.对全部受试者进行眼震电图检杳.比较PD组和对照组跟踪运动增益值(gain,G)的差异,运动减少组和静止性震颤组跟踪运动的差异,PD患者双侧跟踪运动的非对称性和健康对照者的差异.结果 PD患者双侧跟踪运动的增益值(G左:0.79±0.10、G右:0.78±0.11)较对照组(G左:0.86±0.05、G右:0.85±0.06)明显降低(U=394.500、t=3.547,均P<0.01),运动减少组(G左:0.79±0.14、G右:0.75±0.14)与静止性震颤组(G左:0.79±0.06、G右:0.81±0.07)眼球跟踪运动增益值差异无统计学意义(t=-0.100、2.005,均P0.05).病例组左右两侧的跟踪运动非对称性(1.03±0.97)明显大于对照组(0.87±0.86,U=755.500,P<0.05).结论 PD患者眼球跟踪运动速度明显减慢,但不存在类型间的差异,两侧跟踪运动存在不对称性.     

Insufficiency of trunk extension and impaired control of muscle force in Parkinson’s disease with camptocormia

ObjectiveTo examine the aetiology of parkinsonian camptocormia, a non-fixed pathological forward bending of the trunk, by measuring trunk muscle activation and force regulation in Parkinson patients with (PD + CC) and without (PD) camptocormia matched for disease severity, and in age- and sex-matched healthy controls (HC).MethodsThe isometric forces of trunk extension and flexion were measured in PD + CC, PD and HC. Neuromuscular efficiency (increase of extension force per increase of paravertebral muscle surface electromyography signal) and the ability to maintain a constant submaximal trunk extension force were examined.ResultsPeak trunk extension force was significantly lower in PD + CC and PD than in HC, with PD + CC non-significantly weaker than PD. Compared with HC and with PD, the neuromuscular efficiency of trunk extension was significantly reduced in PD + CC. The variability of the force output (coefficient of variation) was significantly larger for PD + CC than for HC or PD.ConclusionThe reduced neuromuscular efficiency of trunk extension separates PD + CC from PD. Moreover, control of the trunk extensor force is impaired in PD + CC.SignificanceThere is weakness and a force control deficit in parkinsonian camptocormia suggesting a disturbed sensory-motor integration, which may contribute to myopathic changes in the trunk extensor muscles.     

High intensity eccentric resistance training decreases bradykinesia and improves quality of life in persons with Parkinson's disease: A preliminary study

Persons with Parkinson disease (PD) often demonstrate bradykinesia during mobility tasks. Bradykinesia combined with other PD-related movement deficits may contribute to self-reported reductions in quality of life. At this time, no studies have examined the effects of resistance exercise as an intervention to reduce bradykinesia and improve self-reported quality of life. Therefore, we examined changes in muscle force production, clinical measures of bradykinesia, and quality of life following 12 weeks of a high intensity eccentric resistance exercise program in persons with mild to moderate PD. Twenty individuals with idiopathic PD were matched into an experimental or an active control group. All participants were tested prior to and following a 12-week intervention period. The experimental group performed high intensity quadriceps contractions on an eccentric ergometer 3 days a week for 12 weeks. The active control group participated in an evidence based exercise program of PD. The outcome variables were quadriceps muscle force, clinical bradykinesia measures (gait speed, timed up and go) and disease specific quality of life (Parkinson's disease questionairre-39 [PDQ-39]). Data was analyzed using separate 2 (group) × 2 (time period) ANOVAs. Results demonstrated significant time by group interaction effects for gait speed, timed up and go, and the composite PDQ-39 score (p < 0.05). Muscle force, bradykinesia, and QOL were improved to a greater degree in those that performed high intensity eccentric resistance training compared to an active control group. Additional research is needed to determine if this type of training has long-term impact and if it results in an alteration of the natural history of mobility and QOL decline in persons with PD.     

Apoptosis in young and old denervated rat skeletal muscle

Introduction: We investigated the apoptotic response to different degrees of denervation in young and older rats randomized into control (C), partial (PD), and complete denervation (CD) of muscles innervated by the sciatic nerve. Methods: Muscle wet weight to body weight (MWW/BW), myosin heavy chain (MHC) isoforms, and fiber cross‐sectional area were determined in gastrocnemius and soleus muscles. Apoptotic responses were determined by changes in myonuclei and expression of Bcl‐2 and BAX. Results: PD and CD resulted in significant reductions in MWW/BW and FCSA in both young and older rats. Older controls had greater apoptotic responses than young controls. Apoptotic responses were greater in PD and CD than in C in both age groups. No statistical interaction between denervation and age group was seen. Conclusions: Older age was associated with increased level of apoptosis, but older muscle was not more vulnerable to the effect of denervation. Muscle Nerve 55 : 262–269, 2017     

Skeletal muscle fiber function and rate of disease progression in amyotrophic lateral sclerosis

The contractile properties of single muscle fibers reflect the functional status of muscle at the cellular level and have not been described in amyotrophic lateral sclerosis (ALS). Chemically skinned single muscle fibers (n = 173), obtained by needle biopsy from six men with ALS, were activated with Ca(2+), allowing maximal force measurements and specific force (SF) estimates. Maximum unloaded shortening velocity (V(o)) was determined using the slack test. The results were compared with muscle from healthy controls. Markers of disease progression included rate of change of ALS functional rating scale score, rate of change of forced vital capacity, and disease duration. Compared with controls, ALS patients had decreased whole muscle SF (measured by a combination of computerized tomography and isokinetic testing) but normal single fiber SF. The V(o) was greater for type I fibers in ALS. Patients with slower disease progression had increased single fiber size and a high percentage of hybrid fibers (expressing multiple myosin heavy chain isoforms). A needle biopsy obtained at the time of ALS diagnosis may assist with predicting rate of disease progression.     

Single muscle fiber size and contractility after spinal cord injury in rats

Spinal cord injury (SCI) results in muscle weakness but the degree of impairment at the level of single fibers is not known. The purpose of this study was to examine the effects of T9-level SCI on single muscle fibers from the tibialis anterior of rats. Significant decreases in cross-sectional area (CSA), maximal force (Po), and specific force (SF = Po/CSA) were noted at 2 weeks. Atrophy and force-generating capacity were reversed at 4 weeks, but SF remained impaired. Maximum shortening velocity (Vo) did not change after injury. SCI thus appears to affect various contractile properties of single muscle fibers differently. Normal cage activity may partially restore function but new interventions are needed to restore muscle fiber quality.     

Movement velocity dependent muscle strength in Parkinson's disease

We measured isokinetic muscle strength of knee extension and flexion in 18 patients with Parkinson's disease who showed marked laterality in symptom severity and compared strength between the sides in the same patient. In all patient groups, the maximum peak torque of the more affected side was significantly less than for the less affected side at 15 revolutions per minute (r.p.m.) and 30 r.p.m. with the difference between the sides being larger at 30 r.p.m. than at 15 r.p.m., while at 5 r.p.m. there were no significant differences between sides. In the Yahr stage I group, the maximum peak torque in both extension and flexion at each velocity showed no significant difference between the sides. In contrast, in the stage II and III groups the maximum peak torque at 5 r.p.m. showed no significant difference between the sides, while at 15 r.p.m. and 30 r.p.m. these values showed a tendency and a significant difference between the sides, respectively, with the more affected side being weaker. These results suggest that muscle weakness in patients with Parkinson's disease increases with performance velocity, especially as the disease progresses.     

Muscle force,motor nerve conduction velocity and compound muscle action potentials after parathyroidectomy for secondary hyperparathyroidism

OBJECTIVE: We studied the motor nerve conduction velocity (MNCV) and the amplitude of compound muscle action potentials (CMAP) in patients with symptomatic secondary hyperparathyroidism at preoperative and 3 months post-operative period, to find the factors affecting muscle force after parathyroidectomy. METHODS: Twenty-six patients with symptomatic secondary hyperparathyroidism with levels of intact parathyroid hormone (iPTH) over 6.8 pmol/l who underwent total parathyroidectomy and autotransplantation of 60 mg of tissue were included in this research. Extension force of the quadriceps muscle was measured at 60 degrees of right knee flexion and expressed as Newtons (N) in peak force and average force. Nerve conduction studies of four limbs were checked and the MNCV and CMAP of right femoral and tibial nerves were analyzed and correlated with the muscle force. RESULTS: Three months after operation, the peak force increased from 272 +/-108 to 315 +/- 123 N (P=0.015) and the average force from 215 +/- 94 to 253 +/- 103 N (P=0.006). MNCV and latencies of femoral and tibial nerves did not show definite change, but the amplitude of CMAP increased significantly from 7.1 +/- 4.1 to 10.7 +/- 3.2 mV (P=0.005) at femoral stimulation and from 9.8 +/- 4.6 to 11.7 +/- 4.3 (P=0.007) and 13.2 +/- 5.9 to 14.9 +/- 6.0 (P=0.011) at proximal and distal tibial stimulation. CONCLUSION: The improvement of muscle force after surgery was found to be parallel to the increment of the amplitude of CMAP but not to nerve conduction velocity or latency. We propose that the weakness of the patients with secondary hyperparathyroidism is probably related to alteration of muscle fiber contraction.     

Lower extremity isokinetic muscle strength in patients with Parkinson’s disease

We evaluated lower extremity isokinetic muscle strength to determine affected muscle groups and their dependence on movement velocity, and to establish the relationship between muscle strength and clinical severity, as well as muscle strength and falls, in Parkinson’s disease (PD). Twenty-five patients diagnosed with PD and 24 healthy volunteers were enrolled in this study. Lower extremity muscle strength was measured using an isokinetic dynamometer. Each participant’s clinical status was examined in accordance with the Unified Parkinson’s Disease Rating Scale; fall history was also recorded. We observed a significant decrease in isokinetic muscle strength in the patient group, especially in both hip and knee flexors and extensors. Decreased muscle strength was independent of velocity, and correlated with clinical severity and falls. Movement velocity-independent lower extremity isokinetic muscle weakness has been observed in patients with PD, especially in the knee and hip joints. The evaluation of isokinetic muscle strength may be a useful tool for the assessment of clinical severity and falls in PD.     

Muscle involvement in association with filarial chyluria

Twenty unselected consecutive patients of filarial chyluria were evaluated clinically, electromyographically, and histopathologically for neuromuscular dysfunction. None of the patients showed clinical evidence of muscle wasting or weakness suggesting myopathy, although generalized muscle weakness was complained by all of them particularly while climbing the stairs or on getting up or during lifting heavy weights. Electromyographic abnormalities were found in nine patients and slight histopathological abnormalities in two. The average duration of motor unit potentials and the mean amplitude were reduced, compatible with myopathy. There were no fibrillation potentials. Histological abnormalities consisted of a marked variation in muscle fibre size, sarcolemmal nuclear proliferation, and mild interstitial fatty infiltration. None of the patients showed evidence of clinical neuropathy, abnormalities in conduction velocity along the nerves or signs of segmental demyelination in the biopsy of the nerve. Our data suggest that muscle weakness in these patients is myopathic in nature without peripheral nerve involvement, and is possible due to hypoproteinaemia and hypolipidaemia, as these patients lose excessive amounts of protein and fat in their urine.     

Preservation of in vitro muscle fiber function in dermatomyositis and inclusion body myositis: a single fiber study

Five patients with untreated dermatomyositis, five with inclusion body myositis, and 16 healthy elderly volunteer subjects (controls) underwent open (dermatomyositis and inclusion body myositis) or percutaneous (controls) muscle biopsy. Biopsied muscles included deltoid, biceps and vastus lateralis. Chemically skinned single muscle fibers were activated with Ca(+2); the slack test was performed to determine maximal unloaded shortening velocity (Vo). Parameters measured include single fiber cross sectional area, maximal force, specific force and Vo. 429 Type I and 94 Type IIA fibers were studied. Cross sectional area and maximal force were greater in inclusion body myositis than dermatomyositis or control for Type I and IIA fibers. Specific force of Type I fibers was similar in inclusion body myositis and dermatomyositis but greater than in controls. Vo was greater in Type I, but not IIA, fibers in dermatomyositis compared with inclusion body myositis and controls. The force and velocity generating capacity of single muscle fibers is preserved in patients with dermatomyositis and inclusion body myositis suggesting that dysfunction of the contractile proteins does not contribute to clinical muscle weakness.     

Central activation, muscle performance, and physical function in men infected with human immunodeficiency virus

Loss of muscle mass and limitations in activity have been reported in persons infected with human immunodeficiency virus (HIV), even those who are otherwise asymptomatic. The extent to which factors other than muscle atrophy impair muscle performance has not been addressed in depth. The purpose of this study was to determine the extent of neuromuscular activation of the knee extensors and ankle dorsiflexors of 27 men infected with HIV receiving antiretroviral therapy and its relationship to muscle performance. The central activation ratio (CAR) was determined using superimposed electrical stimulation during maximum voluntary contractions. In addition to force and power measurements, muscle cross-sectional area and composition was evaluated using computed tomography. Aerobic capacity was determined from treadmill exercise testing. Eleven of the subjects had an impaired ability to activate the knee extensors (CAR = 0.72 +/- 0.12) that was associated with weakness and decreased specific force. The reduced central activation was not associated with muscle area, body composition, aerobic capacity, CD4 count, or medication regimen. Those individuals with low central activation had higher HIV-1 viral loads and were more likely to have a history of AIDS-defining illness. These results suggest the possibility of a different mechanism contributing to muscle impairment in the current treatment era that is associated with impairment of central motor function rather than atrophy. Further investigation is warranted in a larger, more diverse population before more definitive claims are made.     

Anterior cruciate ligament tear induces a sustained loss of muscle fiber force production

Introduction: Patients with anterior cruciate ligament (ACL) tears have persistent quadriceps strength deficits that are thought to be due to altered neurophysiological function. Our goal was to determine the changes in muscle fiber contractility independent of the ability of motor neurons to activate fibers. Methods: We obtained quadriceps biopsies of patients undergoing ACL reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles fiber contractility was assessed in vitro, along with whole muscle strength testing. Results: Compared with controls, patients had a 30% reduction in normalized muscle fiber force at the time of surgery. One month later, the force deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength testing demonstrated similar trends. Discussion: While neurophysiological dysfunction contributes to whole muscle weakness, there is also a reduction in the force generating capacity of individual muscle cells independent of alpha motor neuron activation. Muscle Nerve 58 : 145–148, 2018