Interlimb coordination is not impaired during walking in persons with Essential Tremor Author: Kelly McWilliams Abstract Interlimb coordination between the upper and lower extremities is important in maintaining balance during gait. Although there are numerous studies evaluating gait performance in persons with Essential Tremor (ET) persons that suggest interlimb coordination may be affected, coupling of the arms during walking has yet to be studied . Interlimb coordination in twenty-one participants with mild moderate ET and 10 healthy age-matched adults were compared using cross-covariance techniques . T-tests and Wilcoxin-Mann Whitney tests were performed to compare sagittal shoulder and hip angles during overground gait. Our findings indicate that ipsilateral and contralateral coordination was not impaired in ET participants . This study adds to the growing knowledge of characterizing motor impairments within different movement disorders . Introduction Interlimb coordination (ILe) between the upper and lower extremities is important during gait. While most gait research focuses on lower extremity patterns, the importance of the arm swings in conjunction with the legs is often ignored. In terms of energy expenditure, coordinated arm swings increases the metabolic efficiency of gait (Collins et aI., 2009). Furthermore, it is particularly influential in maintaining stability during gait (Hinrichs and Cavanagh , 1981; Ortega et aI., 2008). This is achieved by reducing whole-body angular momentum around the vertical axis (Park et aI., 2012) .
The cerebellum is often noted for its role in controlling ILC, specifically the temporal control of motor coordination. However, the cerebellum is not the only controller for motor coordination between limbs . A network of brain areas including the cerebellum, supplementary motor area, and the primary motor cortical region are active during ILC of gait and are most influential during task specific motor behavior (Carson 2005; Debaere et al., 2001; Ehrsson et aI., 2000; Gerloff and Andres 2002; Swinnen 2002). Furthermore, neuronal networks within the spine, known as central pattern generators (CPGs), is suspected of playing the largest role in the temporal control of ILC during involuntary rhythmic movements such as locomotion (Guertin 2009; Zehr et aI., 2007). It has been suggested that walking speeds greater than 0.80 m/s accord with a 1 : 1 arm swing to leg swing ratio (Wagenaar and van Emmerik. 2(00).) Explicitly, at normal walking speeds the arms are out-of-phase with each other and the contralateral arm is in-phase with the swing leg (Donker et aI., 2001; Wagenaar and van Emmerik, 2000). Irregular ILC between the upper and lower extremities has been associated with declines in preferred walking speeds (Kwakkel and Wagnenaar, 2002; Meyns et aI., 2012,) . Due to the associations of ILC with slower walking speeds and dynamic instability, ILC is particularly important for populations who suffer from these impairments. Essential Tremor (ET) is a common neurological movement disorder typically characterized by an upper extremity action tremor. ET is the most common movement disorder in adults (Louis and Ferreira, 2010). The hands, forearms, head/neck, and trunk are most commonly subjected to involuntary shaking. The tremor most often presents in a symmetric/bilateral manner. Frequently, this leads to a reduced quality of life and trouble performing activities of daily living (Chandran and Pal, 2013). Currently, there are some indications of neurological deficits in motor control in regards to postural control and gait. Static postural control is typically unaffected for this population, while control of dynamic actions appear to be impaired (Bove et aI., 2006; Fernandez et aI., 2013; Parisi et aI., 2006; Rao et al., 2011; Stolze et aI., 2001). ILC within the ET population has not been investigated even although there is
evidence that suggests possible deficits. Persons with ET exhibit deficits in dynamic stability and walking speed (Earhart et aI., 2009; Rao et aI., 2011; Stolze et aI., 2001). Balance, gait, and motor spatiotemporal function stud ies of ET populations are in fact consistent with typical motor presentations of cerebellar disorders (Stolze et al., 2001; Wuehr et al., 2013Although there is no unanimous agreement of the pathology of ET, these findings indicate that ET likely stems from cerebellar pathways . This is important for ILC because the cerebellum plays an important role in temporal control of motor commands . It is possible that cerebellar dysfunction in ET may disrupt ILC due to its influence on temporal coupling of the extremities . It is possible that impaired ILC in ET would factor into the stability and speed constraints . If this were true , rehabilitation of ILC could potentially be used as a therapeutic target to improve gait dysfunction and fall prevention in ET. The purpose of this study was to compare ILC in mild moderate ET persons with neurologically healthy age matched controls using continuous analyses measures . We hypothesize that ILC will be diminished in ET persons when compared to the healthy controls due to cerebellar dysfunction . Methods Participants All subjects read and signed a written informed consent that was approved by the University's Institutional Review Board before participation . Twenty-one participants (17 men, 4 women) with ET (mean SO age: 72 yr, height: 175 . 4 . 9 cm, body mass: 91.6.9 kg, mean overground gait speed: l.12. 1 m/s) and ten (5 men,S women) age and speed matched neurologically healthy older adults (HOA) (mean So age: 73 yr, height : 165 . 7.0 cm, body mass: 70.3 . 9 kg, overground gait speed : 1.15 . 1 m/s) . Diagnosis of ET was confirmed by a fellowship trained Movement Disorders Neurologist. ET subjects who were taking anti-tremor medication were asked to participate in the overground gait trials while optimally medicated. ET participants were referred to participate in the study by the Center
for Movement Disorders and Neurorestoration at the University of Florida . HOA participants were recruited from the University of Florida and neighboring community. Participants who walked at an average speed less than 0 . 80 m/s were excluded from the study . Additionally, we excluded trials with any voluntary extraneous movement (touching their face, scratching an itch, etc ... ) from the study. Overground galt analysis Participants were fitted with thirtyfive passive retroreflective markers . Markers were placed over bony landmarks and in accordance with Vicon Plugin-Gait full body marker set. Kinematic data was captured using a multi camera optical motion capture system (120 Hz; Vicon Nexus, lake Forest, California). Each subject performed ten overground gait trials along an eight-meter walkway at their self selected preferred walking speed. Two consecutive heel-strikes of the same limb was defined as one gait cycle. Through Vicon Nexus, each heel strike and toe-off was manually labeled based on lower limb trajectory profiles . Respectively, bilateral hip and shoulder sagittal joint angles were calculated as the relative angles between the thigh/pelvis and upper arm/thorax segments. Continuous analysis techniques were applied using custom MATlAB software. Hip and shoulder range of motion (ROM) and cross-covariance coefficients (Ccq were calculated between the hip and shoulder joint angle vectors for both ipsilateral and contralateral relations. Cross-covariance measures the similarity with which two time series vectors change relative to each other. This continuous analyses method enables the coordination patterns to be evaluated along a series of temporal shifts in the data . This provides the opportunity assess whether the hip and shoulder signals are different in shape and/or temporal disposition . The benefit of this method over cross-correlation methods previously used in IlC studies (Huang et al., 2012; Park et al., 2012) is the ability to reduce the influence of the magnitude of the joint angle vectors being compared . The ROM of the hips and shoulders are typically dissimilar in magnitude; therefore, cross-covariance is an effective
analyses method . Please refer to Roemmich et al. (2013) for further details on this continuous analyses method . We compared ET and HOA cross-covariance coefficients at zero time lag (CeCa), which corresponds to the covariance between the hip and shoulder joint angle vectors when no time shift was applied . Maximal cross-covariance coefficients (eee Max) and ROM were also compared . ceca and eee Max values are normalized to a range between -1 (perfectly out-of-phase) and 1 (perfectly in-phase), with a value of zero indicating no covariance between signals . For HOA participants, we averaged each individual's contralateral and ipsilateral measures to create a single contralateral and s i ngle ipsilateral control measure . For example , left hip/left shoulder ceca and right hip/right shoulder ceca was averaged to create a single ipsilateral ceca measure for an individual subject. Independent samples t tests and Wilcoxin-Mann-Whitney tests were used to compare ceca, eee Max , and ROM in the ET group with the HOA group. The established level of significance for both tests was a=O.OS (SPSS 20, IBM, Armonk, New York). Results Interlimb Coordination Comparisons between ET and Controls Overall, we found no significant differences in ROM of the shoulder and hip, walking speed, ipsilateral ceca, ipsilateral eee Max, contralateral ceca, and contralateral eee Max for ET when compared to controls.
ET (n=21) HOA (n=10) Preferred walking speed 1. 12. 13 1. 15. 13 p=0.575 Hip ROM (degrees) 42.84 5 .20 44. 11.46 p=O.512 Shoulder ROM (degrees) 24. SI. 82 28. 68.85 p=0.217 Ipsi lateral CCCO -D.8S.24 -0 . 89. OS p=0.444 (psi lateral CCC Max -0. 93.08 -D. 93.04 p=0.329 Contralateral CCCO O.89.21 0.91.07 p=0.236 Contralateral CCC Max 0 .94.07 0 .95.04 p=O.365 (MeanSD) Discussion Although previous literature has found apparent gait and balance abnormalities in ET that may implicate deficits in ILC between the upper and lower extremities, it has not previously been studied in this population (Kwakkel and Wagnenaar, 2002; Meyns et al., 2012; Stolze 2001) . Inconsistent with our hypothesis, the results indicate that ET does not have disrupted ILC when compared to the age and speed matched healthy older adults . In addition to both measures of ROM (hip, shoulder), continuous analyses measures of ipsilateral and contralateral spatiotemporal coordination (CCCO, CCCMax) were not found to be significantly different than controls. Previous studies provide evidence of gait dysfunction and motor timing deficits in ET consistent with a cerebellar disorder (Buijink et aI., 2015; Rao et aI., 2011) . However, our findings indicate that the
supraspinal pathology of ET may not interrupt spinal neuronal networks that influence ILC between the upper and lower extremities. These networks , known as central pattern generators (CPGs), are commonly attributed for their role in coordinating and regulating the temporal aspect of ILC during rhythmic movements such as walking (Dietz and Michel, 2008; Zehr and Ouysens , 2004). Furthermore, the lower extremities tend to be less affected with tremors and functional capabilities than the upper extremities in ET. Several studies show that ET has minimal gait disturbances when compared to controls (Hoskovcova et al., 2013, Roemmich et aI., 2013, Stolze 2001). Based on their findings , we would expect that if ILC deficits were indeed present, the upper extremities would be the source. However, passive dynamics playa large role of the arm swing during gait, especially as walking speeds decline toward the 0.80 m/s threshold for a 1 : 1 arm swing to leg swing ratio (Goudriaan et aI., 2014; Pontzer et aI., 2009). Muscle activation is known to increase the presence of tremors in the upper extremities . Minimizing muscular influence of the arm swing during gait by decreasing walking speeds may playa role in retaining normallLC for ET. Previous differences in gait in ET versus controls might be due to difference in walking speeds . Herein we matched walking speeds and differences were ameliorated . Our findings are important in supplementing current knowledge of the differences in motor control deficits between ET and other movement disorders such as PO and cerebral palsy . As previously mentioned, ILC is impaired in PO as well as cerebral palsy (Meyns et aI., 2012; Roemmich et aI., 2013). Unlike ET, which tends to affect the extremities and motor behaviors symmetrically, PO and cerebral palsy tend to affect one side of the body more than the other, present with motor asymmetry, and have pronounced gait dysfunction (Hausdorff et aI., 2003; Meyns et al. , 2012; Roemmich et aI., 2013; Vogev et aI., 2007) . ILC cross-covariance values for PO ipsilateral and contralateral coordination , involving the more affected shoulder, were similar to those found for ET (Roemmich et aI., 2013) . However, it is important to note that the mean age of our populations was nearly 10 years greater than in the PO ILC
study and the extent to which this plays a role in the similarity of results is unknown. PO and cerebral palsy ILC studies attributed disruptions in ILC to the most affected arm. Unlike PO and cerebral palsy, midline tremor has been suggested as an indicator of gait dysfunction in ET (Parisi et aI., 2006). It is possible that severe ET or ET persons with high tremor rating scale scores of midline tremor would display impaired ILC. Our findings agree with the idea that the disease pathophysiology of ET and other cerebellar disorders do not proceed along identical pathways but most likely stem from a midline cerebellar syndrome (Louis et aI., 2007). Further research of ET pathology should use our findings of temporal efficacy in ILC to deduce which neurological pathways may be affected. Limitations to this study include the use of mild-moderate ET participants . Severe ET may result in impairments of ILC that were not found in the current study. ET participants were also guided to arrive at the testing facility in their optimally medicated state. Not all participants were treated with anti-tremor medication at the time of the study but it is unknown how this may have affected the results. Anti-tremor medications propranolol and primidone, respectively a beta-adrenergic receptor antagonist and an anticonvulsant, were the only medications participants had taken . Both medications have proven to reduce the magnitude of limb tremor, but also have minimal effect on gait (Stolze et aI., 2001; Zesiewicz et al., 2005). Unlike treadmill gait studies, overground gait analyses are intrinsically limited to preferred walking speeds as well as fewer strides available for analysis. However, treadmill gait is known to alter limb coordination, which is why overground gait was our chosen collection method (Carpi nella et al., 2010). Conclusion ILC was not impaired in persons with Essential Tremor when compared to controls during traditional gait. Continuous measures of cross covariance were applied to evaluate the temporal relationship between shoulder and hip angles (CCCO, CCC Max), as well as the range of motion of the shoulder and
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