Gait Initiation Impairments in Essential Tremor and D isease
Abstract Gait initiation (GI) is a complex, transitional task involving a voluntary shift from a static stable position to a less stable state of dynamic motion Anticipatory postural adjustments (APA s ) precede stepping to generate sufficient forward momentum by separating t he center of pressure (COP) from the center of mass In this study, we investigated APA s and spatiotemporal characteristics of GI in persons with ) and Essential Tremor (ET) PD is characterized by motor deficits which result from basal ganglia and pendunculopontine nucleus dysfunction. Essential Tremor is a neurodegenerative disorder primarily characterized by kinetic tremor in the upper body and cerebellar like motor disturbances We analyzed COP movements during GI and observed that persons with ET generate diminished APA s in comparison to healthy older adults. P ersons with ET also initiated gait with shorter steps which is consistent with previous research demonstrating diminished stepping during GI in persons with cerebellar deficits Spatiotemporal GI characteristics were similar in the PD and ET groups; however, the APA deficits occurred during different phases of GI. We postulate that a greater understanding of dyna mic balance and postural control in the ET population may further the understanding of the ET neuropathology and help clinicians distinguish between the ET and PD phe notyp es to promote appropriate and timely treatment plans.
Introduction Gait initiation (GI) is a complex transitional locomotor t ask which requires a shift from a static, stable state to a n unstable dynamic state of motion. GI is a challenging task that demands balance and postural control due to a decreasing base of support (BOS) from a two leg stance to an alternating single leg stance. A nticipatory postural adjustments (APAs) precede stepping during GI in order to generate momentum for efficient forward motion while the body is balanced between the two feet Indeed, failure to generate sufficient forward momentum during GI has been shown to lead to overall poorer GI performance as evidenced by decreased step length and decr eased step velocity [ 1 ] During quiet stance, movement s of the center of pressure (COP) and center of mass (COM) are relatively coupled. However, as gait is initiated, APAs function to shift the COP posterolaterally toward the stepping limb while the COM uncouples from the COP moving anteriorly and towards the stance limb Because GI requires active postural control to separate the COP from the COM, the outputs of the APAs have been used as investigative tools to o bserve balance dysfun ction and postural i nstability [ 2 ] Indeed, previous research on APAs has suggested that COP excursions during GI may be diminished in pathological populations at increase d their risk of falling [1 3 4 5 ] cterized by motor signs resulting from a degenerative loss of dopaminergic neurons in the substantia nigra of the basal ganglia [ 1 ] The basal ga nglia are understood to be essential in planning and initiating movement, and consequently the APAs have been shown to be diminished in persons with PD when initiating gait [ 1, 3, 4 ] Further, p ersons with PD have demonstrated deficits in postural control and momentum generation during
GI as evidenced by restriction of the separation of the COP and COM when compared to their neurologically healthy peers [2 3 ] Essential Tremor (ET) is a neurodegenerative movement disorder which is characterized by an involuntary shaking predominantly in the hands, arms, neck, and head that worsens with movement. While static postural control appears to remain relatively intact [ 6] recent research has begun to describe a variety of locomotor deficits in ET. A recent study reported decreases in cadence and walking speed in persons with ET which were accompanied by impairment in dynamic stability as evidenced by reduction in double support time when compared to controls [ 7] Moreover, persons with ET demonstrated cerebellar like d eficits in dynamic stabili ty during tandem walking tasks [ 8] Locomotor deficits in this population have also been described more generally in a clinical setting, as persons with ET demonstrate reduced performance on clinical measures of functional mobility whereas static balance control was unaffected [ 9] Despite the wealth of information reg arding the effects of ET on gait, mobility and static postural control, little is known about the effects of ET on dynamic postural control during transitional locomotor periods such as GI. Therefore, the purpose of this study is to investigate APAs and spatiot emporal characteristics of GI in persons with PD and ET, and to compare t hese among the two groups and their neurologically healthy peers. As dynamic stability and gait deficits seem to be evident in ET but more mild than in persons with PD, w e hypothesize that persons with ET will demonstrate GI deficits which are similar but less severe than persons with PD We also postulate that further understanding of dynamic instability in ET may assist clinicians in different iating the ET and PD phenotypes, as ET is one of the most common movement disorders
in the adult population and yet approximately 30 50% of persons with ET are misdiagnosed with PD or other tremor disorders [ 10] Methods Twenty three participant s with Essential Tremor (age: 67.74 6.00 y, height : 170.97 9.25 cm, weight: 93.25 21.23 kg ) were referred from the Center for Movement Disorders and Neurorestoration at the University of Florida. All participants were evaluated and diagnosed by a trained movement disorder neurologist, and were optimally treat ed prior to testing. T hirty participants with idiopathic PD ( age: 67.66 6.71 y, height: 170.14 6.27 cm, weight: 82.25 14.62 kg ) were also recruited from the clinic and from the university community. PD participants were evaluated and confirmed to have PD by a trained movement disorder neurologist using the UK Brain Bank criteria. The severity of the disease was determined using the motor portion of scale. All PD participants were tested at their self reported best medicated state. Th irty six age matched healthy older adults (HOA) ( age: 67. 33 4.83 y, height: 169.32 8.57 cm, weight: 80.09 14.47 kg ) volunteered and were screened for neurological and musculoskeletal impairment. The healthy older controls were enrolled from the university and the neighboring community. Before participation in the study, all subjects sig ned a written informed consent that was approved by the University Institutional Review Board. Participants beg a n each experimental trial standing quietly with both feet on one force plate (Bertec Corporation, Columbus, OH) were then asked to pause for several moments before volitionally initiating gait along a 12 meter walkway at their own comfortable pace. Participants were given preference in the placement and
position of their feet on the force plate, and were then restricted to that particular position for the remainder of the trials. Participants performed five GI trials but some trials were eliminated from the analysis if the participant stepped first wi th the contralateral limb The walkway was surrounded b y an 8 camera optical motion capture system (120 Hz; Vicon Nexus, Lake Forrest, CA). Participants wore dark, form fitting clothing and passive, retroreflective markers were placed over the second metat arsal head, lateral malleolus, and calcaneus Heel offs, heel strikes, and toe offs were manually labeled in Vicon Nexus based on marker trajectories. W e measured APA displacements and velocities durin g GI by assessing COP traces using custom written MATLAB software (MathWorks, Natick, MA). We manually distinguished two events during GI that separates the COP trace into three distinct phases. The S1 phase begins with the first sign of the lateral, posterior shift of the COP and ends with the COP positi oned at the most lateral and posterior position to the initial stepping l imb (swing l imb SW limb ). The beginning of the S2 phase is defined as the onset of a lateral shift of the COP in the opposite direction toward the contralateral l imb (stance l imb ST limb ), and ends when the COP is in its most lateral and posterior position under the ST limb The S3 p hase is defined as the forward translation of the COP trace under the ST limb until heel strike of SW limb  Displacement and velocity of the COP was calculated in the anterior posterior ( AP ) and mediolateral ( ML ) directions during the S1, S2, and S3 phases of GI. W e also measured spatiotemporal parameters during GI including: a) the length of the first SW limb step, which was defined as the displacement of the heel marker from static position to first heel strike ; b) time of the first SW limb step as the time between the first heel off and first heel strike of the SW lim b ; and c) the velocity of the first SW limb which was measured as the SW step length divided by SW step time Step length, step time and step velocity were also
measured for the first ST limb step using similar methods Thus, we ultimately calculated the following outcome measures: SW and ST step length, SW and ST step time, and SW and ST step velocity. Analysis As all COP variables violated assumptions of normality, m ean differences for all COP variables were compared among the HOA, ET, and PD groups using Mann Whitney U tests with Bonferroni corrections for multiple comparisons. O ne way ANOVAs were conducted to compare age, mass height and mean spatiotemporal variables among groups. Level of sig nificance was set at .05 for both the Mann Whitney U tests (prior to Bonferroni correction) and the one way ANOVAs. Results Persons with ET had a significantly d iminished S3 AP displacement ( 0 .0 70 9 0 .0 27 6 vs. 0 .0 87 7 0.0 42 4 m p=.013 ) when compared to HOA. Persons with PD had a significantly diminished S1 AP disp lacement (0. 0178 0 .0095 vs. 0 .0272 0 .0193 m p=.003), S1 ML displacement ( 0 .0179 0 .0111 vs. 0 0244 0 .0156 m, p=.017), S1 AP velocity (0.052 0 .0 26 9 vs. 0 .1016 0 .0 62 4 m /s, p<.001) and S1 ML velocity ( 0 .052 8 0 .026 3 vs. 0 .0883 0 .0 55 4 m /s, p=.002) when compared to HOA When comparing persons with ET to those with PD persons with PD had si gnificantly decreased S1 AP ( 0.0 52 0 0.0 26 9 vs. 0.0 94 9 0.0 71 7 m/s, p=.004) and S1 ML ( 0.0 52 8 0.0 26 3 vs. 0.0 86 1 0.0 54 6 m /s. p=.005) vel ocities than persons with ET Persons with ET had a significantly diminished SW step length (0.47 0.11 vs. 0.54 0.09 m p=.022 ) and ST step length (0.99 0.16 vs. 1.11 0.16 m p=.027 ) when compared to HOAs. Persons with PD had a significantly diminished SW step length (0.47 0.11 vs. 0.54
0.09 m, p = .018 ) ST step length (0.98 .21 vs. 1.11 0.16 m p=.012 ) SW step velocity (0.86 0.20 vs. 1.03 0.22 m/s p=.006 ) and ST step velocity (1.35 0.25 vs. 1.52 0.26 m/s p= 0 .037 ) when compared to HOAs. There were no significant differences in any spatiotemporal GI measures w hen comparing persons with ET to those with PD Discussion The ability to effectively utilize the APAs during GI is essential to momentum generation while maintaining stability during the transition from a static state to dynamic locomotion. While previous research has described gait and static postural control in persons with ET, this is the first study to assess the effects of ET on the dynamic postural control mechanisms underlying GI and subsequent spatiotemporal output. Further, this is the first study to our knowledge to compare dynamic postural control in persons with ET and PD two neurological movement disorders with simi lar phenotypes. In this study, we found that persons with ET demonstrated diminished S3 AP displacement and shorter steps during GI in comparison to healthy older adults. We also found that persons with PD demonstrated diminished S1 AP and ML velocitie s in comparison to persons with ET and that stepping during GI is similar in persons with ET and PD. GI disturbances in persons with PD likely result from dysfunction of both the basal ganglia and the pedunculopontine nucleus (PPN) in the brainstem. The basal ganglia are important in early motor planning and execution, and research has shown that there is a strong correlation between substantia nigral dopamine neuron degeneration and the clinical manifestation of PD  However, as dopaminergic treatment does not typically resolve all PD motor deficits [ 14, 15, 16] descending path ways from the basal ganglia to the PPN likely play a
role in the manifesta tion of PD motor signs as well [ 17] It has been well documented in animal models that the PPN exerts a modulatory influence over basal ganglia activity during GI [ 13, 18, 19 ] and Takakusa and colleagues suggest that dopamine deficiency may cause excessive GABAergic inhibition from the basal ganglia on the PPN and mesencephalic locomotor region, leading to parkinso nian gait and APA abnormalities seen in our study  Our results suggest tha t persons with ET also exhibit GI disturbances despite lesser dopaminergic d ysfunction when compared to PD [ 20] Though the basal ganglia remain relatively unaffected, previous research has shown that the cerebellum and brainstem are affe cted in ET [ 21, 22, 23 24 ] While there is surmounting evidence that these two structures play an important role in ET etiology, the precise functional, biochemical, or morphological cause is still unknown and highly controversial [ 21, 25, 26 27 ] The implication of cerebellar dysfunction in ET has been supported by a multitude of cerebellar like motor deficits observed in persons with ET, such as tandem walking difficulties, gai t ataxia, and intention tremor [ 34 35] Further, w hile the cerebellum has primarily been thought to influence movement c oordination and adaptation [ 29 ] several other studies have indeed reported implications of the cerebellum in var ious movement initiation tasks [ 30, 31, 32, 33 ] GI d eficits have also been previously observed in persons with cerebellar disease. Timmann and Horak found that persons with cerebellar ataxia maintained temporal control of APAs, but initiated gait with shorter, slower steps [29 ] Indeed, these results are v ery similar to our findings in ET, which further suggest a similarity between the spatiotemporal characteristics of persons with ET and PD. Timmann and Horak also noted the similarity of GI performance in cerebellar patients to persons with PD, and these investigators postulated that the short and slow steps observed in cerebellar patients may have resulted as a compensatory mechanism for gait
ataxia as opposed to the centrally indu ced bradykinesia observed in PD [29 ] We suggest that this may also be the case in pers ons with ET affected by ataxia [ 34 35] although steady state gait analysis was beyond the scope of this study. Limitations Eight participants with ET were taking medication at the time of testing, while the rest of the subjects were not taking medication. Medications to treat ET are not entirely effective in eliminating the symptoms, and many persons with ET do not benefit from them [ 34, 35 ] Furthermore, we were unable to calculate COP C OM char act eristic s due to lack of full body marker placement during t rials. Finally 25% of our subjects had only three GI trials du e to sub jects initiating gait with the contralateral limb after first trial. Conclusion GI is a complex transitory phase that challenges dynamic and postural stability and balance. In this study, we investigated APA and spatiotemporal features of GI in persons with PD, ET, and age matched healthy controls. We found t hat APA and spatiotemporal parameters were affected both the ET and PD groups, as both persons with ET and PD took shorter steps and demonstrated reduced APAs when compared to healthy older controls. We postulate that GI is impaired in PD as a result of dy sfunction of the basal ganglia and PPN, and that GI may be impaired in ET due to cerebellar deficits. Through kinetic and kinematic analysis, this study suggests that there are APA deficits during GI in persons with ET which are different than persons with PD. Since there are no quantifiable diagnostic measures to distinguish between early onset PD and ET, the results of this study may further the understanding of difference s in neuropathology between PD and ET.
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Figure 1 : APA displacements during GI in HOA, PD, and ET.
Figure 6 : Comparisons in SW step velocity during GI in HOA, PD, and ET. Persons with PD had a significantly diminished SW step velocity in comparison to HOA. Figure 7 : Comparisons in ST step velocity during GI in HOA, PD, and ET. Persons with PD h ad a significantly diminished ST step velocity in comparison to HOA