Motor function analysis: from animal models to patients ZNZ lecture 27.04.2016 Linard Filli Sensorimotor Lab University Hospital Zurich Linard.Filli@usz.ch
Content of lecture Basic neuroanatomy of motor control (locomotion) Sensorimotor assessment in animal models Sensorimotor testing in patients
Neuroanatomical basis of movements modified from Elsevier Science USA 2002
Evidence for supraspinal locomotor regions in humans In humans, the fmri activity patterns during the imagination of standing, walking and running resemble the anatomical localisation of the MLR, CLR and PLR in animals. K. Jahn et al., NeuroImage 39, 2008
Ischemic stroke model rat Zörner et al., 2010 Neocortex changed substantially during evolution of species, whereas other brain areas (brainstem, cerebellum, midbrain) stayed more similar between species
Stroke: hemiplegia Hemiparetic gait: One affected body side, 1 unaffected body side Leg: - Extension (spastic, stiff) knee - Drop foot (impaired dorsal extension) - Internal rotation - Circumduction of leg Arm: - Shoulder adducted - Elbow flexed - Pronation of wrist nsmec.wordpress.com
Relevance of walking function in neurological disorders Stolze et al., 2004 more than 60% of patients with neurological disorders show deficits in gait function more than one third of neurological patients show falls
Consequences of Walking Dysfunction Wilson et al., Neurology, 2002 Immobility, retreat, isolation, economic disadvantages and increased risk of death in elderly
Walking deficits Walking deficits Deficit and recovery after CNS injury Traumatic disorder Transient impact with partial or complete recovery e.g. stroke, spinal cord injury time after onset Neurodegenerative or inflammatory diseases progressive e.g. Parkinson s Disease, Amyotrophic lateral sclerosis, Multiple sclerosis time after onset
Measures of Locomotor Function Rodents Humans Hamers et al. 2001 LSS BBB Footprints CatWalk Kinematics Ladder Metz et al. 2002 Smith et al. 2006 Courtine et al. 2009 EMG Beam Kunkel-Bagden et al. 1993 Basso et al. 1995 Scoring Pedography EMG Kinematics Clinical walking tests Questionnaires
Measures of Locomotor Function
Why assessing motor function in animals / humans? The human eye is good at recognizing abnormal gait patterns BUT it is very difficult to: - characterize detailed motor dysfunctions - detect moderate changes in motor function over time Need for sensitive, objective, validated methods to quantify sensorimotor functions
Why assessing motor function in animals / humans? Diagnostic clinical tool - Parkinson s Disease - Normal Pressure Hydrocephalus Neural control of movements Efficacy of treatments Functional recovery after specific CNS injuries/ diseases
Measures of Locomotor Function in Animals: SCORES - BBB Artificial order of scoring points Subjective component Basso, Beattie, and Bresnahan Basso et al., J Neurotrauma, 1995
Measures of Locomotor Function in Humans: SCORES - WISCI Walking index for spinal cord injury Ditunno et al., Spinal Cord, 2000
6minWT 10mWT T25FW Measures of Locomotor Function in Humans: Functional Tests High relevancy Validated because widely used in clinics Enright et al., Respiratory Care, 2003; Cattaneo et al., Disabil Rehabil., 2006
Gait Analysis to investigate neural control and recovery of walking kinematic functional EMG recordings number of errors / run phase dispersion (coordination) paw dragging forelimb strokes / run
Spinal cord anatomy in rodents dorsal corticospinal tract rubrospinal tract hypothalamospinal tract lateral reticulospinal tract propriospinal fibers medial reticulospinal tract ventral corticospinal tract lateral vestibulospinal tract medial vestibulospinal tract
Gait analysis in humans
Portable devices to monitor daily activity Actiwatch 2 Description: Omni-directional sensor capable of detecting acceleration in two planes. Type: solid-state piezo-electric accelerometer Size: 43mm x 23mm x 10mm Weight: 16 g Interval length: 15 s Max. recording time at 15s int.: 22.7 days Range: 0.5 2 G Sensitivity: 0.025 G Sampling rate: 32 Hz Notes: waterproofed
Example where gait analysis is used for clinical evaluations or research
Gait analysis as diagnostic tool: Parkinsonian Gait and L-DOPA PD Pat., 53 years OFF 0,2 km/h ON 2,5 km/h T25FW: 23,4 s 9,2 s 6mWT: 82 m 213 m
Parkinsonian Gait and L-DOPA: Gait Research Lab at Univ. Hospital stance OFF_left leg swing stance ON_left leg swing stance OFF_right leg swing stance ON_right leg swing
Assessment of Locomotor Function in Animals and Humans Advantages Disadvantages Patient-based measures Standardized clinical measures document the patient s perspective require little time to complete take into account the use of assistive devices directly related to neurologic examination often used in clinical trials simple and quick do not identify mechanisms underlying gait dysfunction subjective low sensitivity require a skilled examiner do not identify mechanisms underlying gait dysfunction limited precision and responsiveness often non linear low sensitivity Timed measures 3-dimensional gait analysis simple readily quantified require limited training published norms available often used in clinical trials identify mechanisms underlying gait dysfunction provide precise electrophysiological, kinematic, kinetic, and spatiotemporal data highly objective do not identify mechanisms underlying gait dysfunction low sensitivity for compensatory strategies require expensive equipment and skilled examiner limited to a few specialized laboratories often low clinical impact very time-consuming modified from Cameron et al., Curr Neurol Neurosci Rep, 2011
Summary: gait analysis should include Global Gait Analysis Reliable, objective, sensitive, comprehensive Time measures reference of gait performance relevance of gait changes (e.g. induced by therapy) kinem./kinetic Analysis Detailed changes in gait pattern underlying deficits or functional improvements subjective selfassessements is there a subjective benefit for the patient?