Motor function analysis: from animal models to patients

Transcription

1 Motor function analysis: from animal models to patients ZNZ lecture Linard Filli Sensorimotor Lab University Hospital Zurich

2 Content of lecture Basic neuroanatomy of motor control (locomotion) Sensorimotor assessment in animal models Sensorimotor testing in patients

3 Neuroanatomical basis of movements modified from Elsevier Science USA 2002

4 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

5 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

6 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

7 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

8 Consequences of Walking Dysfunction Wilson et al., Neurology, 2002 Immobility, retreat, isolation, economic disadvantages and increased risk of death in elderly

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10 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

11 Measures of Locomotor Function Rodents Humans Hamers et al LSS BBB Footprints CatWalk Kinematics Ladder Metz et al Smith et al Courtine et al EMG Beam Kunkel-Bagden et al Basso et al Scoring Pedography EMG Kinematics Clinical walking tests Questionnaires

12 Measures of Locomotor Function

13 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

14 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

15 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

16 Measures of Locomotor Function in Humans: SCORES - WISCI Walking index for spinal cord injury Ditunno et al., Spinal Cord, 2000

17 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

18 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

19 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

20 Gait analysis in humans

21 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: G Sensitivity: G Sampling rate: 32 Hz Notes: waterproofed

22 Example where gait analysis is used for clinical evaluations or research

23 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

24 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

25 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

26 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?