Integrating Transcranial Magnetic Stimulation in Physiotherapy for Patients with Stroke

Transcription

1 Integrating Transcranial Magnetic Stimulation in Physiotherapy for Patients with Stroke Hospital Authority Convention 2015 AH II Technology Advancement & Innovation 19 May 2015 Dr. Rosanna Chau Bobath Instructor(IBITA) FHKCOP; FHKSMS; DHSc ; MSc(HC-Physio) ; MHSc(Geron) Dip (Acup) ; PD (Physio) Department Manager, Physiotherapy Department Kowloon Hospital Ms. Helen Luk DHSc Candidate; MHSc(Geron) Dip (Acup) ; PD (OSH); BSc (Physio) Senior Physiotherapist Queen Elizabeth Hospital

2 Transcranial Magnetic Stimulation (TMS) Non-invasive pain-free direct brain stimulation (Barker et al., 1985) Passing a large, brief current through a wire coil placed on scalp Transient current produces a large & changing magnetic field Magnetic field penetrates the scalp & induces a secondary eddy current in conductive intracranial tissues Excite neurons in the brain neuronal depolarization Able to activate cortical neurons at a depth of 1.5-2cm beneath the scalp (Epstein et al., 1990; Rudiak & Marg, 1994); Affect deeper cells trans-synaptically (Paus et al., 1997)

3 Commonly Used TMS Units Nexstim Magstim Magpro NeuroStar

4 Navigated TMS (Neuronavigator) - Frameless Stereotaxic System An accessory to TMS Assist in precise placement of TMS coils to target brain site indicated on an MRI scan

5 Utility of Transcranial Magnetic Stimulation Single Pulse Measure motor threshold, motor evoked potential Mapping motor cortical outputs Diagnostic Measure connection between brain & muscle, e.g. disorders affecting facial, cranial nerves & spinal cord Paired Pulse Measure intracortical facilitation & inhibition Study corticocortical interactions Therapeutic Stimulate / inhibit brain activities for function enhancement Repetitive Stimulation High frequency vs. low frequency To both hemisphere To the same hemisphere

6 Therapeutic Application of TMS Modulate cortical excitability for normalization of activity in the targeted brain region e.g. Depression Suppress activity in brain region & induce paradoxical behavioral facilitations through distant effects e.g. Neglect Enhance motor performance Facilitate adaptive brain plasticity Help to develop models of functional connectivity between different brain regions Depression Stroke Neglect Aphasia Epilepsy Myoclonic, focal status epilepticus Movement disorders Dystonia Parkinson disease Neuropathic pain Auditory hallucinations Tinnitus, Migraine

7 Repetitive Transcranial Magnetic Stimulation in Stroke Rehabilitation

8 Interhemispheric Competition Model Healthy Subjects After Physical Rehabilitation Training strategy Balanced interaction between the 2 hemisphere Cortical excitability in affected primary motor cortex Transcallosal inhibition from the intact to the damaged motor cortex Imbalance of interhemispheric inhibition Strategies for Promoting Motor Recovery after Stroke To re-establish a normalized interhemispheric balance between the lesioned & healthy hemispheres

9 Principles of rtms Technique to Enhance Post- Motor Recovery Treatment strategies Interhemispheric Competition Model Motor deficits in patients are due to: output from the affected hemi-sphere excessive interhemispheric inhibition from the unaffected hemisphere to the affected hemi-sphere 1 2 excitability in the unaffected hemisphere excitability in affected hemisphere (--) (+) Unaffected Hemisphere + Affected Hemisphere Inhibitory Lowfrequency rtms Lowfrequency rtms Highfrequency rtms Excitatory Highfrequency rtms

10 Enhancing Motor Recovery after Stroke Using Repetitive Transcranial Magnetic Stimulation (rtms) Inhibitory Lowfrequency rtms rtms (--) (+) rtms Excitatory Highfrequency rtms Tretriluxana et al., 2013 Seniów et al., 2012 Wang et al., 2012 Conforto et al., 2012 Takeuchi et al., 2008 Nowak et al., 2008 Kirton et al., 2008 Dafatakis et al., 2008 Liepert et al., 2007 Fregni et al., 2006 Boggio et al., 2006 Fregni et al., 2006 Mansur et al., 2005 Takeuchi et al., 2005 Kakuda et al., 2013b Kakuda et al., 2013a Sung et al., 2013 Takeuchi et al., 2009 Talelli et al., 2007 Khedr et al., 2010 Yozbatiran et al., 2009 Khedr et al., 2009 Talelli etal., 2007 Malcom et al., 2007 Kim et al., 2006 Khedr et al., 2005

11 Inhibitory rtms over Unaffected Hemisphere (1) Low-frequency rtms Author yrs Study design Patient group Stimulation parameter Stimulation area Results Takeuchi et al., 2005 Doubleblinded, crossover, Chronic (6-60 mo) 1Hz, 90% resting motor threshold, 25 mins, 1500 pulses Unaffected 1 o motor cortex 20% peak pinch acceleration immediately after intervention, no improvement on pinch force Mansur et al., 2005 Fregni et al., 2006 Singleblinded, crossover, Singleblinded, randomized, Subacute ( 12 mo) Subacute 1Hz, 100% resting motor threshold, 10 mins, 600 pulses, 3 sessions 1Hz, 100% resting motor threshold, 20 mins, 1200 pulses x 5 days Unaffected 1 o motor cortex Unaffected 1 o motor cortex 16 & 11% in simple & choice reaction times; 33% in Purdue Pegboard Test, no improvement in index finger tapping test 15 & 5% in JTHHT (post-rx & 14 days FU); 50% in simple & choice reaction times (both post- Rx & 14 days FU), 60% in Purdue Pegboard test (both post- Rx & 14 days FU) Boggio et al., 2006 Single-case study, doubleblinded Chronic (23 mo) 1Hz, 100% rmt, 20 mins, 1200 pulses, 2 session( 2 mo apart btw session) Unaffected 1 o motor cortex 5 o &15 o / 10 o &20 o of thumb & finger mov t (after 1 st & 2 nd rtms sessions resp.), no change in Modified Ashworth scale

12 Inhibitory rtms over Unaffected Hemisphere (2) Low-frequency rtms Author yrs Liepert et al., 2007 Nowak et al., 2008 Takeuchi et al., 2008 Study design Double-blinded, crossover, Double-blinded, crossover, Double-blinded, crossover, Patient group Acute (<14 day) Subacute (1-4 mo) Chronic (7-121 mo) Stimulation parameter 1Hz, 90% of resting motor threshold, 25 mins 1Hz, 90% resting motor threshold, 10 mins 1Hz, 90% of resting motor threshold, 25 mins Stimulation area Unaffected 1 o motor cortex Unaffected 1 o motor cortex Unaffected 1 o motor cortex Results No improvement in peak grip force, 10% in Nine Hole Peg Test 25% in vel. & freq. of index finger tapping, 30% of vel. & timing of grasping mov t 30% & 20% in pinch acceleration & peak pinch force immediately & at 1 week post-rx Dafotakis et al., 2008 Double-blinded, crossover, Subacute to chronic (1-15 mo) 1Hz, 100% resting motor threshold, 10 mins Unaffected 1 o motor cortex 30% in efficiency & 40% in timing of grip force kinetics when grasping & lifting an object Kirton et al., 2008 Single-blinded, randomized, Chronic (3-13 yrs) 1Hz, 100% resting motor threshold, 20mins x 8 days Unaffected 1 o motor cortex 9% of Medboune Ax of UE fx, 20% grip strength

13 Inhibitory rtms over Unaffected Hemisphere (3) Low-frequency rtms Author yrs Study design Patient group Stimulation parameters Stimulation area Results Wang et al., 2012 Conforto et al., 2012 Doubleblinded, randomized, Doubleblinded, randomized, Chronic ( yr) Acute (5-45 days) 1Hz, 10 mins, 90% of rmt, 600 pulses + 30mins task-orientated training, 5/wk,2 weeks 1Hz, 90% of resting motor threshold, 25 mins (1500 pulses) Unaffected leg area, 1 o motor cortex Unaffected 1 o motor cortex corticomotor excitability symmetry, spatial gait symmetry, motor control & walking ability in rtms gp 12.3% in the Jebsen-Taylor test & pinch force (0.5 N) in the active group Seniów et al., 2012 Doubleblinded, randomized, Subacute ( 3 mo) 1Hz, 90% of resting motor threshold, 1800 pulses, (30 mins), 5/wk,3 weeks Unaffected 1 o motor cortex 12.3% in the Jebsen-Taylor test & pinch force (0.5 N) in the active group Tretriluxana et al., 2013 Crossover, Chronic (4.8 yrs) 1Hz, 90% resting motor threshold, 20mins (1200 pulses) Unaffected 1 o motor cortex total mov t time & peak grasp aperture, but no changes in peak transport vel. or time of peak transport vel or time of peak aperture after active rtms. Active rtms gp completed RTG actions with a more coordinated pattern

14 Excitatory rtms over Affected Hemisphere (1) Kim et al., 2006 Malcom et al., 2007 Yozbatiran et al., 2009 High-frequency TMS Study Author yrs design Khedr et al., Singleblinded, 2005 randomized, Singleblinded, crossover, Doubleblinded, randomized, Nonblinded, real rtms only Patient group Acute (5-10 days) Chronic (4-41 mo) Chronic (>1 yrs) Chronic (>11 week) Stimulation parameter Stimulatio n area 3Hz, 10s,120% resting Affected motor threshold, 10 trains, 50s intertrain interval, 300 pulses, 10 daily stimulation 1 o motor cortex 10Hz, 2s, 80% resting motor threshold, 8 trains, 58s intertrain interval, 160 pulses, finger mov t task 40s, 28s break btw 20Hz, 2s, 90% resting motor threshold, 50 trains, 28s intertrain interval, 2000 pulses, 10 consecutive days, follow-by CIMT at 90% working hour 20Hz, 2s, 40 trains, 28s intertrain interval, 90% resting motor threshold, 1600 pulses Affected 1 o motor cortex Affected 1 o motor cortex Affected post. precentral gyrus at hand knob Results 45% & 75% hand fx (Sandinavian Stroke Scale, NIHSS, BI) immediately & 10 days after last session of rtms 75% & 125% in mov t accuracy & 25% % 20% in mov t time (sequential finger mov t task); higher in MEP amplitude Hand fx (Wolf Motor Function Test, Motor Activity Log) in both gps because of the effect of CIMT, no additive effect of rtms No sign. effect on Fugl- Meyer score, 20% Grip strength, 80% & 120% in hand fx (Nine hole peg test)

15 Excitatory rtms over Affected Hemisphere (2) High-frequency TMS Author yrs Khedr et al., 2009 Khedr et al., 2010 Kakuda et al., 2013a Kakuda et al., 2013b Study design Randomized, shamed controlled Doubleblinded, randomized, Doubleblinded, Randomized, crossover, shamed controlled Single group, pretest posttest design Patient group Acute (7-20 days) Acute (5-15 days) Chronic (>12 mo) Chronic (>12 mo) Stimulation parameter (i) 1Hz, 15min, 900 pulses, 100% resting MT; (ii) 3Hz, 10s, 30 trains, intertrain interval 2s, 900 pulses, 130% MT; (iii) sham rtms, daily x 5 days 3 groups: (i) 3 Hz, 5s, 50 trains, 750 pulses, 130% rmt; (ii) 10Hz, 2s, 37 trains, 740 pulses, 100% rmt; (iii) sham rtms; daily x 5 days 10Hz, 10s, 90% of resting motor threshold, intertrain interval 50s, 20 trains (2000 pulses), 2 sessions (real vs sham rtms) 10Hz, 10s, 90% of rmt, intertrain interval 50s, 20 trains (2000 pulses) +60mins mobility training, 2/dayx10 days Stimulation area 1Hz unaffected 3Hz affected 1 o motor cortex Affected 1 o motor cortex Bilateral leg motor area, 1 o motor cortex Bilateral leg motor area, 1 o motor cortex Results Both real rtms sig. improves keyboard tapping & pegboard collection tests, improvement was sign. higher in the 1Hz gp. No sig. diff. in hand grip test Sign. in Hemispheric Stroke Scale for motor power (hand grip & Sh abd), NIHSS, & mrs in both rtms gps. Effects were maintained till 1 yr FU Sig. walking vel. & physiological cost index in real rtms gp Combined rtms+mobility training sig. walking vel. physiological cost index, & time to perform timed up & go test

16 Other rtms Protocol: TBS, Bi-hemisphere Stimulation Other stimulation protocol Author yrs Study type Patient group Stimulation parameter Stimulation area Results Talelli et al., 2007 Singleblinded, randomized, Chronic ( mo) Each burst: 3 pulse at 50Hz given at 5Hz, 80% active motor threshold, i) itbs, 20 trains, 10 burst,8s intertrain interval, 600 stimuli; (ii) ctbs, con t train of 100 bursts, 600 stimuli; (iii) sham TMS itbs on affected hemisphere; ctbs unaffected 1 o motor cortex Only itbs sign. motor behaviour & the physiological measures of the paretic hand. 90% mov t speed immediately & last for 40mins, no significant effect on peak grip force Takeuchi et al., 2009 Doubleblinded, crossover Chronic (>6 mo) (i) 1Hz, 50s, 90%rMT, 20mins, 1000 pulses+sham; (ii) 10Hz, 5s, 20 trains, 1000 pulses+sham; (iii) Bil 1 & 10Hz 1Hz unaffected 10 Hz affected 1 o motor cortex Bil rtms & 1Hz rtms improves acceleration in the paretic hand. 10Hz has no effect on motor fx Sung et al., 2013 (consecutive suppressivefacilitatory TMS protocol) Singleblinded, randomized, Chronic (3-12 mo) Bilateral stimulation a) 1Hz (contra)+itbs(ip) b)sham(contra)+itbs(ip) c) 1Hz(contra)+sham(ip) d) Bilateral sham 20 daily sessions 1Hz, 90%rMT, 10 mins (600 pulses); itbs: 80%rMT, 3pulse at 50Hz at 5Hz, 2s, 100 trains (600 pulses) Combined 1Hz+iTBS showed greater muscle strenght, Fugl-Meyer, Wolf Motor Function test & reaction time improvement

17 Benefits of rtms in Stroke - Meta-analysis 18 selected articles, 392 patients positive effect on motor recovery (effect size of 0.55) in, esp subcortical (mean effect size, 0.73) showing neural activity in unaffected hemisphere associated with motor recovery additional cortical showed neural activity in the frontal & parietal motor areas - might counteract the effect of rtms good for all stages of Post- competition & imbalance could be remedied by reducing the cortical excitability in the unaffected hemisphere using rtms Low-frequency rtms over the contra-lesional hemisphere more beneficial than high-frequency rtms over ipsilesional hemisphere No statistical evidence found for publication bias, heterogeneity

18 rtms in Stroke Management Cochrane Review Included 19 trials with 588 participants rtms not associated with improved ADL nor sig. effect on motor function Current evidence is not yet sufficient to support the routine use of rtms for the treatment of Sig. heterogeneity in time between and recruitment (from 4 hours to 6 years) measurement time point (end of the treatment period or within one month) rtms protocols (stimulation parameters of frequency, intensity, pulses) different motor function assessments Strict inclusion criteria limiting applicability Small sample size (10 to 123) affecting adequate power to detect a betweengroups difference Potential side effects e.g. seizure found to be rare or nil Further trials with larger sample sizes are needed to determine a suitable rtms protocol & the long-term functional outcome Hao Z, Wang D, Zeng Y, Liu M. Repetitive transcranial magnetic stimulation for improving function after. Cochrane Database Syst Rev. 2013;5:CD doi: / CD008862

19 Local PT Experience in KCC

20 TMS Suite in QEH Designated/ Enclosed treatment venue Avoid disturbance Install separated high voltage power supply for each stimulator unit

21 Focused Target Clientele Target Clientele Stroke Upper limb with motor control (power 2-) No history of cancer or unstable medical condition Exclusion Criteria Substantial cognitive impairment with Mini Mental State Test <24 Diagnosis of mental illness Pathological conditions referred to as contra-indications for rtms in guideline suggested by Wassermann (eg. Cardiac pacemaker, intracranial implants, implanted medication pumps, epilepsy) Unstable cardio-pulmonary conditions

22 Repetitive Transcranial Magnetic Stimulation (rtms) Conventional rtms Application of regularly repeated single TMS pulses High frequency: > 1Hz (for facilitation) Low frequency: <1Hz (for inhibition) Patterned rtms Repetitive application of short rtms bursts at a high inner frequency interleaved by short pauses of no stimulation e.g. Theta burst stimulation ctbs : for inhibition itbs : for facilitation

23 Stimulation Protocols For excitatory rtms over affected hemisphere Strong intensity, numerous numbers, and long duration are most effective for motor recovery For inhibitory rtms over unaffected hemisphere Subthreshold stimulation on unaffected hemisphere (e.g. 90% rmt) excitability of stimulated motor cortex facilitation effect on the contralateral motor cortex Suprathreshold stimulation on unaffected hemisphere (e.g. 120% rmt) excitability of stimulated motor cortex excitability of the opposite homogenous motor cortex via activation of interhemispheric inhibition cancel out the facilitation effect on contralateral motor cortex No consensus on the optimal stimulation protocol rtms Protocol in KCC Inhibitory Low-frequency rtms over contra-lesional site 1Hz x 1500 pulse at 90% rmt x 10 sessions + PT upper limb training program *Safe and can be achieved same benefits with ease in locating hot spot

24 Safety Assurance in TMS Hao Z, Wang D, Zeng Y, Liu M. Repetitive transcranial magnetic stimulation for improving function after. Cochrane Database Syst Rev. 2013;5:CD doi: / CD008862

25 Staff Credentialing Criteria in KCC PT with at least 5 years post-graduate experiences in the relevant field(s) Successful completion of structured training including theory & practicum of at least 40 hours by recognized training institute Attainment of at least a pass in formal examination * Audit on compliance to intervention protocol & safety measures

26 Patient Screening Record Form

27 Safety Assurance Side effect Control measures Patient screening Hearing protection Hearing Seizure Emergency stand-by Vital sign Monitoring Headache

28 PT Upper Limb Rehabilitation Program Transcranial Magnetic Stimulation Robotic Therapy Acupuncture Functional Electrical Stimulation Manual Therapy Virtual Reality

29 Pilot Study Preparation: Consolidate skill Formulate guideline/ protocol Establish reliability of outcome measures Type of Ischaemic Stroke Duration of Subacute: 2 week post- onset (average 8.5 weeks) Chronic: 8 with average of weeks Age patients completed the pilot program Box & Block Test Action Research Arm Test Outcome Measures Chronic (n=8) Subacute (n=2) Fugl- Meyer Score +3.3% +6.5% Box and Block Test +22% +30.5% Tap Test +17.5% +25% Action Research Arm Test +10.2% Overall demonstrating positive results after the rtms+ UL rehab No adverse effects reported

30 Summary rtms is a safe intervention Stringent staff credentialing system Proper patient screening Effective Appropriate control measures implementation Continuous evaluation/ audit rtms Positive effect on motor recovery esp. in upper limb For each stage of acute, subacute and chronic Subcortical benefits more Post-stimulated effect lasting for 1-2 hours Benefits are more sustainable when followed by post-stimulation training rtms can be an effective adjunct PT intervention in rehabilitation

31 Thank You!