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Program Written Summary
Audio-Digest Neurology
Volume 04, Issue 02
January 21, 2013

Treatment of Spasticity with OnabotulinumtoxinA – Allan Herskowitz, MD
Robotics in Rehabilitation for Stroke and Cerebral Palsy – Hermano I. Krebs, PhD

From The 18th Annual Brain Injury Symposium: Practical Application And Innovation, Presented By Baptist Hospital Rehabilitation Center, Baptist Health South Florida, And Cosponsored With Baptist Neuroscience Center
Digital Media $24.99
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The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program.

Neurology Program Info  Accreditation InfoCultural & Linguistic Competency Resources

Rehabilitation After Stroke

From the 18th Annual Brain Injury Symposium: Practical Application and Innovation, presented by Baptist Hospital Rehabilitation Center, Baptist Health South Florida, and cosponsored with Baptist Neuroscience Center

Educational Objectives

The goal of this program is to improve the rehabilitation of patients who have suffered strokes. After hearing and assimilating this program, the clinician will be better able to:

1. Educate patients about the mechanism, benefits, and side effects of botulinum toxin (BTX) when used for treatment of spasticity.

2. Select appropriate patients for use of BTX injection in conjunction with physical therapy to treat spasticity of the upper extremities after stroke.

3. Summarize functional objectives and goals of managing spasticity with BTX.

4. Elaborate on advances in understanding of brain plasticity and how they affect the development of robotic therapy for rehabilitation of the extremities after stroke.

5. Assess evidence supporting the benefits of robot-assisted therapy in producing long-lasting gains in movement that are potentially transferable to untrained tasks.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Krebs is a founder and equity holder of Interactive Motion Technologies, and receives royalties from Interactive Motion Technologies and Intuitive Surgical. Dr. Herskowitz and the planning committee reported nothing to disclose.

Treatment of Spasticity with OnabotulinumtoxinA

Allan Herskowitz, MD, Voluntary Faculty Assistant Clinical Professor of Neurology, University of Miami Miller School of Medicine and Herbert Wertheim College of Medicine at Florida International University; Chief, Neurology Section, Baptist Hospital, Miami, FL

Botulinum toxin (BTX): protein purified from bacterium (Clostridium botulinum); remains at site of injection and does not enter bloodstream; affects neuromuscular junction; wears off after ≈3 mo; causes few side effects, aside from excessive weakness if too much injected; no systemic toxicity seen; among several serotypes, type A used because of greater efficacy and shorter onset of action; acts by blocking release of acetylcholine at receptor site to prevent conduction; increasing dilution increases spreading of injected material, which helps with treatment of spasticity by maximizing amount of muscle affected (for cosmetic use, spreading undesirable and causes side effects); BTX used mostly for neurologic applications; approved indications  include facial hemispasm, blepharospasm, cervical dystonia, hyperhidrosis, migraine, spasticity, and overactive bladder; injection technique  landmarks guiding injection less obvious than those used for cosmetic applications; knowledge of anatomy necessary for neuromuscular injection (often guided by electromyography [EMG]); must inject within 24 hr of dilution

Treatment of spasticity in upper limbs

Fingers and thumb in palm without active extension: therapeutic goal improved quality (eg, even small improvement may allow grasping); considerations include number of muscles involved, site(s) of injection, and use of EMG-guided needle; muscles involved include flexor digitorum superficialis and profundus, flexor pollicis longus, adductor pollicis, and flexor pollicis brevis

Pronated forearm with spastic wrist and finger flexors: improved ability to open hand may allow patient to grasp walker; may also prevent infections of skin; involved muscles include pronators and flexors (eg, flexor carpi radialis, flexor carpi ulnaris)

Excessive flexor tone at elbow: commonly seen in patients after stroke; involves adduction, hypersupination, and sometimes hands; involved muscles include brachioradialis and biceps (EMG needles not usually necessary)

Internally rotated adducted shoulder: condition common; causes difficulty inserting hand into sleeve while dressing, excessive sweating, and infections; involved muscles vary in size and required dose (eg, larger muscles require higher doses); higher doses not as problematic when treating spasticity as when treating cervical dystonia, cosmetic problems, facial hemispasm, or migraine; in spasticity, excessive laxity not harmful

Selection of cases for treatment with BTX: in general, treatment with BTX effective if manual flexion of limb into correct position possible; if limb too stiff to flex manually, surgery probably required to release shortened tendon and fibrosis

Dose: for dystonia of hands, speaker starts with low dose and gradually increases to avoid causing weakness; repeat injections at intervals of 3 mo because body loses anamnestic response; if injections more frequent, response of antibodies result in need for higher doses; 500 to 600 units maximum recommended dose at one time (toxicity possible); botulinum B may be used if antibodies to botulinum A develop

Thumb in palm: involved muscles include adductor pollicis, flexor pollicis longus, and thenar group; functional outcomes include improved ability to grasp

Clenched fist: important to treat aggressively and early in combination with physical therapy (eg, use of splint) to release muscles gradually; enables patient to wash palm; helps prevent maceration of skin and noxious odor

Flexed wrist: involves flexor carpi radialis and extensor carpi radialis longus and brevis; treatment enables patient to insert hand into narrow opening (eg, sleeves, braces) and reduces pain and symptoms of carpal tunnel syndrome

Pronated forearm: causes difficulty orienting hand; treat by injecting pronators

Flexed elbow: injection of larger doses possible because of size of muscle; improves ability to dress and reach for things; reduces maceration of skin

Predictability of treatment: depends on condition being treated; with migraines, BTX produces variable improvement; with hyperhidrosis, BTX predictably inhibits sweating for 6 to 9 mo; with spasticity, relaxation of muscles predictable, except in extreme cases

Adducted or internally rotated shoulder: treatment allows patient to reach for objects; involved muscles (eg, subscapularis, teres major) sometimes difficult to inject

Identification of muscles: Functional Anatomy for the Electromyographer textbook that shows origin, insertion, and function of all muscles and gives anatomic landmarks

Interdisciplinary treatment team: physiatrist; orthopedist; neurosurgeon; neurologist; occupational, speech, and physical therapists; orthotist; nurses; social worker; pharmacist; billing specialist

Assessment of goals: important to determine needs of patient before starting treatment; medications that relax muscles may cause side effects, eg, sleepiness, confusion; phenol toxic and causes irreversible damage to nerves; consult with physical therapist on functional objectives and follow-up after injection

Upper motor neuron (UMN) syndrome: physical phenomena commonly seen include spasticity, rigidity, tremor, clonus, and dystonia; BTX helpful if problem focal but not for large areas, eg, tremor of entire arm; important to assess extent of deficit to determine amount of BTX needed; spasticity in legs may allow patient to ambulate with support, whereas treatment with BTX could weaken leg; negative effects of UMN syndrome  include slowness, weakness, loss of dexterity, and decreased selective control of muscles; synergy patterns in upper and lower extremities  include adducted thumb and equinovarus foot, flexed wrist and extended knee, and flexed elbow and adducted thighs

Functional objectives: improve potential for therapeutic options; improve mobility and activities of daily living; maximize relief of pain; decrease impact of hypertonicity; improve range of motion; improve muscle tone; improve outcomes of physical and occupational therapy

Options for management: decrease pain; provide appropriate therapies; oral medications (eg, tizanidine [Zanaflex], baclofen, diazepam [Valium]) have side effects; BTX; phenol and alcohol blocks no longer used because of side effects and irreversibility; intrathecal baclofen with pump often helpful for patients with severe spasticity of lower extremities; surgery (eg, selective dorsal rhizotomy, tenolysis)

Before intervention: assess status of patient; communicate with team members; establish goals of treatment; manage expectations of patient and caregiver(s) and explain obtainable outcomes

After intervention: reevaluate functional goals; redesign splints (important for maintaining advances); assess for adverse effects after chemoneurolysis; communicate with patient and caregiver(s)

Goals of management of spasticity: decrease spasticity; improve function and independence; decrease pain; reduce or prevent contractures (which cause permanent shortening of tendons and fibrosis if untreated); improve ambulation; facilitate hygiene; ease rehabilitation procedures; save time of caregiver(s) by improving functional ability of patient

Traditional approach: removal of noxious stimuli; rehabilitation therapy; oral medications (not all patients need BTX); neurolysis; orthopedic or neurosurgical procedures (last resorts for fixed contractures)

Robotics in Rehabilitation for Stroke and Cerebral Palsy

Hermano I. Krebs, PhD, Adjunct Professor, Department of Neurology and Division of Rehabilitative Medicine, University of Maryland School of Medicine, Baltimore; Principal Research Scientist and Lecturer, Newman Laboratory for Biomechanics and Human Rehabilitation, Massachusetts Institute of Technology, Cambridge

Background: assistive technology (eg, wheelchair, glasses) helps individuals interact with environment; therapeutic robotics help clinician deliver therapy and possibly help patient avoid need for assistive technology

Magnitude of clinical need: 795,000 strokes occur annually in United States, and 70% of survivors need therapy; need is larger elsewhere; as cause of death, stroke ranks third in developed world but first in developing world; need expected to increase as population ages

Paradigm shift in neuroscience: previously believed that brain could not recover after stroke; now know brain has plasticity that enables recovery; study of plasticity (Nudo, 2007)  monkeys with small lesion in area of brain controlling hand divided into groups with and without subsequent training; in group that received no training of hand, area of brain representing hand shrank; in group that received therapeutic training, same area of brain maintained size or grew; “neurons that fire together wire together”  if 2 neurons fire together, they reinforce each other (no change seen in strength of connection if neuron fires alone); if neurons fire at different times, depression occurs over long term

Guidelines: American Heart Association guidelines (2010)  robot-assisted motor rehabilitation for upper extremities has class I evidence level A recommendation for outpatient and chronic patients and class II level A recommendation for inpatients (fewer patients evaluated); class I signifies benefit outweighs risk, and treatment indicated; level A indicates multiple patients evaluated from multiple randomized trials; class II level A signifies benefits greater than risk, additional studies needed, and administration of treatment considered reasonable; Department of Veterans Affairs (VA) guidelines  robot-assisted therapy recommended as adjunct to traditional therapy for upper extremities; concluded evidence insufficient to support use of robotic devices for training of lower extremities after stroke

Randomized clinical trial (Lo et al, 2010): multisite study performed by VA compared robot-assisted therapy with usual care and intensive therapy; therapy in all arms matched for frequency (3 therapy sessions per week); therapy in robotic and intensive arms matched for intensity (number of movements performed); treatment lasted 12 wk with 6 mo of follow-up; outcomes  included improvement of 5 points (Fugl-Meyer scale) in robotic group over usual care, and 3 points over intensive therapy; population  patients had moderate-to-severe impairment of upper extremity (Fugl-Meyer score 7-38); stroke occurred ≥6 mo before participation in study; patients with history of multiple strokes not excluded; types of robots used  shoulder-elbow; wrist; antigravity; hand; design  patients who completed usual care could choose to receive intensive therapy or robotic therapy; during study, usual care therapy found to have no impact and stopped partway through study to save money

Results: at 12 wk  significant difference seen between robotic and usual care arms only in Stroke Impact Scale (SIS; strong trend seen in Fugl-Meyer scale); average score between robotic and usual-care arms >5 points (improvement increased over time as therapists became familiar with robotic technology); at 6 mo after end of study  significant differences seen between treatments for all scales (ie, Fugl-Meyer representing impairment, Wolf representing function, and SIS representing quality); at 36 wk  difference of 2 points seen in favor of robotic over intensive arm; however, fixed-model analysis (based on patients from all 3 arms) found robotic therapy slightly inferior

Economic analysis (Wagner et al, 2011): cost of usual care considered baseline; intensive therapy increased cost ≈$7000; robotic therapy increased cost ≈$5000 (savings statistically significant); total cost of care ≈$17,000 in robotic arm and ≈$19,000 in intensive and usual care groups; after end of study  cost for intensive therapy increased over time; cost for robotic therapy arm decreased further with additional time (suggesting difference not caused by placebo effect)

Generalizability of study: ≈66% of 200 screened individuals enrolled in study, as compared to Constraint-Induced Movement Therapy (CIMT) trial in which only 6% of 3600 screened individuals enrolled; technology and process of rehabilitation used in study could have broad application

Variables influencing outcome

Number of repetitions: therapists typically deliver ≈45 movements in 45-min session; Lynch et al (2005)  evaluated identical numbers of movements of shoulder delivered by continuous passive motion (CPM) and standard therapy; no differences in neurologic scales found between arms; CPM arm had improved joint stability

Feedback: healthy individuals learn new movement rapidly with mechanical guidance, but retention of skill poor; individuals who do not have mechanical guidance but have feedback throughout trial learn more slowly but have better transference; individuals given feedback after 5 attempts did not learn as well as other 2 groups but had best transference and retention

Passive vs active participation: study compared 2 groups of children with cerebral palsy; one group played with robot with goal of hitting target (active therapy); second group watching video while robot allowed to move limbs (passive therapy); significant difference found between groups, with most gain seen in active group; active participation important for improvement in adults after stroke and children with cerebral palsy

Summary of benefits: effects of robotic therapy for upper extremities long-lasting; when patients trained in reaching and tested on drawing circles, gains observed in both tasks; therefore, effects of training generalized to untrained tasks

Suggested Reading

Baguley IJ et al: Investigating muscle selection for botulinum toxin-A injections in adults with post-stroke upper limb spasticity. J Rehabil Med 43:1032, 2011; Bakheit AM: The pharmacological management of post-stroke muscle spasticity. Drugs Aging Nov 9, 2012 [Epub ahead of print]; Cigna E et al: Botulinum toxin type A in the healing of chronic lesion following bilateral spasticity of gluteus muscle. Int Wound J Oct 19, 2012 [Epub ahead of print]; Fasoki SE et al: New horizons for robot-assisted therapy in pediatrics. AM J Phys Med Rehabil 91(11Suppl 3):S280, 2012; Formica D et al: The passive stiffness of the wrist and forearm. J Neurophysiol 108:1158, 2012; Hefter H et al: Classification of posture in poststroke upper limb spasticity: a potential decision tool for botulinum toxin A treatment? Int J Rehabil Res 35:227, 2012; Kheder A, Nair KP: Spasticity: pathophysiology, evaluation and management. Pract Neurol 12:289, 2012; Lo AC et al: Robot-assisted therapy for long-term upper-limb impairment after stroke. N Engl J Med 2010 May 13;362(19):1772-83; Lynch D et al: Continuous passive motion improves shoulder joint integrity following stroke. Clin Rehabil 2005 Sep;19(6):594-9. Marcniak CM et al: Does botulinum toxin type a decrease pain and lessen disability in hemiplegic survivors of stroke with shoulder pain and spasticity?: a randomized double-blind, placebo-controlled trial. Am J Phys Rehabil 91:1007, 2012; Merholtz J et al: Electromechanical and robot-assisted arm training for improving generic activities of daily living, arm function, and arm muscle strength after stroke. Cochrane Database Syst Rev 6:CD006876, 2012; Naumann M et al: Immunogenicity of botulinum toxins. J Neural Trans Sep 25, 2012 [Epub ahead of print]; Norouzi-Gheidari N et al: Effects of robot-assisted therapy on stroke rehabilitation in upper limbs: systematic review and meta-analysis of the literature. J Rehabil Res Dev 49:479, 2012; Nudo RJ: Postinfarct cortical plasticity and behavioral recovery. Stroke 2007 Feb;38(2 Suppl):840-5; Page SJ et al: Portable upper extremity robotics is as efficacious as upper extremity rehabilitative therapy: a randomized controlled pilot trial. Clin Rehabil Nov 12, 2012 [Epub ahead of print]; Rosales et al: Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke: a randomized controlled trial. Neurorehabil Neural Repair 26:812, 2012; Santamato A et al: Efficacy and safety of higher doses of botulinum toxin type a NT 201 free from complexing proteins in the upper and lower limb spasticity after stroke. J Neural Trans Sep 7, 2012 [Epub ahead of print]; Schweighofer N et al: Task-oriented rehabilitation robotics. Am J Phys Med Rehabil 91(11Suppl 3):S270, 2012; Stein J: Robotics in rehabilitation: technology as destiny. Am J Phys Med Rehabil 91(11Suppl 3):S199, 2012; Teasell R et al: Evidence to practice: botulinum toxin in the treatment of spasticity post stroke. Top Stroke Rehabil 19:115, 2012; Thomas AM, Simpson DM: Contralateral weakness following botulinum toxin for poststroke spasticity. Muscle Nerv 46:443, 2012; Wagner TH et al: An economic analysis of robot-assisted therapy for long-term upper-limb impairment after stroke. Stroke 2011 Sep;42(9):2630-2.

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