Principles of spasticity management Management of spasticity C

Principles of spasticity management Management of spasticity C. L. I. M. B. Continuum of Learning to Improve Management with Botulinum Toxin DYS SE 000025 Date of preparation: May 2017 This programme is initiated and funded by IPSEN. Dysport® (Clostridium botulinum type A toxin haemagglutinin complex) prescribing information is available at this meeting.

Management of spasticity: contents Upper motor neurone syndrome and spasticity pathophysiology Harmful effects of spasticity Structuring spasticity management Treatments for spasticity

Learning goals The objectives of this module are to provide: • A recap of spasticity pathophysiology • Best practice suggestions for spasticity management • An overview of the available treatments for managing patients with spasticity

Upper motor neurone syndrome and spasticity pathophysiology

Spastic paresis • Spasticity arises from prolonged disinhibition of spinal reflexes as a result of Upper Motor Neurone (UMN) lesion • These spinal reflexes include stretch, flexor and extensor reflexes and are under supraspinal control by inhibitory and excitatory descending pathways • Stretch reflexes are proprioceptive reflexes, and can be either phasic or tonic Bandi S, Ward AB. 2010. Spasticity. In: JH Stone, M Blouin, editors. International Encyclopedia of Rehabilitation. Available online: www. cirrie. buffalo. edu/encyclopedia/en/article/32/ (Accessed June 2016).

Development of spasticity after UMN damage Rehabilitation unit Acute care Damage to central motor pathways Immediate Paralysis Delayed Plastic rearrangement Flaccidity Spinal reactivity Supraspinal command Immobilisation in shortened position Contracture Spasticity Spastic dystonia Spastic co contraction Other Overactivity Graphic provided and reproduced with permission from Prof. Anthony B Ward Bandi S, Ward AB. 2010. Spasticity. In: JH Stone, M Blouin, editors. International Encyclopedia of Rehabilitation. Available online: www. cirrie. buffalo. edu/encyclopedia/en/article/32/ (Accessed June 2016).

Disabling features of spasticity • There are three main disabling features of spasticity: (1) Paresis i. e. reduced voluntary recruitment of skeletal motor units Gracies JM, et al. Muscle Nerve 2005; 31: 535– 51. (2) Soft tissue contracture In particular muscle shortening and joint retraction (3) Muscle overactivity i. e. , reduced ability to relax muscle

Visco-elastic changes in immobilised muscles and joints • Untreated, spasticity can cause shortening of muscles and tendons, leading to contractures • After immobilisation, connective tissue and fat can replace sarcomeres • Left unchecked, this process can end in contractures and permanent loss of joint mobility Kheder A, et al. Practical Neurology 2012; 12: 289– 98.

Alterations occurring in spastic muscle Alteration in muscle fibre size and fibre type distribution Proliferation of extracellular matrix material, measured both morphologically and biochemically Lieber R, et al. Muscle Nerve 2004; 29: 615– 62. Increased stiffness of spastic muscle cells and, to a lesser extent, spastic muscle tissue Inferior mechanical properties of extracellular material in spastic compared to normal muscle

Harmful effects of spasticity

What are the common symptoms of spasticity? Increased muscle tone Overactive reflexes Difficulty with care and hygiene Abnormal posture Contractures Bone and joint deformities Pain Involuntary movements Decreased functional abilities and delayed motor development Web. MD: www. webmd. com/pain management spasticity (Accessed June 2016)

Clinical and functional problems associated with severe spasticity Emotion / social Physical • • Non specific pain Discomfort Painful muscle spasm Difficulties with activities of daily living (e. g. washing, dressing, eating, toileting, maintaining hygiene, sexual activity) Problems with posture and mobility Physical deformity and long–term contracture Pressure ulcers Bavikatte G et al. BJMP 2009; 2: 29– 34. • • • Emotional (e. g. low mood, distorted self image, impaired motivation) Impact on fulfilment of life roles as a partner or a parent Sleep disturbance – due to pain and discomfort Vocational – impact on employment / education Social isolation – due to restricted mobility

The vicious cycle of spasticity Unopposed contraction due to spastic dystonia Prevents muscle lengthening Biomechanical changes in the contracted muscles Abnormal limb posture Soft tissue shortening Adapted from: Turner Stokes L, Ward AB, et al. National guidelines. RCP and BSRM, 2009.

Long-term problems of spasticity Decreased functional activity can result in: Pressure sores 1 Cardiovascular problems 2 Thrombophlebitis 2 Urinary tract and bowel problems 2 Osteoporosis 2 Respiratory infections 2 1. American Association of Neurological Surgeons. Spasticity. www. aans. org/Patient%20 Information/Conditions%20 and%20 Treatments/Spasticity. Accessed April 2016 2. Med. Merits – Spasticity www. medmerits. com/index. php/article/spasticity/P 10. Accessed June 2016.

Structuring spasticity management

Spasticity is a serious disorder requiring a structured management and treatment plan Spasticity, if left untreated, can lead to a host of serious complications, including… Degenerative joint disease Pain from muscle spasms Limb deformity and altered body mechanics Muscle shortening Need for special wheelchairs and seating Bandi S, Ward AB. 2010. Spasticity. In: JH Stone, M Blouin, editors. International Encyclopedia of Rehabilitation. Available online: www. cirrie. buffalo. edu/encyclopedia/en/article/32/ (Accessed June 2016)

Discharge Principles of spasticity management Patient assessment Define treatment goals Identify expected outcomes Review and record Treatment Measurement Adapted from: Turner Stokes L, Ward AB, et al. National guidelines. RCP and BSRM, 2009.

Multi-professional approach to spasticity management Community therapists and nurses (longer–term treatment) Engineer (Posture & Movement Analysis) Orthotist (Splints) Nurse (Education) Service Secretary (Organisation & Management) Patient & Carer Physiotherapist (Treatment, Exercise, FES) Occupational Therapist (Treatment, Casts & Splints) Rehabilitation Medicine Physician, Neurologist Stroke Physician (Medical management, Bo. NT-A treatment) Orthopaedic surgeon Rx: Treatment; Ex: Exercise; FES: Functional electrical stimulation. Turner Stokes L, Ward AB, et al. National guidelines. RCP and BSRM, 2009. Ward AB. Personal communication 2015.

Aims of treatment Improve function – Mobility – Dexterity Provide symptom relief – Ease pain • Muscle shortening • Tendon pain • Postural effects – Decrease spasms – Orthotic wearing Ward AB. Personal communication 2015. Improve posture – Body image Decrease carer burden – Care and hygiene – Adjust positioning and dressings Optimise service responses – Avoid unnecessary treatments – Facilitate therapy – Delay / prevent surgery

Making the most of the clinic visit • • Assessment Identifying goals for treatment Setting expectations for patient, family and team Planning treatment and agenda for longer term management Making necessary referrals to team members Carrying out treatment(s) Planning review appointments Decision on further treatment at review Schema provided by Anthony Ward • Identifying the main problems of the patient • Which muscles / pattern is responsible for these problems • Setting up the right injection protocol and optimise injection procedure • Dosage • Dilution • Injection control • Immediate post injection treatment

Principles of spasticity management: Agreeing a treatment pathway CLINICAL INVESTIGATION HISTORY INDIVIDUAL PROBLEM FUNCTIONAL IMPACT SPASTICITY PATTERN / MUSCLES FORMULATE & AGREE TREATMENT GOALS Selection of suitable therapy Evaluation of therapy success Graphic provided and reproduced with permission from Axel Schramm • • • Impairment Activity Participation

Treatment options for spasticity

Aims of treatment • Patients who develop spasticity require ongoing rehabilitation programmes, initiated as early as possible, to alleviate their symptoms, help them to relearn motor skills and, ultimately, to regain at least some of their independence 1 • Typically, rehabilitation programmes are now based on intramuscular injections of botulinum toxin and muscle stretching and training exercises to overcome paresis 1 1. Ward A, et al. European Neurological Review 2016; 11(1): e. Pub ahead of print.

Treatment of spasticity: When to start? • Exercises that target both the muscular and neurological components of paresis can improve function and quality of life 1 • Early treatment can: 2 – Help prevent learned non use – Provide the opportunity for early application of physical treatments – Stimulate sensory feedback 1. 1. Ward A, et al. European Neurological Review 2016; 11(1): e. Pub ahead of print. 2. Turner Stokes L, Ward AB, et al. National guidelines. RCP and BSRM, 2009.

Management strategy for adults with ‘problem’ spasticity Prevention of physical aggravating factors Management strategy Team decision-making with patient Physical treatments (posture management, physiotherapy, splints) Treatment options Generalised spasticity Oral agents Multi-focal and focal spasticity Interventions are almost always combined e. g. physical management programmes and systemic medication Medical treatments Regional spasticity Intramuscular Bo. NT Phenol nerve/muscle blockade Orthopaedic surgery Physical rehabilitation therapy Adapted from Turner Stokes L, Ward AB et al. National guidelines. RCP and BSRM. January 2009. Intrathecal baclofen Intrathecal phenol Neurosurgery

Aims of physical therapy Maintain muscle and soft tissue length across joints Facilitate care giving Turner Stokes L, Ward AB, et al. National guidelines. RCP and BSRM, 2009. Facilitate active control of any residual movements to allow for active participation in tasks

Options for occupational and physical therapy • • • Stretching and casting Posture and positioning Orthotics Cooling or heating of muscles Dynamic physiotherapy technique Electrical stimulation – Functional Electrical Stimulation (FES) – Transcutaneous electrical nerve stimulation (TENS) Bavikatte G, et al. BJMP 2009; 2(3): 29– 34

Oral agents Drug Baclofen® 1 Mechanism of action Common side effects (see SPCs for complete lists) GABA ergic Sedation, drowsiness, nausea Undesirable hypotonia – usually relieved by dose adjustment Baclofen® 1 (intrathecal) Decreased ambulation speed, muscle weakness Tizanidine® 2 Agonist at alpha 2 adrenoreceptors Drowsiness, fatigue, dizziness, dry mouth, nausea, gastrointestinal disturbances, and a reduction in blood pressure, hepatotoxicity Dantrolene® 3 Inhibits release of intramuscular calcium stores Drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea, potential for hepatotoxicity Gabapentin® 4 GABA A receptor Binding site at alpha 2 delta subunit of voltage gated calcium channels Viral infection, pain, abnormal gait, leukopenia, anorexia, somnolence, dizziness, ataxia, fatigue, myalgia, back pain, twitching, nausea, diarrhoea, hypertension, vasodilatation Pregabalin® 5 GABA – binds to an auxiliary subunit of voltage gated calcium channels Nasopharyngitis, appetite increase, dizziness, headache, arthralgia, back pain, pain in limb, cervical spasm, gait abnormal 1. Baclofen® Summary of Product Characteristics. www. medicines. org. uk/emc/medicine/23850 (Accessed June 2016) 2. Tizanidine® Summary of Product Characteristics. www. medicines. org. uk/emc/medicine/24095 (Accessed June 2016) 3. Dantrolene® Summary of Product Characteristics. www. medicines. org. uk/emc/medicine/1610 (Accessed June 2016) 4. Gabapentin ® Summary of Product Characteristics. www. medicines. org. uk/emc/medicine/25430 (Accessed June 2016) 5. Pregabalin ® Summary of Product Characteristics. www. medicines. org. uk/emc/medicine/14651 (Accessed June 2016)

Bo. NT type A: Licensed neurological indications Drug Indication DYSPORT® 1 • Symptomatic treatment of focal spasticity of the upper limbs in adults and dynamic equinus foot deformity in ambulant paediatric cerebral palsy patients, two years of age or older • In adults for symptomatic treatment of spasmodic torticollis, blepharospasm, hemifacial spasm abobotulinumtoxin. A BOTOX® 2 onabotulinumtoxin. A XEOMIN® 3 incobotulinumtoxin. A • Treatment of focal spasticity, including: o Dynamic equinus foot deformity due to spasticity in ambulant paediatric cerebral palsy patients, two years of age or older o Wrist and hand disability due to upper limb spasticity associated with stroke in adults o Ankle disability due to lower limb spasticity associated with stroke in adults • Symptomatic relief of blepharospasm, hemifacial spasm and idiopathic cervical dystonia (spasmodic torticollis) • Prophylaxis of headaches in adults with chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine) • Management of bladder dysfunctions in adult patients who are not adequately managed with anticholinergics o Overactive bladder with symptoms of urinary incontinence, urgency and frequency o neurogenic detrusor overactivity with urinary incontinence due to subcervical spinal cord injury (traumatic or non traumatic), or multiple sclerosis • Post stroke spasticity of the upper limb presenting with flexed wrist and clenched fist in adults • Symptomatic treatment of blepharospasm, cervical dystonia of a predominantly rotational form (spasmodic torticollis) 1. Dysport® Summary of Product Characteristics. www. medicines. org. uk (Accessed June 2016) 2. BOTOX® Summary of Product Characteristics. www. medicines. org. uk (Accessed June 2016) 3. Xeomin® Summary of Product Characteristics. www. medicines. org. uk (Accessed June 2016)

Chemical neurolysis • Chemical neurolysis is effective in treating spasticity in large, powerful muscle groups close to the trunk such as adductors of the thighs Intraneural injection of phenol Phenol or alcohol destruction of peripheral nerves by protein coagulation • Side effects include skin sloughing, wound infection, necrosis of muscle near the injection site and pain Nair KP et al. BMJ 2014; 349: g 4737.

Surgical therapy Neurosurgical techniques • • Selective dorsal rhizotomy, very rarely done in adults 2 Peripheral neurotomy 2 Orthopaedic procedures • • • Tendon lengthening or transfer Osteotomy Joint arthrodesis • Interrupts the sensory input for stretch • reflexes • • Pain reduction Prevention of further joint deformity Increased range of joint motion • • • Infections Altered sensory responses Transient bladder incontinence (not peripheral neurotomy) Adverse muscle atrophy Unintended weakening of the agonist muscle Complications of infection Improper placement of tendon attachment • • Patel A. US Neurology 2010: 47– 51. 2. Ayuzawa S et al Brain Nerve 2014: : 66(9), 1057 68.

Advantages of Bo. NT over other focal treatments Local intramuscular injection of Bo. NT is an established, well tolerated treatment in the pharmacological management of focal spasticity Ease and convenience of injection – electrical localization of muscles is required in some, but not all No sensory disturbance Effect lasts up to 12 weeks, so it can be used in the subacute situation to prevent the development of contractures, where neurological recovery may occur Can be an adjunct to splinting or surgery The ability to titrate the dose in individual patients requiring repeated injections for specific functional effects Can be used in conjunction with other pharmacological treatments to achieve the desired total effect (e. g. with systemic anti spasticity agents, with phenol neurolysis, and with intrathecal baclofen) Low risk of adverse effects 1. Turner Stokes L, Ward AB, et al. National guidelines. RCP and BSRM, 2009. 2. Walton K, et al. Practical Neurology 2003; 3: 342– 53

Splinting provides a prolonged stretch to a muscle and can be used together with Bo. NT with the aim of improving muscle length, correcting and preventing contractures and maximise function 1 • The aim of splinting is to correct and prevent contractures and in doing so facilitate improved function through increased range of movement 2 • The rationale underpinning splinting is to provide a prolonged stretch to maintain or promote change in a body structure 2 1. Turner Stokes L, Ward AB, et al. National guidelines. RCP and BSRM, 2009. 2. Splinting for the prevention and correction of contractures in adults with neurological dysfunction. COT and ACPIN Guidelines 2015.

Casting Clinical research has revealed a relationship between the use of casting and a reduction in tone, as well as improvement in Range Of Motion (ROM) • Serial casting – Application and removal of a series of casts to correct deformity, lengthen contractures, and reduce spasticity • Inhibitive casting – One time cast with the aim to reduce muscle tone • Drop-out casts – Serial casts that can be inhibitory as well (portion of a cylindrical cast is removed to allow the involved joint to move further into the desired range) • Bivalve casts – Cast is cut to ensure the correct positioning 1. Stoeckmann T. Top Stroke Rehabil 2001; 8(1): 27– 35. Precautions for casting • Poor skin integrity / small wounds • Fluctuating oedema • Reduced sensation • Cognitive impairment • Agitation

Taping • Adhesive taping has the potential to enhance the effect of Bo. NT A therapy – Greater reduction of spastic hypertonia in stroke patients – Short term reduction of spasticity related disability • In comparison to splint positioning taping: Has faster results Santamato A, et al. Clin Rehabil 2015; 29(1): 50– 8. Is more effective Is more comfortable

Summary

Summary • Spasticity is a disabling condition that, if left untreated or sub optimally treated, can lead to a host of serious conditions and health–related quality of life issues • The management of spasticity is complex and a multi professional team working together with the patient and family/carers is recommended • A number of treatments are available for the management of spasticity, including physical therapy, oral agents, botulinum toxin type A, casting and splinting, and chemical and surgical neurolysis • Physical therapy should always be used to manage spasticity and can be adjunctive to oral medications, botulinum toxin, nerve blockade and surgical therapy

Group discussion Considering your practice: • How do you identify patients who may require management for spasticity? • Where might patients ‘get lost’ in your local referral pathway? – Are there steps that could be taken to raise awareness of spasticity? • Are there areas where co ordination within the local referral pathway and multi professional team could be improved?