Spasticity Mechanisms and Management

1. SpasticityMechanisms and Management Allison Oki, MD October 11, 2014

2. Objectives • Video – Development/Basic Mechanics of Gait • Overview Motor Disorders, Hypertonia, Spasticity • Pathophysiology • Cerebral Palsy • UMN syndrome - Consequences of Spasticity • Medical Management • Neurosurgical Interventions: ITB and SDR

3. Development • Bipeds center of mass (COM) level of S2 • Inherently unstable • Continual postural adjustment to maintain COM within base of support • Sit 6 mo • Crawl 9 mo • Independent walking 12 mo • Gait maturation at 6.5 years

4. Motor System • Motor system hierarchical • chain of command • extends from the cortical centers down to the nerves that innervate the muscles

5. Components of Motor System • Supplementary motor cortex • Cortical motor control centers • Basal Ganglia • Cerebellum • Brainstem Motor nuclei • Central pattern Generators

6. Motor Pyramid

7. Pyramidal and Extrapyramidal Upper Motor Neurons Pyramidal direct corticospinal tract • Fine coordination motion Extrapyramidal indirect cortco-bulbo-spinal tracts (vestibular/ reticular tracts) • Balance, posture, coordination

8. Central Pattern Generators • Located in the SC generate a consistent specific movement pattern • Analogy – piano key and note, central pattern generator when stimulated produces the same movement pattern • Anterior horn of SC • Pyramidal – lateral • Extrapyramidal - medial

9. Motor Disorders • Disorders of multiple neural components • basal ganglia • cerebellum • cerebral cortex • brainstem • descending spinal tracts • Hypertonia is a component of many motor disorders • Spasticity, dystonia and rigidity

10. Motor Disorders Pyramidal • cortical projections to the brainstem (corticobulbar) • SC (corticospinal) clinically: weakness and increased stretch reflexes “pyramidal” “upper motor neuron” weakness Extra-pyramidal • Injury to BG, cerebellum or non-primary motor cortical areas clinically: abnormal motor control without weakness or changes in spinal reflexes

12. What is spasticity? “Spasticity is a motor disorder characterized by a velocity dependent increase in tonic stretch reflexes, with exaggerated tendon jerks resulting from hyperexcitability of the stretch reflex, as one component of the upper motor neuron syndrome” Lance 1980 • Resistance to stretch increases with increasing speed and varies with the direction of the joint movement • Rapid rise in resistance to stretch above a threshold speed or joint angle Sanger et al, Classification and Definition of Disorders Causing Hypertonia in Childhood, Pediatrics 2003

13. Hypothetical Mechanism

14. DescendingInhibition Sensory Excitation Pathophysiology of SpasticityTheories • Imbalance between excitatory and inhibitory impulses to the alpha motor neuron in the spinal cord • Due to a loss of descending inhibitory input to the alpha motor neuron due to injury to the cortical spinal tracts

15. Cerebral Palsy: Definition • Primary abnormality of movement and posture secondary to a nonprogressive lesion of a developing brain • Represents a group of disorders rather than a single entity • Abnormal motor control and tone in the absence of underlying progressive disease

16. Epidemiology CP • Most common motor disorder of childhood • 3.6/1000 school age children • Higher survival rate of premature infants • Etiology – majority of term infants do not have an identifiable cause • Causative factors • Prematurity • Infection • Inflammation • Coagulopathy • Greatest RF prematurity <37wks • Incidence highest in the very premature

17. Pathology CP • >80% abnormal neuroimaging • PVL – white matter near the lateral ventricles • Premature 90% vs term 20% • IVH • Corticospinal tract fibers to LE are medial to UE → spastic diparesis

18. Common Gait Deviations CP

20. Upper Motor Neuron Syndrome UMNS Positive • Spasticity • Spastic Dystonia • Clonus/ hyper-reflexia • Reflex flexor and extensor spasms • Associated reactions Negative • Weakness • Fatigue • Loss of selective motor control • Sensory deficits • Incoordination • Poor balance Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron Syndrome, Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor Neuron Syndrome, 2008

21. David Scrutton et al, Management of the Motor Disorders of Children with Cerebral Palsy, H. Kerr Graham, Ch.8 Mechanisms of Deformity

22. UMNS UMNS disability = positive + negative + rheologic properties Rheologic properties: viscoelastic properties of the muscle and other soft tissues • Structural changes occur in the muscle cells causing intrinsic muscle stiffness (Olsen et al. 2006) Combined effects of all signs → chronic unidirectional postures and movements that are generated by a net balance of muscle torques exerted across the involved joints Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron Syndrome, Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor Neuron Syndrome, 2008

23. UMNS Torque – force generated by muscle acting through a bony lever arm →rotational movement Normal movement is bi- or multi-directional, agonist and antagonist torques create motion • UMNS → net unidirectional movements (positive signs) often persist as postures because voluntary bi- or multi-directional movement is impaired (negative signs) → chronic effects on soft tissue, joint structures and bone Allison Brashear, Spasticity and Other Forms of Muscle Overactivity in the Upper Motor Neuron Syndrome, Nathaniel H. Mayer, Ch.1 Positive Signs and Consequences of an Upper Motor Neuron Syndrome, 2008

24. Why is spasticity important? Clinically diagnosed and treated Musculoskeletal and neurologic exam Tone, reflexes, strength, coordination Spasticity → significantdisability ADLs Seating Comfort Contracture Loss of ROM Negative impact on function Bone deformity Pain Skin Hygiene Ability to provide cares Allison Brashear, Elie Elovic, Spasticity Diagnosis and Management, 2010, Ch 1.1 Why is spasticity important?

25. Secondary effects of Spasticity May effect function and long-term outcome • Persistent muscle imbalance → muscle/tendon contractures → joint or bone deformities • weak antagonists muscles → require passive stretch for a minimum of 6 out of 24 hrs to maintain muscle length (Tardieu 1988) and to avoid development of a fixed contracture (Eames 1999) Abnormal forces across joints → prolonged abnormal posture, increase energy expenditure, impair function, and negatively affect both the caregiver’s and patient’s QOL L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press, p.40

26. Abnormal Forces across Joints • Ankle and subtalar → fixed equinus, equinovarus or equinovalgus hindfoot deformities • Adductor and iliospoas spasticity → hip subluxation and dislocation • Once a critical degree (50%) of hip subluxation is present, dislocation is inevitable unless intervention occurs (Reimers 1987) • The resultant pelvic obliquity compromises sitting balance → chronic pain L. Andrew Koman, et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press

27. Bone Deformity Abnormal muscle forces act on a growing skeleton • Hips and spine → essential in weight bearing and positioning • Femur → muscle and gravity loading forces during growth • Muscle forces in CP → increased anteversion of femoral neck • hip flexion, adduction and internal rotation of the femur → femoral head in a superoposterolateral direction, out of the acetabulum → coxa valgus: deformation of the femoral head and shallow acetabulum Randall L. Braddom, Physical Medicine and Rehabilitation, 3rd Edition, Chapter 54: Cerebral Palsy, p.1249

28. Hip Dysplasia

29. Hip Subluxation James R. Gage et al, The Identification and Treatment of Gait Problems in Cerebral Palsy, 2009, Kevin Walker, Chapter 3.4 Radiographic Evaluation of the Patient with Cerebral Palsy

30. Bone Deformity Asymmetric muscle pull → deformity of the spine • Kyphosis, scoliosis, rotational deformities • Comfort • Tone • Sitting • Standing alignment • Balance • Severe → respiratory function compromise Randall L. Braddom, Physical Medicine and Rehabilitation, 3rd Edition, Chapter 54: Cerebral Palsy, p.1249

31. Goals of Spasticity Management • Decrease spasticity • Improve functional ability and independence • Decrease pain associated with spasticity • Prevent or decrease incidence of contractures • Prevent bony deformity • Improve ambulation, mobility, function • Facilitate hygiene • Ease rehabilitation procedures • Improve ease of caregiving

32. Traditional Step-Ladder Approach to Management of Spasticity Neurosurgical procedures Orthopedic procedures Neurolysis Oral medications Rehabilitation Therapy Remove noxious stimuli

33. Interdisciplinary team • Patient and family • Neurologist • Neurosurgeon • Occupational therapist • Physical Therapist • Physiatrist • Orthopedic Surgeon • Primary care physician

34. Rehabilitation Therapy • Stretching • Weight bearing • Inhibitory casting • Bracing • Strengthening • EMG biofeedback • Electrical stimulation • Positioning

35. Oral Pharmacologic Management Baclofen Diazepam Clonidine Tizanidine Dantrolene Sodium Allison Brashear, Elie Elovic, Spasticity Diagnosis and Treatment, 2010, Ch.15 Pharmacologic Management of Spasticity: Oral Medications

36. Systemic medications: limitations • Sedation • Hypotension • Confusion • Weakness • Nausea • For generalized rather than focal spasticity

37. Baclofen – GABA analog • Binds to presynaptic GABA-B receptors in the brainstem, dorsal horn of SC and other CNS sites • Depresses both monosynaptic and polysynaptic reflexes by blocking the release of NTS • Inhibition of gamma motor neuron activity to the muscle spindle • Because these reflexes facilitate spastic hypertonia, inhibition reduces the overactive reflex response to muscle stretching or cutaneous stimulation

38. Baclofen • Dystonia • Baclofen some supraspinal activity that may contribute to clinical side effects • Orally – relatively low concentrations in CSF Side Effects • Central SE – drowsiness, confusion, attentional disturbances • Others – hallucinations, ataxia, lethargy, sedation and memory impairment • Lower seizure threshold • Sudden withdrawal → seizures, hallucinations

39. Baclofen Pharmokinetics • Relatively well absorbed, peak effect 2 hrs, t ½ 2.5-4 hours • Excreted unchanged by kidney, 6-15% metabolized in the liver • Schedule 3x a day due to short half life Considerations: • Cerebral lesions more prone to SE • DOC for spinal causes

40. Diazepam - Benzodiazepine • MOA: does not directly bind to GABA receptors • Promotes the release of GABA from GABA-A neurons • Enhanced pre-synaptic inhibition, likely why useful in epilepsy • All CNS depressants • Anti-anxiety, hypnotic, anti-spasticity and anti-epileptic Side Effects: • Sedation and lethargy • Impair coordination and prolonged use can lead to physical/psych dependence • Effective doses vary considerably, upper doses primarily limited by SE • Rapid withdrawal → irritability, tremors, nausea and seizures

42. Neuromuscular Blockade Goal: Restore balance between agonist and antagonist muscles Why is this important? • Shortened over contracted muscles → decreased muscle growth despite linear bone growth → antagonist muscles become over-lengthened → weakness and imbalance • Contractures → bone and joint deformity → impaired function • Early intervention – life long patterns of mobility • Blockade of agonist muscles → improved stretch, ROM, increased resting length, antagonist muscles can continue activity and strengthening Ann H. Tilton, Injectable Neuromuscular blockade in the treatment of Spasticity and Movement disorders, Journal of Child Neurology, 2003:18:S50-66

43. Botulinum Toxin A in the management of spasticity related to CP BTX-A is currently used for children of all ages with CP for spasticity management as determined by the practitioner • This use is off-label in the US • Dysport (British formulation), approved in UK and EU for “treatment of dynamic equinus foot deformity due to spasticity in ambulant pediatric CP patients, two years of age or older…UE spasticity post-stroke, spasmodic torticollis, blepharospasm, and hemifacial spasm” L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press

44. NMJ – connection between the peripheral nerve and muscle fibers Signals from the motor neuron are transmitted by the release of Ach from presynaptic vesicles Ach crosses the synaptic cleft and attaches to post-synaptic receptors → muscle contraction Neuromuscular Junction L. Andrew Koman, MD et al, Botulinum Toxin Type A in the Management of Cerebral Palsy, 2002, Wake Forest University Press

45. Neuromuscular Junction Chemodenervation, The Role of Chemodenervation in the Management of Hyperkinetic Movement Disorders, We Move 2007

46. Selected Literature Review 1990 several studies supported the safety and efficacy of therapeutic BTX in children with CP • Goals: decreasing spastic equinus, improving crouch knee gait, decreasing hip flexion, improving hand use • Studies demonstrated changes in muscle tone (reduction in spasticity scores), improvements in ROM, and kinematic changes in gait analysis • However, functional benefit was not demonstrated in blind, randomized controlled trials • 2013 Systematic review of interventions for children with CP: state of the evidence – BTX was recommended for spasticity reduction and improved walking Iona Novak et Al, A systematic Review of interventions for children with cerebral palsy: state of the evidence, Developmental Medicine & Child Neurology, 2013

47. Selected Literature Review Why is it so difficult to show functional benefit? • Weakness and poor coordination co-exist in persons with spasticity, perhaps reducing muscle overactivity is not sufficient to see a functional change in the absence of a robust post-treatment program • Variability in injection protocols • patient selection • Insensitive outcome measures • Individualized treatment Geoffrey L. Sheean, Botulinum treatment of Spasticity: Why is it so difficult to show a functional benefit?, Current Opinion in Neurology, 2001, 14: 771-776

48. BoNT Indications • Dynamic deformity –function, pain, progressive deformity • Equinus, crouch gait, pelvic obliquity • UE • Focal dystonia • Muscle imbalance • Sialhorrhea Contraindications • Allergic rxn to toxin or vehicle • Resistance to toxin effects • Significant muscle weakness • Failure to respond to injections • Fixed contracture

49. Most common weakness Hoarseness or trouble talking Dysarthria Loss of bladder control Trouble breathing Trouble swallowing FDA warning label and risk mitigation strategy 2009 Advise patients to seek immediate medical attention if they develop any of these symptoms Side Effects

50. Equinus Gastrocnemius Soleus Posterior tibialis