Pathophysiology of spasticity

PATHOPHYSIOLOGY OF SPASTICITY

1. SPASTICITY - PATHOPHYSIOLOGY and management DR. SUMIT S. KAMBLE SENIOR RESIDENT DEPT. OF NEUROLOGY GMC, KOTA

2. Spasticity is frequent and often disabling feature of neurological disease . Spasticity is motor disorder that is characterized by velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper excitability of the stretch reflex, as one component of the upper motor neuron syndrome . J.W.Lance (1980 )

3. CHARACTERISTIC FEATURES Velocity dependence- increased tone of spasticity is velocity dependent, that is, the faster the stretch, the greater the muscle resistance ‘Clasp-knife’ phenomenon- spastic limb initially resists movement and then suddenly gives way, like the resistance of a folding knife blade Distribution- differential distribution with antigravity muscles being more affected

4. ACCOMPANIMENTS OF SPASTICITY Positive features Clonus - involuntary rhythmic contractions, response to sudden sustained stretch, alternate loading and off-loading of muscle spindles Spasms- sudden involuntary movements involving multiple muscle groups and joints, repetitive and sustained, represent an exaggerated reflex withdrawal response to nociceptive stimuli Exaggerated tendon reflexes Babinski sign

5. Negative components Spastic co-contraction- inappropriate activation of antagonistic muscles during voluntary activity. It is due to loss of reciprocal inhibition during voluntary contraction Motor weakness Slowed movements Loss of dexterity

6. COMPLICATIONS Spasticity if left untreated or sub-optimally treated, may lead to consequences, such as: Muscle contractures (leading to abnormal body segment loading and sensory change), Limb deformity and altered body mechanics , P ressure sores, Difficulty in the management of pressure sores, Pain from muscle spasms, Degenerative joint disease, Loss of function, and Mood problems and inability to participate in rehabilitation.

7. VICIOUS CYCLE OF SPASTICITY

8. PATHOPHYSIOLOGY Muscle tone Visco -elastic properties of muscle Neural drive from spinal motor neurons Control Cortical - motor areas of the cortex facilitate ventromedial reticular formation Supraspinal descending pathways Inhibitory pathway - dorsal reticulospinal tract , which arises in the ventromedial reticular formation Excitatory pathways Medial reticulospinal tract - arising in the bulbopontine tegmentum , major pathway Vestibulospinal tract

9. NORMAL PHYSIOLOGY Function of muscle spindle It is receptor organ for stretch reflex It is play important role in maintaining the muscle tone.

10. INNERVEATIONS OF SPINDLES

11. GOLGI TENDON ORGAN

12. RECIPROCAL INHIBITION

13. PATHOPHYSIOLOGY Immediately after SCI , there are depressed spinal reflexes during state of spinal shock, followed by development of hyperreflexia and spasticity over the following weeks to month . P athophysiology of spasticity is not completely understood; however, it is believed to arise primarily from loss of the effect of numerous descending inhibitory pathways. These include reciprocal 1a interneuronal inhibition, presynaptic inhibition, renshaw -mediated recurrent inhibition, group II afferent inhibition, and Golgi tendon organs . Axonal collateral sprouting and denervation super sensitivity are change that may also play a role in the development of spasticity.

14. MECHANISM AT VARIOUS LEVELS Cortical & Supraspinal descending pathways Loss of cortical facilitation of the inhibitory pathway(dorsal reticulospinal tract) Partial spinal cord lesion, which destroys the inhibitory pathways but preserves the excitatory fibres Complete spinal cord lesion affecting both inhibitory and excitatory pathways Spinal Cord Loss of recurrent inhibition- mediated by motor axon collaterals and Renshaw cell Loss of reciprocal inhibition- mediated by antagonistic muscle spindle afferents

15. Reduced inverse stretch reflex- mediated by Golgi tendon organs Reduced presynaptic inhibition of muscle spindle afferents Spinal motor neuron Denervation supersensitivity Collateral sprouting Muscles and joints Shortening of sarcomeres Loss of elastic tissue Fibro-fatty deposits in muscles and tendons

16. Upper extremity patterns Adduction and internal rotation of the shoulder Flexion of the elbow and wrist Pronation of the forearm Flexion of the fingers and adduction of the thumb PECTORALIS MAJOR LATISSIMUS DORSI TERES MAJOR BICEPS BRACHIORADIALIS BRACHIALIS PRONATOR TERES AND QUADRATUS FLEXOR CARPI RADIALIS AND ULNARIS FLEXOR DIGITORUM PROFUNDUS AND SUPERFICIALIS ADDUCTOR POLLICIS

17. Lower extremity patterns HIP ADDUCTION AND FLEXION KNEE FLEXION ANKLE PLANTAR FLEXION OR EQUINOVARUS POSITIONING KNEE EXTENSION EQUINUS AND/OR VALGUS ANKLE GREAT TOE DORSIFLEXION ADDUCTOR MAGNUS ILIOPSOAS HAMSTRINGS (MEDIAL MORE OFTEN THAN LATERAL) TIBIALIS POSTERIOR SOLEUS GASTROCNEMIUS QUADRICEPS FEMORIS PERONEUS LONGUS EXTENSOR HALLUCIS LONGUS

18. ADDUCTED/INTERNALLY ROTATED SHOULDER FLEXED ELBOW PRONATED FOREARM FLEXED WRIST CLINCHED FIST THUMB IN PALM DEFORMITY STRIATAL TOE EQUINOVARUS STIFF KNEE FLEXED KNEE ADDUCTED THIGHS

19. ASSESSMENT

20. M odified Ashworth scale Most frequently used clinical methods for estimation of spasticity

21. Tardieu scale

22. Waternberg Pendulum Test P atient is seated or lying with lower leg hanging over end of couch. E xaminer then extends the leg to the horizontal position, while patient is told to relax. L eg is then released and allowed to swing freely under the action of gravity. With the use of electrogoniometers , swing of the leg about knee joint may be evaluated In individuals with spasticity, reduction of swing is generally found.

23. MANAGEMENT When to treat Not all spasticity requires treatment- inappropriate treatment of spasticity may lead to loss of function, when spasticity is counterbalancing effects of paresis May need to be treated when it causes Pain Difficulty performing ADL Impaired mobility, whether related to ambulation or transfers Poor joint positioning I ncreased risk for development of contracture Skin breakdown

24. Aims to reduce the impact of spasticity to prevent secondary complications Goals relief of discomfort improved sitting, standing and walking, facilitated activities of daily living reduced burden of care improved body image and self-esteem prevention of complications

25. Identification and elimination of triggers Non pharmacological interventions Passive movements Exercises Posture & Standing Physical modalities Medications Oral Injectables Surgical

26. Identification and elimination of triggers Patient and carer education to recognise these triggers is important part of management Pressure ulcers Ingrown toenails Skin infections Injuries Constipation Urinary tract infection Deep vein thrombosis Improper seating Ill-fitting orthotics

27. Passive movements Passive stretching decreases excitability of motor neurones and maintains visco -elastic properties of muscles and joints Prolonged stretching can help to treat contractures Stretching can be facilitated by using casts or splints, sometimes used together with botulinum toxin injections No conclusive evidence whether therapy is effective but no evidence that it is harmful

28. Exercises Improve motor control and cardiovascular fitness in people with UMN disorders Posture and standing Stretches spastic muscles and decrease sensitivity of stretch reflex and brain stem reflexes that trigger spasticity Weight bearing and standing also help to improve psychological wellbeing, to improve bone mineral density, facilitate pulmonary drainage and helps bowel and bladder functions Proper positioning of limbs and trunk is essential to prevent aggravation spasticity and development of contractures Devices such as splints help to position limbs properly

29. Physical modalities These physical modalities work through either modulating the visco -elastic properties of muscles and tendons Ultrasound Cryotherapy Vibration Shockwave therapy Magnetic stimulation Transcutaneous electrical nerve stimulation (TENS) limited evidence base to support the use

30. Medications Principles of drug therapy Weakness is a side effect of all antispasticity drugs, usually due to unmasking of underlying UMN weakness A ‘start low and go slow’ policy limits these unwanted functional effects Reach maximal tolerated dose for a sufficiently long period before stopping a drug and labeling it as ineffective Patients not responding to one drug may respond to another

31. Sudden stopping of even an apparently ‘ineffective’ drug may cause a rebound increase in spasticity. It is better to taper initial drug while simultaneously introducing the second drug. C ombination of two drugs should be tried if the spasticity does not respond to a single agent It is important to time the doses according to the patient’s activity, care and therapy

32. Oral agents Gamma aminobutyric acid (GABA) ergic system Baclofen Gabapentin Benzodiazepines α-2 adrenergic system Tizanidine Block calcium release into the muscles Dantrolene Cannabinoids

33. Baclofen Most widely used oral antispasticity drug Mechanism GABA-B receptor agonist Reduces calcium influx ↓s release of excitatory neurotransmitters(glutamate & aspartate) Down-regulates activity of 1a sensory afferents, spinal interneurones & motor neurones Dose starting - 5 mg thrice daily Maintenance- ↑d by 5–10 mg weekly, until there is an optimal effect Max- 90–120 mg per day

34. Adverse effects Weakness , drowsiness and dizziness Sexual dysfunction & urinary incontinence Reduces seizure threshold Sudden withdrawal may also cause seizures and hallucinations, sometimes accompanied by extreme hyperthermia and increased spasticity (baclofen withdrawal syndrome) Caution pregnancy- animal studies show impaired sternal ossification and omphalocele

35. Benzodiazepines Act on GABA-A receptors, enhances the presynaptic inhibitory effect of GABA and decreases spasticity Absorbed faster than baclofen , acts faster, and has a longer lasting effect Drowsiness and behavioural side effects limit its use during the daytime Particularly useful to treat spasticity that interferes with sleep Clonazepam is particularly useful to treat nocturnal spasms U sual starting dose is 0.5 mg at night Maximum dose of 1 mg

36. Tizanidine Mechanism α-2 receptor agonist Inhibits excitatory spinal interneurones and tracts from locus coeruleus Dose Starting dosage is 2 mg at bedtime, increased by 2 mg weekly to a maximum of 36 mg, divided into 3–4 daily doses Adverse effects Dry mouth, gastrointestinal disturbance, hypotension and acute hepatitis Sudden stopping of tizanidine can lead to a hyperadrenergic syndrome, characterised by anxiety, tremor, hypertension and tachycardia

37. Dantrolene Mechanism Blocks calcium release from sarcoplasmic reticulum and interferes with excitation–contraction coupling of the skeletal muscle Acts directly on the muscle and so is less sedative Dose Starting dose is 25 mg daily for the first week, increased in steps of 25 mg per week to a top dose of 100 mg 3–4 times daily Adverse effects M uscle weakness, sedation, diarrhoea Most important side effect is hepatotoxicity, and so liver function must be monitored carefully

38. Cannabinoids Cannabinoid receptors in dorsal spinal cord, basal ganglia, hippocampus and cerebellum, and these modulate spasticity Cannabidiol & Nabiximols limited role in managing treatment-resistant spasticity May be worth trying in patients who are not responding to a combination of two drugs in adequate doses 30–40% of people show a response, treatment effect should be reviewed at 4–6 weeks and continued only if there is an objective improvement Concerns about its long-term effects on cognition, behaviour and mental health

39. Botulinum toxin Prepared from the bacterium Clostridium botulinium Mechanism Heavy chain binds to and becomes internalised into presynaptic nerve endings Degrades synaptosomal -associated protein 25, a protein required for fusion of acetylcholine vesicles to the presynaptic membrane. Inhibits release of acetylcholine, thereby blocking neuromuscular transmission Afferent effect Analgesic effect Reversal Effect is reversed by nerve sprouting and reinnervation which develops over 3-4 months

40. Usage Particularly useful in treatment of focal spasticity. Electromyography , nerve stimulator or ultrasound can be used to identify the target muscle Postinjection interventions such as physiotherapy, splinting and serial casting help to maximize benefits Patient should be reassessed 4–6 weeks after the initial injections to assess the efficacy of the injections If required, further injections should be planned after 3–4 months Adverse effects Muscle weakness, urinary incontinence, falls, fever and pain.

41. Phenol Chemical neurolysis 5% concentration Injected directly into peripheral nerves cause destruction of neural tissue by protein coagulation Usage effective in treating spasticity that occurs in large, powerful muscle groups close to the trunk- thigh adductors blocks to the medial popliteal muscles to aid spastic foot drop, or obturator nerve blocks either in patients with scissoring gait or to improve perineal hygiene and seating posture A neurostimulator with a Teflon-coated needle electrode is used for guidance

42. Often has effects lasting many months(~6mths) and can be repeated if necessary Nerve sprouting may lead to recurrence of spasticity Adverse effects N erve injury, causalgia or neuropathic pain because of sensory fiber damage, T issue edema, venous thrombosis, and compartment syndrome resulting from large amounts of phenol in constrained space Skin sloughing and wound infection.

43. Phenol Injection of phenol guided by nerve stimulation for obturator nerve for treatment of adductor spasticity

44. Alcohol A cts as a local anesthetic by decreasing sodium and potassium conductance at the nerve membrane at low concentrations. It causes protein denaturation at higher concentration Adverse effects Causes pain during injection

45. Local anesthetics B lock nerve conduction by changing membrane permeability to sodium ions Effect is completely reversible E ffect starts within 3-15 minutes after the injection and lasts from 45 minutes to 8-12 hours Lidocaine , etidocaine and bupivacaine are used for nerve blocks 3 mg/kg of 0.25 to 0.75% solution bupivacaine

46. Intrathecal baclofen Indication - S ignificant lower-limb spasticity which persists despite adequate treatment with at least two oral antispasticity drugs concomitantly Principle- Oral baclofen has only very low bioavailability to GABAergic neurones in spinal cord Administered intrathecally , arelatively small dose of baclofen can give a high concentration of drug within the spinal cord Patients should initially be screened using a temporary catheter with an initial test dose is 50 micrograms.

47. Device comprises a subcutaneous pump which stores and delivers programmable doses of baclofen through a catheter into the spinal subarchanoid space can be adjusted to vary the doses delivered, depending on the level of patient activity and needs antispastic effects of intrathecal baclofen are obtained at 1% of daily oral dose Complications Procedure related complications- infection, skin erosions, cerebrospinal fluid leak. Abruptly stopping ITB can cause high fever, confusion, rebound spasticity and muscle rigidity, similar to neuroleptic malignant syndrome Signs of overdose are drowsiness, dizziness , somnolence, seizures, respiratory depression and loss of consciousness progressing to coma.

48. Intrathecal baclofen

49. Neurosurgical management F or severe spasticity following the failure of noninvasive management (adequate medical and physical therapy)

50. PERIPHERAL NEUROTOMY Indications

51. Procedure It involves microdissection guided by neuro -stimulation at low intensity Extent of the nerve resection- must be limited to a maximum to 4/5 fibres , over a length of 5 mm, to prevent any regrowth Care must be taken with the sensory fibres , if too many cut in the sensory peripheral nerve, may induce neurogenic pain Results ( Mertens et al., 180 pts ) Reduction of spasticity in 82% of cases, with recurrence in only 8% Reduction in pain 85%, and a reduction in cutaneous lesions 78% 10% functional improvement, recovery of some ability to walk

52. Microsurgical DREZotomy Principle Modern dorsal rhizotomy is a hyper-selective rhizotomy At the periphery, nerve fibres are mixed Technique of Dorsal Root Entry Zone- otomy ( DREZotomy ) consists of selective cutting of fibres at the dorsal root zone, including a large area up to the superfcial layers of the posterior grey matter

53. Technique was especially developed for treating neurogenic pain Indication Severe and regional spasticity, possibly associated with chronic intractable pain Procedure Lesion, max depth 3mm is placed 45° in the ventromedial direction at dorsal radicular spinal junction

54. Results ( Mertens and Sindou (1998) ) n =151 patients with lower limb spasticity, follow-up 5.6 yrs Decreased hypertonia - 78% Ashworth < 2 Decreased spasms - 88% Increased voluntary mobility - 11% Decreased pain - 82 %

55. Spinal cord stimulation Principle Selective stimulation of the larger fibres in order to inhibit the activity of the smaller nociceptive fibres and so to decrease the nociceptive input at the level of the spinal cord Level of stimulation dependent on the topography of the spasticity Electrode must be placed in the posterior epidural space in order to stimulate the dorsal columns Various authors report improvement varying from 50% to 80% over a period of 2 to 5 yrs , some report no significant improvement Currently considered as an alternative only if other conservative and surgical treatments do not work

56. Stratified management approach European Journal of Neurology 2002, 9 (suppl. 1): 48–52

57. THANK YOU

58. REFERECES Spasticity: pathophysiology, evaluation and management Practical Neurology 2012;12:289–298 Sheean G. 2002. The pathophysiology of spasticity. European Journal of Neurology 9 ( Suppl 1):3-9. Pathophysiology of spasticity Journal of Neurology, Neurosurgery , and Psychiatry 1994;57:773-777 Pathophysiology of Spasticity: Implications for Neurorehabilitation BioMed Research International Volume 2014 (2014), Article ID 354906 , Dejong Neurology 7 th edition UPTODATE.COM