Approximately 450,000 people in the United States live with SCI.

1. Lecture 31: Spinal Cord Injury and Spasticity Epidemiology: • Approximately 450,000 people in the United States live with SCI. • There are about 10,000 new SCIs every year; the majority of them (82%) involve males between the ages of 16 and 30. • Main causes: motor vehicle accidents (36%), violence (28.9%), or falls (21.2%).

2. Spinal Cord Injury • Paresis: partial loss of voluntary control of muscle activity • Plegia: total loss of voluntary motor control • Para: two extremities are involved—forelimbs (arms) or hindlimbs (legs) • Hemi: half of the body (left or right) is involved • Quadri: all four extremities are involved • Spastic: with positive signs of spasticity (hyperreflexia) • Flaccid: without positive signs of spasticity (areflexia)

3. Level of SCI Outcome SupraspinalHemisyndromes Cervical Quadriparesis or quadriplegia (spastic or flaccid) Thoracic Lower paraparesis or paraplegia (likely spastic) Lumbar Lower paraparesis or paraplegia (flaccid) Spinal Cord Injury

4. SCI: Cervical Injuries • Commonly quadriplegia • Above the C-4 level may require a ventilator • C-5 injuries often result in shoulder and biceps control, but no control at the wrist or hand • C-6 injuries generally yield wrist control, but no hand function • C-7 and T-1 injuries: can straighten arms but may have dexterity problems with the hand and fingers

5. SCI: Thoracic-Lumbar Injuries • Commonly paraplegia • Hands not affected • At T-1 to T-8, poor trunk control as the result of lack of abdominal muscle control • Lower T injuries (T-9 to T-12) allow good trunk control and good abdominal muscle control; sitting balance is very good • Lumbar and sacral injuries yield decreasing control of the hip flexors and legs

6. Minutes to hours: • Spinal shock • Depression of all reflexes; complete paralysis Days to weeks or months: • Development of typical consequences • Spasticity; partial recovery of motor and sensory functions SCI: Stages Months to years: therapy

7. SCI: Nonmotor Problems • Chronic pain • Loss of sensation • Loss of bladder control • Loss of control of other internal organs

8. SCI: Origin of Sensorimotor Problems • Damage to descending and ascending spinal tracts • Destruction of the spinal neuronal apparatus

9. Spasticity • James Lance: Velocity-dependent increase in the spinal stretch reflex with exaggerated tendon jerks • Hughlings Jackson: Spasticity is a combination of positive and negative signs. They are relatively independent; treating one group of signs should not be expected to help the other group.

10. Positive signs: Negative signs: • paresis • lack of dexterity • fatigability • contractures • flexor/extensor spasms • clonus • clasp-knife • Babinski reflex • exaggerated cutaneous reflexes • autonomic hyperreflexia • dystonia Spasticity: Positive and Negative Signs

11. Spasticity: Possible Mechanisms • Increase in the gain of the stretch reflex loop • Change in the threshold of the tonic stretch reflex loop • Lack of postsynaptic inhibition of alpha-motoneurons (in particular, deficit in reciprocal inhibition, in Ib inhibition, and in Renshaw cell action) • Lack of presynaptic inhibition of inputs to alpha-motoneurons • Increased stiffness of peripheral structures

12. Spasticity: Babinski Reflex • A typical withdrawal reaction induced by a tactile stimulus to the sole of the foot • Imprecisely called the Babinski reflex

13. Spasticity: Clonus Typical clonus induced by a quick foot dorsiflexion.

14. Quantitative Assessment of Spasticity • Clinical scales (Ashworth, spasms) • Functional scales (ADL) • Monosynaptic reflexes • Suppression of monosynaptic reflexes by vibration (test of presynaptic inhibition) • Wartenberg test

15. EMG H-reflex M-response A EMG H-reflex M-response St St vibration EMG EMG H-reflex H-reflex M-response M-response B St St vibration Spasticity: Lack of Presynaptic Inhibition In a healthy person, muscle vibration leads to a strong suppression of the H-reflex (A). In a person with spasticity, the suppression may be absent or even replaced with facilitation (B).

16. Score Description of Muscle Tone 1 No increase in tone 2 Slight increase in tone, giving a “catch” when affected segment is moved in flexion or extension 3 More marked increase in tone, but affected segment is easily flexed and extended 4 Considerable increase in tone; passive movement is difficult 5 Affected part is rigid in flexion or extension Spasticity: The Ashworth Scale

17. Score Frequency of Spasms 0 No spasms 1 Mild spasms induced by stimulation 2 Infrequent full spasms occurring less frequently than once per hour 3 Spasms occurring more frequently than once per hour 4 Spasms occurring more frequently than ten times per hour Spasticity: The Spasm Scale

18. Baclofen (GABA agonist) • oral • intrathecal Spasticity: Drug Therapies • Clonidine and tizanidine (2 adrenergic agonists) • Opioids (act on opioid receptors in dorsal horns)

19. Spine Pump Catheter Computer Spasticity: A Scheme of Intrathecal Delivery of Baclofen

20. Effective suppression of reflexes: • Elimination of monosynaptic reflexes • Elimination of clonus • Decrease of spasms Unmasking of residual voluntary movements: • No movement reversal by hyperactive reflexes • Smoother trajectories Spasticity: Intrathecal Baclofen Danger of overdose, weakness, tolerance, etc.

21. IC Position in an Intact Muscle In an intact muscle, IC can be shifted to produce any force at any length.

22. IC Position in a Spastic Muscle In a spastic muscle, control of the IC position is impaired, and the muscle cannot leave the activation zone.

23. 1000 SOL Changes in ankle clonus under intrathecal baclofen Changes in Babinski resp. under intrathecal baclofen 2000 TA 0 3000 TIME According to This View, a Decrease in Spastic Signs Can Be Accompanied by Improved Voluntary Movements

24. Intrathecal Baclofen Effects on Voluntary Movement Elbow extension performed “as fast as possible” before (thin lines) and after (thick lines) a dose of baclofen. 2 Time (s) 0

25. Spasticity: Practical Issues With Intrathecal Baclofen • Infection; hardware malfunction; refills • Dose adjustment within the 24-h cycle (sleep, using extensor tone, avoiding atrophy) • Drug holidays (tolerance, morphine or diazepam)

26. Spasticity: Physical Therapy • Stretching • Inhibitory posturing • Functional training • Splinting

27. Destructive chemical therapies: • Botulinum toxin (blocks neuromuscular transmission) • Phenol/alcohol (damage nerve and weaken muscle) Neurosurgical procedures: • Selective dorsal rhizotomy • DREZ-tomy (dorsal root entry zone lesions) Treatment of Spasticity

28. Treatment of Spasticity • Orthopaedic surgery: tendon lengthening • Functional electrical stimulation: substitution for voluntary movement

29. Demyelination of axons within the CNS • Epidemiology: • prevalence ranges from 10 to 100 per 1,000,000 • peaks between 25 and 65 years • more frequent in females • strong genetic component (chance is 15 times higher in a sibling of a patient) • clustering in space and time (high-risk areas are Northern Europe and North America) Multiple Sclerosis

30. Multiple Sclerosis: Mechanism of Demyelination • Role of immune system (suppressor T-cells)? • Viral infection? • Macrophages and mononuclear cells can strip away myelin.

31. Optic nerve: • Sudden onset of blurred vision • Dull ache in the eye • Impaired acuity (rarely blindness) Multiple Sclerosis: Clinical Features (Depending on Which Tract Is Affected) Olfactory and auditory nerves: unilateral deafness

32. Brain stem pathways: • Impairment of balance • Intentional tremor • Discoordination of limbs • Dysarthria • Facial weakness and numbness • Unilateral ophthalmoplegia Multiple Sclerosis: Clinical Features (Depending on Which Tract Is Affected)

33. Spinal cord: • Commonly high in posterior columns • Tingling in hands and arms • Discoordination (if spindle afferents are affected) • Instability of stance (if lower limbs are affected) Pyramidal tract: • Heaviness • Dragging of legs • Weakness, even acute paraplegia • Spasticity Multiple Sclerosis: Clinical Features (Depending on Which Tract Is Affected)

34. Involved Structure % Posterior column 40 Pyramidal tract 37 Brain stem 30 Optic nerve 23 “Cerebellar” 17 Symptoms and Signs of Multiple Sclerosis

35. Fatigue in Multiple Sclerosis • Viewed as a very different feeling from generic fatigue • Disproportionate to the amount of effort • Debilitating • Loss of force has a clear central component • Apparent neural component in the fatigue

36. Other Features of Multiple Sclerosis • Loss of control of bladder (urine retention) • Transient dysarthria or ataxia • Epilepsy • Mental changes (such as euphoria, depression, social disinhibition, and impaired memory)

37. Multiple Sclerosis: Lab Findings • Delayed evoked potentials • MRI can show plaques on affected tracts

38. Treatment of Multiple Sclerosis • Spontaneous improvements are typical • Hormone therapy (corticotropine, prednisolone) • Modification of diet (polyunsaturated fatty acids) • Hyperbaric oxygenation • Immunosuppressive treatment • Antispastic treatment

39. Prognosis for Multiple Sclerosis • Very uncertain • First episode may be followed by 20 years of no symptoms, and then MS strikes again • Older persons and males do worse • Average duration: 25 to 30 years • Average rate of clinical relapse: 1 per 2 years