Spinal cord disorders Brains without brawn

1. Spinal cord disorders Brains without brawn • Ziv Williams, MD • Department of Neurosurgery • Massachusetts General Hospital • Harvard Medical School

2. Pathophysiology of spinal cord injury

3. Primary injury • Immediate • Axonal injury with loss of nerve conduction. • Damage to oligodendrocytes and myeline sheath leading to reduced nerve conduction.

4. Secondary injury • Minutes to days. • Wallarian degeneration. • Edema leading to cord expansion and additional compression. • Activation of apoptotic mechanisms (Caspase pathway) • Scar tissue formation from reactive astrocytes and glial scar.

5. Late injury • Weeks to months. • Glial scar tissue and lack of growth ‘conduit’ within damaged spinal cord. • Lack of sufficient local neurotrophic growth factors. • Brain derived neurotrophic factor (BDNF). • Glial derived neurtrophic factor (GDNF) • Intrinsic myelin associated inhibitors. • Myelin-associated glycoprotein. • Nogo-66 and amino-Nogo. • Limited intrinsic ability to re-grow damaged axons.

6. Presentation of spinal cord injury

8. Spinal cord anatomy (brief overview)

9. Motor control • Corticospinal tract • Responsible for fine voluntary motor control/muscle contraction • From the primary motor cortex, internal capsule, decussates at the level of the medulla, travels to supply the contralateral side

10. Rubrospinal tract • Responsible for voluntary motor control mostly of large muscles. • Facilitates flexion and inhibits extension of Involuntary limb movement • Red nucleus, decussate in the brainstem, travels to supply the contralateral side • Vestibulospinal tract • Activates proximal limb extensors (anti-gravity) and inhibits flexors for maintained balance and posture. • Vestibular nuclei, anterior funiculus, travels to supply the ipsilateral side

11. Sensation • Spinothalamic tract • Nociception (pain and temperature) • Decussates 2-3 levels above the dermatome and then travels up ipsilateral cord. Continues as lateral spinothalamic tract.

12. Dorsal column • Two-point discrimination, vibration and conscious proprioception • Travels up contralateral dorsal column and medial leminiscus. Decussate at the the dorsal column nuclei in the medulla • Spinocerebellar tract • Unconscious proprioception (limb position for posture stability) • Travels up ipsilateral cord, through Clark’s column and terminate in the cerebellum.

13. Side of injury at the level of the spinal cord • Ipsilateral • Fine and gross motor control • Posture and anti-gravity • Light touch discrimination, vibration and proprioception • Contralateral • Pain and temperature

14. Signs and symptoms of spinal cord injury

15. Strength • Weakness and/or complete paralysis • Loss of descending corticospinal/rubrospinal tracts with preserved muscle bulk and tone • Atrophy and absent muscle tone is rarely seen with spinal cord injury (lower motor neuron or peripheral nerve disease)

16. Reflex changes • Reflex changes with loss of inhibitory control from descending pathways • Hyper-reflexia – elevated deep-tendon reflex. • Babinski sign –foot and toe extension.

17. Sensation • Loss of tactile and vibration sensation • Loss of nociceptive sensation • Loss of proprioceptive sensation

18. Injury overview • Corticospinal pathway damage • Ipsilateral weakness, diminished fine motor control below the level of the lesion. • Hyper-reflexia and Babinski sign. • Dorsal column damage • Ipsilateral loss of tactile discrimination, vibratory, and position sensation below the level of the lesion. • Spinothalamic tract damage • Contralateral loss of pain and temperature 2-3 levels bellow level of injury.

19. Spinal cord disorders

20. Heritable • Infectious • Inflammatory • Metabolic • Mechanical • Motor neuron

21. Heritable disorders

22. Friedreich’s ataxia • Pathogenesis • Most common progressive spinal ataxia. • Carrier prevalence is 1:100 • Caused by recessive chromosome 9 mutation in the gene coding for Frataxin (necessary for mitochondrial function). • Affects the following • Corticospinal tracts. • Posterior columns. • Spinocerebellar tracts. • Associated with fiber loss and gliosis

23. Clinical manifestations • Bilateral symptoms • Loss of fine motor control and weakness • Loss of proprioception and discrimination/vibration sensation. • Unsteady gait and teetering/swaying while standing. • Hypo-reflexia • Diagnosis • Clinical manifestation. • Familiar inheritance. • Treatment • Supportive. • Genetic counseling.

24. Infectious disorders

25. Tabes Dorsalis • Pathogenesis • Syphilis (Treponema Pallidum). • Produced by meningovascular inflammation. • Affects the following • Dorsal root of the posterior horn • Posterior columns • Manifests as demyelination and inflammatory changes.

26. Clinical manifestations • Normally manifest 15-20 years after infection. • Symptoms bilateral and equal. • Shooting and burning pains. • Impaired tactile discrimination, vibratory, and conscious position sensation • Hypo-reflexia • Maintained strength (early). • Diagnosis • Serum treponemal antibodies. • CSF demonstrating elevated lymphocytes. • Treatment • Penicillin infusion. • Symptomatic treatment for pain and gait instability.

27. Inflammatory disorders

28. Transverse myelitis • Pathogenesis • Often preceded by a viral or upper respiratory illness prior • Acutely evolving inflammatory-demyelinative disruption of the spinal cord. • Affects the following • called ‘transverse’ because it commonly occupies a narrow horizontal band across the spinal cord • Posterior columns • Manifests as demyelination and inflammatory changes.

29. Clinical manifestations • Characterized by paraparesis or paraplegia that evolves over hours to days. • No clear offending mechanism such as trauma. • Ascending sensory (commonly ascending to the mid trunk level). • Hyper-reflexia. • Diagnosis • Elevated lymphocytes and increase total protein in the CSF (no oligo-clonal bands like multiple sclerosis). • MRI demonstrates a cross-sectional focal edema/swelling of the spinal cord. • Treatment • High dose steroids. • Supportive care.

30. Metabolic disorders

31. Subacute combined degeneration • Pathogenesis • Vitamin B12 deficiency. • Essential factor in succinyl CoA metabolism. • Necessary for producing fatty acids in the lipid membranes of myelin • Absorption insufficiency and malnutrition. • Affects the following • Begins in the posterior columns of the lower spinal and peripheral nerves. • Followed by the upper columns and corticospinal tract. • Manifests as patchy loss of myelin and myelin sheath swelling.

32. Clinical manifestations • Bilateral symptoms • Sensory changes, often come before motor changes. • Loss of vibration, two point discrimination and conscious proprioception. • Lower extremity weakness. • Diagnosis • Serum B12 levels and red blood cell count • Treatment • Vitamin B12 administration. • Treat the source of deficiency. • Recovery depends on the duration of initial symptoms • The greatest improvement occurring in patients with symptoms present for less than 3 months.

33. Mechanical disorders

34. Compressive spinal cord injury • Pathogenesis • Mechanical compression • Traumatic bone fragment. • Disk herniation. • Tumor. • Disruption of ascending and/or descending tracts • Clinical presentation • Site and severity dependent

35. Brown-sequard syndrome • Corticospinal/rubrospinal tract disruption • Ipsilateral paralysis • Ipsilateral hyper-reflexia • Ipsilateral Babinski sign • Dorsal column disruption • Ipsilateral loss of tactile discrimination, vibratory, and proprioception • Spinothalamic tract disruption • Contralateral loss of pain and temperature sensation 2-3 segments below the level of injury.

36. Complete cord transaction/injury • Initial presentation • Spinal shock normally for the first 1-4 weeks. • Sensory loss in all modalities. • Muscular flaccidity (complete loss of tone and voluntary movement). • Complete loss of reflexes (hypo-reflexia). • Though to occur via transient hyperpolarization and desensitization of spinal cord neurons bellow the level of injury . • Late presentation • Persistent paralysis and sensory loss. • Hyper-reflexia, Babinski sign. • Muscle rigidity.

37. Diagnosis • Physical exam • Imaging studies (hematoma or bone fragment) • Treatment • High dose steroids for acute compressive injury (limits secondary injury due to edema if given within 8 hours). • Surgical treatment for compressive injury. • Addition of radiation treatment and/or chemotherapy for tumor.

38. Current treatment

39. Current treatment options • Medical • Steroids (solumedrol or decadron). • Acute trauma. • Tumor • Transverse myelitis • Vasopressors (neosynephrine or dopamine) . • Acute trauma • Disease specific treatment • Subacute combined degeneration • Tabes dorsalis • Supportive • All cases

40. Surgical • Bony decompression. • Stabilization (if fracture or bony erosion). • Lesion removal/resection. • Preventative • Trauma prevention. • Genetic counseling.

41. Ongoing research

42. Stem cell • Autologous pluripotent stem cells. • Induced pluripotent stem cells. • Growth inhibitor antagonists • Nogo receptor antagonists • Promotes myelin regrowth. • Neurotrophic factors • Brain-derived neurotrophic factor (BDNF) • Glial-derived neurotrophic factor (GDNF)

43. Thank you