A. Epidemiology
[Figure] "Schematic of Upper Spinal Cord"

1. ~10,000 cases per year in USA
   1. Most commonly associated with trauma
   2. 25-50% of patients with spinal injury have serious head trauma also
   3. 37% from motor vehicle crashes, violent crimes 26%, falls 24%, sports injuries 7%
2. Majority of SCI occur in cervical spine
3. Second most common injury is to thoracolumbar (T11-L2) area
4. Thoracic spine injuries are very uncommon due to rib cage strength
5. Cauda equina (below L2) has peripheral (Schwann cell myelin) nerves
   1. Injuries in these areas carry better prognosis than upper spinal cord
   2. This is because peripheral nerves can often regenerate

B. Pathophysiology [1]

1. Both primary and secondary injuries occur
2. Both traction and compression forces involved in initial injury
   1. Displaced bone fragments and other materials cause direct injury
   2. Blood vessels damaged, axons disrupted, neural-cell membranes broken
   3. Microhemorrhages occur rapidly in grey matter and spread
   4. Secondary ischemia results when cord swelling exceeds venous blood pressure
   5. Ischemia, release of neurotoxins, electrolyte shifts exacerbate cell death
3. Secondary Injury
   1. Hypoperfusion in grey matter after injury extends to surrounding white matter
   2. Hypoperfusion slows or blocks action potentials along axons
   3. This leads to "spinal" or neurogenic shock, reduces blood pressure
   4. Reduced blood pressure leads to worsened hypoperfusion
   5. Release of excitatory neurotransmitters in large doses are neurotoxic
   6. Glutamate in large doses is particularly damaging
   7. Glutamate binding to AMPA receptors can induce nerve and glial cell death
   8. Delayed apoptosis of neurons and oligodendrocytes may be due to glutamate

C. Findings Suggesting Serious SCI [2]

1. Patient presents with back pain or neck pain and ANY of the following:
2. Neurologic Deficit: bilateral or progressive neuropathy
3. Trauma
   1. Recent significant trauma
   2. Recent mild trauma in a patient >50 years old
4. History of prolonged glucocorticoid use
5. Osteoporosis
6. History of recent infection
7. Older patient with new-onset back pain
8. History of or concurrent cancer
9. Temperature >38°C (100.4°F)
10. Drug or alcohol abuse
11. Unexplained wieght loss
12. Low back pain (LBP) that is worse at rest or during the night
13. Disability caused by LBP and of >4 weeks' duration
14. Perianal numbness with bowel syndrome and/or bladder dysfunction
15. MRI and/or CT evaluation should be carried out
16. Most important prognostic indicator is retention of sacral (S4/5) pinprick sensation 72 hours to 1 week after SCI [1]

D. Evaluation

1. Spinal Immunobilization must be in place before examination
   1. Lateral cervical spine films are most helpful
   2. Antero-posterior films should also be done
   3. Poorly visualized areas or unexplained neurological deficits warrent CT scan
   4. Cervical spine injury can be evaluated with clinical criteria prior to radiography
2. Clinical Criteria for Low Probability Cervical Spinal Injury [3]
   1. No midline cervical tenderness
   2. No focal neurologic deficits
   3. Normal alertness
   4. No intoxication
   5. No painful, distracting injury
   6. Sensitivity 99%, negative predictive value 99.8%, positive predictive value 2.7%
3. Airway stabilization is necessary for injuries C4/5 and above
4. Neurologic Examination is critical
   1. All nerve levels should be assessed
   2. Major diaphragmatic innervation with C4 nerves
   3. C5/C6 deltoid/biceps through S2,3,4 bladder/bowel
   4. Unexplained nerve deficits should be evaluated with CT and/or MRI scans
5. Cardiovascular Instability
   1. Lesions above T6 level may lead to damage to sympathetic autonomic fibers
   2. Bradycardia and (orthostatic) hypotension
   3. Severe instability can lead to "neurogenic" shock

E. Differential Diagnosis of SCI

1. Trauma
2. Neoplastic Disease
   1. Metastatic Disease (breast, lung, prostate, kidney, lymphoma)
   2. Less commonly due to primary tumors of the spine
3. Infections
   1. Epidural abscess
   2. Osteomyelitis
   3. Consider tuberculosis
4. Epidural Hematoma
5. Disc Herniation
6. Spinal Stenosis

F. Overview of Acute Treatment

1. Spinal Immobilization
2. Airway Management
3. Cardiovascular Stabilization
4. High dose glucocorticoids (if within 8 hours of injury)
5. Bladder Catheter

G. Treatment Summary

1. Immobilization of spine with reduction of subluxations as needed
2. Airway protection / stabilization
   1. Permanent mechanical ventilation often required with C4 or higher
   2. C5/6 lesions may require some ventilatory assistance
   3. Nerve fibers from C5/6 innervate intercostal muscles
3. Reduction of Edema [4,5]
   1. High dose methylprednisolone improves outcomes when used within 8 hours of injury
   2. Typically, 20-40 mg/kg IV bolus initially followed by constant infusion
   3. Infusion of 5.4mg/kg/hr for 48 hours more effective than 24 hours [4]
   4. Increased rates of severe pneumonia and sepsis were seen in 48 versus 24 hour groups
   5. Steroids likely reduce edema and also block production of lipid peroxidation products
   6. Methylprednisolone initiated within 3 hours of injury can be discontinued at 24 hours [1]
4. Deep Vein Thrombosis (DVT)
   1. >5% of patients develop DVT and/or symptomatic pulmonary emboli
   2. Greatest risk is within 6 months of injury
   3. Pneumatic compression stockings and low dose heparin should be given
5. Any foreign object in the spinal cord should be surgically removed
6. Naloxone hydrochloride is also effective in improving outcome [5]
7. Pegorgotein, a scavenger of oxygen free radicals, of no benefit in closed head injury [6]
8. Treatment of Spacticity
9. Electrical stimulation devices are constantly being improved [1]
10. NeuroControl Freehand System
    1. Implant electrically stimulates arm and hand muscles
    2. Allows partial restoration of grasping, holding and releasing objects by single hand
11. Specialist should be engaged in acute and long-term therapeutic plan
    1. Long term plans focus on quality of life
    2. Major focus on bowel and bladder dysfunction and erectile dysfunction
12. Future Prospects
    1. Goal is to allow re-attachment of axon fibers and prevenet nerve cell death
    2. At present, there are no medications which stimulate CNS nerve regrowth
    3. Axon transection in the CNS leads to "dying back" of axons and cell body death
    4. Certain embryogenic factors present may protect nerves and allow regrowth of axons
    5. Tirilazad, a lipid peroxidation inhibitor, was less effective than 48 hour steroids [4]

References

1. McDonald JW and Sadowsky C. 2002. Lancet. 359(9304):417
2. Arce D, Sass P, Abul-Khoudoud H. 2001. Am Fam Phys. 64(4):631
3. Hoffman JR, Mower WR, Wolfson AB, et al. 2000. NEJM. 343(2):94
4. Bracken MB, Shepard MJ, Holford TR. 1997. JAMA. 277(20):1597
5. Bracken MB and Holford TR. 1993. J Neurosurg. 79:500
6. Young B, Runge JW, Waxman KS, et al. 1996. JAMA. 276(7):538