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Updates in management of spinal cord injury
1. Updates in
Spinal Cord Injury Management
Mohamed Hassanein
Lecturer of Neurosurgery
Suez Canal University
2. Damage to the spinal cord that temporarily or
permanently causes changes in its function
Direct trauma to the spinal cord results in loss of
motor, sensory and autonomic functions caudal to
the site of cord injury.
Results in devastating consequences for the
physical, social and vocational well-being of patients
SCI is a complicated condition with no definite cure
available
Spinal Cord Injury(SCI)
3. Epidemiology
• 250,000 - 500,000 people worldwide sustain a SCI each year.
• Annual incidence of SCI : 10 - 80 cases / million/year.
• Global prevalence of SCI: 230 - 1000 cases / million.
• More prevalent in males (75%) !!!!
• Bimodal age distribution: 16- 30 years (> 65%), ≥ 65 years
Classification
Complete: Absence of sensory & motor function in lowest sacral
segment after resolution of spinal shock
Incomplete: Presence of sensory & motor function in lowest sacral
segment (preserved function below the defined neurological level)
More favorable prognosis
4. Etiology
Traumatic:
The cause in 90% of SCI cases (MVA, Falls, Violence)
15% of patients with spinal fractures got SCIs
Other causes:
• Degenerative (spondylosis)
• Neoplastic
• Inflammatory, Infectious
• Vascular disorders
• Iatrogenic
• Pathological fractures (eg. osteoporosis)
• Development disorders
5. • 1ry & 2ry injury mechanisms
inflammation, hemorrhage,
apoptosis, and necrosis.
• Neurons and astrocytes are forced
into apoptosis or necrosis Axonal
degeneration.
• Reactive astrocytes secrete
chondroitin sulfate proteoglycans
Physical and chemical barrier.
• CSPGs impedes endogenous repair
processes (axonal sprouting and
synaptic reorganization).
Acute Phase
Pathophysiology
6. • Cavitation develops in the
epicenter of the lesion.
• Surrounded by connective
scar tissues and contains CSF.
• Reactive astrocytes changes
into scar-forming astrocytes.
• Impede regenerating axons
from crossing the lesion.
Chronic Phase
Pathophysiology
10. • Stabilization & Critical Care Admission
• NGT (Aspiration-Ileus), Foley catheter(Retention)
• Blood Pressure Augmentation
• Methylprednisolone (MPSS) within 8 hours of injury
• Early Surgical Decompression (within 24 h)
• Neuroprotection (Hypothermia-CSF Drainage)
• Prevention and Treatment of Complications
• Physical Rehabilitation
Management in Hospital
Current Care
11. MPSS Evidence
NASCIS II (National Acute Spinal Cord Injury Study , 1992)
Reported a modest beneficial effect of high dose MPSS
If initiated < 8hrs of injury continue for 24 hours
IV loading dose 30mg/kg + Maintenance dose 5.4 mg/kg/hour
NASCIS III (1997)
If initiated < 3hours continue for 24 hours
If initiated 3-8 hours continue for 48 hours
Higher morbidity (sepsis , pneumonia, GI bleeding)
12. IS MPSS Clinically Effective?
• Both studies were criticized for methodology & subgroup
analysis
• Meta-analysis Insufficient evidence as a standard ttt in acute
SCI
• Weak clinical evidence supports MPSS as per NASCIS II protocol
only
• AO Spine 2016 guidelines: Suggest IV MPSS administered over
24 hours if feasible within 8 hours of injury
• Medico-legal issues???
13. Blood Pressure Augmentation
• Maintaining MAP ≥ 85-90 mmHg 7 days post-injury improve
outcome of SCI (level III evidence)
• Neuroprotective effect: Enhancing systemic perfusion
Mitigates ischemia of the injured cord
• Requires euvolemia or slight hypervolemia (IV crystalloid,
Vasopressors, Invasive BP monitoring)
Early Surgical Decompression
STASCIS (Surgical Timing in Acute Spinal Cord Injury Study):
Neurological recovery is enhanced by early decompression
(<24 hours) compared to late surgery (≥24 hours) at 6-mo follow-up.
Central cord syndrome with pre-existing canal stenosis???
Current Care
14. Improve early spinal cord perfusion pressure Reduce
the ischemic territory
CSF drainage and MAP augmentation can act
synergistically to enhance spinal cord blood flow
Therapeutic Hypothermia (32-34°C)
Decreases metabolic rate of spinal cord tissue
Reduces inflammation
Intravascular/Systemic cooling Mitigates
secondary injury mechanisms following SCI
Cerebrospinal Fluid Drainage
16. Rizulole
• Voltage-gated sodium channel blocker
• Decreases presynaptic glutamate release
• Neuroprotecting Decrease excitotoxicity
• Reduce neuronal loss and cavity size
• Used successfully for ALS
• Improvement in motor function and electrophysiology
Minocycline
• 2nd generation tetracycline, Cross the BBB
Potent anti-inflammatory properties
• Inhibits microglial activation, TNF-α,
IL-1β, Cox 2 and matrix proteinases
• Dramatic decreased in lesion sizes and
neuron loss in SCI models
17. Frontiers of Neuroregeneration
• Novel strategies to enhance neuroplasticity and Promote axon
regeneration and sprouting especially in chronic phase SCI
• Inhibit Rho-mediated inhibition of axonal & neurite growth
• Address barriers to recovery
Agents
o Chondroitinase ABC
o Anti-Nogo-A Antibody
o Cethrin
Loss of structural framework
Cystic cavitation,
Astroglial scarring
Inhibitory signaling
18. Cethrin
• Rho antagonists
• Toxin produced by Clostridium botulinum
• Promotes regeneration of cut axons
• Remodels damaged circuits.
• Applied over dura during decompressive surgery
Anti-Nogo-A Antibody
• Bioengineered monoclonal antibody
• Given by intrathecal route
• Promote axonal sprouting and functional recovery
Chondroitinase ABC
• Degrades the chondroitin sulfate
proteoglycans in the glial scar
• Intrathecal and intraparenchymal routes
• Reduce scar and cavity volume.
• Improve motor and sensory function
19. Cell-Based Therapy
Rationale To provide the
injured cord tissue with
• Growth Promoting Factors
• Cell Replacements
• Structural Elements
• Myelinating Units
Sources
Mesenchymal Stem Cells
Olfactory Ensheathing Cells
Schwann Cells
Neural Precursor Cells
Administration
• Intraparenchymal
• Intrathecal
• Intravascular
21. • Synapse with host motor neurons
• Reorganize the neuronal circuits
• Interneurons connect injured neural tracts
• Can activate muscle contraction
Olfactory Ensheathing Cells (OEC)
Differentiated neurons can bridge the lesion
Stem Cell Transplantation
Encircle olfactory neurons along CNS-
nasal mucosa transition
Unique ability to regenerate.
Secrete neurotrophic factors
Support axonal regeneration and
remyelination after SCI
22. Biomaterials
• Recreate structural architecture
mimics the native matrix
• Release growth factors/
Immunomodulatory drugs
• Enhance regeneration and
endogenous cell migration
Self-assembling peptide hydrogels, biocompatible, biodegradable
On exposure to ions/ magnetic fields changes into nanofibrils Guide
the regeneration
23. Neuromodulation
Options
• Functional Electrical Stimulation
• Epidural Stimulation
• Chemogenetics
• Non-Invasive Deep Brain Stimulation
(Magnetic /Electrical Stimulation - Optogenetics)
• Brain-Machine Interfaces
Rationale: Promotion of cortical motor plasticity
& proprioceptive afferents after SCI.
Success in restoring function of
• Upper extremity (writing, eating)
• Lower extremity (supported ambulation)
• Bowel & Bladder (volitional control )
24. Epidural Stimulation (EDS)
Microcurrents through epidural electrodes to cord/conus
Enhance neuroplasticity/Activating central circuits Motor Recovery
Improve refractory neuropathic pain following SCI
Functional Electrical Stimulation (FES)
Microcurrents to nerves/muscles Enhance motor function
Promote synaptogenesis, myelination, and neurite sprouting
Activate preserved circuits
Non-Invasive Deep Brain Stimulation
Transcranial Magnetic Stimulation
Electrical Stimulation
Optogenetics)
25. Brain-Machine Interfaces
• Electronic device is implanted in motor cortex
• Record and decode motor signals from the brain
• Signals can influence motor output through
Muscle electrode, Prosthetic limb, Exoskeleton
In 2016 , a wireless brain-machine-spinal cord
interface was introduces to decode motor
intentional signals into an epidural stimulator
Bypass the injury site to allow the brain to regain control of
an artificial limb or muscles below the injury
Require expensive, specialized equipments, and the expertise to
operate these devices !!!
26. Robotic Exoskeletons
• In 2014, FDA approved the first
robotic exoskeleton in USA For
patients with paraplegia
(ReWalk, ReWalk Robotics, Inc)
• Fits around the legs and back of
patients to facilitate sitting,
standing and walking
Prosthetic Limbs
• AKA Bionic Limbs
• controlled via implanted neuromuscular interfaces
• Direct skeletal attachment by osseointegration