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SCI Overview: Demographics, Terminology, Clinical issues, & Research Approaches b William McKinley MD b Dept. of PM&R b Director SCI Rehabilitation Medicine.

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Presentation on theme: "SCI Overview: Demographics, Terminology, Clinical issues, & Research Approaches b William McKinley MD b Dept. of PM&R b Director SCI Rehabilitation Medicine."— Presentation transcript:

1 SCI Overview: Demographics, Terminology, Clinical issues, & Research Approaches b William McKinley MD b Dept. of PM&R b Director SCI Rehabilitation Medicine

2 Epidemiology of SCI b Incidence: 40 cases per million b Prevalence: 200,000 currently in USA b 200 new SCI / year in Virginia 80/yr at VCU80/yr at VCU –61% Traumatic (MVA, Violence, Fall) –39% Nontraumatic (SS, Neoplasm, ischemia)

3 Epidemiology (Cont.) b Demographics: Age: 31 yrs, 82% male, 56% Caucasian, 63% employed, 54% single (NT/SCI older, male = Female) b Etiology: MVA 37%, Violence 28%, Falls 21% b 90% discharged to home Costs: $40-100K (Acute) - $500K (lifetime)Costs: $40-100K (Acute) - $500K (lifetime) b Life Expectancy: lower than average Cause of Death: Pulmonary, CardiacCause of Death: Pulmonary, Cardiac


5 Model Spinal Cord Injury Care System Locations *Currently funded systems

6 SCI Model Systems b 5 yr ( $1.8 million) b Objectives clinical continuum of careclinical continuum of care national data collectionnational data collection focused research (VCU: Employment)focused research (VCU: Employment) collaborative researchcollaborative research

7 VCU SCI Research b Etiology & Rehab Outcome Studies violent/nonviolentviolent/nonviolent nontraumatic/traumaticnontraumatic/traumatic b Secondary Issues medical complidationsmedical complidations depression/griefdepression/grief substance abusesubstance abuse b Community Reintegration employment / recreationemployment / recreation

8 Key Terminology b Tetraplegia/Paraplegia b Neurologic Level of Injury (NLOI) most caudal normal M/S level (ie: C-5)most caudal normal M/S level (ie: C-5) b Zone of Injury 3 levels distal to NLOI3 levels distal to NLOI b Complete vs Incomplete ASIA ClassificationASIA Classification

9 b A = Complete – No Sacral Motor / Sensory b B = Incomplete – Sacral sensory sparing b C = Incomplete – Motor Sparing (<3) b D = Incomplete – Motor Sparing (>3) b E = Normal Motor & Sensory ASIA Impairment Scale

10 Neurological Recovery Following SCI b Zone of Injury (ZOI) Peripheral Nerve root (PNS) regeneration (1 year)Peripheral Nerve root (PNS) regeneration (1 year) b “Below ZOI” (Incomplete SCI) Neuropraxic recovery (1-3 months)Neuropraxic recovery (1-3 months) Peripheral Sprouting (3-6 months)Peripheral Sprouting (3-6 months) Muscle Hypertrophy (3-6 months)Muscle Hypertrophy (3-6 months)

11 b Prognostic indicators: Incomplete > Complete (motor > pin > light touch)Incomplete > Complete (motor > pin > light touch) Time post-injuryTime post-injury Rate of changeRate of change Neurological Recovery w/in the Zone of Injury

12 b Complete (ASIA A) 0-5% b Sensory Incomplete (ASIA B) 20% b Sensory Incomplete (ASIA B-2) 40% b Motor Incomplete (ASIA C) 60% Prognosis for “Functional” (ASIA D) Recovery (below ZOI)

13 b Mechanism of Injury: Unil fact dislo > Flexion-RotationUnil fact dislo > Flexion-Rotation b Etiology: Spinal stenosis > GSWSpinal stenosis > GSW b MRI: local edema > hemorrhage, transection b SSEP – no better than clinical exam Other Prognostic Factors



16 b Motor b Sensory b Bladder/Bowel b Sexuality b Autonomic Nervous System Clinical Impairments After SCI

17 b Infections (lung, GU) b Spasticity b Pressure Sores b Pain b DVT / PE b Orthostasis b Autonomic Dysreflexia Medical Complications of SCI

18 Functional Impairments b Mobility walking, wheelchair, transfers walking, wheelchair, transfers b Activities of Daily Living (ADL’S) dressing, feeding, groomingdressing, feeding, grooming b Functional Independence Measure (FIM) 1-7 rating scale for function (Dep….Indep)1-7 rating scale for function (Dep….Indep)

19 b C1-C5 motorized W/C b C-5 feeding b C6 manual W/C b C7 key level for functional Independence (transfers, dressing) b C8-T1 finger function b L2/3 ambulation Functional Abilities

20 b “Primary” injury – Immediate nerve damage will lead to nerve degeneration  “Secondary” injury – Delayed nerve injury due to inflammatory response, ischemia, ca++, free radicals b Complete is NOT “complete” Transection is rareTransection is rare 10% can support substantial function10% can support substantial function Post-Traumatic Changes to the Spinal Cord

21 Post-Traumatic SCI changes b Primary cell loss b Secondary Cell loss central hemorrhage/ischemiacentral hemorrhage/ischemia wallarian degenerationwallarian degeneration b Cystic degeneration SyringomyeliaSyringomyelia b Muscle atrophy especially w/LMN lossespecially w/LMN loss

22 Prognosis following SCI b Nerve regeneration - “currently” this does not occur within the CNS b Neurological recovery - can occur in incomplete injuries and w/I the ZOI b Functional improvements - occur in relation to LOI, comp/inc, motivation, staff training, decreased complications

23 Why No SCI Regeneration? b 1. No stimulus for regeneration Nerve Growth Factors (NGF)Nerve Growth Factors (NGF) – (Levi-Montalcini, Nobel Prize) PNS has NGF, CNS does notPNS has NGF, CNS does not –Produced naturally –Protects against cell damage –Stimulates regeneration

24 Why No SCI regeneration (cont) b 2. Inhibitory Factors Oligodendrocytes inhibit axon growth (Schwab-1980’s)Oligodendrocytes inhibit axon growth (Schwab-1980’s) Antibodies can block this inhibitionAntibodies can block this inhibition b 3. Impenetrable Regions Astrocyte scars can block regenerationAstrocyte scars can block regeneration

25 SCI Research Approaches b 1. prevent secondary CNS cell death b 2. Promote Regeneration & Remyelination b 3. Prevent inhibition b 4. Maximize Function (despite impairment)

26 1. Clinical / Pharmacological Studies to prevent secondary Injury b randomized, multi-center trials b outcome measurements: neurological improvementneurological improvement –ASIA, MIS functional improvement (FIM)functional improvement (FIM) –walking, bladder, bowel, sexuality decreased medical complicationsdecreased medical complications –spasticity, pain

27 Methylprednisilone (MP): steroids b Dual mechanism of action: antioxidant: inhibits lipid peroxidationantioxidant: inhibits lipid peroxidation anti-inflammatory: reduces vascular permeabilityanti-inflammatory: reduces vascular permeability NASCIS - National Acute Spinal Cord Injury StudiesNASCIS - National Acute Spinal Cord Injury Studies

28 NASCIS 1 (early 1980's) b 330 patients (double blind randomized, multi-center) b compared high (1,000mg/day) and low (100mg/day) dose MP within 48-72 hours x 10 days b results: *No significant difference between high and low MP and more wound infections in the high dose group

29 NASCIS 2 (“Bracken protocol”- late 1980's) b 470 patients compared both within 8 hours and between 8-12 hours b compared high dose MP (30mg/kg bolus and 5.4mg/kg/h x 23 hrs) vs Naloxone and placebo b Results: * MP within 8 hours had significantly greater motor and sensory recovery than placebo, Naloxone and 8-12 hour group

30 NASCIS 3 (mid-1990's) b comparison of MP with Tirilazed b Tirilazed inhibits lipid peroxidation without glucocorticoid fx b Results: *MP for 48 hours has beneficial effects.Tirilazed at 48 hours similar to MP at 24 hours. Apparent role of lipid peroxidation

31 Gangliosides (Geisler 1991) b GM 1- neuroprotective properties, acts on intracellular calcium b 34 pts with 100mg iv daily x 26 days b Results: *GM 1 patients showed improved LE ASIA motor scores at 1 yr

32 Sygen (Ganglioside) study (mid-1990's) b 720 patients, acute and 12 mo f/u b 100 or 200mg daily for 58 days b Results: neurological improvement @ 1 year no different than placebo

33 4-Aminopyridine (4AP) b selectively blocks K+ channels in cell membranes b improves conduction by prolonging AP b allows propagation through damaged zones normal half-life 3-4 hoursnormal half-life 3-4 hours

34 4AP Clinical studies b Multiple Sclerosis Studies b Fampridine (Phase II) SCI study randomized, blinded studyrandomized, blinded study b potential benefits: improve spasticity, bladder, pain, motor b ? Adverse events: agitation, insomnia, seizures

35 Other Non-pharmacologic trials (to prevent 2nd injury) b Surgical decompression acute decompression of sp cordacute decompression of sp cord lack of randomized prospective trialslack of randomized prospective trials ? Incomplete > Complete SCI? Incomplete > Complete SCI ? timing (4-6 hours), risk factors? timing (4-6 hours), risk factors b Hypothermia decreases metabolic requirementsdecreases metabolic requirements delayed development of hypoxiadelayed development of hypoxia decreased glutamate & free radical releasedecreased glutamate & free radical release animal studies seem encouraginganimal studies seem encouraging

36 SUMMARY: Prevention of Secondary Injury b MP (Bracken Protocol) b ? Gangliosides, 4-AP b ? surgical decompression, new drugs, hypothermia

37 2. Nerve Regeneration Research b stimulate outgrowth in appropriate directions b overcome anti-regenerative characteristics of adult CNS inhibition (Anti-Nogo)inhibition (Anti-Nogo) scar/ impenetrability (Chondroitinase)scar/ impenetrability (Chondroitinase) b convert nerve growth into functional reinnervation

38 Aguayo et. al. (1980's) b Transplanted CNS into PNS – Regeneration occurs! * Axons need “permissive” environment* Axons need “permissive” environment * Schwann cells are critical (NGF’s)* Schwann cells are critical (NGF’s) * results: electrically active small-diameter unmyelinated axon regeneration* results: electrically active small-diameter unmyelinated axon regeneration

39 Current Spinal nerve graft strategies b Transplantation peripheral nerve tissueperipheral nerve tissue fetal cellsfetal cells Genetic precursor cellsGenetic precursor cells –NGF’s, myelin, Antibodies

40 Remyelination Research b Schwann Cell & PNS transplants b Transplanted embryonic stem cells produce oligodendrocytesproduce oligodendrocytes b M-1 antibodies stimulate remyelination

41 3. Removal of inhibition (Schwab) b Oligodendrocyte inhibitory proteins inhibit axon growth and myelin formationinhibit axon growth and myelin formation b when treated with antibodies - increased axon regeneration in rats

42 SUMMARY: Nerve Regeneration b CNS axons need permissive environment (NGF’s)permissive environment (NGF’s) Removal of inhibitionsRemoval of inhibitions b Nerve grafts allow for limited regrowth b ? functional connections

43 4. Maximize Function (Clinical Research studies) b Prevention & management of acute & chronic medical complications b Rehabilitation Outcome studies b Community reintegration & employment

44 Clinical Research b Bladder, spasticity, neuropathic pain b FES b Reversing learned non-use biofeedbackbiofeedback body-weight supported ambulation (BSA)body-weight supported ambulation (BSA)

45 Technological advances & enhancing function b Functional Electrical Stimulation (FES) - Diaphragm - phrenic n stim (resp)Diaphragm - phrenic n stim (resp) Lower ext.- “Parastep” (walking)Lower ext.- “Parastep” (walking) Upper ext. - “Freehand” (grasp)Upper ext. - “Freehand” (grasp) Bladder - FES (voiding)Bladder - FES (voiding) b Implantable pumps (spasms, pain)


47 Current Clinical Trials b Fetal SC transplants to treat progressive syringomyelia b 4-AP for chronic SCI b Neurotropin-secreting transplants b Neural stem cell Tx in chronic SCI b Alternating electrical current sti b Supported treadmill ambulation b Nerve bridging

48 SUMMARY: Future Scenario (Combination Therapies) b Prevent secondary injury steroidssteroids b Enhance Regeneration & Remyelination nerve grafting, NGF’s, overcoming inhibition, guiding axons to targetnerve grafting, NGF’s, overcoming inhibition, guiding axons to target b Enhance Restoration (Rehabilitation, 4 AP, FES, BSA)(Rehabilitation, 4 AP, FES, BSA) b ? Future opportunities Vaccines (neuroprotection), stem cellsVaccines (neuroprotection), stem cells

49 Preparing for research b Avoid irreversible surgical procedures b Prevent complications atrophy (muscle, bone, neuronal)atrophy (muscle, bone, neuronal) contracturescontractures b Revearse learned non-use & atrophy PT, FES, BSA, biofeedbackPT, FES, BSA, biofeedback


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