Spinal Cord Injury Clinical Trial
Official title:
ASIA Motor, Functional and Health Related Quality of Life Outcome in Traumatic Central Cord Syndrome, a Prospective Randomized Study
ABSTRACT/EXECUTIVE SUMMARY BACKGROUND, SIGNIFICANCE & RATIONALE: Between 10-20% of the more
than 6000 cases of spinal cord injury seen annually in the North America have the clinical
pattern of traumatic central cord syndrome (TCCS). These patients are usually older, most
likely have sustained a fall, and have incomplete spinal cord injury characterized by
dysesthetic and weak upper extremities. CT scan of the cervical spine in patients with TCCS
often shows disc/osteophytes complex superimposed on degenerative or congenital spinal
stenosis and MRI reveals signal changes at one or multiple skeletal segments. A minority of
these patients suffer from fracture/subluxations, however, this group of patients are
younger and have been involved in a more dynamic trauma. Since 1951, when Schneider et al
reported this syndrome, controversy has dominated its surgical management. The current
"Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries"
recommendations are only at the level of options, since prospective outcome data are
unavailable.
HYPOTHESIS: in acute traumatic central cord syndrome, surgical decompression of the spinal
cord within five days will result in more rapid motor recovery, than decompression 6 weeks
following injury. To test this hypothesis, we will pursue the following specific aims:
SPECIFIC AIM I: To compare American Spinal Injury Association (ASIA) Motor Scores after
three months post injury in patients with central cord syndrome operated on within five days
of injury to a similar group of patients operated on 6 weeks following injury.
SPECIFIC AIM II: To compare functional outcome, health related quality of life and
posttraumatic syrinx size in patients with traumatic central cord syndrome operated on
within five days to a similar group of patients operated on 6 weeks following injury.
DESIGN: Single center prospective randomized study. PROCEDURE: In a two-year period thirty
patients with traumatic central cord syndrome and cord compression (15 patients in each
group) will be randomized to undergo surgical decompression either within the first five
days or at 6 weeks following spinal cord injury. ASIA motor, functional recovery and health
related quality of life between the two groups will be compared at admission, discharge from
rehab facility 3 months and 12 months after surgery.
JUSTIFICATION Between 10-20% of the more than 6000 cases of cervical spinal cord injury seen
annually in the North America have the clinical pattern of traumatic central cord syndrome
(TCCS) . These patients are usually older, most likely have sustained a fall, and have
incomplete spinal cord injury characterized by dysesthetic and weak upper extremities. CT
scan of the cervical spine in patients with TCCS often shows disc/osteophytes complex
superimposed on degenerative or congenital spinal stenosis and MRI reveals signal changes at
one or multiple skeletal segments. A minority of these patients suffer from
fracture/subluxations, however, these patients are younger and have been involved in a more
dynamic trauma. Since 1951, when Schneider et al reported this syndrome, controversy and
confusion has dominated its surgical management. The current "Guidelines for the Management
of Acute Cervical Spine and Spinal Cord Injuries" recommendations are only at the level of
options, since prospective outcome data are unavailable .
During the past four decades, there has been significant progress in our understanding of
the pathophysiological mechanisms governing traumatic spinal cord injury including central
cord syndrome. Translation of kinetic energy, primarily through hyperextension and less
often fracture dislocations of cervical spine, usually involved with cervical spondylosis or
congenital spinal stenosis, results in anatomical compression of the spinal cord followed by
secondary insults which are time dependent and likely ischemic in nature. Microangiographic
studies of spinal cord in patients with cervical spondylosis have indicated deformation,
stretching and flattening of the spinal cord tracts as well as sulcal microvasculature,
which may be further jeopardized by traumatic hyperextension, resulting in axonal
interruption, swelling and vascular damage, predisposing to sustained spinal cord ischemia
responsible for clinical manifestations of central cord syndrome.
HYPOTHESIS: in acute traumatic central cord syndrome, surgical decompression of the spinal
cord within 1-5 days will result in more rapid motor and functional recovery and results in
a better quality of life than decompression ~6 weeks following injury. To test this
hypothesis, we will pursue the following specific aims: SPECIFIC AIM I: To compare American
Spinal Injury Association (ASIA) Motor Scores after three and 12 months post injury in
patients with central cord syndrome operated on within 1-5 days of injury to a similar group
of patients operated on ~6 weeks (range 5-7 weeks) following trauma. SPECIFIC AIM II: To
compare functional outcome, health related quality of life and posttraumatic syrinx size
three and 12 months after injury in patients with traumatic central cord syndrome operated
on within 1-5 days to a similar group of patients operated on ~6 weeks (5-7 weeks) following
injury.
DESIGN/PROCEDURE Our investigation will be single center prospective randomized pilot study.
Thirty conscious adult (>17 years old) patients with clinically (conventional ASIA exam) and
radiologically (conventional MRI and CT of neck) proven cervical traumatic central cord
syndrome will be screened for this study. These patients are admitted to the University of
Maryland Medical System within 48 hours of their injury and are randomized (computer) into
two surgical groups. Study subjects are fully resuscitated, stable and eligible to sign
consent to go through the research process. None of these patients have radiologically overt
unstable cervical spine injuries or any injury requiring urgent surgical decompression and
stabilization. A computer designed random number generator will divide these patients into
two standard of care surgical groups: Early Surgical Decompression Group ((ESDG [odd #]))
will have surgery 1-5 days after trauma and the late surgical decompression group ((LSDG
[even #])) will be operated after a period of ~ 6 weeks (range 5-7 weeks). Unless medically
indicated to stay in an acute care facility, the LSD Group patients are discharged to a
rehab facility or home to be brought back for surgery. While in hard collar the latter group
will be studied with a CT of the neck at 3 weeks (designed as a research tool) in order to
assure no missed ligamentous injury resulting in glacial instability. If hidden instability
is discovered, depending on its severity, decompression and internal fixation may be
performed earlier than the proposed 6 weeks. Both groups will have detailed conventional
medical, neurological and radiological examination during their hospital stay and while in a
rehab center, at 3 months, 6 months and 12 months postinjury. All the studies will be
clinically conventional except MRI at 12 months post injury which is research related to
measure the size of spinal cord syrinx. While ready to be discharged from a rehab center and
at 3 and 12 months post injury all these patients will have detailed research related
functional studies as depicted in study schedule in form of known outcome measures
(Functional Independence Measure, Spinal Cord Independence Measure, and Walking Index for
Spinal Cord Injury). In this study there won't be a placebo or control group.
Procedure
1. PREHOSPITAL ,Trauma Resuscitation Unit (TRU) & Emergency Department (ED) RESUSCITATION:
In a two-year period, all patients admitted to the STC TRU and UMMS EDs, within 48
hours of their spinal cord injury, will be screened for evidence of acute traumatic
central cord syndrome (TCCS).
2. SCREENING: Patients with incomplete spinal cord injury and MRI evidence of spinal cord
compression and swelling are visited for a complete conventional American Spinal Injury
Association Neurological and Functional Classification of motor, and sensory deficits.
Those with ASIA Impairment Grades B, C and D/E and with the clinical picture of central
cord syndrome will be chosen for possible enrollment. Inclusion/Exclusion Check List is
by now complete.
3. RANDOMIZATION: We (PI or his designee) will use one of the computer programs to
generate random numbers in order to divide 30 patients into two groups of surgical
candidates (Nregnow/digital river Chicago IL 60695-0001). Odd numbers are used for
early (1-5 days) decompression and even numbers for late ((after 6 weeks[5-7 weeks]))
decompression. The software is set in such a manner so that only a single number is
generated for a single patient with a specific alphanumerical user code
(CCSS3001-CCSS3030). Generation of a random number is accomplished by the PI or his
designee. Randomization is part of research process.
4. TIMING OF DECOMPRESSION: Based on the feasibility studies of Tator et al in STASCIS
1(please see the res of protocol), we decided to set the timing of decompression at
five days (1-5 days) and six weeks (5-7weeks) in order to be able to capture most of
the eligible patients. Enrollment will be within 48 hours of the injury. If due to any
reason(s) (e.g. complications) a patient who is randomized for early surgery does not
get operated, still he is followed as "an intent to treat patient" and his/her outcome
will be analyzed. The same is true for a patient who is to have late surgery but due to
a specific reason his surgery is cancelled.
5. OPERATIVE INTERVENTION: Eligible patients with traumatic central cord syndrome, canal
compromise and spinal cord compression will be consented, and randomized into two
groups. Thirty patients (15 patients in each group) will undergo standard surgical
decompression of spinal cord either within the first five days or at 6 weeks following
spinal cord injury. Each of the 15 patients enrolled for late decompression will be
kept in hard collar while in a rehab facility and will undergo research related CT
studies at 3 weeks post admission. If interim imaging studies indicate glacial
translation, earlier decompression and internal fixation may be considered. The choice
of surgical technique for decompression is standard of treatment at the Shock Trauma
Center. Standard surgical decompression of the spinal cord will be by a select group of
Department of Neurosurgery staff with full familiarity with cervical spine surgical
interventions.
6. FOLLOW-UP OF PATIENTS: Before, immediately after and at 72 hours following surgery, at
discharge from acute care or rehab center, 6 weeks, 3, 6, and12 months post injury
patients will have complete conventional ASIA motor and sensory classification
examination. Patients enrolled in the early surgical group will stay in the critical
care or intermediate care unit, or the general floor until discharge to a
rehabilitation center. These patients will have conventional postoperative CT while
inpatient, at 3 and 12 months post injury. A research related CT (at 3 weeks) is
performed in late surgery group in order to evaluate the stability of the sagittal
plane of the cervical spine. Conventional MRI is performed before and immediately
following surgery in every patient of the study and at 12 months (research related MRI)
to evaluate the size of the spinal cord syrinx. SF-36, Functional Independence Scale
(FIM), Walking Index for SCI (WISCI), Spinal Cord Independence Measure (SCIM), will be
checked as an outcome measure research instrument at discharge from rehab facility, at
3 months, and at 12 months following injury in all patients. Patients randomized to
have decompression at 6 weeks will have external fixation with a hard collar and will
be transferred to a rehabilitation center or home for six weeks and then brought back
for surgical decompression. Follow-up of these patients will be identical to the early
operative group.
7. OUTCOME INSTRUMENTS American Spinal Injury Association Motor Score Classification: ASIA
Motor Score. American Spinal Injury Sensory Score Classification: ASIA Sensory Score.
ASIA impairment Score (A, B, C, D, E) Functional Independence Measure (FIM) Spinal Cord
Independence Measure (SCIM). Walking Index of Spinal Cord Injury (WISCI). Health
Related Quality of Life measure SF-36. CT evaluation of cervical spinal cord injury
according to Allen-Ferguson Mechanistic Classification. CT quantification of canal
compromise according to the formula of Fehlings et al. MRI evidence of spinal cord
compression damage and syrinx size at specified intervals.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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