In the last twenty years, spine surgery as a
subspecialty of orthopaedic surgery has enjoyed an explosion of
interest. In 1981, fewer than fifteen spine fellowships were available.
By 2000, more than 200 post-residency opportunities were
available for training related to the spine. Four spine societies
are members of the Council of Musculoskeletal Specialty Societies,
which reports to the board of directors of the American Academy
of Orthopaedic Surgeons. These four societies—the American
Spinal Injury Association, the Cervical Spine Research Society,
the North American Spine Society, and the Scoliosis Research Society—also form
the Federation of Spine Associations, which is charged with coordinating
the spine program for Specialty Day at the annual meeting of the
American Academy of Orthopaedic Surgeons.
These four spine societies attract members with further subspecialized
interests, as reflected in the focus of their research and practice.
Spinal cord injury, the cervical spine, the lumbar spine, and spine
deformities are foci of concentration at the individual society
meetings, although some overlap in topics is inevitable and even
encouraged. Neurosurgically trained spine surgeons are eligible
for membership in these societies, and some physicians believe that
a well-trained spine surgeon can come from either discipline,
provided that the level of education and expertise is appropriate.
This update will highlight the various subspecialties of the spine,
incorporating information from presentations made at the 2001 American
Academy of Orthopaedic Surgeons annual meeting (including Specialty
Day) as well as at the annual meetings of the four subspecialty
societies mentioned above. Major contributions published in The
Journal of Bone and Joint Surgery and Spine during
the year 2000 will also be discussed.
Spine surgery remains a dynamic subspecialty, with major advances
being made every year. Ongoing research in spinal cord regeneration,
disc replacement, endoscopic surgery, and biological adjuncts to
bone-healing are all having an impact on spine surgery. Improvements
in implant design, and unique ways to introduce these implants,
are constantly evolving.
International cooperation in the sharing of advances has allowed
more rapid dissemination of ideas and experiences. The North American
Spine Society sponsors a formal meeting in conjunction with the
Japanese Spine Research Society every other year; the latest meeting
was held in Hawaii in July 2000. The Scoliosis Research Society
frequently holds its annual meeting abroad to encourage international
participation. The Cervical Spine Research Society has corresponding and
European members in seventeen foreign countries. The American Spinal
Injury Association is planning its 2002 meeting in Canada in conjunction
with the International Medical Society of Paraplegia and its 2003
annual meeting in Miami in conjunction with the Brazilian Spinal
Injury Association. This trend toward the international pooling
of ideas and experiences will undoubtedly increase over time.
Surgical Anatomy
Complications of anterior cervical spine surgery, such as airway
compromise, vocal cord involvement secondary to recurrent laryngeal
and superior laryngeal neurapraxias, and dysphagia, have all been
studied extensively1. Attention
to anatomy during dissection, careful retraction during surgery,
and vigilance postoperatively can help to minimize these complications.
Risk factors for postoperative airway complications include obesity,
a prolonged operative time, asthma, and an extensive longitudinal
exposure. Patients with any of these risk factors should be left
intubated overnight and should be extubated only after they have
met clearly defined extubation criteria.
The sympathetic trunk may be more vulnerable to damage during
lower anterior cervical approaches because it is more medially located
within the longus colli muscle at the sixth cervical level than
it is at the third cervical level.
Atlantoaxial Fixation
Atlantoaxial arthrodesis (arthrodesis of the first and second cervical
vertebrae) remains a focus of research since posterior arthrodesis
at this level is not associated with the high success rate of subaxial
arthrodesis. Transarticular screws, inserted according to the method
described by Magerl, are biomechanically quite strong and lead to
impressive rates of fusion when combined with conventional interspinous
wiring and bone-grafting. However, placement of these screws is
dangerous; complications include vertebral artery injury leading
to stroke or death, particularly in patients with unusual anatomy.
Lateral mass screws inserted in the first cervical vertebra (to
a maximum depth of 3.5 mm), coupled with pedicle screws inserted
in the second cervical vertebra, may allow rod fixation and may
supplant Magerl screws in patients in whom a classic posterior fusion
is inadequate2.
Laminaplasty
Several Japanese authors have reported on neck and shoulder pain
after cervical laminaplasty. Axial pain was found in 60% of
these patients. Factors contributing to chronic pain were a prolonged
operative time and denervation of or damage to the cervical facet
joints. Better surgical techniques may decrease these problems.
Aita et al., in a prospective study of twenty-six patients who were
followed for an average of 6.7 years, found that laminaplasty decreased
lordosis and straightened the cervical spine. The decrease in both
range of motion and lordosis continued at diminishing rates from
the third through the fifth postoperative year.
Lateral Mass Plates
Posterior lateral mass screws can be used in the cervical spine for
stabilization as well as for improving fusion rates. Bicortical
screws have been associated with vertebral artery and nerve-root
injuries. Several authors have described unilateral screw fixation
of lateral mass plates as a safe and effective technique. This method
offers a theoretical advantage compared with interspinous wiring
since it resists extension forces.
Natural History
In 1986, Donald Gore of Sheboygan, Wisconsin, reported the magnetic
resonance imaging findings in a population of 200 asymptomatic patients.
Of the 159 patients who were available at the ten-year follow-up,
only 15% had neck pain and only one had required surgery
for radiculopathy. The presence of degenerative change at the level
between the sixth and seventh cervical vertebrae was found to be
an important predictor of the development of neck pain.
Anterior Cervical Plates
Wang et al. followed sixty patients for an average of 2.7 years after
a two-level anterior cervical arthrodesis, performed either with
plates (thirty-two patients) or without them (twenty-eight patients).
All of the patients who were treated with plates had fusion, whereas
25% of the patients who were treated without plates had
a pseudarthrosis. The use of plates did not appreciably increase
the rate of complications.
In a study by DiAngelo et al., in vitro testing
demonstrated that multilevel anterior plates increased stiffness
and decreased local motion of the cervical spine after corpectomy.
However, anterior plates reverse the graft loads and may load the
graft excessively in extension, thereby promoting failure of multilevel
constructs unless they are protected by posterior fixation.
Bolesta and Rechtine reported an unacceptably high rate of pseudarthrosis
(53%) after three and four-level anterior cervical discectomy
and arthrodesis with anterior fixation alone.
Cervical Myelopathy
Surgical and nonsurgical treatment of cervical spondylotic myelopathy
were compared, by an independent reviewer, in a prospective, multicenter
study that was funded by the Cervical Spine Research Society. The
surgically treated patients had better outcomes. Neurologic and
nonneurologic symptoms, as well as functional outcomes, were assessed.
Newey et al. reported on the long-term outcomes of the natural
history of central cord syndrome. At an average follow-up of 8.6
years, survival and function were better in younger patients. Patients
who were less than fifty years old at the time of injury had a far
better functional result than did those who were more than seventy
years old.
In patients with mild cervical myelopathy, increased signal intensity
on magnetic resonance imaging of the cord has not been demonstrated
to be a prognostic factor for a poor outcome or for the severity
of the myelopathy.
Cervical Fusion Cages
Hacker et al., in a multicenter evaluation, reported that the outcomes
associated with use of a BAK/C cage were the same as those
associated with anterior cervical discectomy and fusion performed
without instrumentation. However, an in vitro study
by Wilke et al. demonstrated marked subsidence of three different
cervical interbody implants (the BAK/C, WING, and Acromed
cages).
Idiopathic Scoliosis
Studies at two centers, headed by Carol Weiss in Dallas and Nancy
Hadley Miller in Baltimore, are focusing on the genetic pattern
of idiopathic scoliosis inheritance and providing ongoing insight
into the etiology of this disease3.
Tom Lowe has investigated the correlation between increasing platelet
calmodulin levels and curve progression in idiopathic scoliosis.
Ultimately, calmodulin may serve as a biological marker for identifying
patients who are at risk for curve progression and those who are
not.
Most reports on the surgical treatment of idiopathic scoliosis have
centered on the use of pedicle screws, on selective anterior instrumentation
and fusion, and on complications. Suk et al., Polly et al., and
O’Brien et al. demonstrated that, in experienced hands,
pedicle screws can be placed safely in the thoracic spine in children
with deformity. Suk et al. also reported on the safety of this technique
in patients less than ten years old. It is clear that this is a
technically demanding procedure that requires more precision than
the placement of lumbar pedicle screws does.
Investigators from several centers have reported satisfactory results
with use of a single anterior solid rod for the treatment of isolated
thoracolumbar, lumbar, and thoracic idiopathic scoliosis. The rates
of complications and pseudarthrosis have been low. One group correlated
pseudarthrosis with smoking, thoracic hyperkyphosis, and larger
adolescent body size. However, Clements et al. reported that, in
patients with hyperkyphotic thoracic deformity, posterior instrumentation
was better than anterior instrumentation for control in the sagittal plane.
Adult Spinal Deformity
Pedicle subtraction osteotomy for the treatment of fixed sagittal
imbalance continues to gain support and interest. Reports from St.
Louis and San Francisco have demonstrated promising clinical and
radiographic results with use of this technique. Lee et al. reported
a correlation among sagittal imbalance, reduced lumbar lordosis,
and pelvic tilt. There is increasing interest in pelvic tilt and
pelvic incidence (the relationship between the pelvis, the hip joints,
the sacrum, and the lumbar spine) at centers throughout the world.
High-Grade Spondylolisthesis
In the past, there has been concern that complete reduction of very
high-grade spondylolisthesis leads to a substantial rate of neurologic
deficits of both the fifth lumbar and the sacral nerve roots. Presentations
from the Hospital for Special Surgery and the University of California
at San Francisco focused on techniques associated with partial reduction,
through placement of either sacral screws into the fifth lumbar
vertebral body or fibular dowel grafts from the sacrum into the
fifth lumbar vertebral body, or both. Although both series were small,
these techniques may be an alternative for patients with grade-4
or 5 spondylolisthesis who have a very high-degree slip angle and
inferior displacement of the fifth lumbar vertebra relative to the
top of the sacrum.
Congenital Scoliosis
Hemivertebral resection in the thoracic and lumbar spine is a valuable
surgical treatment for certain congenital deformities. The resection
can be performed through separate anterior and posterior approaches
or, in some cases, through a posterior approach only. There is concern
that circumferential fusion in very young patients might limit development
of the spinal canal. However, a presentation from Karlsbad, Germany,
indicated that circumferential fusion and the use of pedicle screws did
not narrow the spinal canal in these patients.
Spinal Fusion
Guo et al. reported dramatically increased expression of recombinant
human bone morphogenetic protein-4 during fracture-healing.
Cunningham et al. found that recombinant human osteogenic protein-1
(OP-1) (rhBMP-7) offered definite advantages as a posterolateral
bone-graft substitute and expander in a coonhound model. Riew et
al., using a rabbit model, showed that cyclooxygenase-2
inhibitors did not inhibit fusion as substantially as did indomethacin.
Those authors also described a technique of thoracoscopic intradiscal
spinal fusion in pigs in which they used gene therapy to deliver
bone morphogenetic protein-2 to the fusion site.
Sacral Pelvic Fixation
Alegre et al. showed a substantial decrease in the flexion-extension moment
on the screw at the first sacral level when long posterior constructs
were extended either to the ilium or to a screw at the second sacral
level. Schwend et al. reported on an alternative to the Galveston
technique. Clinical investigators at the University of California
at San Francisco and at Washington University in St. Louis reported
the results of iliac-screw fixation. Bilateral fixation with screws
at the first sacral level and the ilium provided a predictable rate
of fusion, with the main complication being prominence of the iliac
screws. The Washington University group found this method to be
particularly helpful in patients having a revision4.
Innovative Techniques
George Picetti, in a study of fifty patients with thoracic idiopathic
adolescent scoliosis, reported the results of endoscopic fusion
and instrumentation after twenty-four to forty-one months of follow-up.
This technique is presently being investigated at several centers.
Picetti found an unacceptably high rate of pseudarthrosis (nine
of nine patients, including two patients who had a rod fracture)
after treatment with Grafton alone. In comparison, only one of the
patients who had an arthrodesis with use of rib graft had a pseudarthrosis.
Many centers have shown that it is feasible to perform endoscopic discectomy
in conjunction with bone-grafting and instrumentation. However,
a longer duration of follow-up will be needed to determine
the ultimate rate of pseudarthrosis.
Management of progressive deformities in very young and very
small children remains an area of intensive investigation. It is
still not known whether there are feasible ways of controlling the
deformity without fusing the spine. Robert Campbell and colleagues
reported on a variety of methods for treating "thoracic
insufficiency syndrome," all of which centered on performing
an opening-wedge thoracostomy and then applying a chest-wall distractor.
Sarwark et al. reported the results of subtraction/decancellation
vertebrectomy in patients with kyphosis due to myelomeningocele.
John Braun and James Ogilvie described a very promising experimental scoliosis
model in immature goats; this model should allow further study of
various treatment options in very skeletally immature patients with
spinal deformity. Wall et al., using an immature-pig model, reported
the results of endoscopic stapling for the treatment of infantile
and juvenile adolescent idiopathic scoliosis. Thompson et al. described
the use of "growing rods" for skeletally immature
patients with paralytic scoliosis.
Richard Lindseth devised a technique for anterior vertebral osteotomy
that is designed to preserve lumbar motion and to correct idiopathic
lumbar scoliosis without fusion. This technique was used in seventeen
patients with adolescent idiopathic scoliosis who had a lumbar curve.
A substantial correction in the coronal plane was achieved and maintained in
these patients.
Although immobilization of a vertebral spinal unit may be effective
in some circumstances, appropriate patient selection, choice of
the optimum disc spacer, and decisions regarding levels of treatment
are all current topics of discussion in the field of lumbar degenerative
disc disease. Other contemporary topics of interest include the
use of minimally invasive therapeutic procedures such as intradiscal
electrothermal therapy for the treatment of internal disc derangement,
lumbar artificial disc replacement, and gene therapy to promote
bone fusion and intervertebral disc regeneration.
Interbody Fusion
Many clinicians believe that interbody fusion is the most reliable
technique available for relieving disabling pain due to lumbar internal
disc derangement or degenerative disc disease in appropriately selected
patients who have had failure of conservative treatment. This may
be accomplished by anterior, posterior, or transforaminal lumbar
interbody fusion.
Interbody fusion is biomechanically superior to traditional posterolateral
intertransverse-process arthrodesis in providing axial support,
and the number of such procedures has increased substantially. To
date, however, there have been no controlled, prospective, randomized
class-I trials, and there have been few unbiased prospective class-II
trials for evaluating the efficacy of either cylindrical or impacted
(trapezoidal or ramped) devices used to facilitate these fusions.
Cages of all forms are currently being used for the treatment of
degenerative disease, trauma, and deformity, with good rates of
success. Shaffrey discussed the clinical misapplication of these
devices as well as their high failure rates when they are used over
multiple segments or in the presence of major circumferential instability5. Reasons for interbody cage failure,
which have been analyzed in several studies, include: (1) the use
of undersized cages, leading to inadequate vertebral distraction;
(2) cage subsidence in patients with poor bone quality; (3) failure
of fusion in patients with segmental instability (spondylolisthesis),
poor implant-host bone contact, or multilevel arthrodesis; (4) use
of anterior stand-alone cages in tall disc spaces; and (5) technical
errors, such as improper cage placement, incorrect cage size, excessive
end-plate and facet-joint removal, and lack of adequate amounts
of bone graft.
Some complications related to cage application are approach-specific.
Complications related to the anterior approach include retrograde
ejaculation (reported in 4% to 8% of male patients),
visceral and vascular injury, and the potential for an incisional
hernia. Complications related to the posterior approach include
paraspinal muscle denervation, dural laceration, and persistent
leg pain due to neural stretch injuries.
Zdeblick and David compared laparoscopic and mini-open anterior
approaches for fusion procedures involving the fourth and fifth
lumbar vertebrae; threaded cylindrical metallic cages were used
in both approaches. They found no substantial differences between
the two groups in terms of operating time, blood loss, or length
of hospital stay. The rate of complications was substantially higher
in the group treated with the laparoscopic approach than it was
in the group treated with the mini-open approach (20% compared
with 4%). Zdeblick and David concluded that there was no
compelling advantage that would warrant use of the laparoscopic
approach for fusion of the fourth and fifth lumbar vertebrae, and
the senior author (Zdeblick) now uses the mini-open approach
exclusively at this level. Regan analyzed the rate of complications in
127 consecutive patients who had undergone laparoscopic anterior
lumbar interbody fusion. He reported four cage-related failures
that led to reoperation because of symptomatic nerve-root compression,
four cases of retrograde ejaculation (a prevalence of 4.8% among
male patients), and two conversions to open procedures because of
excessive bleeding. There were seventeen major complications (a
prevalence of 13.4%), mostly in the first forty patients.
Posterior lumbar interbody fusion allows decompression of neural
structures as well as interbody fusion and segmental stabilization
with either transpedicular or transfacet instrumentation, all through
one incision. The theoretical advantages of anterior lumbar interbody
fusion include better anterior-column support due to maximization
of the end-plate contact surface, better direct visualization, improved
restoration of lordosis, lack of trauma to the posterior paraspinal musculature,
and technical ease. To date, there are no clinical data on humans
that would allow a comparison of the efficacy of various cage designs
or of different approaches to their application.
Transforaminal lumbar interbody fusion is a newer alternative to
current techniques of posterior lumbar interbody fusion. It involves
a more lateralized posterolateral entry to the interbody space through
resection of the superior and inferior articular processes of the
involved level. There is concern about the overall stability of
the construct because the procedure involves removal of both facet
joints for bilateral cage placement6.
Genetic Therapy and Spinal Applications
Several products have emerged in the last two years for use as bone-graft
extenders. Demineralized bone matrices have demonstrated osteoinductivity
in animal models. Several osteoconductive matrices (allograft cancellous
chips, cortical spacers, ceramic graft extenders, and coral) have
been used with varying success in human clinical series.
Genetic tissue-engineering has led to the development of two human
recombinant bone morphogenetic proteins, osteogenic protein-1 (OP-1)
(rhBMP-7) and recombinant human bone morphogenetic protein-2
(rhBMP-2). Grauer et al., using a rabbit model of intertransverse-process
lumbar fusion, compared three different groups: autograft alone,
carrier alone, and carrier with osteogenic protein-1. At
five weeks, five of the eight rabbits in the autograft group, none
of the eight rabbits in the carrier-only group, and all eight rabbits
in the osteogenic protein-1 group had a solid fusion on
manual palpation. Biomechanical results supported the presence of
a solid fusion, which correlated with the radiographic findings. Histological
testing demonstrated that the fusion masses in the animals that
had been treated with autograft were composed primarily of fibrocartilage
while those in the animals that had been treated with osteogenic
protein-1 demonstrated predominantly maturing bone7.
Boden et al. reported the results of a prospective, randomized, controlled
clinical trial of patients who had been treated with an interbody
fusion cage filled with rhBMP-28.
Fourteen patients with single-level lumbar degenerative disc disease
that had been refractory to prolonged conservative treatment randomly
underwent a lumbar interbody arthrodesis with use of a tapered cylindrical
threaded cage filled with either rhBMP-2 on a collagen
sponge (eleven patients) or autologous bone graft (three controls).
The patients and controls were evaluated at six, twelve, and twenty-four
months postoperatively with use of radiographs interpreted
by three independent radiologists and with the Oswestry Low Back Pain
Disability Questionnaire. All of the patients who had been treated
with rhBMP-2 had a solid fusion compared with two of the
three controls. The rhBMP-2 group had improved scores on
the questionnaire at three months, but both groups had similar scores
at twelve months. Boden et al. concluded that there was consistent
and unequivocal osteoinduction by a recombinant growth factor in
this fusion model.
Investigators have cultured cells from both the anulus fibrosus and
the nucleus pulposus in vitro. Osteogenic protein-1
has stimulated these cells to grow and to produce cell-associated
matrix through exogenous stimulation. The purpose of this research
is to alter the disc-degeneration cascade in order to decrease associated
pain syndromes that occur with the aging process. Matsumoto et al.
reported the results of gene therapy with use of a viral (adenovirus) vector
to introduce genes responsible for the production of specific growth
factors into the intervertebral disc9.
These growth factors can stimulate proteoglycan synthesis and may
soon be able to be produced in vivo through these
genetic modification techniques.
Intradiscal Electrothermal Therapy
Saal and Saal prospectively evaluated sixty-two patients who underwent
intradiscal electrothermal therapy for chronic discogenic low-back
pain10. The patients had had the
pain for an average of sixty months and were followed for an average
of sixteen months postoperatively. Various patient questionnaires
demonstrated that 81% of the patients had a decrease in
pain while 19% had no improvement. Karasek and Bogduk also
reported a dramatic reduction in pain in patients with internal
disc derangement who were treated with this procedure11. Wetzel et al. reported only a 6.9% failure
rate in their patient population. The exact mechanism resulting
in pain relief is unknown. A recent study of human cadavera indicated
that the thermal probe used in intradiscal electrothermal therapy produced
a maximum temperature of 64.0°C within 1 to 2 mm of the catheter
and that less than 5% of the discal surface area achieved
temperatures sufficient for collagen denaturation.
Lumbar Intervertebral Disc Replacement
Batterjee et al. reported on seventeen patients who had received
a Prosthetic Disc Nucleus (PDN) for degenerative disc disease after
conservative treatment had failed. This implant, which is composed
of a hydrogel core encased in a high-molecular-weight
polyethylene jacket, has been shown to mimic the shrinking and swelling
behavior of the healthy disc during loading and unloading of the
spine. Batterjee et al. found that, after two years of follow-up,
most patients had a decrease in low back pain and an increase in
range of motion as evidenced by improvements in the scores on the
Oswestry Low Back Pain Disability Questionnaire and the visual analog scale.
Kotani et al. described an artificial intervertebral disc prosthesis
consisting of a triaxial three-dimensional fabric combined with
ultra-high-molecular-weight polyethylene fiber with spray-coated
bioactive ceramics on the surface. Histological examination in a
sheep model demonstrated biological bonding of the three-dimensional
fabric discs to the vertebral end plates, and biomechanical testing
showed preservation of segmental spinal mobility. Marnay et al.
reported the eight-to-ten-year results following disc replacement
with an implant composed of Plasmapore-covered keeled titanium
plates with an inner concave polyethylene dome. The prosthesis was placed
at three levels in three patients, at two levels in twenty patients,
and at one level in twenty-one patients. All patients had had at
least ten years of low-back pain that had been refractory to conservative
treatment. Overall, thirty-four (77%) of the patients had
an excellent or good result and four (9%) had a poor result.
At the time of the last examination, none of the prostheses had
been removed, their mobility remained functional without bone resorption,
and good integration was visualized on computed tomography scanning.
Spinal Trauma
Wood et al. performed a very well-done prospective, randomized
study comparing operative with nonoperative treatment of "stable" thoracolumbar
burst fractures without neurologic deficit. Fifty-five consecutive
patients were enrolled over a five-year period, and the
average duration of follow-up was forty-seven months. No
substantial long-term advantage was found to be associated
with operative treatment of these fractures.
Summary
Recent major advances may ultimately change the way that we treat
lumbar degenerative disease. These advances have included the application
of minimally invasive heating catheters to alter the collagen matrix
of the disc, newer interbody fusion techniques, intervertebral disc
replacement, and tissue-engineering designed to develop bone-graft
substitutes that hold the potential for improved fusion rates as
well as techniques leading to discal repair and regeneration. As
with all innovations, careful, prospective, long-term trials
need to be undertaken in order to understand the benefits and shortcomings
associated with each.
In the past decade, spinal cord injury research has focused on the
understanding of posttraumatic cellular events, the development
of neuroprotective agents, mechanical neural repair by nerve-grafting,
and repair through the use of molecular technology. Although the
early results are promising, the cure for spinal cord injury appears
to be years away. The purpose of this section is to review recent
advances in the understanding of the pathophysiology of spinal cord
injury and the effectiveness of novel neuroprotective agents.
Pathophysiology of Injury
The spinal cord may sustain several stages of injury. The first, or
primary, injury is the direct trauma that usually is due to impingement
of bone and disc fragments or to stretching by distraction or hyperflexion.
The degree of neuronal injury is directly related to the transferred
kinetic injury. Histologic examination immediately following injury
often shows only small petechial hemorrhage and little disruption
of axonal fibers. However, over the next six to twenty-four hours,
progressive necrosis occurs in the zone of injury of the gray matter
and then in the white axonal tracts. This late necrosis has been
called the secondary injury. For the past two decades, most of the
research on spinal cord injury has focused on understanding these
mechanisms and devising treatments for the secondary injury. Diminished
vascular perfusion, alterations in biomechanics, adverse biochemical
cascades, and molecular and cellular events are all components of
the secondary injury.
Following spinal cord injury, there is failure of axonal repolarization
due to alteration of sodium, potassium, and calcium channels. Intracellular
and intramitochondrial Ca++ accumulates,
thereby uncoupling oxidative phosphorylation. When adenosine
triphosphate production fails, cellular death ensues. Intracellular
Ca++ activates phospholipase A2, causing breakdown
of myelin and of the neuronal cell membrane. Oxygen free radicals
are formed, leading to destructive lipid peroxidation reactions.
Cellular inflammation is initiated, leading to the release
of destructive enzymes. Inadequate tissue perfusion from low systemic
blood pressure, loss of spinal cord autoregulation, and intramedullary
vascular injury worsen these cellular events.
Pharmacologic Interventions
The National Acute Spinal Cord Injury Studies II and III, in which
high-dose methylprednisolone was investigated for use as an antioxidant,
demonstrated a modest improvement in neurologic recovery when this
agent was administered within eight hours after injury. Hurlbert
reanalyzed the data from these two studies and did not find a significant
relationship between recovery and use of methylprednisolone at the
one-year follow-up interval12.
Even worse, there was a sixfold increase in pulmonary deaths in
patients who had received methylprednisolone for forty-eight hours
compared with those who had received it for twenty-four hours. Coleman
et al. reviewed the data from the same studies and drew similar
conclusions: that the statistical methods that had been used were
questionable, that the benefit of methylprednisolone was minimal
or nonexistent, and that a reappraisal of methylprednisolone
as a standard of care is warranted13.
Matsumoto et al. reported on the complications of high-dose methylprednisolone
in a randomized, double-blind study14.
Forty-six patients with an acute injury (an injury sustained less
than eight hours before presentation) were treated with either methylprednisolone
(twenty-three patients) or a placebo (twenty-three patients). Pulmonary
complications occurred in eight of the patients who had been treated
with methylprednisolone compared with only one of the patients who
had received the placebo. Similarly, gastrointestinal complications
occurred in four of the patients who had been treated with methylprednisolone compared
with none of the patients who had received the placebo. These findings
were similar to those reported in the National Acute Spinal Cord Injury
Studies II and III, but they were minimized in those reports.
Traumatic brain injury or ischemia results in the release of excitatory
amino acids such as glutamate and aspartate. Overstimulation of
glutamate receptors by excitatory amino acids can initiate processes
that ultimately lead to neuronal death. This process is termed excitotoxicity.
Antagonists to the N-methyl-d-aspartate
receptor, such as gacyclidine, have shown promise as neuroprotective
agents in closed head injuries. Both Gaviria and Feldblum demonstrated
a positive time-dependent, dose-dependent relationship
between use of gacyclidine and attenuation of spinal cord injury.
These studies highlight the importance of understanding the cellular mechanisms
of secondary injury and developing strategies that address these
adverse processes.
Melatonin is the hormone produced by the pineal gland. It is
a powerful free oxygen radical scavenger that penetrates intracellularly
and has an important role in protecting intracellular organelles,
including the nucleus. Fujimoto demonstrated a substantial neuroprotective
effect when melatonin was administered from zero to four hours after
spinal cord injury in a rat model. Kaptanoglu compared melatonin
with methylprednisolone, also in a rat model, and found decreased
free radical formation to baseline in both groups. However, ultrastructural changes
were more significantly limited by melatonin. Other antioxidants,
such as EPC-K1, a phosphate-diester linkage of vitamins
E and C, have also been shown to attenuate spinal cord injury.
Spinal Cord-Cooling
Hypothermia and spinal cord-cooling have long been proposed as
neuroprotective methods. Diminished temperature is theorized to
decrease the inflammatory response of the injured area. With less
polymorphonuclear leukocyte accumulation, there is decreased activation
of destructive enzymes. Other protective mechanisms of hypothermia
include diminished release of excitatory amino acids, decreased
free radical formation, and improved energy metabolism. Cord-cooling applied
locally by laminectomy has fallen out of favor because
of the instability created by the laminectomy, the difficulty in
temperature control, and poor outcomes. Systemic hypothermia has
been utilized successfully as a tissue-protective measure
during cardiac and neurosurgical procedures. Several studies have
been performed to evaluate its use in patients with spinal cord
injury.
Chatzipanteli evaluated the effect of mild central hypothermia (32°C)
on injured spinal cords and found a decrease in polymorphonuclear
leukocytes and enzymatic activity. Yu, using a rat contusion model,
found that epidural temperature decreased with mild systemic hypothermia
(21° to 22°C). In addition, the rats that were treated with hypothermia
had a better neurologic outcome and fewer histologic changes following
injury than did the controls.
Dimar et al. reported the results of local spinal cord-cooling
in a rat model. Local hypothermia to 19°C was applied for two hours
with use of a specially designed frame15.
Animals with a moderate incomplete injury (but not those with a
severe cord injury) showed a significant improvement compared with
controls15.
Summary
Research on spinal cord injury is rapidly increasing our understanding
of the cellular and biochemical effects leading to secondary injury.
So-called designer medications that affect individual cell-membrane
receptors or ion-exchange channels and prevent cellular events such
as apoptosis appear to be neuroprotective. Mild systemic hypothermia
is also a promising therapy. However, these strategies are only
useful around the time of injury. Prevention of these injuries has
received surprisingly little emphasis in the orthopaedic literature
and is clearly the best strategy. For patients with permanent deficits, regeneration
or repair—"The Cure"—is higly
anticipated. Unfortunately, these investigations are proceeding
slowly, but they do show promise at this time.
The annual meeting of the American Spinal Injury Association
will be held on May 3 through 6, 2002, at the Hyatt Regency Hotel
in Vancouver, British Columbia, Canada. It will be presented in
conjunction (for the first time) with the annual meeting of the
International Medical Society of Paraplegia.
The 2002 annual meeting of the Cervical Spine Research Society
will be held at the Fountainebleau Hilton, Miami Beach, Florida,
on December 5, 6, and 7. There will not be an Instructional Course
for this meeting.
The annual meeting of the North American Spine Society will be
held on October 30 through November 2, 2002, in Montreal, Quebec,
Canada. The Meeting of the Americas II, a combined meeting with
the North American Spine Society, the Latin American Spine Society,
and the Brazilian Spine Society, will be held in the spring of 2002
(location to be determined).
The annual meeting of the Scoliosis Research Society will be held
on September 19, 20, and 21, 2002, in Seattle, Washington. Fundamentals
of Spine Deformity—Part 2 will be held on September 18
in Seattle. The 2002 International Meeting on Advanced Spine Techniques
will be announced later this year.
The Federation of Spine Associations will present the spine program
at Specialty Day on February 16, 2002, during the annual meeting
of the American Academy of Orthopaedic Surgeons in Dallas, Texas.
Apfelbaum RI, Kriskovich
MD,Haller JR. On the incidence, cause, and prevention of recurrent laryngeal nerve
palsies during anterior cervical spine surgery. Spine,2000;25: 2906-12. 252906
2000
[PubMed]
Panjabi MM, Shin EK, Chen NC,Wang
JL. Internal morphology of human cervical pedicles. Spine,2000;25: 1197-205. 251197
2000
[PubMed]
Hadley Miller N. Spine update: genetics of familial idiopathic scoliosis. Spine,2000;25: 2416-8. 252416
2000
[PubMed]
Wilson-Holden TJ, Padberg
AM, Parkinson JD, Bridwell KH, Lenke LG,Bassett GS. A prospective comparison of neurogenic mixed evoked potential
stimulation methods: utility of epidural elicitation during posterior
spinal surgery. Spine,2000;25: 2364-71. 252364
2000
[PubMed]
Shaffrey CI. Indications for
threaded interbody devices. Read at the Annual Meeting of the Federation
of Spine Associations; 2001 Mar 3; San Francisco, CA.
Savas PEHarris BMHilibrand ASPelligrino
AVaccaro ARAlbert TJSiegler S. Transforaminal lumbar interbody
fusion: the effect of various instrumentation techniques. Read at
the Annual Meeting of the North American Spine Society; 2000 Oct
25-28; New Orleans, LA.
Grauer JN, Patel TC, Erulkar
JS, Troiano NW, Panjabi MM,Friedlaender GE. Evaluation of OP-1 as a graft substitute for
intertransverse process lumbar fusion. Spine,2001;26: 127-33. 26127
2001
[PubMed]
Boden SD, Zdeblick TA, Sandhu
HS,Heim SE. The use of rhBMP-2 in interbody fusion cages.
Definitive evidence of osteoinduction in humans: a preliminary report. Spine,2000;25: 376-81. 25376
2000
[PubMed]
Matsumoto TMasuda KAn HSAndersson
GBJRueger DCNatick MAThonar EJ. Tissue engineered intervertebral
disc: enhancement of formation with osteogenic protein-1.
Read at the Annual Meeting of the North American Spine Society;
2000 Oct 25-28; New OrleansLA.
Saal JA,Saal JS. Intradiscal electrothermal treatment for chronic discogenic low
back pain: a prospective outcome study with minimum 1-year
follow-up. Spine,2000;25: 2622-7. 252622
2000
[PubMed]
Karasek M,Bogduk N. Twelve-month follow-up of a controlled
trial of intradiscal thermal anuloplasty for back pain due to internal
disc disruption. Spine,2000;25: 2601-7. 252601
2000
[PubMed]
Hurlbert RJ. Methylprednisolone for acute spinal cord injury: an inappropriate
standard of care. J Neurosurg,2000;93: 1-7. 931
2000
[PubMed]
Coleman WP, Benzel D,Cahill
DWDucker TGeisler FGreen BGropper MRGoffin JMadsen PW 3rdMaiman
DJOndra SLRosner MSasso RCTrost GRZeidman S. A critical appraisal of the reporting of the National
Acute Spinal Cord Injury Studies (II and III) of methylprednisolone
in acute spinal cord injury. J Spinal Disord,2000;13: 185-99. 13185
2000
[PubMed]
Matsumoto T, Tamaki T, Kawakami
M, Yoshida M, Ando M,Yamada H. Early complications of high-dose methylprednisolone
sodium succinate treatment in the follow-up of
acute cervical spinal cord injury. Spine.
2001;26: 426-30. 26426
Spine.
2001
Dimar JR 2nd, Shields CB, Zhang
YP, Burke DA, Raque GH,Glassman SD. The role of directly applied hypothermia in spinal cord
injury. Spine.
2000;25: 2294-302. 252294
Spine.
2000