Spinal cord injury (SCI) is a condition with devastating consequences for the patient, family, and society. Although effective treatments for SCI remain limited, there have been many advances in recent years, which have promise for the future from a clinical translational perspective. This issue of Neurosurgical Focus explores some of the current basic science, preclinical, and clinical research directed towards this goal. Clinical investigations are also discussed with regard to the treatment and management of different types of SCI and of SCI in different populations. The issue concludes with a review of the current, ongoing, and planned clinical trials, providing a glimpse of the promising new therapies being developed for the treatment of SCI.
Michael G. Fehlings and Allyson Tighe
Henry Ahn and Michael G. Fehlings
In this report, the authors suggest evidence-based approaches to minimize the chance of perioperative spinal cord injury (POSCI) and optimize outcome in the event of a POSCI.
A systematic review of the basic science and clinical literature is presented.
Authors of clinical studies have assessed intraoperative monitoring to minimize the chance of POSCI. Furthermore, preoperative factors and intraoperative issues that place patients at increased risk of POSCI have been identified, including developmental stenosis, ankylosing spondylitis, preexisting myelopathy, and severe deformity with spinal cord compromise. However, no studies have assessed methods to optimize outcomes specifically after POSCIs. There are a number of studies focussed on the pathophysiology of SCI and the minimization of secondary damage. These basic science and clinical studies are reviewed, and treatment options outlined in this article.
There are a number of treatment options, including maintenance of mean arterial blood pressure > 80 mm Hg, starting methylprednisolone treatment preoperatively, and multimodality monitoring to help prevent POSCI occurrence, minimize secondary damage, and potentially improve the clinical outcome of after a POSCI. Further prospective cohort studies are needed to delineate incidence rate, current practice patterns for preventing injury and minimizing the clinical consequences of POSCI, factors that may increase the risk of POSCI, and determinants of clinical outcome in the event of a POSCI.
Toshitaka Seki and Michael G. Fehlings
Although posttraumatic syringomyelia (PTS) develops in up to 30% of patients after spinal cord injury (SCI), the pathophysiology of this debilitating complication is incompletely understood. To provide greater insight into the mechanisms of this degenerative sequela of SCI, the authors developed and characterized a novel model of PTS.
The spinal cords of 64 female Wistar rats were injured by 35-g modified aneurysm clip compression at the level of T6–7. Kaolin (5 μl of 500 mg/ml solution) was then injected into the subarachnoid space rostral to the site of the injury to induce inflammatory arachnoiditis in 22 rats. Control groups received SCI alone (in 21 rats), kaolin injection alone (in 15 rats), or laminectomy and durotomy alone without injury (sham surgery in 6 rats).
The combination of SCI and subarachnoid kaolin injection resulted in a significantly greater syrinx formation and perilesional myelomalacia than SCI alone; SCI and kaolin injection significantly attenuated locomotor recovery and exacerbated neuropathic pain (mechanical allodynia) compared with SCI alone. We observed that combined SCI and kaolin injection significantly increased the number of terminal deoxytransferase-mediated deoxyuridine triphosphate nick-end labeled–positive cells at 7 days after injury (p < 0.05 compared with SCI alone) and resulted in a significantly greater extent of astrogliosis and macrophage/microglial-associated inflammation at the lesion (p < 0.05).
The combination of compressive/contusive SCI with induced arachnoiditis results in severe PTS and perilesional myelomalacia, which is associated with enhanced inflammation, astrogliosis, and apoptotic cell death. The development of delayed neurobehavioral deficits and neuropathic pain in this model accurately reflects the key pathological and clinical conditions of PTS in humans.
The safety of percutaneous vertebroplasty and kyphoplasty
Michael G. Fehlings
Michael G. Fehlings and Babak Arvin
In this special edition of Journal of Neurosurgery: Spine, a series of systematic reviews sponsored by the Section on Disorders of the Spine and Peripheral Nerves of the American Association of Neurological Surgeons/Congress of Neurological Surgeons is presented. This collection of comprehensive reviews summarizes the medical evidence related to the surgical management of cervical degenerative disc disease. Several of the key conclusions are discussed in this introduction to the issue:
There is Class II evidence to suggest that the clinical condition remains stable when observed over a 3-year period in patients with mild-to-moderate cervical spondylotic myelopathy (CSM) and age younger than 75 years.
There is consistent Class III evidence that the duration of symptoms, and possibly advancing age, negatively affect outcome in patients with CSM.
There is Class II evidence that somatosensory evoked potentials have prognostic value in patients with CSM. There is Class I evidence to show that electromyographic abnormalities (as well as the presence of radiculopathy) are predictive of the development of myelopathy in minimally symptomatic patients with cervical stenosis and spinal cord compression.
The presence of a low signal on T1-weighted images, high signal on T2-weighted images, and the presence of cord atrophy on preoperative MR images are indicators of a poor outcome in CSM.
There is Class III evidence to show that anterior or posterior surgical approaches that effectively decompress the cervical canal promote short-term improvements in outcome. However, there appears to be a risk of late kyphosis in patients who undergo laminectomy or anterior cervical discectomy alone compared with patients in whom decompression is combined with fusion.
The use of BMP-2 is discouraged for anterior cervical spine surgery based on evidence suggesting that the risks outweigh any potential benefits.
Finally, in patients with symptomatic cervical radiculopathy, arthroplasty achieves outcomes that are equivalent to anterior cervical decompression and fusion, although evidence for superiority is lacking.
Further prospective longitudinal data are required to better define the role and timing of surgical intervention in CSM and to determine the appropriate use of cervical arthroplasty in the management of symptomatic cervical degenerative disc disease.
Michael G. Fehlings
Steven Casha and Michael G. Fehlings
Object. Semiconstrained load-sharing implants for spinal fixation accommodate change in the screw—plate interface as bone grafts shrink. The authors evaluated the clinical and radiological outcome in patients after placement of the Codman anterior cervical plate (ACP) system, which allows change in the screw—plate angle.
Methods. The authors undertook a 10-center prospective study with independent blinded evaluation. All patients underwent cervical fusion and placement of ACPs. Clinical and radiological evaluations were performed at 1, 3, 6, 12, and 24 months. Radiographs were examined for screw angles, construct height, fusion, and screw fracture or displacement.
One hundred ninety-five patients were enrolled. The mean follow-up period was 17 months. At 24 months neurological improvement was demonstrated in 68.7% and pain improvement in 76.6% of the patients. Fusion was successful in 93.8%. Varying degrees (most minor) of hardware-related failure occurred in 10.4% of cases; however, reoperation was required in only four (2.1%). A significant change in screw angles occurred over time (mean 6.4° in caudal screw angle [p < 0.001] and 2.4° in the rostral screw angle [p = 0.003]). These changes plateaued by 6 months. A change in construct height (mean 3.48 mm) occurred by 6 months (p < 0.05).
Conclusions. Based on an independent blinded evaluation, the Codman ACP provides effective fixation with load sharing and is effective in achieving fusion with a 94% success rate. Direct comparison with rigidly locked devices is required to establish definitively the optimal method for anterior cervical fixation.
Gwen Schwartz and Michael G. Fehlings
Object. Persistent activation of voltage-sensitive Na+ channels is associated with cellular toxicity and may contribute to the degeneration of neural tissue following traumatic brain and spinal cord injury (SCI). Pharmacological blockade of these channels can attenuate secondary pathophysiology and reduce functional deficits acutely.
Methods. To determine the therapeutic effects of Na+ channel blockers on long-term tissue sparing and functional neurological recovery after traumatic SCI, the authors injected Wistar rats intraperitoneally with riluzole (5 mg/kg), phenytoin (30 mg/kg), CNS5546A, a novel Na+ channel blocker (15 mg/kg), or vehicle (2-HPβCD; 5 mg/kg) 15 minutes after induction of compressive SCI at C7—T1.
Functional neurological recovery of coordinated hindlimb function and strength, assessed 1 week postinjury and weekly thereafter for 6 weeks, was significantly enhanced in animals treated with riluzole compared with the other treatment groups. Seven weeks postinjury the preservation of residual tissue and integrity of descending axons were determined with digital morphometrical and fluorescent histochemical analysis. All three Na+ channel blockers significantly enhanced residual tissue area at the injury epicenter compared with control. Riluzole significantly reduced tissue loss in rostrocaudal regions surrounding the epicenter, with overall sparing of gray matter and selective sparing of white matter. Also, counts of red nuclei neurons retrogradely labeled with fluorogold introduced caudal to the injury site were significantly increased in the riluzole group.
Conclusions. Systemic Na+ channel blockers, in particular riluzole, can confer significant neuroprotection after in vivo SCI and result in behavioral recovery and sparing of both gray and white matter.
Shah N. Siddiqi and Michael G. Fehlings
✓ Lhermitte-Duclos disease is a rare lesion characterized by enlarged cerebellar folia containing abnormal ganglion cells. This case report describes a 51-year-old woman who was initially misdiagnosed as having adult-onset aqueductal stenosis. There were no abnormal findings on computerized tomography (CT), but subsequent magnetic resonance (MR) imaging showed a midline cerebellar lesion extending to the brain stem. This is a unique case of Lhermitte-Duclos disease arising within the cerebellar vermis. The characteristic feature of an enlarged cerebellar hemisphere is absent on CT scans; thus MR imaging is needed to confirm the diagnosis. If diagnosed late, this generally benign lesion becomes difficult to resect totally and has a poorer prognosis. Only two reports have mentioned the MR imaging characteristics of Lhermitte-Duclos disease; both described only T2-weighted images. This case illustrates the full spectrum of MR imaging features of this disease. Both T1- and T2-weighted studies showed enlarged cerebellar folia within the lesion. The T1-weighted image showed a mixed iso- and hypodense signal and the T2-weighted image a homogeneously increased signal; with gadolinium administration the lesion did not enhance. The latter feature supports the theory that this disease is a hamartoma rather than a tumor.
Michael G. Fehlings and William S. Tucker
✓ A case of a cavernous hemangioma located within Meckel's cave and involving the gasserian ganglion is described in a patient presenting with facial pain and a trigeminal nerve deficit. Although these lesions have been reported to occur in the middle fossa, this is believed to be the first case of such a vascular malformation arising solely from within Meckel's cave.