Eric J. Woodard

Development and implementation of intraoperative magnetic resonance imaging and its neurosurgical applications.

OBJECTIVE We describe the development and implementation of a new open configuration magnetic resonance imaging (MRI) system, with which neurosurgical procedures can be performed using image guidance. Our initial neurosurgical experience consists of 140 cases, including 63 stereotactic biopsies, 16 cyst drainages, 55 craniotomies, 3 thermal ablations, and 3 laminectomies. The surgical advantages derived from this new modality are presented. METHODS The 0.5-T intraoperative MRI system (SIGNA SP, Boston, MA), developed by General Electric Medical Systems in collaboration with the Brigham and Womens Hospital, has a vertical gap within its magnet, providing the physical space for surgery. Images are viewed on monitors located within this gap and can also be acquired in conjunction with optical tracking of surgical instruments, establishing accurate intraoperative correlations between instrument position and anatomic structures. RESULTS A wide range of standard neurosurgical procedures can be performed using intraoperative MRI. The images obtained are clear and provide accurate and immediate information to use in the planning and assessment of the progress of the surgery. CONCLUSION Intraoperative MRI allows lesions to be precisely localized and targeted, and the progress of a procedure can be immediately evaluated. The constantly updated images help to eliminate errors that can arise during frame-based and frameless stereotactic surgery when anatomic structures alter their position because of shifting or displacement of brain parenchyma but are correlated with images obtained preoperatively. Intraoperative MRI is particularly helpful in determining tumor margins, optimizing surgical approaches, achieving complete resection of intracerebral lesions, and monitoring potential intraoperative complications.

Efficacy and safety of surgical decompression in patients with cervical spondylotic myelopathy: results of the AOSpine North America prospective multi-center study.

BACKGROUND Cervical spondylotic myelopathy is the leading cause of spinal cord dysfunction worldwide. The objective of this study was to evaluate the impact of surgical decompression on functional, quality-of-life, and disability outcomes at one year after surgery in a large cohort of patients with this condition. METHODS Adult patients with symptomatic cervical spondylotic myelopathy and magnetic resonance imaging evidence of spinal cord compression were enrolled at twelve North American centers from 2005 to 2007. At enrollment, the myelopathy was categorized as mild (modified Japanese Orthopaedic Association [mJOA] score ≥ 15), moderate (mJOA = 12 to 14), or severe (mJOA < 12). Patients were followed prospectively for one year, at which point the outcomes of interest included the mJOA score, Nurick grade, Neck Disability Index (NDI), and Short Form-36 version 2 (SF-36v2). All outcomes at one year were compared with the preoperative values with use of univariate paired statistics. Outcomes were also compared among the severity classes with use of one-way analysis of variance. Finally, a multivariate analysis that adjusted for baseline differences among the severity groups was performed. Treatment-related complication data were collected and the overall complication rate was calculated. RESULTS Eighty-five (30.6%) of the 278 enrolled patients had mild cervical spondylotic myelopathy, 110 (39.6%) had moderate disease, and 83 (29.9%) had severe disease preoperatively. One-year follow-up data were available for 222 (85.4%) of 260 patients. There was a significant improvement from baseline to one year postoperatively (p < 0.05) in the mJOA score, Nurick grade, NDI score, and all SF-36v2 health dimensions (including the mental and physical health composite scores) except general health. With the exception of the change in the mJOA, the degree of improvement did not depend on the severity of the preoperative symptoms. These results remained unchanged after adjusting for relevant confounders in the multivariate analysis. Fifty-two patients experienced complications (prevalence, 18.7%), with no significant differences among the severity groups. CONCLUSIONS Surgical decompression for the treatment of cervical spondylotic myelopathy was associated with improvement in functional, disability-related, and quality-of-life outcomes at one year of follow-up for all disease severity categories. Furthermore, complication rates observed in the study were commensurate with those in previously reported cervical spondylotic myelopathy series.

Perioperative and delayed complications associated with the surgical treatment of cervical spondylotic myelopathy based on 302 patients from the AOSpine North America Cervical Spondylotic Myelopathy Study

OBJECT Rates of complications associated with the surgical treatment of cervical spondylotic myelopathy (CSM) are not clear. Appreciating these risks is important for patient counseling and quality improvement. The authors sought to assess the rates of and risk factors associated with perioperative and delayed complications associated with the surgical treatment of CSM. METHODS Data from the AOSpine North America Cervical Spondylotic Myelopathy Study, a prospective, multicenter study, were analyzed. Outcomes data, including adverse events, were collected in a standardized manner and externally monitored. Rates of perioperative complications (within 30 days of surgery) and delayed complications (31 days to 2 years following surgery) were tabulated and stratified based on clinical factors. RESULTS The study enrolled 302 patients (mean age 57 years, range 29-86) years. Of 332 reported adverse events, 73 were classified as perioperative complications (25 major and 48 minor) in 47 patients (overall perioperative complication rate of 15.6%). The most common perioperative complications included minor cardiopulmonary events (3.0%), dysphagia (3.0%), and superficial wound infection (2.3%). Perioperative worsening of myelopathy was reported in 4 patients (1.3%). Based on 275 patients who completed 2 years of follow-up, there were 14 delayed complications (8 minor, 6 major) in 12 patients, for an overall delayed complication rate of 4.4%. Of patients treated with anterior-only (n = 176), posterior-only (n = 107), and combined anterior-posterior (n = 19) procedures, 11%, 19%, and 37%, respectively, had 1 or more perioperative complications. Compared with anterior-only approaches, posterior-only approaches had a higher rate of wound infection (0.6% vs 4.7%, p = 0.030). Dysphagia was more common with combined anterior-posterior procedures (21.1%) compared with anterior-only procedures (2.3%) or posterior-only procedures (0.9%) (p < 0.001). The incidence of C-5 radiculopathy was not associated with the surgical approach (p = 0.8). The occurrence of perioperative complications was associated with increased age (p = 0.006), combined anterior-posterior procedures (p = 0.016), increased operative time (p = 0.009), and increased operative blood loss (p = 0.005), but it was not associated with comorbidity score, body mass index, modified Japanese Orthopaedic Association score, smoking status, anterior-only versus posterior-only approach, or specific procedures. Multivariate analysis of factors associated with minor or major complications identified age (OR 1.029, 95% CI 1.002-1.057, p = 0.035) and operative time (OR 1.005, 95% CI 1.002-1.008, p = 0.001). Multivariate analysis of factors associated with major complications identified age (OR 1.054, 95% CI 1.015-1.094, p = 0.006) and combined anterior-posterior procedures (OR 5.297, 95% CI 1.626-17.256, p = 0.006). CONCLUSIONS For the surgical treatment of CSM, the vast majority of complications were treatable and without long-term impact. Multivariate factors associated with an increased risk of complications include greater age, increased operative time, and use of combined anterior-posterior procedures.

Stretch-associated injury in cervical spondylotic myelopathy: new concept and review.

THE SIMPLE PATHOANATOMIC concept that a narrowed spinal canal causes compression of the enclosed cord, leading to local tissue ischemia, injury, and neurological impairment, fails to explain the entire spectrum of clinical findings observed in cervical spondylotic myelopathy. A growing body of evidence indicates that spondylotic narrowing of the spinal canal and abnormal or excessive motion of the cervical spine results in increased strain and shear forces that cause localized axonal injury within the spinal cord.During normal motion, significant axial strains occur in the cervical spinal cord. At the cervicothoracic junction, where flexion is greatest, the spinal cord stretches 24% of its length. This causes local spinal cord strain. In the presence of pathological displacement, strain can exceed the material properties of the spinal cord and cause transient or permanent neurological injury.Stretch-associated injury is now widely accepted as the principal etiological factor of myelopathy in experimental models of neural injury, tethered cord syndrome, and diffuse axonal injury. Axonal injury reproducibly occurs at sites of maximal tensile loading in a well-defined sequence of intracellular events: myelin stretch injury, altered axolemmal permeability, calcium entry, cytoskeletal collapse, compaction of neurofilaments and microtubules, disruption of anterograde axonal transport, accumulation of organelles, axon retraction bulb formation, and secondary axotomy. Stretch and shear forces generated within the spinal cord seem to be important factors in the pathogenesis of cervical spondylotic myelopathy.

An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate.

Clinically available injectable hydrogels face technical challenges associated with swelling after injection and toxicity from unreacted constituents that impede their performance as surgical biomaterials. To overcome these challenges, we developed a system where chemical gelation was controlled by a conjugate Michael addition between thiol and acrylate in aqueous media, with 97% monomer conversion and 6 wt.% sol fraction. The hydrogel exhibited syneresis on equilibration, reducing to 59.7% of its initial volume. It had mechanical properties similar to soft human tissue with an elastic modulus of 189.8 kPa. Furthermore, a mesh size of 6.9 nm resulted in sustained release of methylprednisolone sodium succinate with a loading efficiency of 2 mg/mL. Functionalization with 50 μg/mL of an oligolysine peptide resulted in attachment of freshly isolated murine mesenchymal stem cells. The rational design of the physical, chemical and biological properties of the hydrogel makes it a potentially promising candidate for injectable applications.

Anterior versus posterior surgical approaches to treat cervical spondylotic myelopathy: Outcomes of the prospective multicenter AOSpine north America CSM study in 264 patients

Study Design. A prospective observational multicenter study. Objective. To help solve the debate regarding whether the anterior or posterior surgical approach is optimal for patients with cervical spondylotic myelopathy (CSM). Summary of Background Data. The optimal surgical approach to treat CSM remains debated with varying opinions favoring anterior versus posterior surgical approaches. We present an analysis of a prospective observational multicenter study examining outcomes of surgical treatment for CSM. Methods. A total of 278 subjects from 12 sites in North America received anterior/posterior or combined surgery at the discretion of the surgeon. This study focused on subjects who had either anterior or posterior surgery (n = 264, follow-up rate, 87%). Outcome measures included the modified Japanese Orthopedic Assessment scale, the Nurick scale, the Neck Disability Index, and the Short-Form 36 (SF-36) Health Survey version 2 Physical and Mental Component Scores. Results. One hundred and sixty-nine patients were treated anteriorly and 95 underwent posterior surgery. Anterior surgical cases were younger and had less severe myelopathy as assessed by mJOA and Nurick scores. There were no baseline differences in Neck Disability Index or SF-36 between the anterior and posterior cases. Improvement in the mJOA was significantly lower in the anterior group than posterior group (2.47 vs. 3.62, respectively, P < 0.01), although the groups started at different levels of baseline impairment. The extent of improvement in the Nurick Scale, Neck Disability Index, SF-36 version 2 Physical Component Score, and SF-36 version 2 Mental Component Score did not differ between the groups. Conclusion. Patients with CSM show significant improvements in several health-related outcome measures with either anterior or posterior surgery. Importantly, patients treated with anterior techniques were younger, with less severe impairment and more focal pathology. We demonstrate for the first time that, when patient and disease factors are controlled for, anterior and posterior surgical techniques have equivalent efficacy in the treatment of CSM. Level of Evidence: 3

Risk factors for false positive transcranial motor evoked potential monitoring alerts during surgical treatment of cervical myelopathy.

Study Design. Retrospective consecutive series review. Objective. To examine performance of transcranial motor-evoked potential (TcMEP) monitoring in patients undergoing surgery for cervical myelopathy and potential risk factors for false positive alerts. Summary of Background Data. Although use of TcMEP monitoring has been increasing and has been specifically recommended in patients with cervical myelopathy, rates and risk factors for false positive alerts have not been established. Methods. Intraoperative neuromonitoring data for 52 consecutive patients undergoing surgery for cervical myelopathy were reviewed. All major TcMEP alerts were identified. Comprehensive demographic and clinical data, preoperative imaging studies, operative, and anesthesia records were reviewed. Results. Six of 52 patients (12%) experienced a major TcMEP alert consisting of sustained >80% loss of amplitude. There were no somatosensory-evoked potential (SSEP)-related alerts. In 2 cases, an intraoperative wake-up test was negative and in 3 cases, surgery was completed without a wake-up test and without recovery of TcMEP signals. No new postoperative neurologic deficits were observed in these patients. One patient with new postoperative weakness was correctly predicted by loss of TcMEP signals. No new deficit was observed in the remaining 46 patients. Statistical analysis revealed significantly higher body mass index (28.8 vs. 35.0; P = 0.032) and length of surgery (191 vs. 283 minutes; P = 0.019) in patients with false positive alerts. Conclusion. In this series of cervical myelopathy patients, sensitivity and specificity of TcMEP for detection of clinically significant intraoperative cord injury were 100% and 90%, respectively. Sensitivity and specificity of SSEP were 0% and 100%, respectively. The positive predictive value of a TcMEP alert was 17%. Possible risk factors for false positive TcMEP alerts include obesity and increased length of surgery. This study supports superior sensitivity of TcMEP compared with SSEP monitoring but identifies a relatively high false positive rate even in a selected high-risk cervical myelopathy population when this modality is applied in practice.

Blockade of Peroxynitrite‐Induced Neural Stem Cell Death in the Acutely Injured Spinal Cord by Drug‐Releasing Polymer

Therapeutic impact of neural stem cells (NSCs) for acute spinal cord injury (SCI) has been limited by the rapid loss of donor cells. Neuroinflammation is likely the cause. As there are close temporal‐spatial correlations between the inducible nitric oxide (NO) synthase expression and the donor NSC death after neurotrauma, we reasoned that NO‐associated radical species might be the inflammatory effectors which eliminate NSC grafts and kill host neurons. To test this hypothesis, human NSCs (hNSCs: 5 × 104 to 2 × 106 per milliliter) were treated in vitro with “plain” medium, 20 μM glutamate, or donors of NO and peroxynitrite (ONOO−; 100 and 400 μM of spermine or DETA NONOate, and SIN‐1, respectively). hNSC apoptosis primarily resulted from SIN‐1 treatment, showing ONOO−‐triggered protein nitration and the activation of p38 MAPK, cytochrome c release, and caspases. Therefore, cell death following post‐SCI (p.i.) NO surge may be mediated through conversion of NO into ONOO−. We subsequently examined such causal relationship in a rat model of dual penetrating SCI using a retrievable design of poly‐lactic‐co‐glycolic acid (PLGA) scaffold seeded with hNSCs that was shielded by drug‐releasing polymer. Besides confirming the ONOO−‐induced cell death signaling, we demonstrated that cotransplantation of PLGA film embedded with ONOO− scavenger, manganese (III) tetrakis (4‐benzoic acid) porphyrin, or uric acid (1 μmol per film), markedly protected hNSCs 24 hours p.i. (total: n = 10). Our findings may provide a bioengineering approach for investigating mechanisms underlying the host microenvironment and donor NSC interaction and help formulate strategies for enhancing graft and host cell survival after SCI. Stem Cells 2009;27:1212–1222

Respiratory Abnormalities Resulting from Midcervical Spinal Cord Injury and their Reversal by Serotonin 1A Agonists in Conscious Rats

Respiratory dysfunction after cervical spinal cord injury (SCI) has not been examined experimentally using conscious animals, although clinical SCI most frequently occurs in midcervical segments. Here, we report a C5 hemicontusion SCI model in rats with abnormalities that emulate human post-SCI pathophysiology, including spontaneous recovery processes. Post-C5 SCI rats demonstrated deficits in minute ventilation (Ve) responses to a 7% CO2 challenge that correlated significantly with lesion severities (no injury or 12.5, 25, or 50 mm × 10 g weight drop; New York University impactor; p < 0.001) and ipsilateral motor neuron loss (p = 0.016). Importantly, C5 SCI resulted in at least 4 weeks of respiratory abnormalities that ultimately recovered afterward. Because serotonin is involved in respiration-related neuroplasticity, we investigated the impact of activating 5-HT1A receptors on post-C5 SCI respiratory dysfunction. Treatment with the 5-HT1A agonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH DPAT) (250 μg/kg, i.p.) restored hypercapnic Ve at 2 and 4 weeks after injury (i.e., ∼39.2% increase vs post-SCI baseline; p ≤ 0.033). Improvements in hypercapnic Ve response after single administration of 8-OH DPAT were dose dependent and lasted for ∼4 h(p ≤ 0.038 and p ≤ 0.024, respectively). Treatment with another 5-HT1A receptor agonist, buspirone (1.5 mg/kg, i.p.), replicated the results, whereas pretreatment with a 5-HT1A-specific antagonist, 4-iodo-N-[2-[4(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (3 mg/kg, i.p.) given 20 min before 8-OH DPAT negated the effect of 8-OH DPAT. These results imply a potential clinical use of 5-HT1A agonists for post-SCI respiratory disorders.

Initial experience with intraoperative magnetic resonance imaging in spine surgery.

Study Design A case series of 12 patients who underwent spine surgery in an intraoperative magnetic resonance imager (IMRI). Objectives To determine the advantages, limitations, and potential applications to spine surgery of the IMRI. Summary of Background Data Existing stereotactic navigational systems are limited because images are obtained before surgery and are not updated to reflect intraoperative changes. In addition, they necessitate manual registration of fiducial landmarks on the patient’s anatomy by the surgeon to the previously obtained image data set, which is a potential source of error. The IMRI eliminates these difficulties by using intraoperative acquisition of MRI images for surgical navigation with the capacity for both image update and image-guided frameless stereotaxy. The IMRI is a novel cryogenless superconducting magnet with an open configuration that allows the surgeon full access to the patient during surgery and intraoperative imaging. Methods T1- and T2-weighted fast spin echo images were obtained for localization, after surgical exposure and after decompression during the course of 12 spine surgeries performed in the IMRI. Results The authors performed a series of 12 procedures in the IMRI that included three lumbar discectomies, three anterior cervical discectomies with allograft fusion, three cervical vertebrectomies with allograft fusion, two cervical foraminotomies, and one decompressive cervical laminectomy. The system provided rapid and accurate localization in all cases. The adequacy of decompression by MRI during surgery was confirmed in 10 of 12 cases. Conclusions The IMRI provided accurate and rapid localization in all cases and confirmed the adequacy of decompression in the majority of cases. Future applications of the IMRI to spine surgery may include intraoperative guidance for resection of spine and spinal cord tumors and trajectory planning for spinal endoscopy or screw fixation.