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Mohammed F. Shamji and Alina Shcharinsky

OBJECT

Failed-back surgery syndrome has been historically used to describe extremity neuropathic pain in lumbar disease despite structurally corrective spinal surgery. It is unclear whether specific preoperative pain characteristics can help determine which patients may be susceptible to such postoperative disabling symptoms.

METHODS

This prospective study analyzed surgical microdiscectomy patients treated for lumbar, degenerative, painful radiculopathy. Clinical parameters included general demographics, preoperative and postoperative clinical examination status, self-reported pain and disability scores, and neuropathic pain scores. The screening tests for neuropathic pain were the Douleur Neuropathique 4 and Leeds Assessment of Neuropathic Symptoms and Signs, with correlation tested for ordinal score and screen positivity. Multiple logistic regression analysis was used to define predictors of postoperative symptomatology.

RESULTS

Twelve percent of the 250 patients with radiculopathy who underwent microdiscectomy experienced persistent postoperative neuropathic pain (PPNP) with only modest, if any, relief of leg pain. The condition was highly associated with abnormal preoperative screen results for neuropathic pain, but not sex, smoking status, or preoperative pain severity (α = 0.05). Good correlation was seen between the 2 screening tests used in this study for both absolute ordinal score (Spearman ρ = 0.84; p < 0.001) and the threshold for terming the patient as having neuropathic pain features (Spearman ρ = 0.48; p < 0.001). Younger age at treatment also correlated with a higher likelihood of developing PPNP (p = 0.03).

CONCLUSIONS

This population exhibited a low overall frequency of PPNP. Higher neuropathic pain screening scores correlated strongly with likelihood of significant postoperative leg pain. Further work is required to develop more accurate prognostication tools for radiculopathy patients undergoing structural spinal surgery.

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Mohammed F. Shamji, Mohammed Bafaquh and Eve Tsai

✓ Ankylosing spondylitis (AS) is a chronic inflammatory disease that can cause significant functional complications by affecting the sacroiliac joints and axial skeleton. Despite a longstanding knowledge about the familial associations of this disease, particularly among patients positive for human leukocyte antigen (HLA)–B27, the fundamental pathogenetic mechanism by which this disease arises in genetically susceptible individuals remains ill defined. Furthermore, the molecular predilection for characteristic articular site involvement remains under ongoing investigation. Current theories about the HLA-B27 association range from the presentation of novel arthritogenic peptides, to abnormal autoimmune stimulation, to anomalous microbial tolerance. The immune effectors of this damage include CD4+, CD8+, and natural killer cells, with marked heterogeneity at different sites. Biomechanical stresses may trigger this disease by exposing the body to previously immune-sequestered autoantigens or by providing a route for bacterial seeding. Environmental triggers such as infection have not been definitively established but may represent a primary pathogenic step in a molecular-mimicry process. In this article, the authors review the current literature on the origin and pathophysiology of AS, focusing on genetic and molecular associations, consequent pathomechanisms, and associated triggers. An improved understanding of the sequence of molecular events that predispose and initiate the onset of this disease will allow for more specific and targeted therapy and better avoidance of the significant side effects of systemic immunomodulation.

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Nardin Samuel, Mohammed F. Shamji and Mark Bernstein

OBJECT

Neurosurgical patients bear a varying degree of anxiety when confronted with having to undergo surgery or even visit with a neurosurgeon in consultation. Previous studies have suggested that patient perceptions can heavily influence the patient-physician encounter. Accordingly, a better understanding of these perceptions can marshal our knowledge regarding strategies for improving patient-physician interactions during such an apprehensive time. The aim of the present study was to qualitatively examine patient values and preferences for a neurosurgeon who participates in extraclinical activities (i.e., a “neurosurgeon+”) and understand the factors that influence these perceptions.

METHODS

Semistructured face-to-face interviews with 47 neurosurgical patients were conducted. Patients were recruited from the Toronto Western Hospital neurosurgery clinics for cranial and spinal conditions. Descriptive summary statistics were used to characterize the study participants. Family members were encouraged to contribute to the interviews. Interviews were audio-recorded, transcribed, and subjected to thematic analysis by using open and axial coding.

RESULTS

Patients generally indicated that they want to feel confident in their neurosurgeon. A number of factors contribute to this confidence, including a strong positive referral from another physician. Patients are inclined to search for information pertaining to the qualifications of neurosurgeons online, and a perception of the neurosurgeon’s adeptness given his or her qualifications is important for patients. Although there were some differences in patient values between those in the cranial and spinal groups, overall, neurosurgical patients tend to positively view their neurosurgeon’s involvement in extraclinical duties.

CONCLUSIONS

This study details the first comprehensive clinical qualitative study of patient perceptions of neurosurgeons and provides a descriptive framework for understanding patient values in this clinical domain.

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Harrison J. Westwick and Mohammed F. Shamji

OBJECT

Most spinal meningiomas are intradural lesions in the thoracic spine that present with both local pain and myelopathy. By using the large prospective Surveillance, Epidemiology, and End Results (SEER) database, the authors studied the incidence of spinal meningiomas and examined demographic and treatment factors predictive of death.

METHODS

Using SEER*Stat software, the authors queried the SEER database for cases of spinal meningioma between 2000 and 2010. From the results, tumor incidence and demographic statistics were computed; incidence was analyzed as a function of tumor location, pathology, age, sex, and malignancy code. Survival was analyzed by using a Cox proportional hazards ratio in SPSS for age, sex, marital status, primary site, size quartile, treatment modality, and malignancy code. In this analysis, significance was set at a p value of 0.05.

RESULTS

The 1709 spinal meningiomas reported in the SEER database represented 30.7% of all primary intradural spinal tumors and 7.9% of all meningiomas. These meningiomas occurred at an age-adjusted incidence of 0.193 (95% CI 0.183–0.202) per 100,000 population and were closely related to sex (337 [19.7%] male patients and 1372 [80.3%] female patients). The Cox hazard function for mortality in males was higher (2.4 [95% CI1.7–3.5]) and statistically significant, despite the lower lesion incidence in males. All-cause survival was lowest in patients older than 80 years. Primary site and treatment modality were not significant predictors of mortality.

CONCLUSIONS

Spinal meningiomas represent a significant fraction of all primary intradural spinal tumors and of all meningiomas. The results of this study establish the association of lesion incidence and survival with sex, with a less frequent incidence in but greater mortality among males.

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Mohammed F. Shamji and Brien G. Benoit

✓Optic pathway gliomas (OPGs) are the most common primary neoplasm of the optic pathway. These lesions usually present in childhood and can arise anywhere along the optic pathway; they occur more frequently in women; and they rarely undergo late progression. Management strategies after the initial diagnosis are controversial, compounded by the different behaviors exhibited by sporadic and syndromic tumors. Neurofibromatosis Type 1 (NF1), with aberrant oncogenic signaling and consequent predisposition to intracranial tumors, is the most common associated syndrome, with nearly 20% of NF1 patients developing OPGs. A comorbid NF1 diagnosis has implications for tumor location with greater predilection for optic nerve involvement, whereas chiasmal and postchiasmal lesions are more frequently seen in sporadic cases. Syndromic OPGs often exhibit more indolent behavior and lower rates of clinical progression, and the majority of these are diagnosed by routine neuroophthalmological screening. When treatment is indicated, however, the molecular abnormalities that constitute this syndrome can limit the available chemotherapy and radiotherapy options because clinicians fear secondary malignancy and cerebrovascular complications. Furthermore, radiotherapy early in life can impair an individual's intellectual development, endocrine function, and physical growth, thereby limiting the role of this modality in the treatment of this childhood lesion. Differential gene expression and histogenesis among sporadic and syndromic OPGs may account for the different tumor behaviors, but studies correlating specific genetic and proteomic changes with patient outcome are pending. Loss of heterozygosity at 10 and 17q are more common among patients with NF1, and Ki67 labeling intensity of 2–3% and low p53 labeling intensity seem prognostic of aggressive tumor behavior. Recent advances in the development of a preclinical mouse model of NF1-associated OPG will permit investigation into improved detection strategies and chemotherapeutic and radiotherapy treatment protocols.

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Daipayan Guha, Robert F. Heary and Mohammed F. Shamji

OBJECT

Decompression without fusion for degenerative lumbar stenosis is an effective treatment for both the pain and disability of neurogenic claudication. Iatrogenic instability following decompression may require further intervention to stabilize the spine. The authors review the incidence of postsurgical instability following lumbar decompression, and assess the impact of surgical technique as well as study design on the incidence of instability.

METHODS

A comprehensive literature search was performed to identify surgical cohorts of patients with degenerative lumbar stenosis, with and without preexisting spondylolisthesis, who were treated with laminectomy or minimally invasive decompression without fusion. Data on patient characteristics, surgical indications and techniques, clinical and radiographic outcomes, and reoperation rates were collected and analyzed.

RESULTS

A systematic review of 24 studies involving 2496 patients was performed, assessing both open laminectomy and minimally invasive bilateral canal enlargement. Postoperative pain and functional outcomes were similar across the various studies, and postoperative radiographie instability was seen in 5.5% of patients. Instability was seen more frequently in patients with preexisting spondylolisthesis (12.6%) and in those treated with open laminectomy (12%). Reoperation for instability was required in 1.8% of all patients, and was higher for patients with preoperative spondylolisthesis (9.3%) and for those treated with open laminectomy (4.1%).

CONCLUSIONS

Instability following lumbar decompression is a common occurrence. This is particularly true if decompression alone is selected as a surgical approach in patients with established spondylolisthesis. This complication may occur less commonly with the use of minimally invasive techniques; however, larger prospective cohort studies are necessary to more thoroughly explore these findings.

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Mohammed F. Shamji, Harrison J. Westwick and Robert F. Heary

OBJECT

Structural spinal surgery yields improvement in pain and disability for selected patients with spinal stenosis, spondylolisthesis, or a herniated intervertebral disc. A significant fraction of patients exhibit persistent postoperative neuropathic pain (PPNP) despite technically appropriate intervention, and such patients can benefit from spinal cord stimulation (SCS) to alleviate suffering. The complication profile of this therapy has not been systematically assessed and, thus, was the goal of this review.

METHODS

A comprehensive literature search was performed to identify prospective cohorts of patients who had PPNP following structurally corrective lumbar spinal surgery and who underwent SCS device implantation. Data about study design, technique of SCS lead introduction, and complications encountered were collected and analyzed. Comparisons of complication incidence were performed between percutaneously and surgically implanted systems, with the level of significance set at 0.05.

RESULTS

Review of 11 studies involving 542 patients formed the basis of this work: 2 randomized controlled trials and 9 prospective cohorts. Percutaneous implants were used in 4 studies and surgical implants were used in 4 studies; in the remainder, the types were undefined. Lead migration occurred in 12% of cases, pain at the site of the implantable pulse generator occurred in 9% of cases, and wound-related complications occurred in 5% of cases; the latter 2 occurred more frequently among surgically implanted devices.

CONCLUSIONS

Spinal cord stimulation can provide for improved pain and suffering and for decreased narcotic medication use among patients with PPNP after lumbar spinal surgery. This study reviewed the prospective studies forming the evidence base for this therapy, to summarize the complications encountered and, thus, best inform patients and clinicians considering its use. There is a significant rate of minor complications, many of which require further surgical intervention to manage, including lead migration or implant infection, although such complications do not directly threaten patient life or function.

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Mohammed F. Shamji, Chad Cook, Sean Tackett, Christopher Brown and Robert E. Isaacs

Object

Cervical spine fusion is performed for various indications in patient populations ranging from young and healthy to aged and frail. Whereas disease pathoanatomy dictates the surgical approach, preoperative neurological status does not necessarily implicate a specific technique. Although one expects anterior decompression to be performed over fewer segments in healthier patients who experience fewer complications and faster recovery, the impact of pre-operative myelopathy on perioperative complications remains unclear. No large-scale study has evaluated rates of common complications for cervical fusion or their association with surgical approach and neurological status.

Methods

Data for 96,773 patients who underwent cervical fusion for degenerative disease between 1988 and 2003 were collected from the Nationwide Inpatient Sample database. Patients were grouped according to surgical approach (anterior versus posterior) and preoperative neurological status (myelopathic versus nonmyelopathic). Multivariate regression was used to evaluate group effects on selected postoperative complications, length of stay, and disposition at the time of hospital discharge. Although this technique can control for the observed covariates, the absence of key information such as the number of fused levels precludes statistical comparison between patients who underwent anterior or posterior approaches.

Results

In this study the authors confirmed that preoperative neurological status impacts perioperative morbidity. For example, patients who were nonmyelopathic and underwent an anterior approach were 7 years younger than the rest of the cohort, and they had a mortality rate of 0.05%. Transfusion was required in 0.34%, and venous thromboembolism occurred in 0.04%. Conversely, these rates were > 13-fold higher in patients with myelopathy who underwent a posterior approach. Furthermore, independent of approach, preoperative myelopathy is highly prognostic of death, pneumonia, transfusion, infection, length of stay, and posthospital disposition. These outcomes at least doubled, with some increasing > 10-fold.

Conclusions

This nationwide study clarifies the frequency and associations of inpatient complications encountered when treating cervical spine disease. Whereas immediate complications due to anterior approaches are limited, patients with myelopathy who undergo a posterior approach have a more sobering outlook. This study shows that clinical myelopathy augments rates of complication during cervical fusion, regardless of the approach. The exclusion of pathoanatomical data from the Nationwide Inpatient Sample database, of key importance in guiding the surgical approach, prevents any conclusions being drawn about the merits and disadvantages of anterior versus posterior surgery.

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Mohammed F. Shamji, Liufang Jing, Jun Chen, Priscilla Hwang, Odelia Ghodsizadeh, Allan H. Friedman, William J. Richardson and Lori A. Setton

Object

Biochemical irritation of the dorsal root ganglion (DRG) after intervertebral disc herniation contributes to radiculopathy through tumor necrosis factor–α (TNFα)–mediated inflammation. Soluble TNF receptor Type II (sTNFRII) sequesters this cytokine, providing clinical benefit. Previous work involving conjugation of sTNFRII with thermally responsive elastin-like polypeptide (ELP) yielded a chimeric protein (ELP–sTNFRII) with in vitro anti-TNFα bioactivity. Furthermore, temperature-triggered ELP aggregation into a “depot” prolongs protein residence time following perineural injection. In this study the authors evaluated the inflammatory phenotype of DRG explants after TNFα stimulation, and assessed the abilities of sTNFRII or ELP–sTNFRII to attenuate these neuro-inflammatory changes.

Methods

Rat lumbar DRGs (35 animals) were treated in 6 groups, as follows: control; TNFα (25 ng/ml); TNFα with low-(0.2 μg/ml) or high-dose (1 μg/ml) sTNFRII; and TNFα with low-(52.5 μg/ml) or high-dose (262.5 μg/ml) ELP–sTNFRII. After 24 hours, supernatant was evaluated for inflammatory cytokines (interleukin [IL]–1, IL-6, and IL-10); prostaglandin E2; and metabolites (glutamate, lactate, and pyruvate). Single-factor analysis of variance with post hoc Dunn analysis (α = 0.05) was used to assess treatment differences.

Results

Incubation of explants with TNFα caused metabolic stress reflected by an increased lactate/pyruvate ratio (1.8 ± 0.5–fold) and extracellular glutamate (79 ± 8% increase). Inflammatory activation was observed with heightened IL-6 release (5.2 ± 1.4–fold) and prostaglandin E2 production (14 ± 3–fold). An autoregulatory response occurred with an 11.8 ± 0.6–fold increase in sTNFRI shedding. Treatment with high doses of sTNFRII or ELP–sTNFRII reversed all changes. Values are expressed as the mean ± standard deviation.

Conclusions

These results demonstrate that TNFα stimulation of DRG explants yields a phenotype of neurotoxic metabolite release and inflammatory mediator expression. Coincubation with either sTNFRII or ELP–sTNFRII antagonizes TNFα activity to abrogate these changes, suggesting potential for therapeutic intervention to treat peripheral nerve inflammatory disease.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010