Mohamad Bydon

Genetics of intracranial aneurysms.

DESPITE ADVANCES IN the treatment of intracranial aneurysms (IA) in recent years, the overall outcome of patients with aneurysmal subarachnoid hemorrhage has shown only modest improvement. Given this poor prognosis, diagnosis of IA before rupture is of paramount importance. Currently, there are no reliable methods other than screening imaging studies of high-risk individuals to diagnose asymptomatic patients. Multiple levels of evidence suggest that environmental factors acting in concert with genetic susceptibilities lead to the formation, growth, and rupture of aneurysms in these patients. Epidemiological studies have already identified aneurysm-specific risk factors such as size and location, as well as patient-specific risk factors, such as age, sex, and presence of medical comorbidities, such as hypertension. In addition, exposure to certain environmental factors such as smoking have been shown to be important in the formation of IA. Furthermore, substantial evidence proves that certain loci contribute genetically to IA pathogenesis. Genome-wide linkage studies using relative pairs or rare families that are affected with the Mendelian forms of IA have already shown genetic heterogeneity of IA, suggesting that multiple genes, alone or in combination, are important in the disease pathophysiology. The linkage results, along with association studies, will ultimately lead to the identification of IA susceptibility genes. Identification of the genes important in IA pathogenesis will not only provide novel insights into the primary determinants of IA, but will also result in new opportunities for early diagnosis in the preclinical setting. Ultimately, novel therapeutic strategies based on biology will be developed, which will target these newly elucidated genetic susceptibilities.

Recurrent back and leg pain and cyst reformation after surgical resection of spinal synovial cysts: systematic review of reported postoperative outcomes.

BACKGROUND CONTEXT With improvements in neurological imaging, there are increasing reports of symptomatic spinal synovial cysts. Surgical excision has been recognized as the definitive treatment for symptomatic juxtafacet cysts. However, the role for concomitant fusion and the incidence of recurrent back pain and recurrent cyst formation after surgery remain unclear. PURPOSE To determine the cumulative incidence of postoperative symptomatic relief, recurrent back and leg pain after cyst resection and decompression, and synovial cyst recurrence. STUDY DESIGN Systematic review of the literature. PATIENT SAMPLE All published studies to date reporting outcomes of synovial cyst excision with and without spinal fusion. OUTCOME MEASURES Cyst recurrence and Kawabata, Macnab, Prolo, or Stauffer pain scales. METHODS We performed a systematic literature review of all articles published between 1970 and 2009 reporting outcomes after surgical management of spinal synovial cysts. RESULTS Eighty-two published studies encompassing 966 patients were identified and reviewed. Six hundred seventy-two (69.6%) patients presented with radicular pain and 467 (48.3%) with back pain. The most commonly involved spinal level was L4-L5 (75.4%), with only 25 (2.6%) and 12 (1.2%) reported synovial cysts in the cervical or thoracic area, respectively. Eight hundred eleven (84.0%) patients were treated with decompressive surgical excision alone, whereas 155 (16.0%) received additional concomitant spinal fusion. Six hundred fifty-four (92.5%) and 880 (91.1%) patients experienced complete resolution of their back or leg pain after surgery, respectively. By a mean follow-up of 25.4 months, back and leg pain recurred in 155 (21.9%) and 123 (12.7%) patients, respectively. Sixty (6.2%) patients required reoperation, of which the majority (n=47) required fusion for correction of spinal instability and mechanical back pain. Same-level synovial cyst recurrence occurred in 17 (1.8%) patients after decompression alone but has been reported in no (0%) patients after decompression and fusion. CONCLUSIONS Surgical decompression results in symptomatic resolution in the vast majority of patients; however, recurrent back pain occurs in a significant number of patients. Cyst recurrence occurs in less than 2% of patients but has never been reported after cyst excision with concomitant fusion. The lack of cyst recurrence after concomitant fusion supports the need to investigate the value of fusion of the involved motion segment in the treatment of symptomatic synovial cysts of the spine.

Molecular Genetic Analysis of Two Large Kindreds With Intracranial Aneurysms Demonstrates Linkage to 11q24-25 and 14q23-31

Background and Purpose— Both environmental and genetic factors contribute to the formation, growth, and rupture of intracranial aneurysms (IAs). To search for IA susceptibility genes, we took an outlier approach, using parametric genome-wide linkage analysis in extended IA kindreds in which IA is inherited as a simple Mendelian trait. We hereby present the molecular genetic analysis of 2 such families. Methods— For genome-wide linkage analysis, we used a 2-stage approach. First, using gene chips in affected-only analysis, we identified genomic regions that provide maximum theoretical logarithm of odds (lod) scores. Next, to confirm or exclude these candidate loci, we genotyped all available family members, both affected and unaffected, using polymorphic microsatellite markers located within these regions. Results— We obtained significant lod scores of 4.3 and 3.00 for linkage to chromosomes 11q24-25 and 14q23-31, respectively. Conclusions— Molecular genetic analysis of 2 large IA kindreds confirms linkage to chromosome 11q and 14q, which were suggested to contain IA susceptibility genes in a previous study of Japanese sib pairs. Independent identification of these 2 loci strongly suggests that IA susceptibility genes lie within these regions. While demonstrating the genetic heterogeneity of IA, these results are also an important step toward cloning IA genes and ultimately understanding its pathophysiology.

The Current Role of Steroids in Acute Spinal Cord Injury

BACKGROUND Acute spinal cord injury (ASCI) is a catastrophic event that can profoundly affect the trajectory of a patients life. Debate continues over the pharmacologic management of ASCI, specifically, the widespread but controversial use of the steroid methylprednisolone (MP). Treatment efforts are impeded because of limitations in understanding of the pathobiology of ASCI and the difficulty in proving the efficacy of therapies. METHODS This review presents the pathophysiology of ASCI and the laboratory and clinical findings on the use of MP. RESULTS The use of MP remains a contentious issue in part because of the catastrophic nature of ASCI, the paucity of treatment options, and the legal ramifications. Although historical data on the use of MP in ASCI have been challenged, more recent studies have been used both to support and to oppose treatment of ASCI with steroids. CONCLUSIONS ASCI is a devastating event with a complex aftermath of secondary damaging processes that worsen the initial injury. Although the results of NASCIS (National Acute Spinal Cord Injury Study) II and III trials led to the widespread adoption of a high-dose MP regimen for patients treated within 8 hours of injury, subsequent studies have called into question the validity of NASCIS conclusions. Further evidence of the ineffectiveness of the MP protocol has led to declining confidence in the treatment over the last decade. At the present time, high-dose MP cannot be recommended as a standard of care, but it remains an option until supplanted by future evidence-based therapies.

The impact of obesity on short- and long-term outcomes after lumbar fusion

Study Design. Retrospective cohort study. Objective. To compare short- and long-term outcomes in obese versus nonobese patients undergoing instrumented posterolateral fusion of the lumbar spine. Summary of Background Data. Obesity is an important public health issue due to the negative effects on quality of life. Some studies have shown an association between obesity and higher rates of complications and unfavorable outcomes after spine surgery. Methods. We retrospectively reviewed medical records for all adult patients undergoing 1- to 3-level posterolateral fusion for degenerative spine disease between 1992 and 2012 at a single institution. Patients were divided into obese (body mass index > 30 kg/m2) and nonobese cohorts to compare complications, reoperation rates, and symptom resolution at the last follow-up. A regression model was used to estimate relative risk ratios. Results. During the study period, 732 patients underwent lumbar fusion, with 662 (90.44%) nonobese patients and 70 (9.56%) obese patients in the cohort. Obese patients had significantly higher blood loss intraoperatively (P = 0.002) and a longer average length of stay (P = 0.022). Moreover, obesity was independently associated with a significantly increased risk of developing a postoperative complication (risk ratio 2.14; 95% confidence interval, 1.10–4.16) and surgical site infection (risk ratio 3.11; 95% confidence interval, 1.48–6.52). At the last follow-up, a higher proportion of obese patients had radiculopathy (P = 0.018), motor deficits (P = 0.006), sensory deficits (P = 0.008), and bowel or bladder dysfunction (P = 0.006) than nonobese patients. Conclusion. In this study, obese patients undergoing lumbar fusion had higher blood loss, longer lengths of stay, higher complication rates, and worse functional outcomes at the last follow-up than nonobese patients. These findings suggest that both surgeons and patients should acknowledge the significantly increased morbidity profile of obese patients after lumbar fusion. Level of Evidence: 4

Epidural steroid injection resulting in epidural hematoma in a patient despite strict adherence to anticoagulation guidelines: Case report

Epidural steroid injections are relatively safe procedures, although the risk of hemorrhagic complications in patients undergoing long-term anticoagulation therapy is higher. The American Society for Regional Anesthesia and Pain Medicine has specific guidelines for treatment of these patients when they undergo neuraxial anesthetic procedures. In this paper, the authors present a case in which the current American Society for Regional Anesthesia and Pain Medicine guidelines were strictly followed with respect to withholding and reintroducing warfarin and enoxaparin after an epidural steroid injection, but the patient nevertheless developed a spinal epidural hematoma requiring emergency surgical evacuation. The authors compare the case with the 8 other published cases of postinjection epidural hematomas in patients with coagulopathy, and the specific risk factors that may have contributed to the hemorrhagic complication in this patient is analyzed.

Incidence and prognostic factors of c5 palsy: a clinical study of 1001 cases and review of the literature.

BACKGROUND C5 palsy is a known cause of postoperative deltoid weakness. Prognostic variables affecting the incidence of the palsy have been poorly understood. OBJECTIVE To determine the incidence and perioperative characteristics/predictors of C5 palsy after anterior vs posterior operations. METHODS All patients undergoing C4-5 operations for degenerative conditions were retrospectively reviewed over 21 years. Anterior operations included an anterior cervical discectomy and fusion (ACDF) or a corpectomy, whereas posterior operations included laminectomy and fusion (± foraminotomies). RESULTS Of the total 1001 operations, in 49.0% anterior and 51.0% posterior cases, there was an overall C5 palsy incidence of 5.2% (52 cases): 1.6% and 8.6%, respectively (P < .001). Of the 99 corpectomies, the palsy incidence of 4.0% was not only higher than ACDFs (1.0%), but also followed an upward trend with increasing corpectomy levels (P = .009). Of the 69 posterior and 83 anterior C4-5 foraminotomies, the incidence of C5 palsy was statistically higher in the posterior (14.5%) vs anterior (2.4%) cohort (P = .01). Multiple logistical regression identified older age as the strongest predictor of C5 palsy in the anterior (P = .02) and C4-5 foraminotomy in the posterior (P = .06) cohort. This condition improved within 3 to 6 months in 75% of patients in the anterior and 88.6% in the posterior cohort after a mean follow-up of 14.4 and 27.6 months, respectively. CONCLUSION In one of the largest cohorts on C5 palsy, we found in anterior operations an increasing number of corpectomy levels had a higher incidence of C5 palsy; however, older age was the strongest predictor of C5 palsy. In posterior operations, C4-5 foraminotomy carried the strongest correlation.

Adjacent segment disease after anterior cervical discectomy and fusion in a large series.

BACKGROUND Adjacent segment disease (ASD) development is known to occur after anterior cervical discectomy and fusion (ACDF). OBJECTIVE To study the relationship between index ACDF levels and the location of ASD development (above/below), as well as the effect of fusion length on ASD development. METHODS We report 888 patients who underwent ACDF for cervical spondylosis over a twenty-year period at a single institution. Of these patients, 108 had re-do surgery due to symptomatic ASD. Patients were followed for an average of 92.4 ± 52.6 months after the index ACDF. RESULTS In agreement with previous ACDF case series, we found the highest rates of cervical spinal degenerative disease requiring surgery at C5/C6, followed by C6/C7. Interestingly, neither the inherent location of index ACDF nor the length of instrumented arthrodesis appeared to correlate with the propensity to develop ASD. However, patients were more likely to develop ASD above the index level of fusion. This was true even for patients undergoing a second revision surgery due to recurrent ASD. Importantly, our data are consistent with existing in vitro biomechanical data in cadaveric spines. CONCLUSION We describe in detail the location and length of arthrodesis for index ACDFs, as well as first and second revision fusion surgeries in one of the largest Western cohorts in the literature. Our findings support the theory that iatrogenically introduced stress and instability at adjacent spinal segments contribute to the pathogenesis of ASD.

Impact of resident participation on morbidity and mortality in neurosurgical procedures: an analysis of 16,098 patients

OBJECT The authors sought to determine the impact of resident participation on overall 30-day morbidity and mortality following neurosurgical procedures. METHODS The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who had undergone neurosurgical procedures between 2006 and 2012. The operating surgeon(s), whether an attending only or attending plus resident, was assessed for his or her influence on morbidity and mortality. Multivariate logistic regression, was used to estimate odds ratios for 30-day postoperative morbidity and mortality outcomes for the attending-only compared with the attending plus resident cohorts (attending group and attending+resident group, respectively). RESULTS The study population consisted of 16,098 patients who had undergone elective or emergent neurosurgical procedures. The mean patient age was 56.8 ± 15.0 years, and 49.8% of patients were women. Overall, 15.8% of all patients had at least one postoperative complication. The attending+resident group demonstrated a complication rate of 20.12%, while patients with an attending-only surgeon had a statistically significantly lower complication rate at 11.70% (p < 0.001). In the total population, 263 patients (1.63%) died within 30 days of surgery. Stratified by operating surgeon status, 162 patients (2.07%) in the attending+resident group died versus 101 (1.22%) in the attending group, which was statistically significant (p < 0.001). Regression analyses compared patients who had resident participation to those with only attending surgeons, the referent group. Following adjustment for preoperative patient characteristics and comorbidities, multivariate regression analysis demonstrated that patients with resident participation in their surgery had the same odds of 30-day morbidity (OR = 1.05, 95% CI 0.94-1.17) and mortality (OR = 0.92, 95% CI 0.66-1.28) as their attending only counterparts. CONCLUSIONS Cases with resident participation had higher rates of mortality and morbidity; however, these cases also involved patients with more comorbidities initially. On multivariate analysis, resident participation was not an independent risk factor for postoperative 30-day morbidity or mortality following elective or emergent neurosurgical procedures.

Adjacent segment disease after anterior cervical discectomy and fusion: Clinical outcomes after first repeat surgery versus second repeat surgery

Study Design. Retrospective clinical study. Objective. To study the long-term effects of repeat cervical fusion after development of adjacent segment disease (ASD). Summary of Background Data. ASD is a well-recognized development after anterior cervical discectomy and fusion (ACDF). Although there are data on the development of ASD after ACDF, the incidence of ASD after repeat ACDF has not been well established. Methods. We collected 888 consecutive patients who underwent ACDF for cervical degenerative disease during a 20-year period at a single institution. Patients were followed for an average of 94.0 ± 78.1 months after the first ACDF. Results. Of the 888 patients who underwent ACDF, 108 patients developed ASD, necessitating a second cervical fusion. Among these 108 patients, 27 patients later developed recurrent ASD, requiring a third cervical fusion. Thus, in this series, the incidence of ASD after ACDF is 12.2%, statistically increasing to 25% after a second cervical fusion (P = 0.0002). Notably, ASD occurred 47.0 ± 44.9 months after the first ACDF and statistically decreased to 30.3 ± 24.9 months after a second cervical fusion (P = 0.01). Of the 77 patients who underwent a second cervical fusion via an anterior approach, 23 developed recurrent ASD requiring a third cervical fusion. In contrast, of the 31 patients who had a posteriorly approached second cervical fusion, only 4 developed recurrent ASD requiring a third cervical fusion. Conclusion. We present a cohort of patients undergoing multiple sequential operations due to ASD during a 20-year period. In this series of 888 patients, the incidence of ASD development is lowest after the first ACDF. Patients who undergo a second cervical fusion develop ASD at both higher and faster rates. Moreover, patients who had a second cervical fusion via an anterior approach had a higher chance of developing recurrent ASD versus patients who had a posterior approach. Level of Evidence: 3