Wesley Hsu

Postoperative cognitive function as an outcome of regional anesthesia and analgesia

Background and Objectives: It has been suggested that intraoperative neuraxial (spinal, epidural) anesthesia may decrease postoperative cognitive dysfunction when compared with general anesthesia, but the issue remains controversial. We systematically reviewed the data from published studies to determine the effect of intraoperative neuraxial anesthesia versus general anesthesia on postoperative cognitive dysfunction and delirium. Methods: Studies were identified by searching the PubMed database of the National Library of Medicine (1966 to 2003) for terms related to cognitive dysfunction after surgery. Inclusion criteria were a comparison of intraoperative neuraxial anesthesia versus general anesthesia, and the outcome of postoperative cognitive dysfunction. A total of 196 abstracts were identified, and 24 articles were analyzed. Each article was reviewed, and data were extracted from tables or text or extrapolated from figures as needed. Results: Of the 24 trials obtained, 19 were randomized and 4 were observational (nonrandomized) trials (1 trial was a combination of randomized and observational data). The age of patients studied was typically greater than 60 years, and a wide range of neuropsychometric tests were used to evaluate cognitive function. The majority of trials (23/24 of all trials and 18/19 of randomized trials) did not demonstrate a benefit from neuraxial anesthesia in decreasing the incidence of postoperative cognitive dysfunction. Conclusions: The use of intraoperative neuraxial anesthesia does not appear to decrease the incidence of postoperative cognitive dysfunction when compared with general anesthesia. There are methodologic and study-design issues present in many studies, and further elucidation of the pathophysiology of postoperative cognitive dysfunction may provide a direction for future studies.

Epidural abscesses of the CNS

Epidural abcessess can involve the intercranial or spinal compartments and can result in potentially devastating neurological injuries. Although rare, incidence of spinal epidural abscesses (SEAs) is increasing as predisposing factors such as injected-drug use, chronic immunosuppression, and spinal surgery become more common. Whereas symptoms of SEAs can include fever, back pain, and neurological dysfunction, the presentation of intracranial epidural abscesses (ICEAs) is less well defined. Neuroimaging narrows the potential diagnoses and enables prompt empirical therapy until specific microbiological diagnosis is made. Surgical intervention is an integral part of treatment for epidural abscesses in patients with neurological symptoms or who have not responded to medical management. Prognosis for both SEAs and ICEAs is typically poor because of delayed diagnosis and intervention and is dependent on the neurological status at the time of diagnosis. Increased clinical awareness can greatly improve outcomes by helping to diagnose patients earlier.

Generation of chordoma cell line JHC7 and the identification of Brachyury as a novel molecular target: Laboratory investigation

OBJECT Chordoma is a malignant bone neoplasm hypothesized to arise from notochordal remnants along the length of the neuraxis. Recent genomic investigation of chordomas has identified T (Brachyury) gene duplication as a major susceptibility mutation in familial chordomas. Brachyury plays a vital role during embryonic development of the notochord and has recently been shown to regulate epithelial-to-mesenchymal transition in epithelial-derived cancers. However, current understanding of the role of this transcription factor in chordoma is limited due to the lack of availability of a fully characterized chordoma cell line expressing Brachyury. Thus, the objective of this study was to establish the first fully characterized primary chordoma cell line expressing gain of the T gene locus that readily recapitulates the original parental tumor phenotype in vitro and in vivo. METHODS Using an intraoperatively obtained tumor sample from a 61-year-old woman with primary sacral chordoma, a chordoma cell line (JHC7, or Johns Hopkins Chordoma Line 7) was established. Molecular characterization of the primary tumor and cell line was conducted using standard immunostaining and Western blotting. Chromosomal aberrations and genomic amplification of the T gene in this cell line were determined. Using this cell line, a xenograft model was established and the histopathological analysis of the tumor was performed. Silencing of Brachyury and changes in gene expression were assessed. RESULTS The authors report, for the first time, the successful establishment of a chordoma cell line (JHC7) from a patient with pathologically confirmed sacral chordoma. This cell line readily forms tumors in immunodeficient mice that recapitulate the parental tumor phenotype with conserved histological features consistent with the parental tumor. Furthermore, it is demonstrated for the first time that silencing of Brachyury using short hairpin RNA renders the morphology of chordoma cells to a more differentiated-like state and leads to complete growth arrest and senescence with an inability to be passaged serially in vitro. CONCLUSIONS This report represents the first xenograft model of a sacral chordoma line described in the literature and the first cell line established with stable Brachyury expression. The authors propose that Brachyury is an attractive therapeutic target in chordoma and that JHC7 will serve as a clinically relevant model for the study of this disease.

Delayed intracranial delivery of a nitric oxide donor from a controlled-release polymer prevents experimental cerebral vasospasm in rabbits.

OBJECTIVE:Decreased local availability of nitric oxide (NO) may mediate chronic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Previous reports have shown that early treatment with NO prevents vasospasm in animals. We evaluated the efficacy of controlled-release polymers that contain the NO donor diethylenetriamine (DETA-NO) for the delayed treatment of vasospasm in a rabbit model of SAH. METHODS:DETA-NO 20% (wt/wt) was incorporated into ethylene-vinyl acetate (EVAc) polymers. Animals (n = 52) were randomized to two experimental groups. In the first group (n = 32), animals received SAH and implantation of either 20% DETA-NO/EVAc polymer at a dose of 0.5 mg/kg of DETA-NO (n = 16) or empty EVAc polymer (n = 16). Polymers were implanted 24 (n = 16) or 48 hours (n = 16) after SAH. In the second group (n = 20), animals received SAH and implantation of either 20% DETA-NO/EVAc polymer at a dose of 1.3 mg/kg (n = 10) or empty EVAc (n = 10). Polymers were implanted 24 (n = 10) or 48 hours (n = 10) after SAH. An additional group (n = 16) underwent either sham operation (n = 6) or SAH only (n = 10). Animals were killed 3 days after hemorrhage, and the basilar arteries were processed for morphometric measurements. Results were analyzed using Student’s t test. RESULTS:Treatment with 20% DETA-NO/EVAc polymers at a dose of 1.3 mg/kg significantly increased basilar artery lumen patency when administered at 24 (97 ± 6% versus 73 ± 10%; P = 0.0396) or 48 hours (94 ± 6% versus 71 ± 9%; P = 0.03) after SAH. Treatment with 20% DETA-NO/EVAc polymers at a dose of 0.5 mg/kg administered 48 hours after SAH significantly increased lumen patency (82 ± 8% versus 68 ± 12%; P = 0.03); a dose of 0.5 mg/kg, 24 hours after SAH, did not reach statistical significance (74 ± 7% versus 65 ± 9%; P = 0.16). The SAH-only group had a lumen patency of 67 ± 12%. CONCLUSION:Delayed treatment of SAH with controlled-release DETA-NO polymers prevented experimental posthemorrhagic vasospasm in the rabbit. This inhibition was dose-dependent. This further confirms the role of NO in the pathogenesis of vasospasm.

Intraoperative localization of thoracic spine level with preoperative percutaneous placement of intravertebral polymethylmethacrylate.

Objective To evaluate the safety and utility of preoperative vertebroplasty for intraoperative localization of thoracic spinal levels. Summary of Background Data Intraoperative fluoroscopy or plain radiographs are traditionally used to localize thoracic spine levels during thoracic spine operations. Unfortunately, such localization can occasionally be difficult in the midthoracic levels due to lack of landmarks, scapular shadows, and the body habitus of the morbidly obese. There are multiple techniques described in the literature that allow for preoperative localization of thoracic spinal levels during approaches to the posterior thoracic spine. For efficient and accurate intraoperative localization of thoracic spinal levels during anterior thoracic spine procedures, we describe a method that uses preoperative percutaneous placement of polymethylmethacrylate (PMMA) into the vertebral body using standard vertebroplasty technique. Methods Four patients with morbid obesity and symptomatic thoracic disc herniations underwent preoperative vertebroplasty procedures using standard percutaneous techniques. The PMMA cement was used to expeditiously identify thoracic spinal levels of interest using intraoperative fluoroscopy. Results All 4 patients underwent successful vertebroplasty procedures without complications. The PMMA cement was easily identified intraoperatively and led to the correct identification of the thoracic spinal levels of interest. Conclusions Preoperative placement of PMMA into thoracic vertebral bodies using standard vertebroplasty technique provides a safe, efficient, and reliable method of localizing thoracic spine levels intraoperatively. Such procedures can be performed in the outpatient setting and can be associated with extremely low morbidity when done by experienced practitioners. This procedure should be reserved for patients in whom a surgeon anticipates difficulty using standard radiographs or fluoroscopy to localize thoracic spinal levels intraoperatively.

Novel placement of cortical bone trajectory screws in previously instrumented pedicles for adjacent-segment lumbar disease using CT image-guided navigation

OBJECT Symptomatic adjacent-segment lumbar disease (ASLD) after lumbar fusion often requires subsequent surgical intervention. The authors report utilizing cortical bone trajectory (CBT) pedicle screw fixation with intraoperative CT (O-arm) image-guided navigation to stabilize spinal levels in patients with symptomatic ASLD. This unique technique results in the placement of 2 screws in the same pedicle (1 traditional pedicle trajectory and 1 CBT) and obviates the need to remove preexisting instrumentation. METHODS The records of 5 consecutive patients who underwent lumbar spinal fusion with CBT and posterior interbody grafting for ASLD were retrospectively reviewed. All patients underwent screw trajectory planning with the O-arm in conjunction with the StealthStation navigation system. Basic demographics, operative details, and radiographic and clinical outcomes were obtained. RESULTS The average patient age was 69.4 years (range 58-82 years). Four of the 5 surgeries were performed with the Minimal Access Spinal Technologies (MAST) Midline Lumbar Fusion (MIDLF) system. The average operative duration was 218 minutes (range 175-315 minutes). In the entire cohort, 5.5-mm cortical screws were placed in previously instrumented pedicles. The average hospital stay was 2.8 days (range 2-3 days) and there were no surgical complications. All patients had more than 6 months of radiographic and clinical follow-up (range 10-15 months). At last follow-up, all patients reported improved symptoms from their preoperative state. Radiographic follow-up showed Lenke fusion grades of A or B. CONCLUSIONS The authors present a novel fusion technique that uses CBT pedicle screw fixation in a previously instrumented pedicle with intraoperative O-arm guided navigation. This method obviates the need for hardware removal. This cohort of patients experienced good clinical results. Computed tomography navigation was critical for accurate CBT screw placement at levels where previous traditional pedicle screws were already placed for symptomatic ASLD.

Local delivery of interleukin-2 and adriamycin is synergistic in the treatment of experimental malignant glioma.

SummaryIntroduction: Local delivery of adriamycin (ADR) via biodegradable polymers has been shown to improve survival in rats challenged intracranially with 9L gliosarcoma. Likewise, local delivery of interleukin-2 (IL-2) has been shown to extend survival in experimental brain tumor models. In the current study, we hypothesized that local delivery of ADR and IL-2 might act synergistically against experimental intracranial glioma.Methods: Polyanhydride polymers (PCPP-SA) containing 5% ADR by weight were prepared using the mix-melt method. IL-2 polymer microspheres (IL-2 MS) were produced via the complex coacervation of gelatin and chondroitin sulfate in the presence of IL-2. Sixty male Fisher 344 rats received an intracranial challenge with a lethal dose of 9L gliosarcoma cells. In addition, a group of rats were injected with either IL-2 MS or empty microspheres. Five days later they received ADR or blank polymer. There were a total of four treatment groups: (1) empty microspheres, blank polymer; (2) empty microspheres, ADR polymer; (3) IL-2 MS, blank polymer; and (4) IL-2 MS, ADR polymer.Results: Compared to control animals treated with empty microspheres and blank polymer, animals receiving empty microspheres and ADR polymer (P < 0.0004), IL-2 MS and blank polymer (P < 0.0005), and IL-2 MS combined with ADR polymer (P < 0.0000002) all showed statistically significant improvement in survival. In addition, animals receiving the IL-2/ADR combination had significantly extended survival compared to either ADR or IL-2 alone (P < 0.000003 and P < 0.0004, respectively).Conclusions: Both ADR and IL-2, when delivered locally, are effective monotherapeutic agents against experimental intracranial gliosarcoma. The combination ADR and IL-2 therapy is more effective than either agent alone.

Multidisciplinary Management of Primary Tumors of the Vertebral Column

Opinion statementPrimary spinal neoplasms are rare tumors that can lead to significant morbidity secondary to local bone destruction and invasion into adjacent neurological and vascular structures. These tumors represent a clinical challenge to even the most experienced physicians and require a multidisciplinary approach to ensure optimal patient outcomes. This review will discuss the most common primary bone tumors and focus on recent surgical, medical, and radiation treatment advances.

Transoral approaches to the cervical spine.

A NUMBER OF anterior approaches to the craniocervical junction have been described to allow exposure to the midline and lateral aspects of both the cranial base and upper cervical spine. The transoral-transpharyngeal approach, a technique that is well known to many spine surgeons, provides surgical access to the anterior clivus, C1, and C2. Transoral approaches provide the fundamental anatomy and technique upon which the more complex jaw-splitting approaches are based. This article discusses fundamental concepts regarding anatomy, perioperative considerations, and technical aspects critical to this important approach to the craniocervical junction. The transoral-transpharyngeal approach remains the “gold standard” for anterior approaches to the cervical spine. Endoscopic endonasal and endoscopic transcervical approaches are promising alternatives that may become more mainstream as experience with these approaches increases.

Surgical Management of Cervical Spondylotic Myelopathy.

Cervical spondylosis is a common degenerative condition that is a significant cause of morbidity. This review discusses the pathophysiology and natural history of cervical spondylotic myelopathy and focuses on the current literature evaluating the clinical management of these patients.