Ventral cervico-thoracic meningeal cyst resulting in myelopathy: Case report and literature review.

BACKGROUND: Spinal meningeal (dural) cysts rarely cause spinal cord compression and/or myelopathy. CASE DESCRIPTION: A 38-year-old male presented with 6 weeks of worsening bilateral lower extremity paresthesias and an unsteady gait. Notably, the patient was involved in a snowmobile accident 7 years ago that resulted in trauma to his thoracic spine for which he had undergone a corpectomy and posterior fusion. A full spine MRI was obtained to evaluate his new paresthesias and myelopathy, which revealed a large extra-axial fluid collection consistent with a meningeal cyst extending from C2 to T4. This caused severe spinal cord compression, maximal at the T1-3 level. The patient underwent a T1-3 laminectomy initially accompanied by partial cyst resection/ drainage, but ultimately he returned and required a subsequent cystoperitoneal shunt. Following the final surgery, the patient's symptoms gradually resolved over 6 months postoperatively. CONCLUSION: Spinal meningeal cysts rarely cause back pain and/or neurological symptoms. MRI is the diagnostic study of choice for defining this entity. Operative intervention must be tailored to the symptoms, location, extent, and type of the cyst. If cysts recur after partial resection and drainage, cystoperitoneal shunt placement is warranted.

Traumatic brain injury reduction in athletes by neck strengthening (TRAIN).

Reporting of sports-related concussions (SRCs) has risen dramatically over the last decade, increasing awareness of the need for treatment and prevention of SRCs. To date most prevention studies have focused on equipment and rule changes to sports in order to reduce the risk of injury. However, increased neck strength has been shown to be a predictor of concussion rate. In the TRAIN study, student-athletes will follow a simple neck strengthening program over the course of three years in order to better understand the relationship between neck strength and SRCs. Neck strength of all subjects will be measured at baseline and biannually over the course of the study using a novel protocol. Concussion severity and duration in any subject who incurs an SRC will be evaluated using the Sports Concussion Assessment Tool 5th edition, a questionnaire based tool utilizing several tests that are commonly affected by concussion, and an automated eye tracking algorithm. Neck strength, and improvement of neck strength, will be compared between concussed and non-concussed athletes to determine if neck strength can indeed reduce risk of concussion. Neck strength will also be analyzed taking into account concussion severity and duration to find if a strengthening program can provide a protective factor to athletes. The study population will consist of student-athletes, ages 12-23, from local high schools and colleges. These athletes are involved in a range of both contact and non-contact sports.

High prevalence of prior contact sports play and concussion among orthopedic and neurosurgical department chairs.

OBJECTIVE Increased understanding of the consequences of traumatic brain injury has heightened concerns about youth participation in contact sports. This study investigated the prevalence of high school and collegiate contact sports play and concussion history among surgical department chairs. METHODS A cross-sectional survey was administered to 107 orthopedic and 74 neurosurgery chairs. Responses were compared to published historical population norms for contact sports (high school 27.74%, collegiate 1.44%), football (high school 10.91%, collegiate 0.76%), and concussion prevalence (12%). One-proportion Z-tests, chi-square tests, and binary logistic regression were used to analyze differences. RESULTS High school contact sports participation was 2.35-fold higher (65.3%, p < 0.001) for orthopedic chairs and 1.73-fold higher (47.9%, p = 0.0018) for neurosurgery chairs than for their high school peers. Collegiate contact sports play was 31.0-fold higher (44.7%, p < 0.001) for orthopedic chairs and 15.1-fold higher (21.7%, p < 0.001) for neurosurgery chairs than for their college peers. Orthopedic chairs had a 4.30-fold higher rate of high school football participation (46.9%, p < 0.001) while neurosurgery chairs reported a 3.05-fold higher rate (33.3%, p < 0.001) than their high school peers. Orthopedic chairs reported a 28.1-fold higher rate of collegiate football participation (21.3%, p < 0.001) and neurosurgery chairs reported an 8.58-fold higher rate (6.5%, p < 0.001) compared to their college peers. The rate at which orthopedic (42.6%, p < 0.001) and neurosurgical (42.4%, p < 0.001) chairs reported having at least 1 concussion in their lifetime was significantly higher than the reported prevalence in the general population. After correction for worst possible ascertainment bias, all results except high school contact sports participation remained significant. CONCLUSIONS The high prevalence of youth contact sports play and concussion among surgical specialty chairs affirms that individuals in careers requiring high motor and cognitive function frequently played contact sports. The association highlights the need to further examine the relationships between contact sports and potential long-term benefits as well as risks of sport-related injury.

Hyperbaric Oxygen Therapy in the Treatment of Acute Severe Traumatic Brain Injury: A Systematic Review.

There has been no major advancement in a quarter of a century for the treatment of acute severe traumatic brain injury (TBI). This review summarizes 40 years of clinical and pre-clinical research on the treatment of acute TBI with hyperbaric oxygen therapy (HBO2) in the context of an impending National Institute of Neurologic Disorders and Stroke-funded, multi-center, randomized, adaptive Phase II clinical trial -the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial. Thirty studies (eight clinical and 22 pre-clinical) that administered HBO2 within 30 days of a TBI were identified from PubMed searches. The pre-clinical studies consistently reported positive treatment effects across a variety of outcome measures with almost no safety concerns, thus providing strong proof-of-concept evidence for treating severe TBI in the acute setting. Of the eight clinical studies reviewed, four were based on the senior author's (GR) investigation of HBO2 as a treatment for acute severe TBI. These studies provided evidence that HBO2 significantly improves physiologic measures without causing cerebral or pulmonary toxicity and can potentially improve clinical outcome. These results were consistent across the other four reviewed clinical studies, thus providing preliminary clinical data supporting the HOBIT trial. This comprehensive review demonstrates that HBO2 has the potential to be the first significant treatment in the acute phase of severe TBI.

Phantom-based standardization of CT angiography images for spot sign detection.

PURPOSE: The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance. METHODS: A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%. RESULTS: A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p < 0.001). All spot signs identified in the non-calibrated analysis remained positive after calibration. Calibrated CTA images had higher sensitivity for ICH expansion (76 vs 52%) but inferior specificity (35 vs 63%) compared with uncalibrated images. CONCLUSION: Normalization of CTA images using phantom data is a feasible strategy to obtain consistent image quantification for spot sign analysis across different sites and may improve sensitivity for identification of ICH expansion.

Meningeal Hemangiopericytoma with Intracranial Metastases in an HIV-Positive Male: Case Report and Review of the Literature.

BACKGROUND: Meningeal hemangiopericytoma is a rare, aggressive CNS tumor that tends to invade locally, metastasize, and has a high rate of recurrence. HIV classically increases the risk of 3 AIDS-defining malignancies: Kaposi's sarcoma, non-Hodgkin's lymphoma and invasive cervical cancer. More recently, considerable interest has been paid to the link between HIV and a wider range of non-AIDS-defining cancers. An HIV-positive patient with meningeal hemangiopericytoma is described. CASE DESCRIPTION: A 36-year-old HIV-positive male presented with worsening headache and ataxia. The patient had experienced similar neurologic symptoms 4 months prior and MRI at that time had showed an extra-axial left cerebellar mass most consistent with benign meningioma. Repeat MRI showed the tumor had increased in size by a factor of greater than 20 in this 4-month period, with 4 small additional foci of similar enhancement. Subtotal resection was performed on the mass and final pathological diagnosis was meningeal hemangiopericytoma. CONCLUSIONS: This represents the first reported case of meningeal hemangiopericytoma in an HIV-positive patient. This is also the shortest time to intracranial metastasis ever reported for a meningeal hemangiopericytoma. Although the increased risk in the HIV-positive population of non-AIDS-defining cancers that has been observed in recent years can largely be attributed to cancers with a known viral pathogenesis, it is speculated that HIV infection in this patient may have contributed to the occurrence or unique behavior of this rare tumor.

Electromyographic normalization procedures for determining exercise intensity of closed chain exercises for strengthening the quadriceps femoris muscles.

The purpose of this study was to compare the electromyographic (EMG) amplitudes of the quadriceps femoris (QF) muscles during a maximum voluntary isometric contraction (MVIC) to submaximal and maximal dynamic concentric contractions during active exercises. A secondary purpose was to provide information about the type of contraction that may be most appropriate for normalization of EMG data if one wants to determine if a lower extremity closed chain exercise is of sufficient intensity to produce a strengthening response for the QF muscles. Sixty-eight young healthy volunteers (39 female, 29 male) with no lower extremity pain or injury participated in the study. Surface electrodes recorded EMG amplitudes from the vastus medialis obliquus (VMO), rectus femoris (RF), and vastus lateralis (VL) muscles during 5 different isometric and dynamic concentric exercises. The last 27 subjects performed an additional 4 exercises from which a second data set could be analyzed. Maximum isokinetic knee extension and moderate to maximum closed chain exercises activated the QF significantly more than a MVIC. A 40-cm. lateral step-up exercise produced EMG amplitudes of the QF muscles of similar magnitude as the maximum isokinetic knee extension exercises and would be an exercise that could be considered for strengthening the QF muscles. Most published EMG studies of exercises for the QF have been performed by comparing EMG amplitudes during dynamic exercises to a MVIC. This procedure can lead one to overestimate the value of a dynamic exercise for strengthening the QF muscles. We suggest that when studying the efficacy of a dynamic closed chain exercise for strengthening the QF muscles, the exercise be normalized to a dynamic maximum muscle contraction such as that obtained with knee extension during isokinetic testing.

Imaging of insulinlike growth factor type 1 receptor in prostate cancer xenografts using the affibody molecule 111In-DOTA-ZIGF1R:4551.

UNLABELLED: One of the pathways leading to androgen independence in prostate cancer involves upregulation of insulinlike growth factor type 1 receptor (IGF-1R). Radionuclide imaging of IGF-1R in tumors might be used for selection of patients who would most likely benefit from IGF-1R-targeted therapy. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of IGF-1R expression in prostate cancer xenografts using a small nonimmunoglobulin-derived binding protein called an Affibody molecule. METHODS: The IGF-1R-binding Z(IGF1R:4551) Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with (111)In. The binding of radiolabeled Z(IGF1R:4551) to IGF-1R-expressing cells was evaluated in vitro and in vivo. RESULTS: DOTA-Z(IGF1R:4551) can be stably labeled with (111)In with preserved specific binding to IGF-1R-expressing cells in vitro. In mice, (111)In-DOTA-Z(IGF1R:4551) accumulated in IGF-1R-expressing organs (pancreas, stomach, lung, and salivary gland). Receptor saturation experiments demonstrated that targeting of DU-145 prostate cancer xenografts in NMRI nu/nu mice was IGF-1R-specific. The tumor uptake was 1.1 ± 0.3 percentage injected dose per gram, and the tumor-to-blood ratio was 3.2 ± 0.2 at 8 h after injection. CONCLUSION: This study demonstrates the feasibility of in vivo targeting of IGF-1R-expressing prostate cancer xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical tool for stratification of patients with prostate cancer for IGF-1R-targeting therapy.

Multicentric chordoma: a case report and review of the literature.

BACKGROUND AND IMPORTANCE: Chordomas are relatively rare tumors that arise from the neuraxis. Most often, chordomas are single lesions that metastasize late. There have been very few cases of chordomas arising from multiple foci along the neuraxis. Here, we present a case of a multicentric chordoma. CLINICAL PRESENTATION: The patient presented with pain in her right neck and soreness in her right shoulder that she had experienced for about 2.5 years that she attributed to a muscle strain. She experienced worsening of her symptoms, which prompted her to seek medical care. The patient underwent an occiput-to-C6 posterolateral fusion with autograft and an occiput-to-C6 posterior segmental instrumentation, along with decompression of the spinal cord. One month after the initial surgery, the patient underwent a second surgery. The C2 and C3 vertebral bodies were completely resected, and a C1-C4 anterior fusion was then carried out. A C5 vertebrectomy and C4-C6 fusion were also performed at this time. The patient then received proton beam radiation to the entire affected area. CONCLUSION: Recent studies have suggested that chordomas arise from benign notochordal tumors. We suggest that our patient suffered from multicentric chordomas with possible benign notochordal tumors. Although benign notochordal tumors do not require surgical resection, the possibility of transformation to a malignant lesion requires close follow-up.

A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury.

OBJECT: Oxygen delivered in supraphysiological amounts is currently under investigation as a therapy for severe traumatic brain injury (TBI). Hyperoxia can be delivered to the brain under normobaric as well as hyperbaric conditions. In this study the authors directly compare hyperbaric oxygen (HBO2) and normobaric hyperoxia (NBH) treatment effects. METHODS: Sixty-nine patients who had sustained severe TBIs (mean Glasgow Coma Scale Score 5.8) were prospectively randomized to 1 of 3 groups within 24 hours of injury: 1) HBO2, 60 minutes of HBO(2) at 1.5 ATA; 2) NBH, 3 hours of 100% fraction of inspired oxygen at 1 ATA; and 3) control, standard care. Treatments occurred once every 24 hours for 3 consecutive days. Brain tissue PO(2), microdialysis, and intracranial pressure were continuously monitored. Cerebral blood flow (CBF), arteriovenous differences in oxygen, cerebral metabolic rate of oxygen (CMRO2), CSF lactate and F2-isoprostane concentrations, and bronchial alveolar lavage (BAL) fluid interleukin (IL)-8 and IL-6 assays were obtained pretreatment and 1 and 6 hours posttreatment. Mixed-effects linear modeling was used to statistically test differences among the treatment arms as well as changes from pretreatment to posttreatment. RESULTS: In comparison with values in the control group, the brain tissue PO2 levels were significantly increased during treatment in both the HBO2 (mean +/- SEM, 223 +/- 29 mm Hg) and NBH (86 +/- 12 mm Hg) groups (p < 0.0001) and following HBO2 until the next treatment session (p = 0.003). Hyperbaric O2 significantly increased CBF and CMRO2 for 6 hours (p < or = 0.01). Cerebrospinal fluid lactate concentrations decreased posttreatment in both the HBO2 and NBH groups (p < 0.05). The dialysate lactate levels in patients who had received HBO2 decreased for 5 hours posttreatment (p = 0.017). Microdialysis lactate/pyruvate (L/P) ratios were significantly decreased posttreatment in both HBO2 and NBH groups (p < 0.05). Cerebral blood flow, CMRO2, microdialysate lactate, and the L/P ratio had significantly greater improvement when a brain tissue PO2 > or = 200 mm Hg was achieved during treatment (p < 0.01). Intracranial pressure was significantly lower after HBO2 until the next treatment session (p < 0.001) in comparison with levels in the control group. The treatment effect persisted over all 3 days. No increase was seen in the CSF F2-isoprostane levels, microdialysate glycerol, and BAL inflammatory markers, which were used to monitor potential O2 toxicity. CONCLUSIONS: Hyperbaric O2 has a more robust posttreatment effect than NBH on oxidative cerebral metabolism related to its ability to produce a brain tissue PO2 > or = 200 mm Hg. However, it appears that O2 treatment for severe TBI is not an all or nothing phenomenon but represents a graduated effect. No signs of pulmonary or cerebral O2 toxicity were present.

3-Tesla intraoperative MR imaging for neurosurgery.

Intraoperative magnetic resonance (MR) image-guided neurosurgery has been performed since 1994. Using a 1.5-Tesla (T) intraoperative MR imaging system, we have performed more than 750 interventional procedures. Having validated the safety and efficacy of this surgical technique that is relatively amenable to nearly all new in-hospital MR suites, we sought to adapt this approach at our sister hospital where a new short-bore 3-T MR suite was being installed. Using many of the lessons learned from our initial experience at 1.5-T, we designed a new interventional suite that would enable surgery to be performed entirely within a 3-T MR environment. All surgical instrumentation including electrocautery, fiberoptic headlamp, power drill, and ultrasonic aspirator was entirely MR-compatible. A few items with limited ferromagnetism were utilized within the magnetic field under strict precaution. From 2/04 to 7/05, those cases initially performed within the 3-T surgical suite included one drainage and reservoir placement for a cystic craniopharyngioma, five brain biopsies and two craniotomies; one for open brain biopsy and another for lesion resection. The craniopharyngioma was successfully aspirated and had the reservoir catheter placed within the cyst. All five brain biopsies yielded diagnostic tissue. The craniotomy for mass resection demonstrated radiation necrosis. Although the metallic artifact from the biopsy needle was more prominent than at 1.5-T, accurate image interpretation was possible. Surgical needles, disposable scalpel, disposable razor, and surgical stapler were minimally ferromagnetic and safely controlled by the surgeon. There were no adverse events associated with any procedure. MR-guided neurosurgery can be safely and effectively performed at 3-T. The surgical environment at 3-T is comparable to that present at 1.5-T.

The initial use of free-running electromyography to detect early motor tract injury during resection of intramedullary spinal cord lesions.

OBJECTIVE: The resection of intramedullary spinal cord lesions (ISCLs) can be complicated by neurological deficits. Neuromonitoring has been used to reduce intraoperative risk. We have used somatosensory evoked potentials (SEPs) and muscle-derived transcranial electrical motor evoked potentials (myogenic TCE-MEPs) to monitor ISCL removal. We report our retrospective experience with the addition of free-running electromyography (EMG). METHODS: Thirteen patients underwent 14 monitored ISCL excisions. Anesthesia was maintained with minimal inhalant to reduce motoneuron suppression and enhance the myogenic TCE-MEPs. Free-running EMG was examined in the four limbs for evidence of abnormal bursts, prolonged tonic discharge, or sudden electrical silence. Warning of an electromyographic abnormality or myogenic TCE-MEP loss prompted interventions, including blood pressure elevation, a pause in surgery, a wake-up test, or termination of surgery. Pre- and postoperative neurological examinations determined the incidence of new deficits. RESULTS: The combined use of free-running EMG and myogenic TCE-MEPs detected all eight patients with a new motor deficit after surgery; there was one false-positive report. In three of the eight true-positive cases, an electromyographic abnormality immediately anticipated loss of the myogenic TCE-MEPs. Two patients with abnormal EMGs but unchanged myogenic TCE-MEPs experienced mild postoperative worsening of motor deficits; myogenic TCE-MEPs alone would have generated false-negative reports in these cases. CONCLUSION: During resection of ISCLs, free-running EMG can supplement motor tract monitoring by TCE-MEPs. Segmental and suprasegmental elicitation of neurotonic discharges can be observed in four-limb EMG. Abnormal electromyographic bursts, tonic discharge, or abrupt electromyographic silence may anticipate myogenic TCE-MEP loss and predict a postoperative motor deficit.

Ligand control of interaction in vivo between ecdysteroid receptor and ultraspiracle ligand-binding domain.

Ecdysteroids (Ecs) enhance the formation of Ec receptor-ultraspiracle protein (EcR-USP) heterodimers which regulate gene transcription. To study EcR-USP heterodimerization, fusion proteins were constructed from the LBDs (ligand-binding domains) of Drosophila EcR or USP and the activation or DNA-binding region of GAL4 respectively. Reporter gene ( lacZ ) activation was fully dependent on the co-expression of the two fusion proteins and thus constitutes a reliable measure for the interaction in vivo between the two LBDs in the yeast cell. To identify structures involved in heterodimerization, a total of 27 point mutations were generated in the EcR and USP LBDs at selected sites. Heterodimerization and its inducibility by ligand were mainly affected by mutations in the dimerization interface and in the ligand-binding pocket of EcR respectively. However, also mutations not located in these structures or even in the LBD of USP influenced ligand-dependent heterodimerization. Together with previously reported ligand-binding studies, the existence of such local, intra- and inter-molecular mutation effects suggest that ligand-induced dimerization results from a synergistic interaction between ligand-binding and heterodimerization functions in EcR LBD, and that it depends on global features of the LBDs of EcR and USP and on their mutual surface compatibility.

Ligand-induced heterodimerization between the ligand binding domains of the Drosophila ecdysteroid receptor and ultraspiracle.

The insect ecdysteroid receptor consists of a heterodimer between EcR and the RXR-orthologue, USP. We addressed the question of whether this heterodimer, like all other RXR heterodimers, may be formed in the absence of ligand and whether ligand promotes dimerization. We found that C-terminal protein fragments that comprised the ligand binding, but not the DNA binding domain of EcR and USP and which were equipped with the activation or DNA binding region of GAL4, respectively, exhibit a weak ability to interact spontaneously with each other. Moreover, the heterodimer formation is greatly enhanced upon administration of active ecdysteroids in a dose-dependent manner. This was shown in vivo by a yeast two-hybrid system and in vitro by a modified electromobility shift assay. Furthermore, the EcR fragment expressed in yeast was functional and bound radioactively labelled ecdysteroid specifically. Ligand binding was greatly enhanced by the presence of a USP ligand binding domain. Therefore, ecdysteroids are capable of inducing heterodimer formation between EcR and USP, even when the binding of these receptor proteins to cognate DNA response elements does not occur. This capability may be a regulated aspect of ecdysteroid action during insect development.