Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study.

INTRODUCTION: Despite advancements in medical and surgical therapies, clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH) continue to be poor. Currently, aSAH pathophysiology remains poorly understood. No aSAH biomarkers are commonly used in the clinical setting. This exploratory study used metabolomics profiling to identify global metabolic changes and metabolite predictors of long-term outcome using cerebrospinal fluid (CSF) samples of aSAH patients. METHODS AND METHODS: Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons. RESULTS: Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively. CONCLUSIONS: Our preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis.

A Review of Cerebral Shunts, Current Technologies, and Future Endeavors.

Objective. The use of cerebrospinal shunts is the standard of care for hydrocephalus. However, shunts are extremely vulnerable to failure and lack noninvasive methods to monitor their viability. We review current shunt technologies and attempts to improve their function. Methods. A PubMed search was performed to find literature on shunts and shunt function. Company brochures and websites were also used. Results. Fixed and variable pressure valves from four major companies are discussed. Also reviewed are siphon resistive devices, intracranial pressure sensors, and recent attempts on the development of cerebrospinal fluid sensors, including a micromechanical flow sensor we have recently developed. Conclusions. While variable pressure valves and siphon resistive devices have both had considerable success in dealing with variable intracranial pressure, a more sophisticated, continuous monitoring system is needed to ensure shunt viability and patient safety. An integrated flow sensor may provide the ability to track fluid flow and determine shunt functionality.

Resection of lateral temporal lobe arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) can be formidable lesions to treat. There are four modalities available for treatment: expectant management, radiosurgery, embolization, and microsurgery. In order to make a decision about treatment, the surgeon must consider the natural history of the lesion versus the rate of treated morbidity and mortality. Characteristics of temporal lobe AVMs such as their location, the potential for deep-seated arterial feeders and deep venous drainage, increase the risk of early clinical onset, hemorrhage, and overall morbidity and mortality (Fleetwood and Steinberg; Lancet 359:863-873, 3) and provide an additional challenge to surgeons attempting to remove the lesion while preserving eloquent local structures. METHODS: In this paper, we demonstrate our technique for the microsurgical resection of lateral temporal lobe AVMs. In order to maximize access to the lesion for safe resection, a large craniotomy is utilized, with the malformation separated from the MCA feeding arteries and underlying cortex, with care taken not to compromise en passage vessels. The entire nidus is resected and intraoperative angiography confirms appropriate resection. CONCLUSIONS: Microsurgical resection remains an important part of the treatment paradigm for temporal lobe AVMs. In appropriately selected patients, this can be done with minimal morbidity.

Telemedical Interdisciplinary Care Team Evaluation and Treatment of People With Low Back Pain: A Retrospective Observational Study.

Objective: To evaluate the effects of an interdisciplinary care team (ICT) model delivered by telemedicine on patients with low back pain (LBP). Design: Retrospective analysis of deidentified pre-existing data. Setting: Retrospective observational study of patients presenting with LBP to a nationwide telemedicine practice using an ICT model. Participants: Over a 9-month period all patients with a diagnosis related to LBP and who had an ICT evaluation (medical doctor, advanced practice provider, health coach, and physical therapist) were included in the study (n=36). A minimum of 2 follow-up physical therapy visits were required for inclusion. Interventions: Patients were evaluated for LBP, received a diagnosis, and were offered a multidisciplinary treatment plan. Additional real-time audio visual medical, health coaching, registered dietician, and physical therapy services were received as deemed clinically appropriate. Main Outcome Measures: Baseline, 30 day, and final pain (mean 81 day) measurements via numerical pain rating scale (NPRS). Baseline and final Patient-Reported Outcomes Measurement Information System (PROMIS)-10 Global Mental/Physical domains. Secondary Outcome Measures: Use of prescription medication, referral for imaging, need for injections, or surgery. Results: 36 patients met criteria. Pain levels included mild (n=6, 16.7%), moderate (n=19, 52.8%), and severe (n=11, 30.6%). Clinically significant pain improvements were noted in 83.3% (n=25) of those with moderate or severe pain. PROMIS Mental and Physical Health categorization from Fair/Poor to Good/Excellent significantly improved over time. The initial 20% (n=7) in Fair/Poor Mental Health improved to 6.3% (n=2) at finish, while the 80% (n=28) in Good/Excellent Mental Health at start improved to 93.8% (n=30) at finish. Regarding Physical Health, 51.4% (n=18) rated Fair/Poor at start and 31.3% (n=10) at finish, while the 48.6% (n=17) rated Good/Excellent at start improved to 68.8% (n=22) at finish. The need for prescription medication was low (n=6, 16.7%) and spinal imaging orders were negligible (n=1, 2.8%). Injections were warranted in 11.4% (n=4) of patients and surgical referral with operative treatment in 2.8% (n=1). Conclusion: Interdisciplinary care delivered through telemedicine can significantly improve pain and support improved health-related quality of life in patients with LBP, with low rates of imaging, prescription, and interventional use.

Genome-wide Association Analysis Across 16,956 Patients Identifies a Novel Genetic Association Between BMP6, NIPAL1, CNGA1 and Spondylosis.

STUDY DESIGN: A case-control genome-wide association study (GWAS) on spondylosis. OBJECTIVE: Leveraging Geisinger's MyCode initiative's multimodal dataset, we aimed to identify genetic associations with degenerative spine disease. SUMMARY OF BACKGROUND DATA: Degenerative spine conditions are a leading cause of global disability; however, the genetic underpinnings of these conditions remain under-investigated. Previous studies using candidate-gene approach suggest a genetic risk for degenerative spine conditions, but large-scale GWASs are lacking. METHODS: We identified 4434 patients with a diagnosis of spondylosis using ICD diagnosis codes with genotype data available. We identified a population-based control of 12,522 patients who did not have any diagnosis for osteoarthritis. A linear-mix, additive genetic model was employed to perform the genetic association tests adjusting for age, sex, and genetic principal components to account for the population structure and relatedness. Gene-based association tests were performed and heritability and genetic correlations with other traits were investigated. RESULTS: We identified a genome-wide significant locus at rs12190551 (odds ratio = 1.034, 95% confidence interval 1.022-1.046, P = 8.5 × 10-9, minor allele frequency = 36.9%) located in the intron of BMP6. Additionally, NIPAL1 and CNGA1 achieved Bonferroni significance in the gene-based association tests. The estimated heritability was 7.19%. Furthermore, significant genetic correlations with pain, depression, lumbar spine bone mineral density, and osteoarthritis were identified. CONCLUSION: We demonstrated the use of a massive database of genotypes combined with electronic health record data to identify a novel and significant association spondylosis. We also identified significant genetic correlations with pain, depression, bone mineral density, and osteoarthritis, suggesting shared genetic etiology and molecular pathways with these phenotypes.Level of Evidence: N/A.

Aneurysmal subarachnoid hemorrhage and severe, catheter-induced vasospasm associated with excessive consumption of a caffeinated energy drink.

Excessive consumption of over-the-counter stimulants is associated with coronary vasospasm, thrombotic complications, and sudden cardiac death. Their effects on cerebrovascular physiology are not yet described in the neurointerventional literature. Patients are increasingly exposed to high levels of these vasoactive substances in the form of caffeinated energy drinks and specialty coffees. We report a case of aneurysmal subarachnoid hemorrhage (SAH) and severe, catheter-induced vasospasm during attempted endovascular repair of a ruptured anterior communicating artery (AComA) aneurysm in the setting of excessive energy drink consumption. We review the literature and alert clinicians to this potentially serious complication.

Patient factors associated with 30-day morbidity, mortality, and length of stay after surgery for subdural hematoma: a study of the American College of Surgeons National Surgical Quality Improvement Program.

OBJECTIVE: Surgery for subdural hematoma (SDH) is a commonly performed neurosurgical procedure. This study identifies patient characteristics associated with adverse outcomes and prolonged length of stay (LOS) in patients who underwent surgical treatment for SDH. METHODS: All patients in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) who were treated via craniotomy or craniectomy for SDH between 2005 and 2012 were identified. Patient demographics, comorbidities, and 30-day outcomes were described. Multivariate regression was used to identify predictors of adverse events. RESULTS: A total of 746 surgical procedures performed for SDH were identified and analyzed. Patients undergoing this procedure were 64% male with an average age (± SD) of 70.9 ± 14.1 years. The most common individual adverse events were death (17%) and intubation for more than 48 hours (19%). In total, 34% experienced a serious adverse event other than death, 8% of patients returned to the operating room (OR), and the average hospital LOS was 9.8 ± 9.9 days. In multivariate analysis, reduced mortality was associated with age less than 60 years (relative risk [RR] = 0.47, p = 0.017). Increased mortality was associated with gangrene (RR = 3.5, p = 0.044), ascites (RR = 3.00, p = 0.006), American Society of Anesthesiologists (ASA) Class 4 or higher (RR = 2.34, p = 0.002), coma (RR = 2.25, p < 0.001), and bleeding disorders (RR = 1.87, p = 0.003). Return to the OR was associated with pneumonia (RR = 3.86, p = 0.044), male sex (RR = 1.85, p = 0.015), and delirium (RR = 1.75, p = 0.016). Serious adverse events were associated with ventilator dependence preoperatively (RR = 1.86, p < 0.001), dialysis (RR = 1.44, p = 0.028), delirium (RR = 1.40, p = 0.005), ASA Class 4 or higher (RR = 1.36, p = 0.035), and male sex (RR = 1.29, p = 0.037). Similarly, LOS was increased in ventilator dependent patients by 1.56-fold (p = 0.002), in patients with ASA Class 4 or higher by 1.30-fold (p = 0.006), and in delirious patients by 1.29-fold (p = 0.008). CONCLUSIONS: Adverse outcomes are common after surgery for SDH. In this study, 18% of the patients died within 30 days of surgery. Factors associated with adverse outcomes were identified. Patients and families should be counseled about the serious risks of morbidity and death associated with acute traumatic SDH requiring surgery.

Management of acute traumatic spinal cord injury.

OPINION STATEMENT: Spinal cord injury (SCI) causes significant morbidity and mortality. Clinical management in the acute setting needs to occur in the intensive care unit in order to identify, prevent, and treat secondary insults from local ischemia, hypotension, hypoxia, and inflammation. Maintenance of adequate perfusion and oxygenation is quintessential and a mean arterial pressure >85-90 mm Hg should be kept for at least 1 week. A cervical collar and full spinal precautions (log-roll, flat, holding C-spine) should be maintained until the spinal column has been fully evaluated by a spine surgeon. In patients with SCI, there is a high incidence of other bodily injuries, and there should be a low threshold to assess for visceral, pelvic, and long bone injuries. Computed tomography of the spine is superior to plain films, as the former rarely misses fractures, though caution needs to be exerted as occipitocervical dislocation can still be missed. To reliably assess the spinal neural elements, soft tissues, and ligamentous structures, magnetic resonance imaging is indicated and should be obtained within 48-72 h from the time of injury. All patients should be graded daily using the American Spinal Injury Association classification, with the first prognostic score at 72 h postinjury. Patients with high cervical cord (C4 or higher) injury should be intubated immediately, and those with lower cord injuries should be evaluated on a case-by-case basis. However, in the acute setting, respiratory mechanics will be disrupted with any spinal cord lesion above T11. Steroids have become extremely controversial, and the professional societies for neurosurgery in the United States have given a level 1 statement against their use in all patients. We, therefore, do not advocate for them at this time. With every SCI, a spine surgeon must be consulted to discuss operative vs nonoperative management strategies. Indications for surgery include a partial or progressive neurologic deficit, instability of the spine not allowing for mobilization, correction of a deformity, and prevention of potential neurologic compromise. Measures to prevent pulmonary emboli from deep venous thromboembolisms are necessary: IVC filters are recommended in bedbound patients and low-molecular weight heparins are superior to unfractionated heparin. Robust prevention of pressure ulcers as well as nutritional support should be a mainstay of treatment. Lastly, it is important to note that neurologic recovery is a several-year process. The most recovery occurs in the first year following injury, and therefore aggressive rehabilitation is crucial.

Multimodal evaluation of CSF dynamics following extradural decompression for Chiari malformation Type I.

OBJECT Extradural decompression is a minimally invasive technique for treating Chiari malformation Type I (CM-I) that avoids the complications of dural opening. While there is no agreement on which surgical method is optimal, mounting evidence demonstrates that extradural decompression effectively treats clinical symptoms, with a minimal reoperation rate. Neurological symptoms such as headache may be related to obstructed flow of CSF, and one aspect of successful extradural decompression is improved CSF dynamics. In this series, the authors report on their use of phase-contrast cine flow MRI to assess CSF flow as well as satisfactory decompression. METHODS The authors describe their first surgical series of 18 patients with CM-I undergoing extradural decompression and correlate clinical improvement with radiological changes. Patients were categorized as having complete, partial, or no resolution of their symptoms. Posterior fossa area, cisterna magna area, and tonsillar herniation were assessed on T2-weighted MRI, whereas improvement of CSF flow was evaluated with phase-contrast cine flow MRI. All patients received standard pre- and postoperative MRI studies; 8 (44.4%) patients had pre- and postoperative phase-contrast cine, while the rest underwent cine studies only postoperatively. RESULTS All 18 patients presented with symptomatic CM-I, with imaging studies demonstrating tonsillar herniation ≥ 5 mm, and 2 patients had associated syringomelia. All patients underwent suboccipital decompression and C-1 laminectomy with splitting of the dura. Patients with complete resolution of their symptoms had a greater relative increase in cisterna magna area compared with those with only partial improvement (p = 0.022). In addition, in those with complete improvement the preoperative cisterna magna area was smaller than in those who had either partial (0.020) or no (0.025) improvement. Ten (91%) of the 11 patients with improved flow also had improvement in their symptoms. There was 1 postoperative complication of dysphagia and dysphonia. None of the patients have required a second operation. CONCLUSIONS Extradural decompression has the potential to be the first-line treatment for CM-I but has been lacking an objective measure by which to assess surgical success as well as the need for reoperation. An increase in the CSF spaces and improved CSF dynamics may be associated with resolution of clinical symptoms. Including cine imaging as part of routine pre- and postoperative evaluation can help identify which patients are most likely to benefit from surgery.

Delayed surgery after acute traumatic central cord syndrome is associated with reduced mortality.

STUDY DESIGN: A retrospective study of surgically treated patients with acute traumatic central cord syndrome (ATCCS) from the National Trauma Data Bank Research Data Set. OBJECTIVE: To determine the association of time to surgery, pre-existing comorbidities, and injury severity on mortality and adverse events in surgically treated patients with ATCCS. SUMMARY OF BACKGROUND DATA: Although earlier surgery has been shown to be beneficial for other spinal cord injuries, the literature is mixed regarding the appropriate timing of surgery after ATCCS. Traditionally, this older population has been treated with delayed surgery because medical optimization is often indicated preoperatively. METHODS: Surgically treated patients with ATCCS in the National Trauma Data Bank Research Data Set from 2011 and 2012 were identified. Time to surgery, Charlson Comorbidity Index, and injury severity scores were tested for association with mortality, serious adverse events, and minor adverse events using multivariate logistic regression. RESULTS: A total of 1060 patients with ATCCS met inclusion criteria. After controlling for pre-existing comorbidity and injury severity, delayed surgery was associated with a decreased odds of inpatient mortality (odds ratio = 0.81, P = 0.04), or a 19% decrease in odds of mortality with each 24-hour increase in time until surgery. The association of time to surgery with serious adverse events was not statistically significant (P = 0.09), whereas time to surgery was associated with increased odds of minor adverse events (odds ratio = 1.06, P < 0.001). CONCLUSION: Although the potential neurological effect of surgical timing for patients with ATCCS remains controversial, the decreased mortality with delayed surgery suggests that waiting to optimize general health and potentially allow for some spinal cord recovery in these patients may be advantageous. LEVEL OF EVIDENCE: 3.

Oversized self-expanding stents as an alternative to flow-diverters for blister-like aneurysms.

OBJECTIVE: Blister-like aneurysms (BLAs) are challenging to treat. Their friable nature makes them high risk for both traditional microsurgical and endovascular treatments. We discuss employing a single oversized self-expanding stent in the treatment of these treacherous lesions. METHODS: A retrospective review from our institution was conducted. Five patients with BLAs were identified, who went on to be treated with a single oversized self-expanding stent, defined as 1 mm larger than the parent vessel, by the senior author (KRB), who is dual fellowship trained in both cerebrovascular/skull base microsurgery and endovascular neurosurgery. Additionally, a literature review was performed on BLAs treated with sole stenting and outcomes discussed. RESULTS: Our five patients had complete aneurysm occlusion at long-term follow-up and all had good neurological outcomes. The literature review demonstrated that most aneurysms at long-term follow-up were either completed occluded or progressively becoming occluded, with patients overall having a good functional outcome based on the modified Rankin scale (mRS). CONCLUSION: In our experience, oversized self-expanding stents are a treatment option that should be considered for BLAs. This strategy avoids the need for dual antiplatelet therapy and therefore increases its utility in the case of subarachnoid hemorrhage (SAH).

Ethical considerations in deep brain stimulation for psychiatric illness.

Deep brain stimulation (DBS) is an efficacious surgical treatment for many conditions, including obsessive-compulsive disorder and treatment-resistant depression. DBS provides a unique opportunity to not only ameliorate disease but also to study mood, cognition, and behavioral effects in the brain. However, there are many ethical questions that must be fully addressed in designing clinical research trials. It is crucial to maintain sound ethical boundaries in this new era so as to permit the proper testing of the potential therapeutic role DBS may play in ameliorating these devastating and frequently treatment-refractory psychiatric disorders. In this review, we focus on the selection of patients for study, informed consent, clinical trial design, DBS in the pediatric population, concerns about intentionally or inadvertently altering an individual's personal identity, potential use of DBS for brain enhancement, direct modification of behavior through neuromodulation, and resource allocation.

Thoracic epidural teratoma: case report and review of the literature.

PURPOSE: Spinal teratomas comprise a rare subset of spinal cord tumors, and here, we describe an even rarer childhood thoracic extradural-intracanalicular teratoma. The clinical presentation, management, and pathophysiology of these tumors are reviewed to promote recognition and guide treatment of these lesions. METHODS: We report the case of a 21-month-old boy who presented with marked spasticity, as well as failure to ambulate and meet motor milestones. Additionally, we provide a literature review of spinal teratomas, including their clinical presentation, work-up, pathophysiology, and underlying genetics. RESULTS: An MRI of the spine revealed a large dorsal epidural tumor extending from T3 to T10 with heterogeneous contrast enhancement and severe spinal cord compression. The tumor was resected revealing a cystic mass with tissue resembling hair, muscle, as well as cartilage; pathology confirmed the diagnosis of teratoma. Gross total resection was achieved, and the child eventually gained ambulatory function. CONCLUSIONS: Given that spinal teratomas are rare entities that can present with significant neurologic compromise, they must remain on clinicians' differentials. Unfortunately, the exact origin of these tumors remains inconclusive and requires further investigation.

Efficacy and safety of higher dose stereotactic radiosurgery for functional pituitary adenomas: a preliminary report.

OBJECTIVE: Single fraction stereotactic radiosurgery (SRS) is a common adjuvant therapy for hormonally active pituitary adenomas when surgical resection fails to control tumor growth or normalize hypersecretory activity. Marginal doses of 20-24 Gy are used at many centers and here we report our outcome data in patients treated with a higher marginal dose of 35 Gy. METHODS: Thirty-one patients with secretory pituitary adenomas (adrenocorticotropic hormone, n = 15; growth hormone, n = 13; prolactin, n = 2; thyroid-stimulating hormone, n = 1) were treated with 35 Gy to the 50% isodose line, and had a mean follow-up time of 40.2 months (range = 12-96). All patients were evaluated post-SRS for time to hormonal normalization, time to relapse, as well as incidence and time course of radiation-induced hypopituitarism and cranial neuropathies. RESULTS: Initial normalization of hypersecretion was achieved in 22 patients (70%) with a median time to remission of 17.7 months. After initial hormonal remission, 7 patients (32%) experienced an endocrine relapse, with a mean time to relapse of 21 months. New endocrine deficiency within any of the five major hormonal axes occurred in 10 patients (32%). One patient (3%) developed new-onset unilateral optic nerve pallor within the temporal field 3 years after SRS. Three patients (10%) reported transient new or increasing frontal headaches of unclear etiology following their procedures. CONCLUSION: Time to endocrine remission was more rapid in patients treated with 35 Gy, as compared to previously reported literature using marginal doses of 20-24 Gy. Rates of endocrine remission and relapse, post-SRS hypopituitarism, and radiation-induced sequelae were not increased following higher dose treatment.

Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: a meta-analysis.

OBJECT: Seizures are a common presenting sign of intracranial arteriovenous malformations (AVMs). The object of this meta-analysis was to determine if the modality selected to treat AVMs affects the rate of seizure outcomes. METHODS: All published data describing seizure status as an outcome goal over the past 20 years were included in this study. Seizure outcomes following microsurgery (MS), endovascular embolization for cure (EVE), or stereotactic radiosurgery (SRS) were compared using a validated random effect logistic regression approach. RESULTS: 24 studies, with a total of 1157 patients, were analyzed. Overall, the microsurgical group had the best seizure control (p<0.01), with the relative predicted rates of seizure outcome as follows: MS 78.3% (95% CI 70.1% to 85.8%); SRS 62.8% (95% CI 55.0% to 70.0%); and EVE 49.3% (95% CI 32.1% to 66.6%). Patients in the SRS group who had complete obliteration of their AVMs achieved the highest rate of seizure control (85.2% (95% CI 79.1% to 91.2%); p<0.01). The development of new onset seizures occurred more frequently in patients undergoing EVE (39.4% (95% CI 8.1% to 67.8%)) compared with MS (9.1% (95% CI 5.0% to 13.1%)) and SRS (5.4% (95% CI 3.0% to 7.8%)) (p<0.3 and p<0.01, respectively). CONCLUSIONS: This is the first meta-analysis designed to study relative rates of seizure outcomes following the currently utilized AVM treatment modalities. In general, MS results in the highest proportion of seizure control. However, if SRS results in successful obliteration of the AVM, then this modality is the most effective in achieving seizure control.

Congenital os odontoideum arising from the secondary ossification center without prior fracture.

The etiology of os odontoideum has been debated in the literature since the condition was initially described. The authors present the case of a 4-year-old girl who was found to have an os odontoideum with atlantoaxial instability after a motor vehicle collision. Imaging performed 3 years earlier demonstrated an incompletely ossified, cartilaginous, orthotopic os separated from the body of the odontoid process at the level of the secondary ossification center with a short odontoid process. This case presents the earliest imaging demonstration of the presence of a congenital orthotopic os odontoideum at the secondary ossification center. The authors review the pertinent literature and propose that the etiology of os odontoideum is multifactorial and related to the embryology and vascular supply to the odontoid process.

How large is the typical subarachnoid hemorrhage? A review of current neurosurgical knowledge.

BACKGROUND: Despite the morbidity and mortality of subarachnoid hemorrhage (SAH), the average volume of a typical hemorrhage is not well defined. Animal models of SAH often do not accurately mimic the human disease process. OBJECTIVE: The purpose of this study is to estimate the average SAH volume, allowing standardization of animal models of the disease. METHODS: We performed a MEDLINE search of SAH volume and erythrocyte counts in human cerebrospinal fluid as well as for volumes of blood used in animal injection models of SAH, from 1956 to 2010. We polled members of the American Association of Neurological Surgeons (AANS) for estimates of typical SAH volume. Using quantitative data from the literature, we calculated the total volume of SAH as equal to the volume of blood clotted in basal cisterns plus the volume of dispersed blood in cerebrospinal fluid. The results of the AANS poll confirmed our estimates. RESULTS: The human literature yielded 322 publications and animal literature, 237 studies. Four quantitative human studies reported blood clot volumes ranging from 0.2 to 170 mL, with a mean of ∼20 mL. There was only one quantitative study reporting cerebrospinal fluid red blood cell counts from serial lumbar puncture after SAH. Dispersed blood volume ranged from 2.9 to 45.9 mL, and we used the mean of 15 mL for our calculation. Therefore, total volume of SAH equals 35 mL. The AANS poll yielded 176 responses, ranging from 2 to 350 mL, with a mean of 33.9 ± 4.4 mL. CONCLUSIONS: Based on our estimate of total SAH volume of 35 mL, animal injection models may now become standardized for more accurate portrayal of the human disease process.

Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma.

Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance perfusion-weighted imaging (MR-PWI) in discriminating the EGFRvIII-expressing glioblastoma subtype. We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF). Concurrently, 3 independent observers reviewed preoperative 1.5-Tesla (T)/SE or 3.0-Tesla (T)/GE MR perfusion images to determine the maximum relative tumor blood volume (rTBV) of each of these tumors. EGFRvIII-expressing glioblastomas showed significantly higher rTBV, compared with those tumors lacking EGFRvIII expression. This association was observed in both the 1.5T/SE (P = .000) and 3.0T/GE (P = .001) cohorts. By logistic regression analysis, combining the 2 MR system cohorts, rTBV was a very strong predictor of EGFRvIII mutation (odds ratio [rTBV] = 2.70; P = .000; McFadden's ρ(2) = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (A(z) = 0.81). In addition, we found that VEGF upregulation was associated, although without reaching statistical significance, with EGFRvIII expression (P = .16) and with increased rTBV (F-ratio = 2.71; P = .102). These trends suggest that VEGF-mediated angiogenesis may be a potential mediator of angiogenesis to increase perfusion in EGFRvIII-expressing glioblastomas, but there are likely several other contributing factors. This study demonstrates the potential to use rTBV, a MR-PWI-derived parameter, as a noninvasive surrogate of the EGFRvIII mutation.

Morphometric analysis of posterior fossa after in utero myelomeningocele repair.

OBJECT: Myelomeningocele (MMC) is characterized by a defect in caudal neurulation and appears at birth with a constellation of neuroanatomical abnormalities, including Chiari malformation Type II. The authors investigated the effects of antenatal versus postnatal repair of MMC through a quantitative analysis of morphometric changes in the posterior fossa (PF). METHODS: The authors retrospectively reviewed the records of 29 patients who underwent in utero MMC repair, 24 patients who underwent postnatal repair, and 114 fetal and pediatric controls. Tonsillar displacement, cerebellum length, pons length, clivus-supraocciput (CSO) angle, and PF area were compared in antenatal and postnatal MMC repair groups as well as in controls without neural tube defects by using t-tests and correlation coefficients. RESULTS: Initially, the in utero CSO angle was significantly more acute in all patients with MMC--prenatally and postnatally repaired--as compared with controls (57.8° vs 75.4°, p < 0.001); however, the angle rapidly changed and became similar to that in controls between 30 and 31 weeks' gestation to approximately 80°, with antenatal repair having little effect. Postnatally, the CSO angle decreased in controls (R = -0.58) and in the antenatal repair group (R = -0.17). The cerebellum and pons length demonstrated no significant differences in any group. Overall, tonsil descent was corrected in the antenatal repair group as compared with postnatal repair (p < 0.001), and the PF area increased in all 3 groups in utero. Growth was less rapid in patients with MMC compared with controls, but this was corrected by antenatal repair (p = 0.015). CONCLUSIONS: Myelomeningocele was associated with tonsillar herniation and a smaller PF than in control fetuses. Antenatal surgical repair corrected both abnormalities. The CSO angle began significantly more acutely in patients with MMC, but normalized with development regardless of when surgery was performed. Determining the clinical effects of antenatal repair requires further follow-up.