Detection of microbleeds associated with sentinel headache using MRI quantitative susceptibility mapping: pilot study.

OBJECT: Sentinel headaches (SHs) associated with cerebral aneurysms (CAs) could be due to microbleeds, which are considered a sign that an aneurysm is unstable. Despite the prognostic importance of these microbleeds, they remain difficult to detect using routine imaging studies. The objective of this pilot study is to detect microbleeds associated with SH using a magnetic resonance imaging (MRI) quantitative susceptibility mapping (QSM) sequence and then evaluate the morphological characteristics of unstable aneurysms with microbleeds. METHODS: Twenty CAs in 16 consecutive patients with an initial presentation of headache (HA) leading to a diagnosis of CA were analyzed. Headaches in 4 of the patients (two of whom had 2 aneurysms each) met the typical definition of SH, and the other 12 patients (two of whom also had 2 aneurysms each) all had migraine HA. All patients underwent imaging with the MRI-QSM sequence. Two independent MRI experts who were blinded to the patients' clinical history performed 3D graphical analysis to evaluate for potential microbleeds associated with these CAs. Computational flow and morphometric analyses were also performed to estimate wall shear and morphological variables. RESULTS: In the 4 patients with SH, MRI-QSM results were positive for 4 aneurysms, and hence these aneurysms were considered positive for non-heme ferric iron (microbleeds). The other 16 aneurysms were negative. Among aneurysm shape indices, the undulation index was significantly higher in the QSM-positive group than in the QSM-negative group. In addition, the spatial averaged wall shear magnitude was lower in the aneurysm wall in direct contact with microbleeds. CONCLUSIONS: MRI-QSM allows for objective detection of microbleeds associated with SH and therefore identification of unstable CAs. CAs with slightly greater undulation indices are associated with positive MRI-QSM results and hence with microbleeds. Studies with larger populations are needed to confirm these preliminary findings.

Intraventricular extension of an aneurysmal subarachnoid hemorrhage is an independent predictor of a worse functional outcome.

OBJECTIVE: The objective of this study is to determine the impact of intraventricular hemorrhage (IVH) on the cognitive prognosis of subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysm, independent of the presence of intraparenchymal hemorrhage, hydrocephalus or vasospasm. PATIENT AND METHODS: A Retrospective review of a prospectively collected database of patients with aneurysmal SAH from July 2009 to November 2016 was performed. Patients were included if they had a saccular aneurysm with a Hunt-Hess grade (HHG) 1-3. Those who underwent craniectomy/clipping and those with vasospasm were excluded. Patients with IVH were grouped into 5 groups depending on the blood distribution in the ventricles. Functional outcomes studied were modified Rankin score (mRS) 0-2, cognitive impairment and memory impairment, and the presence of amnesia to the event. A univariate followed by a multivariate analysis ware performed. RESULTS: A total of 443 patients were identified and 124 patients met the criterion. There were no significant differences in the proportion of patients with mRS of 0-2 between patients with IVH and those without IVH but with EVD (external ventricular drain). There was a higher proportion of cognitive deficits in patients with IVH (71.95%), compared to those without (31.58%; p = 0.01). Patients with IVH had a higher rate of anterograde amnesia (100% vs. 4.3% p < 0.0001), lower rate of mRS 0-2 (78% vs 100% p < 0.001), and higher rate of cognitive impairment (71.9% vs. 13% p < 0.0001) compared with those who did not require an EVD. Grade 3 and grade 4 were shown to have lower rate of patients with mRS 0-2 and a higher rate of cognitive impairment. In multivariate analysis, independent predictors of cognitive and memory impairment were increasing HHG (OR = 155.33; P < 0.01), ACOM/A1/ACA/anterior choroidal aneurysms, (OR = 5.24; P = 0.04), increasing Fischer scale (OR = 6.93; P = 0.01), and increasing IVH grade (OR = 6.9; P = 0.01). Only worse HHG (OR = 2704.22; P = 0.01) and IVH grade 2-4 were associated (perfect predictor, OR cannot be extracted) with anterograde amnesia. CONCLUSION: IVH is an independent prognosticator of SAH cognitive outcomes. The effect of IVH drainage and other intraventricular therapies on SAH course is an attractive topic for further investigation.

Minimally invasive resection of lumbar intraspinal synovial cysts via a contralateral approach: review of 13 cases.

OBJECT: The authors sought to determine patient-related outcomes after minimally invasive surgical (MIS) lumbar intraspinal synovial cyst excision via a tubular working channel and a contralateral facet-sparing approach. METHODS: All the patients with a symptomatic lumbar intraspinal synovial cyst who underwent surgery at the University of Iowa Hospitals and Clinics with an MIS excision via a contralateral approach were treated between July 2010 and August 2014. There was a total of 13 cases. Each patient was evaluated with preoperative neurological examinations, lumbar spine radiography, MRI, and visual analog scale (VAS) scores. The patients were evaluated postoperatively with neurological examinations and VAS and Macnab scores. The primary outcomes were improvement in VAS and Macnab scores. Secondary outcomes were average blood loss, hospital stay duration, and operative times. RESULTS: There were 5 males and 8 females. The mean age was 66 years, and the mean body mass index was 28.5 kg/m(2). Sixty-nine percent (9 of 13) of the cysts were at L4-5. Most patients had low-back pain and radicular pain, and one-third of them had Grade 1 spondylolisthesis. The mean (± SD) follow-up duration was 20.8 ± 16.9 months. The mean Macnab score was 3.4 ± 1.0, and the VAS score decreased from 7.8 preoperatively to 2.9 postoperatively. The mean operative time was 123 ± 30 minutes, with a mean estimated blood loss of 44 ± 29 ml. Hospital stay averaged 1.5 ± 0.7 days. There were no complications noted in this series. CONCLUSIONS: The MIS excision of lumbar intraspinal synovial cysts via a contralateral approach offers excellent exposure to the cyst and spares the facet joint at the involved level, thus minimizing risk of instability, blood loss, operative time, and hospital stay. Prospective randomized trials with longer follow-up times and larger cohorts are needed to conclusively determine the superiority of the contralateral MIS approach over others, including open or ipsilateral minimally invasive surgery.

Minimally invasive pars approach for foraminal disc herniation.

We present a retrospective cohort study on the outcome of patients with foraminal disc herniations (FDH) treated with partial pars resections using minimally invasive surgery (MIS) through a tube. FDH present a challenge due to the more lateral trajectory needed for their excision and thereby more muscle dissection and possibly facet resection. Forty patients, 19 women and 21 men with a mean age ± standard deviation of 58 ± 12 years, underwent MIS for FDH. Data on length of hospital stay, body mass index and outcomes were collected prospectively and reviewed retrospectively. Average length of stay following surgery was 1 ± 1 days. There was one wound infection and four unsatisfactory results. Using the Macnab score, good to excellent results were achieved in 89% of the patients. Based on these results, MIS surgery with partial pars resection is an attractive option in the treatment of FDH with low morbidity and short hospital stays.

Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient: Case report.

Over the last decade, human cell transplantation and neural stem cell trials have examined the feasibility and safety of these potential therapies for treatment of a variety of neurological disorders. However, significant safety concerns have surrounded these trials due to the possibility of ectopic, uncontrolled cellular growth and tumor formation. The authors present the case of an 18-year-old woman who sustained a complete spinal cord injury at T10-11. Three years after injury, she remained paraplegic and underwent olfactory mucosal cell implantation at the site of injury. She developed back pain 8 years later, and imaging revealed an intramedullary spinal cord mass at the site of cell implantation, which required resection. Intraoperative findings revealed an expanded spinal cord with a multicystic mass containing large amounts of thick mucus-like material. Histological examination and immunohistochemical staining revealed that the mass was composed mostly of cysts lined by respiratory epithelium, submucosal glands with goblet cells, and intervening nerve twigs. This is the first report of a human spinal cord mass complicating spinal cord cell transplantation and neural stem cell therapy. Given the prolonged time to presentation, safety monitoring of all patients with cell transplantation and neural stem cell implantation should be maintained for many years.

Long-term disease and neurological outcomes in patients with pediatric intramedullary spinal cord tumors.

OBJECT: Radical resection is recommended as the first-line treatment for pediatric intramedullary spinal cord tumors (IMSCTs), but it is associated with morbidity, including risk of neurological decline and development of postoperative spinal deformity. The authors report long-term data on clinical and treatment determinants affecting disease survival and neurological outcomes. METHODS: Case records for pediatric patients (< 21 years of age at presentation) who underwent surgery for IMSCTs at the authors' institution between January 1975 and January 2010 were analyzed. The patients' demographic and clinical characteristics (including baseline neurological condition), the treatment they received, and their disease course were reviewed. Long-term disease survival and functional outcome measures were analyzed. RESULTS: A total of 55 patients (30 male and 25 female) were identified. The mean duration of follow-up (± SEM) was 11.4 ± 1.3 years (median 9.3 years, range 0.2-37.2 years). Astrocytomas were the most common tumor subtype (29 tumors [53%]). Gross-total resection (GTR) was achieved in 21 (38%) of the 55 patients. At the most recent follow-up, 30 patients (55%) showed neurological improvement, 17 (31%) showed neurological decline, and 8 (15%) remained neurologically stable. Patients presenting with McCormick Grade I were more likely to show functional improvement by final follow-up (p = 0.01) than patients who presented with Grades II-V. Kaplan-Meier actuarial tumor progression-free survival rates at 5, 10, and 20 years were 61%, 54%, and 44%, respectively; the overall survival rates were 85% at 5 years, 74% at 10 years, and 64% at 20 years. On multivariate analysis, GTR (p = 0.04) and tumor histological grade (p = 0.02) were predictive of long-term survival; GTR was also associated with improved 5-year progression-free survival (p = 0.01). CONCLUSIONS: The prognosis for pediatric IMSCTs is favorable with sustained functional improvement expected in a significant proportion of patients on long-term follow-up. Long-term survival at 10 years (75%) and 20 years (64%) is associated with aggressive resection. Gross-total resection was also associated with improved 5-year progression-free survival (86%). Hence, the treatment benefits of GTR are sustained on extended follow-up.

Long-term incidence and risk factors for development of spinal deformity following resection of pediatric intramedullary spinal cord tumors.

OBJECT: Spinal deformity in pediatric patients with intramedullary spinal cord tumors (IMSCTs) may be either due to neurogenic disability or due to secondary effects of spinal decompression. It is associated with functional decline and impairment in health-related quality-of-life measures. The authors sought to identify the long-term incidence of spinal deformity in individuals who had undergone surgery for IMSCTs as pediatric patients and the risk factors and overall outcomes in this population. METHODS: Treatment records for pediatric patients (age < 21 years) who underwent surgical treatment for histology-proven primary IMSCTs between 1975 and 2010 were reviewed. All patients were evaluated in consultation with the pediatric orthopedics service. Clinical records were reviewed for baseline and follow-up imaging studies, surgical fusion treatment, and long-term skeletal and disease outcomes. RESULTS: The authors identified 55 patients (30 males and 25 females) who were treated for pediatric IMSCTs between January 1975 and January 2010. The mean duration of follow-up (± SEM) was 11.4 ± 1.3 years (median 9.3 years, range 0.2-37.2 years). Preoperative skeletal deformity was diagnosed in 11 (20%) of the 55 patients, and new-onset postoperative deformity was noted in 9 (16%). Conservative management with observation or external bracing was sufficient in 8 (40%) of these 20 cases. Surgical fusion was necessary in 11 (55%). Posterior surgical fusion was sufficient in 6 (55%) of these 11 cases, while combined anterior and posterior fusion was undertaken in 5 (45%). Univariate and multivariate analysis of clinical and surgical treatment variables indicated that preoperative kyphoscoliosis (p = 0.0032) and laminectomy/laminoplasty at more than 4 levels (p = 0.05) were independently associated with development of spinal deformity that necessitated surgical fusion. Functional scores and 10-year disease survival outcomes were similar between the 2 groups. CONCLUSIONS: Long-term follow-up is essential to monitor for delayed development of spinal deformity, and regular surveillance imaging is recommended for patients with underlying deformity. The authors' extended follow-up highlights the risk factors associated with development of spinal deformity in patients treated for pediatric IMSCTs. Surgical fusion allows patients who develop progressive deformity to achieve long-term functional and survival outcomes comparable to those of patients who do not develop progressive deformity.

Nociceptive neuropeptide increases and periorbital allodynia in a model of traumatic brain injury.

OBJECTIVE: This study tests the hypothesis that injury to the somatosensory cortex is associated with periorbital allodynia and increases in nociceptive neuropeptides in the brainstem in a mouse model of controlled cortical impact (CCI) injury. METHODS: Male C57BL/6 mice received either CCI or craniotomy-only followed by weekly periorbital von Frey (mechanical) sensory testing for up to 28 days post-injury. Mice receiving an incision only and naïve mice were included as control groups. Changes in calcitonin gene-related peptide (CGRP) and substance P (SP) within the brainstem were determined using enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Activation of ionized calcium-binding adaptor molecule-1-labeled macrophages/microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were evaluated using immunohistochemistry because of their potential involvement in nociceptor sensitization. RESULTS: Incision-only control mice showed no changes from baseline periorbital von Frey mechanical thresholds. CCI significantly reduced mean periorbital von Frey thresholds (periorbital allodynia) compared with baseline and craniotomy-only at each endpoint, analysis of variance P < .0001. Craniotomy significantly reduced periorbital threshold at 14 days but not 7, 21, or 28 days compared with baseline threshold, P < .01. CCI significantly increased SP immunoreactivity in the brainstem at 7 and 14 days but not 28 days compared with craniotomy-only and controls, P < .001. CGRP levels in brainstem tissues were significantly increased in CCI groups compared with controls (incision-only and naïve mice) or craniotomy-only mice at each endpoint examined, P < .0001. There was a significant correlation between CGRP and periorbital allodynia (P < .0001, r = -0.65) but not for SP (r = 0.20). CCI significantly increased the number of macrophage/microglia in the injured cortex at each endpoint up to 28 days, although cell numbers declined over weeks post-injury, P < .001. GFAP(+) immunoreactivity was significantly increased at 7 but not 14 or 28 days after CCI, P < .001. Craniotomy resulted in transient periorbital allodynia accompanied by transient increases in SP, CGRP, and GFAP immunoreactivity compared with control mice. There was no increase in the number of macrophage/microglia cells compared with controls after craniotomy. CONCLUSION: Injury to the somatosensory cortex results in persistent periorbital allodynia and increases in brainstem nociceptive neuropeptides. Findings suggest that persistent allodynia and increased neuropeptides are maintained by mechanisms other than activation of macrophage/microglia or astrocyte in the injured somatosensory cortex.

Model for End-Stage Liver Disease score for predicting outcome in critically ill medical patients with liver cirrhosis.

PURPOSE: We hypothesized that the Model for End-Stage Liver Disease (MELD) score at admission to the intensive care unit (ICU) can predict in-hospital mortality for patients with liver cirrhosis. We also tested the MELD-natremia (Na) score and compared the predictive value of the 2 models. MATERIALS AND METHODS: This is a retrospective cohort study. A total of 441 consecutive patients with liver cirrhosis admitted to the ICU were included. The MELD and MELD-Na scores and other variables were obtained upon patients' admission to the ICU. RESULTS: The area under the receiver operating characteristic curve to predict in-hospital mortality was 0.77 (95% confidence interval, 0.73-0.82) for the MELD score and 0.77 (95% confidence interval, 0.73-0.81) for the MELD-Na score. CONCLUSION: The MELD scoring system provides useful prognostic information for critically ill patients with liver cirrhosis admitted to an ICU. The MELD and MELD-Na scores had similar predictive value.

Impact of total disc arthroplasty on the surgical management of lumbar degenerative disc disease: Analysis of the Nationwide Inpatient Sample from 2000 to 2008.

BACKGROUND: Spinal fusion is the most rapidly increasing type of lumbar spine surgery for various lumbar degenerative pathologies. The surgical treatment of lumbar spine degenerative disc disease may involve decompression, stabilization, or arthroplasty procedures. Lumbar disc athroplasty is a recent technological advance in the field of lumbar surgery. This study seeks to determine the clinical impact of anterior lumbar disc replacement on the surgical treatment of lumbar spine degenerative pathology. This is a retrospective assessment of the Nationwide Inpatient Sample (NIS). METHODS: The NIS was searched for ICD-9 codes for lumbar and lumbosacral fusion (81.06), anterior lumbar interbody fusion (81.07), and posterolateral lumbar fusion (81.08), as well as for procedure codes for revision fusion surgery in the lumbar and lumbosacral spine (81.36, 81.37, and 81.38). To assess lumbar arthroplasty, procedure codes for the insertion or replacement of lumbar artificial discs (84.60, 84.65, and 84.68) were queried. Results were assayed from 2000 through 2008, the last year with available data. Analysis was done using the lme4 package in the R programming language for statistical computing. RESULTS: A total of nearly 300,000 lumbar spine fusion procedures were reported in the NIS database from 2000 to 2008; assuming a representative cross-section of the US health care market, this models approximately 1.5 million procedures performed over this time period. In 2005, the first year of its widespread use, there were 911 lumbar arthroplasty procedures performed, representing 3% of posterolateral fusions performed in this year. Since introduction, the number of lumbar spine arthroplasty procedures has consistently declined, to 653 total procedures recorded in the NIS in 2008. From 2005 to 2008, lumbar arthroplasties comprised approximately 2% of lumbar posterolateral fusions. Arthroplasty patients were younger than posterior lumbar fusion patients (42.8 ± 11.5 vs. 55.9 ± 15.1 years, P < 0.0000001). The distribution of arthroplasty procedures was even between academic and private urban facilities (48.5% and 48.9%, respectively). While rates of posterolateral lumbar spine fusion steadily grew during the period (OR 1.06, 95% CI: 1.05-1.06, P < 0.0000001), rates of revision surgery and anterior spinal fusion remained static. CONCLUSIONS: The impact of lumbar arthroplasty procedures has been minimal. Measured as a percentage of more common lumbar posterior arthrodesis procedures, lumbar arthroplasty comprises only approximately 2% of lumbar spine surgeries performed in the United States. Over the first 4 years following the Food and Drug Administration (FDA) approval, the frequency of lumbar disc arthroplasty has decreased while the number of all lumbar spinal fusions has increased.

Medical school and residency influence on choice of an academic career and academic productivity among neurosurgery faculty in the United States. Clinical article.

OBJECT: Factors determining choice of an academic career in neurological surgery are unclear. This study seeks to evaluate the graduates of medical schools and US residency programs to determine those programs that produce a high number of graduates remaining within academic programs and the contribution of these graduates to academic neurosurgery as determined by h-index valuation. METHODS: Biographical information from current faculty members of all accredited neurosurgery training programs in the US with departmental websites was obtained. Any individual who did not have an American Board of Neurological Surgery certificate (or was not board eligible) was excluded. The variables collected included medical school attended, residency program completed, and current academic rank. For each faculty member, Web of Science and Scopus h-indices were also collected. RESULTS: Ninety-seven academic neurosurgery departments with 986 faculty members were analyzed. All data regarding training program and medical school education were compiled and analyzed by center from which each faculty member graduated. The 20 medical schools and neurosurgical residency training programs producing the greatest number of graduates remaining in academic practice, and the respective individuals' h-indices, are reported. Medical school graduates of the Columbia University College of Physicians and Surgeons chose to enter academics the most frequently. The neurosurgery training program at the University of Pittsburgh produced the highest number of academic neurosurgeons in this sample. CONCLUSIONS: The use of quantitative measures to evaluate the academic productivity of medical school and residency graduates may provide objective measurements by which the subjective influence of training experiences on choice of an academic career may be inferred. The top 3 residency training programs were responsible for 10% of all academic neurosurgeons. The influence of medical school and residency experiences on choice of an academic career may be significant.

Treatment outcome of aneurysmal subarachnoid hemorrhage in patients aged 70 years and older.

BACKGROUND: The incidence of subarachnoid hemorrhage is increasing, especially in the elderly as life expectancy increases. Aggressive treatment of aneurysms in the elderly is usually avoided because of a presumed poor prognosis. OBJECTIVE: The aim of this study was to assess the outcome of treatment in patients older than 70 years old. METHODS: We performed a retrospective chart review of 150 patients aged 70 years and older who were treated at Jefferson Hospital from 2004 to 2009. Data including World Federation of Neurological Surgeons grade and Hunt and Hess classification, specific management components, and treatment outcome on discharge were analyzed. RESULTS: One hundred ten patients had aneurysms coiled, 9 patients had aneurysms clipped, 11 patients had aneurysms that were not treated, and 20 patients had no visible aneurysms. Overall, increased World Federation of Neurological Surgeons grades correlated strongly with poor clinical outcome. Statistical tests indicate that patients who died (mean, 78.8, n=35) or who went into rehabilitation (mean, 76.5, n=81) were significantly older than patients who were discharged home (mean, 73.1, n=20). However, day of presentation after initial symptom(s) of subarachnoid hemorrhage and placement of ventriculoperitoneal shunt also influenced clinical outcome. Patients who had a ventriculoperitoneal shunt were more likely to go into rehabilitation than patients who did not, and patients without a ventriculoperitoneal shunt were more likely to die. CONCLUSION: Older age should not preclude a patient from aneurysm treatment. Factors such as low Hunt and Hess or World Federation of Neurological Surgeons grades, earlier presentation to the hospital after initial symptoms, early shunting, prompt interventions, and tailored postoperative management can result in favorable clinical outcomes.

Iron regulatory protein-2 knockout increases perihematomal ferritin expression and cell viability after intracerebral hemorrhage.

Iron is deposited in perihematomal tissue after an intracerebral hemorrhage (ICH), and may contribute to oxidative injury. Cell culture studies have demonstrated that enhancing ferritin expression by targeting iron regulatory protein (IRP) binding activity reduces cellular vulnerability to iron and hemoglobin. In order to assess the therapeutic potential of this approach after striatal ICH, the effect of IRP1 or IRP2 gene knockout on ferritin expression and injury was quantified. Striatal ferritin in IRP1 knockout mice was similar to that in wild-type controls 3 days after stereotactic injection of artificial CSF or autologous blood. Corresponding levels in IRP2 knockouts were increased by 11-fold and 8.4-fold, respectively, compared with wild-type. Protein carbonylation, a sensitive marker of hemoglobin neurotoxicity, was increased by 2.4-fold in blood-injected wild-type striata, was not altered by IRP1 knockout, but was reduced by approximately 60% by IRP2 knockout. Perihematomal cell viability in wild-type mice, assessed by MTT assay, was approximately half of that in contralateral striata at 3 days, and was significantly increased in IRP2 knockouts but not in IRP1 knockouts. Protection was also observed when hemorrhage was induced by collagenase injection. These results suggest that IRP2 binding activity reduces ferritin expression in the striatum after ICH, preventing an optimal response to elevated local iron concentrations. IRP2 binding activity may be a novel therapeutic target after hemorrhagic CNS injuries.

Heme oxygenase activity and hemoglobin neurotoxicity are attenuated by inhibitors of the MEK/ERK pathway.

Hemoglobin breakdown produces an iron-dependent neuronal injury after experimental CNS hemorrhage that may be attenuated by heme oxygenase (HO) inhibitors. The HO enzymes are phosphoproteins that are activated by phosphorylation in vitro. While testing the effect of kinase inhibitors in cortical cell cultures, we observed that HO activity was consistently decreased by the MEK inhibitor U0126. The present study tested the hypothesis that MEK/ERK pathway inhibitors reduce HO activity and neuronal vulnerability to hemoglobin. The MEK inhibitors U0126 and SL327 and the ERK inhibitor FR180204 reduced baseline culture HO activity by 35-50%, without altering the activity of recombinant HO-1 or HO-2; negative control compounds U0124 and FR180289 had no effect. Hemoglobin exposure for 16h produced widespread neuronal injury, manifested by release of 59.2+/-7.8% of neuronal lactate dehydrogenase and a twelve-fold increase in malondialdehyde; kinase inhibitors were highly protective. HO-1 induction after hemoglobin treatment was also decreased by U0126, SL327, and FR180204. These results suggest that reduction in HO activity may contribute to the protective effect of MEK and ERK inhibitors against heme-mediated neuronal injury.