Unique and shared inflammatory profiles of human brain endothelia and pericytes.

BACKGROUND: Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed. METHODS: To study the effects of neuroinflammation at the BBB, primary brain endothelial cells and pericytes were isolated from human biopsy tissue. Culture purity was examined using qPCR and immunocytochemistry. Electrical cell-substrate impedance sensing (ECIS) was used to determine the barrier properties of endothelial and pericyte cultures. Using immunocytochemistry, cytometric bead array, and ECIS, we compared the responses of endothelia and pericytes to a panel of inflammatory stimuli (IL-1ß, TNFα, LPS, IFN-γ, TGF-ß1, IL-6, and IL-4). Secretome analysis was performed to identify unique secretions of endothelia and pericytes in response to IL-1ß. RESULTS: Endothelial cells were pure, moderately proliferative, retained the expression of BBB-related junctional proteins and transporters, and generated robust TEER. Both endothelia and pericytes have the same pattern of transcription factor activation in response to inflammatory stimuli but respond differently at the secretion level. Secretome analysis confirmed that endothelia and pericytes have overlapping but distinct secretome profiles in response to IL-1ß. We identified several cell-type specific responses, including G-CSF and GM-CSF (endothelial-specific), and IGFBP2 and IGFBP3 (pericyte-specific). Finally, we demonstrated that direct addition of IL-1ß, TNFα, LPS, and IL-4 contributed to the loss of endothelial barrier integrity in vitro. CONCLUSIONS: Here, we identify important cell-type differences in the inflammatory response of brain pericytes and endothelia and provide, for the first time, a comprehensive profile of the secretions of primary human brain endothelia and pericytes which has implications for understanding how inflammation affects the cerebrovasculature.

MRI interactions of a fully implantable pressure monitoring device.

PURPOSE: To investigate the potential patient risk and interactions between a prototype implantable pressure monitoring device and a 3T clinical magnetic resonance imaging (MRI) machine to guide device design towards MR Conditional safety approval. MATERIALS AND METHODS: The pressure monitor device contained a catheter-mounted piezo-resistive pressure sensor, rechargeable battery, wireless communication system, and inductive pickup coil. Standard testing methods were used to guide experiments to investigate static field induced force and torque, radiofrequency (RF)-induced heating, image artifacts, and the MR's effect on device function. The specific clinical application of intracranial pressure monitoring was considered. RF-induced heating experiments were supported by numerical modeling of the RF body coil, the device, and experimental phantom. RESULTS: Sensing catheter lead length and configuration was an important component of the device design. A short 150 mm length catheter produced a heating effect of less than 2°C and a long 420 mm length catheter caused heating of 7.2°C. Static magnetic field interactions were below standard safety risk levels and the MR did not interfere with device function; however, artifacts have the potential to interfere with image quality. CONCLUSION: Investigation of MR interactions at the prototype stage provides useful implantable device design guidance and confidence that an implantable pressure monitor may be able to achieve MR Conditional safety approval.

Gamma knife surgery for low-grade gliomas.

OBJECT: Data regarding the long-term efficacy of Gamma knife surgery on a large series of patients with low-grade gliomas is lacking. We aimed to review the outcome of patients with low-grade gliomas undergoing Gamma knife surgery at the Lars Leksell Gamma Knife Center at the University of Virginia to clarify its role in the management of these lesions. METHODS: A retrospective review of 49 patients treated between 1989 and 2003 was conducted. The median follow up was 63 months. Gamma knife surgery was generally performed for tumors in eloquent brain, residual tumor post-surgery or for late progression after surgery. RESULTS: Median clinical progression free survival was 44 months and median radiological progression free survival was 37 months. Five-year radiological progression free survival was 37% while clinical progression free survival was 41%. Mortality due to tumor progression occurred in 7 patients (14%). Complete radiological remission was seen in 14 patients (29%). Complications due to Gamma surgery were seen in 4 patients (8%). Of these, two resolved without sequelae, one required surgery for neurological decline and associated radiation induced changes, and one patient suffered a permanent neurological deficit from treatment. CONCLUSION: Gamma knife radiosurgery is a safe treatment for low-grade gliomas and may be considered in patients with residual or recurrent disease.

Acute hydrocephalus secondary to herpes simplex type II meningitis.

A 34-year-old woman presented with a rapid onset of meningitic symptoms. Cerebrospinal fluid (CSF) from a lumbar puncture revealed a leucocytosis with a preponderance of monocytes, elevated protein and reduced glucose. Herpes simplex virus (HSV) type II was subsequently confirmed by polymerase chain reaction (PCR) of CSF. The patient's level of consciousness deteriorated and a CT scan revealed hydrocephalus. The patient required placement of an external ventricular drain for 5 days; however, she made a full recovery without specific antiviral therapy. This is the first reported case of hydrocephalus secondary to isolated HSV type II meningitis.

Paediatric central nervous system tumours in a New Zealand population: a 10-year experience of epidemiology, management strategies and outcomes.

We analysed 166 cases of paediatric central nervous system tumour presenting to Auckland City and Starship Children's Hospital, New Zealand, between 1995 and 2004. The purpose of this study was to perform an audit of paediatric neurosurgical practice in the upper North Island of New Zealand with the objective of assessing patient presentation, demographics, and modality and efficacy of therapy. The overall incidence of central nervous system tumours was 3.42/100,000/year. The incidence rate of medulloblastoma for Maori was over double that for European New Zealanders. Tumour clearance was attempted in 81.3% of patients. Some type of adjunct therapy was received by 45.2% of patients. Overall, 60.8% of patients had satisfactory or good results. Survival rates for pilocytic astrocytoma and ependymoma were consistent with previous studies. Survival data for medulloblastoma demonstrate improved outcomes with complete resection of tumour and with a specialist paediatric neurosurgeon compared with general neurosurgeons. Recent management changes have led to improved outcomes.

Gamma knife surgery for low-grade gliomas.

OBJECT: Data regarding the long-term efficacy of Gamma knife surgery on a large series of patients with low-grade gliomas is lacking. We aimed to review the outcome of patients with low-grade gliomas undergoing Gamma knife surgery at the Lars Leksell Gamma Knife Center at the University of Virginia to clarify its role in the management of these lesions. METHODS: A retrospective review of 49 patients treated between 1989 and 2003 was conducted. The median follow up was 63 months. Gamma knife surgery was generally performed for tumors in eloquent brain, residual tumor post-surgery or for late progression after surgery. RESULTS: Median clinical progression free survival was 44 months and median radiological progression free survival was 37 months. Five-year radiological progression free survival was 37% while clinical progression free survival was 41%. Mortality due to tumor progression occurred in 7 patients (14%). Complete radiological remission was seen in 14 patients (29%). Complications due to Gamma surgery were seen in 4 patients (8%). Of these, two resolved without sequelae, one required surgery for neurological decline and associated radiation induced changes, and one patient suffered a permanent neurological deficit from treatment. CONCLUSION: Gamma knife radiosurgery is a safe treatment for low-grade gliomas and may be considered in patients with residual or recurrent disease.

Transfer of intubated patients with traumatic brain injury to Auckland City Hospital.

BACKGROUND: Delays in patient transfer to definitive neurosurgical care after traumatic brain injury are important in determining neurological outcome. The efficiency of interhospital transfer of patients to Auckland City Hospital (ACH) was analysed and compared with international standards. METHODS: The ACH Department of Critical Care Medicine database for the year 2002 was reviewed, with supplementary information obtained from transfer organizations, hospital notes, radiology archives, and operative logbooks. RESULTS: Thirty-four adult patients with traumatic brain injury and no special reasons for delayed transfer were transported intubated from other hospitals in the North Island of New Zealand. The median time from injury to arrival at ACH was 6.5 h. It took a median 4.4 h for patients to get from initial computed tomographic imaging to ACH. For those requiring evacuation of haematomas, the mean time from arrival at ACH to the start of the operation was 1.4 h. Only 33% of patients from other metropolitan Auckland hospitals, and none from hospitals outside the city, arrived within 4 h from the time of injury. CONCLUSION: Transfer times for brain trauma patients are currently longer than recommended for optimal neurological outcome. Referring hospitals and transfer organizations should review their systems to identify areas for improvement. Direct admission to theatre needs to be expedited within ACH when required. Triage of all trauma patients in metropolitan Auckland with a Glasgow Coma Scale score of less than 14 to ACH would be likely to improve time to treatment. A mobile acute neurosurgical service based in Auckland that would support general surgeons initiating acute decompressive cranial operations would be likely to reduce time to surgery and improve outcomes for patients admitted to hospitals outside Auckland. The development of a mobile acute neurosurgery service which would complete decompressive procedures started by general surgeons would likely improve trauma outcomes for patients injured outside Auckland.

Encephalocoele-- epidemiological variance in New Zealand.

Considerable variation in the epidemiology of encephalocoeles throughout the world has been described in previous studies. We analysed 46 cases of encephalocoele presenting to Auckland and Starship Children's Hospital over the last 25 years to determine if our experience differed from that seen in a typical Western population, and to determine if there was variation between the different racial groups within New Zealand. The overall incidence of encephalocoeles in the area serviced by the neurosurgical services of Auckland and Starship Children's Hospitals was 1 in 13,418 births. This rate is at the higher end of the incidence spectrum compared with previous series. Overall, New Zealand appears to demonstrate a typical Western distribution of encephalocoele location. In people of Pacific Island descent, both the rate of encephaloceles (1 per 8,873 births) and the percentage of sincipital lesions (44%) differed from the rest of the population. Additionally, a higher than expected proportion of sincipital encephalocoeles was seen in male babies (5:1 male to female ratio). In most other regards our population resembles that of western cohorts published in the literature.

Spontaneous spinal hematomas and low-molecular-weight heparin. Report of four cases and review of the literature.

The purpose of this article is to raise awareness of spontaneous spinal hematomas that develop after administration of low-molecular-weight heparin therapy. The authors describe four patients in whom these hematomas developed without precipitating events while receiving a treatment dose of enoxaparin (Clexane) (approximately 1 mg/kg). Spontaneous spinal hematomas (not related to trauma, surgery, or lumbar puncture) are a rare clinical entity. Several causes have been identified, including acquired and congenital clotting abnormalities and underlying vascular lesions. Aspirin, warfarin, tissue plasminogen activator, and heparin have all been implicated in causing spinal hematomas. Concerns regarding the use of low-molecular-weight heparin agents in neuraxis anesthesia have been well documented. Their possible contribution to nontraumatic spinal hematomas has been less well described. The authors believe that low-molecular-weight heparin agents present a small but significant risk of spinal hematoma. This should be considered when prescribing therapy because such a complication may be catastrophic.