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Objective Von Hippel-Lindau (VHL) syndrome is a rare and complex disease. We described in 1996 a three generation VHL 2A kindred with 11 mutation carriers. We aim to share our experience regarding the long-term follow-up of this family and the management of all our other VHL patients focusing on frequently encountered neuroendocrine tumors: pheochromocytoma/paraganglioma and pancreatic neuroendocrine neoplasms (PNEN). Methods All VHL patients in follow-up at our tertiary center from 1980 to 2019 were identified. Clinical, laboratory, imaging and therapeutic characteristics were retrospectively analyzed. Results We identified 32 VHL patients in 16 different families, 7/16 were classified as VHL 2 subtype. In the previously described family, the 4 initially asymptomatic carriers developed a neuroendocrine tumor; 7 new children were born, 3 of them being mutation carriers; 2 patients died, one due to metastatic PNEN-related liver failure. Pheochromocytoma was frequent (22/32), bilateral (13/22;59%), often diagnosed in early childhood when active screening was timely performed, associated with paraganglioma in 5/22, rarely malignant (1/22) and recurred after surgery in some cases after more than 20 years. PNEN occurred in 8/32 patients (25%), and was metastatic in three. Surgery and palliative therapy allowed relatively satisfactory outcomes. Severe disabling morbidities due to central-nervous system and ophthalmologic hemangiomas, and other rare tumors as chondrosarcoma in 2 patients and polycythemia in 1 patient were observed. Conclusions Multidisciplinary approach and long-term follow-up is mandatory in VHL patients to manage the multiple debilitating morbidities and delay mortality in these complex patients.

OBJECTIVE Flow-diverter stents (FDSs) are not generally used for the management of acutely ruptured aneurysms with associated subarachnoid hemorrhage (SAH). Herein, the authors present their experience with FDSs in this scenario, focusing on the antiplatelet regimen, perioperative management, and outcome. METHODS The authors retrospectively reviewed their institutional database for the treatment and outcomes of all patients with acutely ruptured aneurysms and associated SAH from July 2010 to September 2018 who had received an FDS implant as stand-alone treatment within 4 days after diagnosis. The protocol with the use of flow diversion in these patients includes a low threshold for placement of external ventricular drains before stenting, followed by the administration of aspirin and clopidogrel with platelet testing before stent implantation. With this approach, the risk of hemorrhage and stent-related thrombus formation is limited. Demographic, clinical, technical, and imaging data were analyzed. RESULTS Overall, 76 patients (61% females, mean age 42.8 ± 11.3 years) met the inclusion criteria. FDS implantation was performed a median of 2 days after diagnosis. On average, 1.05 devices were used per procedure. There was no procedural mortality directly attributed to the endovascular intervention. Procedural device-related clinical complications were recorded in a total of 6 cases (7.9%) and resulted in permanent neurological morbidity in 2 cases (2.6%). There was complete immediate aneurysm occlusion in 11 patients (14.5%), and persistent aneurysm filling was seen in 65 patients (85.5%). Despite this, no patient presented with rebleeding from the target aneurysm. There was an excellent clinical outcome in 62 patients (81.6%), who had a 90-day modified Rankin Scale score of 0–2. Among the 71 survivors, total or near-total occlusion was observed in 64/67 patients (95.5%) with a 3- to 6-month angiographic follow-up and in all cases evaluated at 12 months. Five patients (6.6%) died during follow-up for reasons unrelated to the procedure or new hemorrhage. CONCLUSIONS Flow diversion is an effective therapeutic strategy for the management of select acutely ruptured aneurysms. Despite low rates of immediate aneurysm occlusion after FDS implantation, the device exerts an important protective effect. The authors’ experience confirmed no aneurysm rerupture, high rates of delayed complete occlusion, and complication rates that compare favorably with the rates obtained using other techniques.

Previous studies suggest that 14–30% of glioblastoma multiforme (GBM) patients and 5–24% of patients with brain metastases demonstrate imaging treatment-effects in the first few months after treatment [1], [2], [3]. These treatment-induced imaging changes, often termed pseudoprogression/radiation-necrosis, are depicted as increasing volumes of contrast-enhancing lesions on MRI, mimicking progression. Therefore, treatment decisions, such as whether to operate on a patient with radiographic deterioration, continue current treatment or change treatment is a daily unsolved struggle. In addition, radiation-based treatments may also induce vascular malformations such as radiation-induced Cavernous malformations (RICM) and capillary telangiectasias. Cavernous malformations are low-flow vascular malformations, characterized by the lack of mural elements of mature vascular structures and intervening parenchymal neural tissue [4]. Radiation induced capillary telangiectasias (RIT), thin-walled ectatic capillaries with intervening normal brain parenchyma, usually occur 3–9 months after irradiation. Cavernomas take a longer time to develop (1–35 years) after radiation [5]. RICMs mostly develop in the pediatric population [6], but are also observed in adults. In a literature search from 2006 by Nimjee et al [7], 76 cases of RICMs were found. A retrospective study conducted at Mayo clinic found 32 RICMs [5]. RICMs latency median was 12.0 years with only 3 diagnosed in the first two years post radiation (9.3%). Kleinschmidt-DeMasters and Lillehei [8] found 13 cases between 2000 and 2016 in their surgical neuropathology databases. The latency median was 18 years. Strenger et al calculated a cumulative index of 2.24%, 3.86%, 4.95%, and 6.74% at 5, 10, 15, and 20 years following radiotherapy of children, respectively [9]. Vinchon et al [10] identified cumulative indices for their cohort in children at 10 years of 8.9%. Although RICMs are rare in adults with astrocytoma, mainly due to poor survival, three cases of long term survivals were reported in the literature to develop RICMs 10, 19 and 26 years post radiotherapy [11]. Gaensler and colleagues reported a series of 20 patients with RITs (6 proven pathologically) for whom the latency was only 2.7 years [12]. 70% of the 20 patients were 1 h (60–105 min) after a conventional injection of contrast agent. Blue/tumor regions in the TRAMs represent efficient clearance of contrast from the tissue (delayed signal early signal). The TRAMs were validated histologically in 51 resected lesions from patients with primary and metastatic brain tumors reaching 92% positive predictive value (PPV) and 100% sensitivity to morphologically active tumor. When studying the histological samples, we found that the common vessels morphology in the blue regions was undamaged vessels lumens, while vessels in the red regions presented different stages of vessel necrosis. Therefore, one explanation for the difference between the two populations may be that vessels in blue/tumor regions provide efficient contrast clearance from the tissue, while the damaged lumens in the red/treatment-effects regions are unable to clear the accumulating contrast, resulting in contrast accumulation. Over 400 adult patients have been recruited thus far to our ongoing TRAMs-based studies in Israel since 2010. As the TRAMs cannot differentiate blood vessels from active tumor (both appearing blue), we studied here whether RCIMs/RITs may mimic tumors in the TRAMs.

Purpose Children with traumatic brain injury (TBI) are at increased risk of posttraumatic epilepsy (PTE); the risk increases according to TBI severity. We examined the long-term incidence and risk factors for developing PTE in a cohort of children hospitalised at one medical centre with moderate or severe TBI. Methods Moderate brain injury was classified as Glasgow Coma Score on Arrival (GCSOA) of 9–13, and severe brain injury as GCSOA ≤8. We collected demographics and clinical data from medical records and interviewed patients and parents at 5–11 years following the TBI event. Results During a median follow-up period of 7.3 years, 9 (9%) of 95 children with moderate-to-severe TBI developed PTE; 4 developed intractable epilepsy. The odds for developing PTE was 2.9 in patients with severe compared to moderate TBI. CT findings showed fractures in 7/9 (78%) of patients with PTE, compared to 40/86 (47%) of those without PTE (p = 0.09). Of the patients with fractures, all those with PTE had additional features on CT (such as haemorrhage, contusion and mass effect), compared to 29/40 (73%) of those without PTE. One of nine (11%) PTE patients and 10 of 86 (12%) patients without PTE had immediate seizures. Two (22%) children with PTE had their first seizure more than 2 years after the TBI. Conclusion Among children with moderate or severe TBI, the presence of additional CT findings, other than skull fractures, seem to increase the risk of PTE. In our cohort, the occurrence of an early seizure did not confer an increased risk of PTE.

Stereotactic radiosurgery (SRS) is a common treatment for intracranial meningiomas. SRS is planned on a pre-therapy gadolinium-enhanced T1-weighted MRI scan (Gd-T1w MRI) in which the meningioma contours have been delineated. Post-SRS therapy serial Gd-T1w MRI scans are then acquired for longitudinal treatment evaluation. Accurate tumor volume change quantification is required for treatment efficacy evaluation and for treatment continuation. We present a new algorithm for the automatic segmentation and volumetric assessment of meningioma in post-therapy Gd-T1w MRI scans. The inputs are the pre- and post-therapy Gd-T1w MRI scans and the meningioma delineation in the pre-therapy scan. The output is the meningioma delineations and volumes in the post-therapy scan. The algorithm uses the pre-therapy scan and its meningioma delineation to initialize an extended Chan–Vese active contour method and as a strong patient-specific intensity and shape prior for the post-therapy scan meningioma segmentation. The algorithm is automatic, obviates the need for independent tumor localization and segmentation initialization, and incorporates the same tumor delineation criteria in both the pre- and post-therapy scans. Our experimental results on retrospective pre- and post-therapy scans with a total of 32 meningiomas with volume ranges 0.4–26.5 cm $$^{3}$$ yield a Dice coefficient of $$87.0\, \pm \, 6.2$$ % with respect to ground-truth delineations in post-therapy scans created by two clinicians. These results indicate a high correspondence to the ground-truth delineations. Our algorithm yields more reliable and accurate tumor volume change measurements than other stand-alone segmentation methods. It may be a useful tool for quantitative meningioma prognosis evaluation after SRS.

We review our experience with four patients who presented to our Medical Center from 2005-2015 with adult idiopathic occlusion of the foramen of Monro (FM). All patients underwent CT scanning and MRI. Standard MRI was performed in each patient to rule out a secondary cause of obstruction (T1-weighted without- and with gadolinium, T2-weighted, fluid-attenuated inversion recovery [FLAIR] and diffusion-weighted imaging [DWI] protocols). When occlusion of the FM appeared to be idiopathic, further high-resolution MRI with multiplanar reconstructions for evaluation of stenosis or an occluding membrane at the level of the FM was performed (T1-weighted without- and with gadolinium, T2-weighted 3D turbo spin-echo). Occlusion of the FM was due to unilateral stenosis and septum pellucidum deviation in two patients, to an occluding membrane in one, and to bilateral stenosis in one patient. Urgent surgical intervention is mandatory when there are signs of increased intracranial pressure while asymptomatic patients may be managed conservatively. In this patient series, truly bilateral stenotic obstruction of the FM was best managed with ventriculoperitoneal shunt and patients with membranous obstruction or unilateral stenosis with septum deviation were treated endoscopically.

Meningiomas are one of the most common brain tumors. World Health Organisation (WHO) Grade II and Grade III meningiomas are grouped together as non-benign meningioma (NBM). There are several controversies surrounding NBM management, including the significance of extent of resection and the efficacy of post-operative radiation and drug treatment. We reviewed the literature to develop recommendations for management of NBM. The questions we sought to answer were: Does gross total resection (GTR) improve patient outcome? Is radiation therapy (RT) warranted after complete or after incomplete resection of NBM? What drug therapies have been proven to improve outcome in patients with NBM? We found that GTR improves outcome in WHO Grade II meningioma, and should be attempted whenever considered safe. GTR correlates less closely to outcome in Grade III meningioma compared to subtotal resection (STR). Extreme measures to completely resect Grade III meningioma are not warranted. RT following GTR of Grade II meningioma does not improve patient outcome, and may be reserved for recurrence. RT improves outcome following STR of Grade II meningioma. RT improves outcome after resection of Grade III meningioma. No drug therapy has been shown to improve outcome in NBM. This review elucidates recommendations for some of the controversies involving NBM.

Ventriculoperitoneal (VP) shunt placement is the mainstay of treatment for hydrocephalus, yet shunts remain vulnerable to a variety of complications. Although fat droplet migration into the subarachnoid space and cerebrospinal fluid pathways following craniotomy has been observed, a VP shunt obstruction with fat droplets has never been reported to our knowledge. We present the first reported case of VP shunt catheter obstruction by migratory fat droplets in a 55-year-old woman who underwent suboccipital craniotomy for removal of a metastatic tumor of the left medullocerebellar region, without fat harvesting. A VP shunt was inserted 1month later due to communicating hydrocephalus. The patient presented with gait disturbance, intermittent confusion, and pseudomeningocele 21days after shunt insertion. MRI revealed retrograde fat deposition in the ventricular system and VP shunt catheter, apparently following migration of fat droplets from the fatty soft tissue of the craniotomy site. Spinal tap revealed signs of aseptic meningitis. Steroid treatment for aseptic "lipoid" meningitis provided symptom relief. MRI 2months later revealed partial fat resorption and resolution of the pseudomeningocele. VP shunt malfunction caused by fat obstruction of the ventricular catheter should be acknowledged as a possible complication in VP shunts after craniotomy, even in the absence of fat harvesting.

The prevalence of skull fractures after mild head trauma is 2 % in children of all ages and 11 % in children younger than 2 years. The current standard management for a child diagnosed with an isolated skull fracture (ISF), in our institute, is hospitalization for a 24-h observation period. Based on data from the literature, less than 1 % of all minor head injuries require neurosurgical intervention. The main objective of this study was to evaluate the risk of neurological deterioration of ISF cases, in order to assess the need for hospitalization. We reviewed the medical charts of 222 children who were hospitalized from 2006 to 2012 with ISF and Glascow Coma Scale—15 at the time of arrival. We collected data regarding demographic characteristics, mechanism of injury, fracture location, clinical symptoms and signs, need for hospitalization, and need for repeated imaging. Data was collected at three time points: at presentation to the emergency room, during hospitalization, and 1 month after admission, when the patients’ parents were asked about the course of the month following discharge. None of the 222 children included in the study needed neurosurgical intervention. All were asymptomatic 1 month after the injury. Two children underwent repeated head CT due to persistence or worsening of symptoms; these CT scans did not reveal any new findings and did not lead to any intervention whatsoever. Children arriving at the emergency room with a minor head injury and isolated skull fracture on imaging studies may be considered for discharge after a short period of observation. Discharge should be considered in these cases provided the child has a reliable social environment and responsible caregivers who are able to return to the hospital if necessary. Hospital admission should be reserved for children with neurologic deficits, persistent symptoms, suspected child abuse, or when the parent is unreliable or is unable to return to the hospital if necessary. Reducing unnecessary hospitalizations can prevent emotional stress, in addition to saving costs for the child’s family and the health care system.

We describe the presentation, management, and outcome of spontaneous spinal epidural hematoma (SSEH) in two tertiary academic centers. We retrospectively reviewed clinical and imaging files in patients diagnosed with SSEH from 2002-2011. Neurologic status was assessed using the American Spinal Injury Association (ASIA) Impairment Scale (AIS). A total of 17 patients (10 females; mean age 54 years, range 10-89) were included. Among patients presenting with AIS A, 5/8 showed no improvement and 3/8 reached AIS C. Among those presenting with AIS C, 5/6 reached AIS E and 1/6 reached AIS D. Of those presenting with AIS D, 3/3 reached AIS E. Mean time-to-surgery (TTS) was 28 hours (range 3-96). TTS surgery in two patients remaining at AIS A was ⩽ 12 hours; in 4/8 patients recovering to AIS E it was > 12 hours, including three patients operated on after > 24 hours. In patients remaining at AIS A, a mean of 4.4 levels were treated compared with means of 3.7 and 3.5 in those with AIS C and E, respectively, at late follow-up. In this series, preoperative neurological status had greater impact on late outcome than time from symptom onset to surgery in patients with SSEH.

OBJECTIVEPosttraumatic epilepsy (PTE) is a known complication of traumatic brain injury (TBI). The true incidence of PTE in children is still uncertain, because most research has been based primarily on adults. This study aimed to determine the true incidence of PTE in a pediatric population with mild TBI (MTBI) and to identify risk factors for the development of epileptic events.METHODSData were collected from electronic medical records of children 0–17 years of age, who were admitted to a single medical center between 2007 and 2009 with a diagnosis of MTBI. This prospective research consisted of a telephone survey between 2015 and 2016 of children or their caregivers, querying for information about epileptic episodes and current seizure and neurological status. The primary outcome measure was the incidence of epilepsy following TBI, which was defined as ≥ 2 unprovoked seizure episodes. Posttraumatic seizure (PTS) was defined as a single, nonrecurrent convulsive episode that occurred > 24 hours following injury. Seizures within 24 hours of the injury were defined as immediate PTS.RESULTSOf 290 children eligible for this study, 191 of them or their caregivers were reached by telephone survey and were included in the analysis. Most injuries (80.6%) were due to falls. Six children had immediate PTS. All children underwent CT imaging; of them, 72.8% demonstrated fractures and 10.5% did not demonstrate acute findings. The mean follow-up was 7.4 years. Seven children (3.7%) experienced PTS; of them, 6 (85.7%) developed epilepsy and 3 (42.9%) developed intractable epilepsy. The overall incidence of epilepsy and intractable epilepsy in this cohort was 3.1% and 1.6%, respectively. None of the children who had immediate PTS developed epilepsy. Children who developed epilepsy spent an average of 2 extra days in the hospital at the time of the injury. The mean time between trauma and onset of seizures was 3.1 years. Immediate PTS was not correlated with PTE.CONCLUSIONSIn this analysis of data from medical records and long-term follow-up, MTBI was found to confer increased risk for the development of PTE and intractable PTE, of 4.5 and 8 times higher, respectively. As has been established in adults, these findings confirm that MTBI increases the risk for PTE in the pediatric population.

We investigated the prevalence, onset, characteristics, and long-term course of epilepsy disease in children who underwent surgical intervention for diagnosed brain tumors.We reviewed the medical records of children with diagnosed brain tumors who underwent surgery during 2004-2014 at the Hadassah Medical Center. All patients with epilepsy were invited to a clinical visit that included a neurologic examination. The primary outcome measures were neurologic status according to the Glasgow outcome score (GOS) and postoperative seizure outcome according to the Engel system. We compared clinical characteristics according to the timing of epilepsy onset.The mean follow-up was 49 months. Of 128 patients included in the study, 44 (34%) had seizures; 23 (18%) developed epilepsy after surgery. Of the 30 patients with epilepsy who survived, 21 (70%) are in Engel class I and 13% Engel are in class II. Forty-five percent of the children are classified as GOS 5. Children who developed epilepsy after surgery were more likely to be in GOS 1-2 than were those who had seizures before surgery (P = 0.0173). Children with seizures were more likely to have cortical tumors and less likely to have tumors of the posterior fossa (P0.001). Children who underwent gross total resection were less likely to have epilepsy (P0.001).We show a high incidence of epilepsy in the late course of pediatric brain tumor disease. In the long term, seizure outcome was excellent. However, postsurgical onset of epilepsy was associated with a less favorable neurologic outcome.

Objective To assess the incidence of cerebrospinal fluid (CSF) leak and meningitis, and the need for prophylactic antibiotics, antipneumococcal vaccination, and surgical interventions, in children with a skull base fracture. Methods We reviewed the records of children with a skull base fracture who were admitted to our tertiary care center between 2009 and 2014. Results A total of 196 children (153 males), age 1 month to 18 years (mean age, 6 ± 4 years), were hospitalized with skull base fracture. Causes of injury were falls (n = 143), motor vehicle accidents (n = 34), and other (n = 19). Fracture locations were the middle skull base in 112 patients, frontal base in 62, and occipital base in 13. Fifty-four children (28%) had a CSF leak. In 34 of these children (63%), spontaneous resolution occurred within 3 days. Three children underwent surgery on admission owing to a CSF leak from an open wound, 3 underwent CSF diversion by spinal drainage, and 4 (2%) required surgery to repair a dural tear after failure of continuous spinal drainage and acetazolamide treatment. Twenty-eight children (14%) received prophylactic antibiotic therapy, usually due to other injuries, and 11 received pneumococcal vaccination. Two children developed meningitis, and 3 children died. Long-term follow up in 124 children revealed 12 children with delayed hearing loss and 3 with delayed facial paralysis. Conclusions This is the largest pediatric series of skull base fractures reporting rates of morbidity and long-term outcomes published to date. The rate of meningitis following skull base fracture in children is low, supporting a policy of not administering prophylactic antibiotics or pneumococcal vaccine. Long-term follow up is important to identify delayed complications.

Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients.One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist.Histological validation confirmed that regions of contrast agent clearance in the TRAMs1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P.0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated.The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

Background and Purpose: Painful vertebral compression fractures in cancer patients reduce quality of life and may limit survival. We assessed pain relief, vertebral height restoration, and kyphosis correction following vertebral augmentation using a novel expandable titanium stent implant in cancer patients with painful vertebral compression fractures. Materials and Methods: Patients .18 years of age with metastatic disease who presented symptomatic compression fractures of vertebral bodies T5–L5, with or without a history of osteoporosis, were included in the study. Back pain at presentation, immediately after vertebral stenting, and at 1-, 3-, 6-, and 12-month follow-up was estimated using the visual analog scale (VAS). Vertebral height and local kyphotic angle (alpha angle) were measured on lateral standing X-ray before and 1–3 months after stenting. Results: Forty-one cancer patients with painful vertebral compression fractures underwent vertebral stenting procedures at 55 levels. There was no perioperative mortality and no significant complication. Median preoperative VAS was 8.0 (range 8–10), falling to 2.0 immediately postop (range 1–6, P 5 0.000) and 0 at all subsequent follow-up (P # 0.012). Mean preoperative vertical height loss was 25.8% (range 0– 84.0%) versus a postoperative mean of 18.0% (range 0–66.0%, P 5 0.000). Median pre- and postoperative kyphotic angle improved from 8.3u (range 0.2u–54.0u) to 7.1u (range 0.2u–25.0u, P 5 0.000). Wilcoxon signed rank test or student’s t-test was used for comparisons. Conclusions: Vertebral augmentation using a novel vertebral stenting system provided immediate and enduring pain relief and improved vertebral height loss and kyphotic angle.

Purpose: The authors present and evaluate a new preoperative planning method and computer software designed to reduce the risk of candidate trajectories for straight rigid tool insertion in image-guided keyhole neurosurgery. Methods: Trajectories are computed based on the surgeon-defined target and a candidate entry point area on the outer head surface on preoperative CT/MRI scans. A multiparameter risk card provides an estimate of the risk of each trajectory according to its proximity to critical brain structures. Candidate entry points in the outer head surface areas are then color-coded and displayed in 3D to facilitate selection of the most adequate point. The surgeon then defines and/or revised the insertion trajectory using an interactive 3D visualization of surrounding structures. A safety zone around the selected trajectory is also computed to visualize the expected worst-case deviation from the planned insertion trajectory based on tool placement errors in previous surgeries. Results: A retrospective comparative study for ten selected targets on MRI head scans for eight patients showed a significant reduction in insertion trajectory risk. Using the authors’ method, trajectories longer than 30 mm were an average of 2.6 mm further from blood vessels compared to the conventional manual method. Average planning times were 8.4 and 5.9 min for the conventional technique and the authors’ method, respectively. Neurosurgeons reported improved understanding of possible risks and spatial relations for the trajectory and patient anatomy. Conclusions: The suggested method may result in safer trajectories, shorter preoperative planning time, and improved understanding of risks and possible complications in keyhole neurosurgery.

Ventriculo-peritoneal (VP) shunt malfunction due to proximal and distal catheter migration has been rarely reported in the literature. Shunt migration has been proposed to occur as a result of a combination of various mechanisms, including the windlass effect, retained memory of the shunt tubing, inadequate shunt fixation, and increased intra-abdominal pressures. We describe a rare case of a 6-week-old child who presented in our department with VP shunt malfunction due to complete proximal migration and coiling of the peritoneal and ventricular VP shunt catheters within a subgaleal pocket at the left occipital area.

Background Catheter, needle, and electrode misplacement in navigated neurosurgery can result in ineffective treatment and severe complications. Objective To assess the Ommaya ventricular catheter localization accuracy both along the planned trajectory and at the target. Methods We measured the localization error along the ventricular catheter and on its tip for 15 consecutive patients who underwent insertion of the Ommaya catheter surgery with a commercial neuronavigation system. The preoperative computed tomography/magnetic resonance images and the planned trajectory were aligned with the postoperative computed tomography images showing the Ommaya catheter. The localization errors along the trajectory and at the target were then computed by comparing the preoperative planned trajectory with the actual postoperative catheter position. The measured localization errors were also compared with the error reported by the navigation system. Results The mean localization errors at the target and entry point locations were 5.9 ± 4.3 and 3.3 ± 1.9 mm, respectively. The mean shift and angle between planned and actual trajectories were 1.6 ± 1.9 mm and 3.9 ± 4.7°, respectively. The mean difference between the localization error at the target and entry point was 3.9 ± 3.7 mm. The mean difference between the target localization error and the reported navigation system error was 4.9 ± 4.8 mm. Conclusion The catheter localization errors have significant variations at the target and along the insertion trajectory. Trajectory errors may differ significantly from the errors at the target. Moreover, the single registration error number reported by the navigation system does not appropriately reflect the trajectory and target errors and thus should be used with caution to assess the procedure risk.

Acute pseudotumoral hemicerebellitis is an exceptionally rare unilateral presentation of acute cerebellitis mimicking a tumor. It typically has a benign course without specific therapy; thus, recognizing this entity is important to avoid needless surgical intervention. MRI provides the key for diagnosis and usually reveals a diffusely swollen cerebellar hemisphere with no well-defined mass. Some patients will require neurosurgical assistance by means of ventriculostomy or posterior fossa decompression. We present a 17-year-old girl with pseudotumoral hemicerebellitis, review the available literature, and discuss the diagnosis and therapeutic dilemma from the neurosurgical perspective.

Rosai-Dorfman disease is a benign non-neoplastic proliferative disorder of histiocytes originally described in the cervical lymph nodes. Extranodal sites were later recognized, and by 1990, they were shown to represent over 40% of cases; however, central nervous system involvement is still considered rare. We review the literature, which shows a steady increase in reports of Rosai-Dorfman disease involving the brain and/or spine.A literature search was performed for the period 1969-2008, using multiple search engines, with keywords Rosai-Dorfman disease, central nervous system Rosai-Dorfman disease and sinus histiocytosis with massive lymphadenopathy.By December 2008, 111 cases of Rosai-Dorfman disease involving the central nervous system had been reported in the literature, including our cases. In the central nervous system, Rosai-Dorfman disease is ubiquitous. Although it is characterized by unique, indeed pathognomonic, histopathological cytoarchitecture, it may be mistaken for many other neoplastic and inflammatory histioproliferative diseases. Surgical resection with post-operative corticosteroids remains the treatment of choice.Rosai-Dorfman disease involving the central nervous system appears to be more common than previously thought and may well assume a more prominent place in the differential diagnoses of dural-based lesions. Expert awareness of the characteristic histopathology and immunohistochemistry of the disease is required for accurate diagnosis.

We present a case of de novo fibrosarcoma in a 43-year-old male, with MRI documented evolution from a 5 mm hyperintense area to 5 cm tumor mass in a 12-month period. The diagnosis of low-grade fibrosarcoma was established by three experienced neuropathologists. The patient underwent gross total resection with adjuvant fractionated conformal radiotherapy. Following first recurrence 3 months later, the patient was reoperated and stereotactic radiosurgery of a residual tumor was performed thereafter. The pathological diagnosis was similar, but with additional extensive radiation effects. Six months later the patient underwent aggressive surgical resection for second recurrence. The pathological diagnosis was WHO grade IV glioblastoma. The etiology of this highly unusual progression from primary mesenchymal neoplasm to high-grade glioma is discussed.

We present an unusual case of ruptured infantile cerebral aneurysm. An eight-month-old infant was delivered to the hospital in poor condition, after convulsions, with no history of trauma. His emergent CT study revealed acute subdural hematoma. The clinical and radiological picture evoked suspicion that the hematoma was of aneurysmal origin. The infant was operated with special preparations and precautions appropriate for aneurysmal surgery, and has shown a good recovery. It is important to consider the possibility of vascular accident in infants with subdural hematoma of nontraumatic origin. A good outcome may be achieved when appropriate preparations are made prior to surgery.

To describe the outcomes of terror victims suffered from traumatic brain injury (TBI).Retrospective chart review of 17 terror and 39 non-terror TBI patients treated in a rehabilitation department during the same period.Variables include demographic data, Injury Severity Scale (ISS), length of stay (LOS) and imaging results. ADL was measured using the Functional Independence Measurement (FIM), cognitive and memory functions were measured using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) battery and the Rivermead Battery Memory Test (RBMT), respectively.Terror TBI patients were significantly younger, had higher ISS score and higher rates of intracerebral haemorrhage (ICH), brain surgery and penetrating brain injuries than the non-terror TBI group. There was no difference in mean LOS, mean FIM values, mean FIM gain and mean cognitive and memory improvement between groups. Terror victims suffered from a higher percentage of post-traumatic epilepsy (35% vs. 10%, p=0.05), whereas the rate of PTSD and the rate of return to previous occupation were similar between groups.Although TBI terror victims had more severe injury, they gained most of ADL functions and their rehabilitation outcomes were similar to non-terror TBI patients. These favourable results were achieved due to a comprehensive interdisciplinary approach to terror victims and also by national support which allowed an adequate period of treatment and sufficient resources as needed.

This paper describes a novel system for precise automatic targeting in minimally invasive neurosurgery. The system consists of a miniature robot fitted with a rigid mechanical guide for needle, catheter, or probe insertion. Intraoperatively, the robot is directly affixed to the patient skull or to a head clamp. It automatically positions itself with respect to predefined targets in a preoperative CT/MRI image following a three-way anatomical registration with an intraoperative 3D-laser scan of the patient face features. We describe the system architecture, surgical protocol, software modules, and implementation. Registration results on 19 pairs of real MRI and 3D laser scan data show an RMS error of 1.0 mm (std = 0.95 mm) in 2 s.

BACKGROUND Amyloidoma (tumoral amyloidosis) is the rarest form of central nervous system (CNS) amyloidosis. CASE A 51-year-old woman presented with recurrent right-sided otitis media and hearing loss. Computed tomography and magnetic resonance imaging revealed a mass in the right temporal lobe. Cytologic findings at the time of stereotactic biopsy for suspected glioma were compatible with amyloidoma. Subsequent histologic and electron microscopic findings confirmed the diagnosis of amyloidoma. Auxiliary testing ruled out systemic amyloidosis and plasma cell dyscrasia. CONCLUSION To our knowledge, this is the first report on the cytologic findings in a case of CNS amyloidoma.

We report a patient with minor head trauma-related bilateral hemispheric subdural hematoma (SDH) and subsequent delayed spinal SDH or presumed migration to the lumbar spine. An acutely confused 88-year-old man presented to the Emergency Department after minor head trauma. Head CT scan revealed a small hemispheric SDH. The patient was admitted for observation. CT scan 6 hours later showed bilateral SDH with extension to the tentorium. Three days later SDH had resolved leaving bilateral subdural hygromas. Local leg weakness localized to the lumbar spine developed on day 6; spinal CT scan and MRI revealed a posterior L5–S1 collection. A pure subacute subdural hematoma compressing the cauda equina was drained after an L5 laminectomy. His lower leg weakness improved. The patient was discharged to rehabilitation two weeks after surgery. Patients with traumatic SDH who develop late-onset neurological deterioration attributable to any region of the spine should be evaluated for spinal SDH.

Minimal invasion computer-assisted neurosurgical procedures with various tool insertions into the brain may carry hemorrhagic risks and neurological deficits. The goal of this study is to investigate the role of computer-based surgical trajectory planning tools in improving the potential safety of image-based stereotactic neurosurgery.Multi-sequence MRI studies of eight patients who underwent image-guided neurosurgery were retrospectively processed to extract anatomical structures-head surface, ventricles, blood vessels, white matter fibers tractography, and fMRI data of motor, sensory, speech, and visual areas. An experienced neurosurgeon selected one target for each patient. Five neurosurgeons planned a surgical trajectory for each patient using three planning methods: (1) conventional; (2) visualization, in which scans are augmented with overlays of anatomical structures and functional areas; and (3) automatic, in which three surgical trajectories with the lowest expected risk score are automatically computed. For each surgeon, target, and method, we recorded the entry point and its surgical trajectory and computed its expected risk score and its minimum distance from the key structures.A total of 120 surgical trajectories were collected (5 surgeons, 8 targets, 3 methods). The surgical trajectories expected risk scores improved by 76% ([Formula: see text], two-sample student's t test); the average distance of a trajectory from nearby blood vessels increased by 1.6 mm ([Formula: see text]) from 0.6 to 2.2 mm (243%). The initial surgical trajectories were changed in 85% of the cases based on the expected risk score and the trajectory distance from blood vessels.Computer-based patient-specific preoperative planning of surgical trajectories that minimize the expected risk of vascular and neurological damage due to incorrect tool placement is a promising technique that yields consistent improvements.

Randomized controlled trials have demonstrated the efficacy of decompressive craniectomy in substantially decreasing mortality and improving functional outcome in middle cerebral artery infarction. The role of intracranial pressure (ICP) monitoring following decompressive craniectomy for stroke has not been well studied. We present a retrospective review of our experience with postoperative ICP monitoring in 12 stroke patients who underwent decompressive craniectomy. All elevations of ICP above a 20 mm Hg threshold were noted. ICP was recorded for 1417 hours during which 68 ICP elevations were seen. Nine out of 12 patients had events of raised ICP, including eight with more than three elevations. A total of 81 interventions were employed to treat elevated ICP; 71 were effective in reducing ICP below the 20 mm Hg threshold. The most frequent intervention was cerebrospinal fluid drainage via an external ventricular drain, which was effective in 85.4% of cases. Eleven out of 12 patients survived (92%) and attained a median modified Rankin Scale score of 4 (interquartile range 4-5) at a mean 15 month follow-up. In our experience, elevated ICP may commonly occur following decompressive craniectomy for stroke. Monitoring ICP influenced postoperative management and standard measures for reducing ICP were usually effective in the current series.

We aimed to assess the efficacy of surgical decompression of metastatic epidural spinal cord compression (MESCC) in patients ≧65 years and review our multidisciplinary surgical decision-making process.We identified all patients operated for MESCC from August 2008 to June 2012. Patients ≧65 years, with a single area of cord compression, back/radicular pain, neurological signs of cord compression, surgery within 48 hours after onset of MESCC-related paraplegia, and follow-up for ≧1 year or until death were included. Files were reviewed retrospectively. The requirement for informed consent was waived. Neurological status was assessed with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Duration of ambulation and survival were assessed with Kaplan-Meier and Cox regression analysis.Twenty-one patients met inclusion criteria (11 women/10 men; mean age 73 years, range 65-87). All presented with debilitating back/neck pain. Ten patients (48%) were not ambulatory before surgery and four suffered urinary incontinence/constipation (19%). Preoperative AIS was E in 5 patients (24%), D in 11 (62%), and C in 5 (24%). Motor symptoms had been present for a mean of 3·8 days (range 1-14). All patients regained ambulation. Overall, mean survival was 320 days (range 19-798) and mean ambulation was 302 days (range 18-747). On 31 March 2013, 7 patients (33%) were alive and ambulatory at a mean of 459 days (range 302-747); 14 patients had died (67%) at a mean of 251 days (range 19-798), with a mean ambulation of 223 days (range 18-730).With careful patient selection, surgery may achieve long duration of ambulation in patients ≧65 years with MESCC.

Background: The role of neurosurgery nurse coordinator is unique in Israel and was developed to provide a comprehensive response to the needs of patients undergoing cranial surgery to remove various types of tumors. The creation of the neurosurgery nurse coordinator role was based on patient and staff needs assessment and focused on two major areas: (1) the patient and his or her family—creating personal and empathic communication with the goal of offering emotional support, providing support to assist in relieving symptoms, coordinating between the patient and/or the patient’s family and the physicians and consultants, and assisting with bureaucratic processes and with familiarization with the hospital’s medical environment; and (2) establishing departmental processes related to improving patient care within a multidisciplinary team. Objective: The aim of this study was to investigate the needs and level of satisfaction of patients and their families, hospitalized in the neurosurgery department for the surgical removal of cranial tumors. Methods: Satisfaction survey is composed of 47 questions. Sample: A convenience sample of 67 patients completed a satisfaction survey related to various aspects of their hospitalization. Findings: The study results reflect patient needs for emotional support, information, and additional education. These findings emphasize the great importance of the position of nurse coordinator in the neurosurgery department.

We report a rare case of a spinal meningioma leading to symptoms of spinal cord compression starting in the third trimester of gestation in a 32-year-old woman. Neurological symptoms, which continued to progress after the patient had given birth, were assumed to be sequelae of pregnancy and delivery, leading to a 6 month delay in diagnosis and treatment. Fortunately a gross total resection was achieved at surgery and the patient recovered fully, without permanent consequences. Associated symptoms of spinal cord compression may be falsely attributed to pregnancy, both by the pregnant women and her treating physician. A high index of suspicion and thorough history and physical examination to identify red flags should be performed in patients with neurological symptoms.

OBJECTIVE : The production of prostaglandin (PG) within brain tumors probably generates excessive amounts of oxygen free radicals that may disrupt microvessel permeability within the tumor and in the adjacent brain. We evaluated the effect of systemic therapy with recombinant human manganese-superoxide dismutase (r-hMnSOD) and with dexamethasone on the vascular permeability (VP) of a brain tumor and the adjacent brain. Treatment effect was also evaluated in control animals subjected to mild penetration injury. METHODS : Fischer rats were injected stereotactically with either 10 5 cells of malignant sarcoma or with vehicle into the right parietal hemisphere. Nine days later, the animals were treated with r-hMnSOD (50 mg/kg of body weight every 12 h [one intravenous, then two intraperitoneal injections] ; serum levels, 1100-1800 μg/ml), dexamethasone (2 mg/kg every 12 h [one intravenous, then two intraperitoneal injections]), or vehicle and were killed after 30 hours for evaluation of VP and PG production. RESULTS : The VP was markedly increased within the tumor (P < 0.001), in the brain adjacent to it, and in the vehicle injection site. The VP of the normal brain was unaffected by r-hMnSOD or dexamethasone treatment, unlike the VP in the tumor, the adjacent brain, and the injection sites of control animals, where it was reduced by 50, 54, and 23%, respectively (P < 0.04), for r-hMnSOD and 50, 41, and 71%, respectively (P < 0.05), for dexamethasone. A one- to threefold increase in synthesis of thromboxane and PGE 2 was measured within the tumor, the adjacent brain, and the injection sites of control animals (P < 0.0001). Treatment with r-hMnSOD had no effect on tumor PG production, but it reduced the synthesis in the brain tissue adjacent to the tumor and in traumatized control animals (P < 0.04). Immunohistochemical evaluation revealed vascular proliferation with abnormal basal membrane, atypical astrocytes, and large numbers of reactive macrophages present in the adjacent brain and at the injection sites of control animals but not within the tumor mass. CONCLUSION : Oxygen free radicals probably enhance vasogenic brain edema resulting from tumor and penetration injury. The edema can be attenuated by systemic r-hMnSOD therapy, which has been proven to be as effective as steroid treatment. An inflammatory response may account for oxygen free radical production in brain tissue adjacent to the tumor and at the injection site of vehicle solution, but other mechanisms probably generate oxygen free radicals within the tumor mass.

Superficial siderosis of the central nervous system (CNS) is a rare disorder caused by deposition of hemosiderin in neuronal tissue in the subpial layer of the CNS due to slow subarachnoid or intraventricular hemorrhage. The most common neurologic manifestations include progressive gait ataxia, sensorineural hearing loss, and corticospinal tract signs. We present a case of superficial siderosis in a 43-year-old man who presented to the Emergency Department with sudden onset bilateral visual deterioration and a loss of consciousness. A hemorrhagic giant prolactinoma was diagnosed based on brain CT scan, T1-weighted MRI, and an endocrine blood examination. Susceptibility-weighted non-contrast MRI showed pathognomonic signs of superficial siderosis in the form of a hypointensity rim surrounding the brainstem, cerebellar fissures, and cranial nerves VII and VIII. This report demonstrates that superficial siderosis can be caused by pituitary apoplexy.

BACKGROUND Traumatic internal carotid artery dissection (CAD) has a potentially grave outcome. Anticoagulant therapy may be ineffective or contraindicated; surgery impractical. We present our experience with endovascular stenting in CAD patients. METHODS From 2004 to 2011, 23 patients with angiographically proven traumatic CAD underwent endovascular stent-assisted arterial reconstruction based on clinical and radiographic criteria: contraindication or failure of anticoagulation, evidence of impending ischemic stroke, or need for urgent intracranial revascularization. Dissections were graded based on degree of stenosis and extent of injury. RESULTS Seventeen patients (73.9%) presented with stroke or transient ischemic attack. Carotid revascularization was achieved with one (11 patients, 48%) or multiple stents (12 patients, 52%); distal protection was used rarely (three patients, 13%). No complications were directly attributed to stenting. Mean dissection-related stenosis improved from 72% ± 28.87% to 4% ± 8.29%. At a mean clinical follow-up of 28.7 months ± 31.9 months, 16 patients (69.6%) improved, six (26.1%) remained stable, and one (4.3%) had died secondary to multiple traumatic injuries. At long-term follow-up, no patient had a transient ischemic attack or stroke or presented evidence of de novo in-stent stenosis or stent thrombosis. There were no neurologic sequelae after partial or total discontinuation of antiplatelet therapy in seven patients undergoing trauma-related surgeries. CONCLUSIONS Selected cases of traumatic CAD can be safely managed by endovascular stent-assisted angioplasty. Procedural complications are infrequent; the need for postprocedure antiplatelet therapy is a concern. Early detection is essential to avoid stroke. Stenting restores the integrity of the vessel lumen immediately, efficiently prevents the occurrence or recurrence of ischemic events, and avoids the need of long-term anticoagulation.

We present a new preoperative planning method for reducing the risk associated with the insertion of straight tools in image-guided keyhole neurosurgery. The method quantifies the risks of multiple candidate trajectories and presents them on a physical model of a head using Augmented Reality (AR) to assist the neurosurgeon in selecting the safest path. The surgeon can then define and/or revise the trajectory in the physical space with AR visualization of risk structures such as blood vessels and ventricles, tool placement uncertainty, and quantitative risk measurements. Then, the neurosurgeon can revise the selected path on the 2D MRI image slices to incorporate all relevant information. Finally, a simulation of the surgery can be performed on the physical head model for a more detailed examination of the possible risks. Our preliminary results on clinical data show that in complex situations the method can improve risk assessment.

We present a new preoperative planning method to quantify and help reduce the risk associated with needle and tool insertion trajectories in image-guided keyhole neurosurgery. The goal is to quantify the risk of a proposed straight trajectory, and/or to find the trajectory with the lowest risk to nearby brain structures based on pre-operative CT/MRI images. The method automatically computes the risk associated with a given trajectory, or finds the trajectory with the lowest risk to nearby brain structures based on preoperative image segmentation and on a risk volume map. The surgeon can revise the suggested trajectory, add a new one using interactive 3D visualization, and obtain a quantitative risk measure. The trajectory risk is evaluated based on the tool placement uncertainty, on the proximity of critical brain structures, and on a predefined table of quantitative geometric risk measures. Our preliminary results on a clinical dataset with eight targets show a significant reduction in trajectory risk and a shortening of the preoperative planning time as compared to the conventional method.

We present a new preoperative planning method for reducing the risk associated with insertion of straight tools in image-guided keyhole neurosurgery. The method quantifies the risks of multiple candidate trajectories and presents them on the outer head surface to assist the neurosurgeon in selecting the safest path. The surgeon can then define and/or revise the trajectory, add a new one using interactive 3D visualization, and obtain a quantitative risk measures. The trajectory risk is evaluated based on the tool placement uncertainty, on the proximity of critical brain structures, and on a predefined table of quantitative geometric risk measures. Our results on five targets show a significant reduction in trajectory risk and a shortening of the preoperative planning time as compared to the current routine method.

Pituitary abscesses are rare. Occasionally they will arise in pre-existing pituitary pathology. We report such an occurrence within a Rathke’s cleft cyst. On the basis of history and imaging, this was indistinguishable from more commonly encountered pituitary pathology.

We describe a new framework and method for the optimal selection of anatomical landmarks and optimal placement of fiducial markers in image-guided neurosurgery. The method allows the surgeon to optimally plan the markers locations on routine diagnostic images before preoperative imaging and to intraoperatively select the fiducial markers and the anatomical landmarks that minimize the Target Registration Error (TRE). The optimal fiducial marker configuration selection is performed by the surgeon on the diagnostic image following the target selection based on a visual Estimated TRE (E-TRE) map. The E-TRE map is automatically updated when the surgeon interactively adds and deletes candidate markers and targets. The method takes the guesswork out of the registration process, provides a reliable localization uncertainty error for navigation, and can reduce the localization error without additional imaging and hardware. Our clinical experiments on five patients who underwent brain surgery with a navigation system show that optimizing one marker location and the anatomical landmarks configuration reduces the average TRE from 4.7mm to 3.2mm, with a maximum improvement of 4mm. The reduction of the target registration error has the potential to support safer and more accurate minimally invasive neurosurgical procedures.

Background S100B protein is a potential biomarker of central nervous system insult. This study quantitatively compared two methods for assessing serum concentration of S100B. Methods A prospective, observational study performed in a single tertiary medical center. Included were fifty two consecutive adult patients undergoing surgery for meningioma that provided blood samples for determination of S100B concentrations. Eighty samples (40 pre-operative and 40 postoperative) were randomly selected for batch testing. Each sample was divided into two aliquots. These were analyzed by ELISA (Sangtec) and a commercial kit (Roche Elecsys®) for S100B concentrations. Statistical analysis included regression modelling and Bland-Altman analysis. Results A parsimonious linear model best described the prediction of commercial kit values by those determined by ELISA (y = 0.045 + 0.277*x, x = ELISA value, R2 = 0.732). ELISA measurements tended to be higher than commercial kit measurements. This discrepancy increased linearly with increasing S100B concentrations. At concentrations above 0.7 μg/L the paired measurements were consistently outside the limits of agreement in the Bland-Altman display. Similar to other studies that used alternative measurement methods, sex and age related differences in serum S100B levels were not detected using the Elecsys® (p = 0.643 and 0.728 respectively). Conclusion Although a generally linear relationship exists between serum S100B concentrations measured by ELISA and a commercially available kit, ELISA values tended to be higher than commercial kit measurements particularly at concentrations over 0.7 μg/L, which are suggestive of brain injury. International standardization of commercial kits is required before the predictive validity of S100B for brain damage can be effectively assessed in clinical practice.

This paper describes a novel image-guided system for precise automatic targeting in minimally invasive keyhole neurosurgery. The system consists of the MARS miniature robot fitted with a mechanical guide for needle, probe or catheter insertion. Intraoperatively, the robot is directly affixed to a head clamp or to the patient's skull. It automatically positions itself with respect to predefined targets in a preoperative CT/MRI image following an anatomical registration with an intraoperative 3D surface scan of the patient's facial features and registration jig. We present the system architecture, surgical protocol, custom hardware (targeting and registration jig), and software modules (preoperative planning, intraoperative execution, 3D surface scan processing, and three-way registration). We also describe a prototype implementation of the system and in vitro registration experiments. Our results indicate a system-wide target registration error of 1.7 mm (standard deviation = 0.7 mm), which is close to the required 1.0-1.5 mm clinical accuracy in many keyhole neurosurgical procedures.

In this study, we examined the expression and functions of related to testes-specific, vespid, and pathogenesis protein 1 (RTVP-1) in glioma cells. RTVP-1 was expressed in high levels in glioblastomas, whereas its expression in low-grade astrocytomas and normal brains was very low. Transfection of glioma cells with small interfering RNAs targeting RTVP-1 decreased cell proliferation in all the cell lines examined and induced cell apoptosis in some of them. Overexpression of RTVP-1 increased astrocyte and glioma cell proliferation and the anchorage-independent growth of the cells. In addition, overexpression of RTVP-1 rendered glioma cells more resistant to the apoptotic effect of tumor necrosis factor–related apoptosis-inducing ligand and serum deprivation. To delineate the molecular mechanisms involved in the survival effects of RTVP-1, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that overexpression of RTVP-1 decreased the phosphorylation of c-Jun-NH2-kinase and increased the expression of Bcl2 and that the protective effect of RTVP-1 was partially mediated by Bcl2. Finally, we found that RTVP-1 regulated the invasion of glioma cells as was evident by their enhanced migration through Matrigel and by their increased invasion in a spheroid confrontation assay. The increased invasive potential of the RTVP-1 overexpressors was also shown by the increased activity of matrix metalloproteinase 2 in these cells. Our results suggest that the expression of RTVP-1 is correlated with the degree of malignancy of astrocytic tumors and that RTVP-1 is involved in the regulation of the growth, survival, and invasion of glioma cells. Collectively, these findings suggest that RTVP-1 is a potential therapeutic target in gliomas. (Cancer Res 2006; 66(8): 4139-48)

Henrietta Szold founded the Hadassah Women's Organization in the United States in 1912 to alleviate widespread disease and poverty in Jerusalem. In 1918, the Rothschild-Hadassah Hospital and the Hadassah School of Nursing opened in central Jerusalem. Chaim Weizmann and Albert Einstein, together with a small group of visionaries, founded the Hebrew University in 1923. After 1933, many physicians and scientists fled from Europe to Jerusalem, where they carried on their tradition of academic research at the university and Hadassah, and British military doctors joined medical rounds and lectures at Hadassah beginning in the 1930s. Young physicians who had graduated from European medical schools were trained in the subspecialties at Hadassah beginning in the 1940s, and the Hebrew University-Hadassah Medical School enrolled its first class in 1949. These were the first academic institutions of their kind in Israel. The Department of Neurosurgery at Hadassah was established in 1941 under the leadership of Dr. Henry Wigderson, who was recruited from the United States. Dr. Aaron Beller became chairman in 1951, Dr. Mordechai Shalit became chairman in 1977, and Dr. Felix Umansky, the current chairman, was appointed in 1993. Today, more than 900 neurosurgical procedures spanning the spectrum of subspecialties and using state-of-the-art techniques and equipment are performed annually.