Acute communicating hydrocephalus after intracranial arachnoid cyst decompression: A report of two cases.

BACKGROUND: Arachnoid cysts (AC) may cause hydrocephalus and neurological symptoms, necessitating surgical intervention. Cyst drainage may result in postoperative complications, however, these interventions are not normally associated with the subsequent development of acute hydrocephalus. Herein, we present two unique cases of AC drainage with postoperative development of acute communicating hydrocephalus. CASE DESCRIPTION: Case 1. A 75-year-old female presented with progressive headaches, cognitive decline, and questionable seizures. Her neurological examination was non-focal, but a head computed tomography scan (CT) identified a large right frontal AC with mass effect. She subsequently underwent craniotomy and decompression of the cyst. Postoperatively, her neurological examination deteriorated, and a head CT demonstrated new communicating hydrocephalus. The opening pressure was elevated upon placement of an external ventricular drain. Her hydrocephalus improved on follow-up imaging, but her neurological examination failed to improve, and she ultimately expired. Case 2. A 61-year-old female presented with headache and seizures attributed to a left parietal AC. She underwent open craniotomy for fenestration of the cyst into the Sylvian fissure. Postoperatively, her neurologic examination deteriorated, and she developed acute communicating hydrocephalus. She was initially managed with external ventricular drainage (EVD). The hydrocephalus resolved after several days, and the EVD was subsequently removed. Late follow-up imaging at 2 years showed that the regression of the AC was maintained. CONCLUSION: Acute development of hydrocephalus is a potential complication of intracranial AC fenestration. A better understanding of intracranial cerebrospinal fluid flow dynamics may better inform as to the underlying cause of this complication.

Pipeline embolization of ruptured, previously coiled cerebral aneurysms: Case series and considerations for management.

PURPOSE: Aneurysmal recurrence represents a significant drawback of endovascular coiling, particularly in aneurysms that have previously ruptured. Given the high recurrence rate of coiled aneurysms and particularly the risk of posttreatment rupture in previously ruptured aneurysms that have been treated by coiling, the question of how best to treat ruptured aneurysms that recur postcoiling remains. MATERIALS AND METHODS: We conducted a retrospective analysis of twenty patients who underwent pipeline embolization of previously ruptured, coiled cerebral aneurysms. RESULTS: Pipeline embolization device (PED) treatment resulted in complete aneurysmal occlusion in 10 patients (62.5%) at first angiographic follow-up, and 11 patients (68.75%) at last follow-up. No PED-related complications were encountered and there were no peri-procedural or postprocedural hemorrhages, or symptomatic ischemic events following flow diversion. CONCLUSIONS: PED as a second-line treatment is a safe and effective modality for achieving aneurysmal occlusion in recurrent, previously ruptured, primarily coiled aneurysms. Additionally, a staged coil-to-PED approach may be considered for the management of acutely ruptured aneurysms to achieve aneurysmal obliteration in an effort to mitigate recurrence, and reduce the amount of postprocedural studies.

Incidence of Neo-Intimal Hyperplasia in Anterior Circulation Aneurysms Following Pipeline Flow Diversion.

INTRODUCTION: Flow diversion of the distal anterior circulation cerebral vasculature may be used for management of wide necked aneurysms not amenable to other endovascular approaches. Follow-up angiography sometimes demonstrates neo-intimal hyperplasia within or adjacent to the stent, however there is limited evidence in the literature examining the incidence in MCA and ACA aneurysms. We present our experience with flow diversion of the distal vasculature and evaluate the incidence of neo-intimal hyperplasia. MATERIALS AND METHODS: Retrospective review of patients who underwent Pipeline embolization device (PED) treatment for ruptured and unruptured anterior circulation aneurysms. RESULTS: A total of 251 anterior circulation aneurysms were treated by pipeline flow diversion, of which 175 were ICA aneurysms, 14 were ACA aneurysms and 18 were MCA aneurysms. 6-month follow-up angiography was available in 207 patients. The incidence of neo-intimal hyperplasia was 15.9%, 21.4%, and 61.1% in ICA, ACA, and MCA aneurysms, respectively. MCA-territory aneurysms developed neo-intimal hyperplasia at a significantly higher rate than aneurysms in other vessel territories. Rates of aneurysmal occlusion did not significantly differ from those patients who did not exhibit intimal hyperplasia on follow-up angiography. CONCLUSION: In our experience, flow diversion of distal wide-necked MCA and ACA aneurysms is a safe and effective treatment strategy. The presence of neo-intimal hyperplasia at 6-month angiography is typically clinically asymptomatic. Given the statistically higher rate of neo-intimal hyperplasia in MCA aneurysms at 6-month angiography, we propose delaying initial follow-up angiography to 12-months and maintaining dual antiplatelet therapy during that time.

Flow diversion in anterior cerebral artery aneurysms.

INTRODUCTION: Anterior cerebral artery (ACA) aneurysms are commonly encountered in clinical practice but can be challenging to treat. Flow diversion is a viable treatment in this population. METHODS: We retrospectively evaluated patients treated at our center from May 2017 to December 2020 who underwent flow diversion for an ACA aneurysm at or distal to the anterior communicating artery (ACOM). We defined ACA aneurysms as any aneurysm involving the ACOM itself, at the junction of the ACA with the ACOM (A1/A2), or in distal A2/A3 branches; both ruptured and unruptured aneurysms were included. Baseline and follow-up clinical and angiographic data were collected; the primary measure was elimination of the aneurysm on follow-up angiogram. Patients underwent flow diversion with a Pipeline stent. A single flow diverting stent was placed in the dominant ACA spanning from the A2 segment extending into the A1 segment; two patients required H-pipe technique. Distal aneurysms were treated with a single Pipeline device deployed across the parent vessel, covering the aneurysm. RESULTS: Two-seven patients underwent a total of 28 flow diversion procedures; median age was 57 and 16 (59.3%) were male. Thirteen (48.2%) patients presented with subarachnoid hemorrhage; of these, four were treated within 6 weeks of the index hemorrhage. Most patients (22; 81.5%) had significant ACA asymmetry. There was one postoperative intracerebral hemorrhage and one groin complication. Follow-up data were available for 19 patients, 15 (78.9%) of which showed no residual aneurysm and 17 (89.5%) had protection of the dome. CONCLUSION: Flow diversion of ACA aneurysms can be a primary treatment modality in an unruptured aneurysm or a complement to initial coil protection of a ruptured aneurysm. Further studies are needed to confirm these results.

Mandatory Neuroendovascular Evolution: Meeting the New Demands.

BACKGROUND: Traditionally, patients undergoing acute ischemic strokes were candidates for mechanical thrombectomy if they were within the 6-h window from onset of symptoms. This timeframe would exclude many patient populations, such as wake-up strokes. However, the most recent clinical trials, DAWN and DEFUSE3, have expanded the window of endovascular treatment for acute ischemic stroke patients to within 24 h from symptom onset. This expanded window increases the number of potential candidates for endovascular intervention for emergent large vessel occlusions and raises the question of how to efficiently screen and triage this increase of patients. SUMMARY: Abbreviated pre-hospital stroke scales can be used to guide EMS personnel in quickly deciding if a patient is undergoing a stroke. Telestroke networks connect remote hospitals to stroke specialists to improve the transportation time of the patient to a comprehensive stroke center for the appropriate level of care. Mobile stroke units, mobile interventional units, and helistroke reverse the traditional hub-and-spoke model by bringing imaging, tPA, and expertise to the patient. Smartphone applications and social media aid in educating patients and the public regarding acute and long-term stroke care. KEY MESSAGES: The DAWN and DEFUSE3 trials have expanded the treatment window for certain acute ischemic stroke patients with mechanical thrombectomy and subsequently have increased the number of potential candidates for endovascular intervention. This expansion brings patient screening and triaging to greater importance, as reducing the time from symptom onset to decision-to-treat and groin puncture can better stroke patient outcomes. Several strategies have been employed to address this issue by reducing the time of symptom onset to decision-to-treat time.

Traumatic cervical internal carotid artery pseudoaneurysm in a child refractory to initial endovascular treatment: case report and technical considerations.

PURPOSE: Optimal management of extracranial carotid artery dissections (eCAD) in pediatric patients is not well documented, and endovascular interventions are rarely reported. METHODS: A 10-year-old girl sustained multiple systemic injuries in a motor vehicle accident, including an eCAD with pseudoaneurysm. She initially failed both aspirin and endovascular stenting with progressive enlargement of a traumatic cervical carotid pseudoaneurysm and stenosis. RESULTS: Second-stage endovascular stent placement with coiling resulted in successful occlusion of the pseudoaneurysm. At 30-month imaging follow-up, the parent vessel remained patent with no evidence of the pseudoaneurysm. CONCLUSION: In the setting of poly-trauma, management of eCAD can be complex especially in the pediatric population. There is little data on the endovascular treatment of eCAD in children. Failed endovascular therapies are extremely rare. Our report supports surveillance imaging as repeat endovascular treatment may be necessary.

Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.

Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.

Delayed retraction of the pipeline embolization device and corking failure: pitfalls of pipeline embolization device placement in the setting of a ruptured aneurysm.

BACKGROUND AND IMPORTANCE: The safety of flow-diverting stents for the treatment of ruptured intracranial aneurysms is unknown. CLINICAL PRESENTATION: A 35-year-old woman with a ruptured dissecting aneurysm of the intradural right vertebral artery and incorporating the right posterior inferior cerebellar artery was treated with a Pipeline Embolization Device (PED). Five days after reconstruction of the diseased right vertebral segment, she was treated for vasospasm, and retraction of the PED was observed, leaving her dissecting aneurysm unprotected. A second PED was placed with coverage of the aneurysm, but vasospasm complicated optimal positioning of the device. CONCLUSION: In addition to the potential risks of dual antiplatelet therapy in these patients, this case illustrates 2 pitfalls of flow-diverting devices in vessels in vasospasm: delayed retraction of the device and difficulty positioning the device for deployment in the setting of vasospasm.

National trends in spinal arteriovenous malformations.

OBJECT: Spinal arteriovenous malformations (AVMs) are rare and understudied vascular lesions that cause neurological insult by mass effect, venous obstruction, and vascular steal. These lesions are challenging entities to treat because of their complicated anatomy and physiology. Current management options include open microsurgery, endovascular embolization, and stereotactic radiosurgery. METHODS: Our study used the National Inpatient Sample database to analyze outcome data for spinal AVMs treated nationwide over an 11-year period from 1995 through 2006. Trends in procedural management, hospital course, and epidemiology of spinal AVMs are investigated. RESULTS: Annually, an average of 300 patients presented with spinal AVMs requiring hospital treatment. The average length of hospital stay for this treatment has declined from more than 9 days in 1995 to 6 days in 2006. However, the average cost of a hospital stay has increased from < $30,000 to nearly $70,000. Whereas one-half of spinal AVMs were treated operatively in 1995, one-third were managed operatively in 2006. CONCLUSIONS: Spinal AVMs are being increasingly treated by endovascular, radiosurgical, or combined means. A discussion of modern strategies to treat these disorders is presented.

National trends in spinal fusion for cervical spondylotic myelopathy.

BACKGROUND: The objective of this study is to provide a retrospective analysis using an NIS database to examine national trends in outcomes for CSM from 1993 to 2002. METHODS: Data for CSM admissions (n = 138792) were extracted from the 1993 to 2002 NIS database to determine overall outcomes, as well as for those patients with CSM who underwent spinal fusion. Data from 1993 to 1997 (period 1) were compared with data from 1998 to 2002 (period 2). RESULTS: The number of patients admitted with CSM increased 2-fold from 3.73 to 7.88 per 100000 US population. Approximately 10% of patients were admitted from the ED and 42% underwent spinal fusion. The number of patients with CSM that underwent spinal fusion increased 7-fold from 0.6 to 4.1 per 100000 people over the period from 1993 to 2002. Most spinal fusions were performed in the 45- to 64-year age group. The number of patients with 2 or more comorbidities increased from 20% to 37%; however, the mortality and adverse outcome rates remained stable, and there was a slight decrease in LOS. CONCLUSIONS: Cervical spondylotic myelopathy is one of the most common disorders treated by spine surgeons. There was a nearly 7-fold increase in the number of spinal fusions for CSM from 1993 to 2002. Despite continued increases in patient medical comorbidities, overall complication rates have remained stable at approximately 10.3% and mortality rates constant at 0.6%.

Molecular events of brain metastasis.

The brain is a privileged site of systemic cancer metastasis. The stages of the metastatic journey from the periphery to the brain are driven by molecular events that tie the original site of disease to the distant host tissue. This preference is not arbitrary but rather a directed phenomenon that includes such critical steps as angiogenesis and the preparation of the premetastatic niche. It appears that the connection between naive brain and cancer cells is made in advance of any metastatic breach of the blood-brain barrier. This contributes to the preferential homing of cancer cells to the brain. Delineation of the guidance mechanisms and elements that influence cancer cell motility and dormancy are important for the advancement of treatment modalities aimed at the remediation of this devastating disease.

Incorporation of bone marrow-derived Flk-1-expressing CD34+ cells in the endothelium of tumor vessels in the mouse brain.

OBJECTIVE: Neoangiogenesis is a prerequisite for the full phenotypic expression and growth of a malignant tumor mass. It is believed to be triggered by tissue hypoxia and involves proliferation and sprouting of the preexisting vessels and the recruitment of endothelial progenitor cells from bone marrow. METHODS: A chimeric mouse model was used to examine the contribution of these progenitor cells to the neovasculature of brain tumor. T-cell knockout (RAG/KO5.2) mice were irradiated lethally, and their bone marrow was repopulated with T-cell depleted green fluorescent protein (GFP)-expressing bone marrow cells. RAG/RT-2 glioma cells were implanted into the striatum of the animals. Neovascular formation at various times of tumor growth was monitored together with the extent of incorporation of GFP+ bone marrow-derived cells within the vascular tree, in particular, cells carrying the endothelial progenitor markers CD34 and Flk-1. RESULTS: The recruitment of GFP+ cells to the growing tumor and their incorporation into the vascular network occurred during the period of increasing vascular density and preceded the expansion of the tumor. The number of marrow-derived cells with endothelial morphology and phenotype was small but significant (4% of all endothelial cells at Day 12); 54% of all tumor vessels contained at least one GFP+ cell. CONCLUSION: Our results suggest that bone marrow cells are recruited to newly formed and remodeled tumor vessels. Their recruitment may occur in response to signals from a highly proliferating milieu, and their role is to support the neovascular complex and to promote tumor growth.

Effects of tumor suppressor gene (p53) on brain tumor angiogenesis and expression of angiogenic modulators.

BACKGROUND: p53 retarded tumor growth by several known mechanisms, including suppression of cell proliferation and inhibition of tumor angiogenesis. Vascular endothelial growth factors (VEGF) and angiopoietins (Ang-1, Ang-2) are major angiogeneic modulators. The current study examined the effect of p53 on the expression of these factors in conjunction with tumor growth and vascular formation. MATERIALS AND METHODS: Growth characteristics of rat glioma cells (RT-2) infected with retrovirus (MSCV) encoding a full-length human wild-type p53 gene were examined by clonogenic assay. Expression of the transgene in vitro was verified by RT-PCR and immunoprecipitation. Tumor morphology, vascular architecture and the expression of VEGF, Ang-1, Ang-2 and Tie-2 were examined by immunohistochemistry and semi-quantitative RT-PCR. RESULTS: p53-infected cells showed retardation in growth and colony formation. In vivo, expression of the transgene resulted in prolonged survival and reduction of tumor volume (62%) and reduced the expression of VEGF (57.8%) and Tie-2 (15.4%) but not Ang-1 and Ang-2. The tumor exhibited increased necrosis (38%), hemorrhage and abnormal vascular architecture. CONCLUSION: p53 causes tumor regression by suppressing tumor proliferation and indirectly induces involution of tumor vessels by fostering unopposed activity of Ang-2 in an environment of diminishing VEGF.

Incorporation of naive bone marrow derived cells into the vascular architecture of brain tumor.

OBJECTIVE: Neovascularization is essential for tumor growth and invasion. Mounting evidence suggests that tumor cells recruit circulating endothelial progenitor cells to promote vasculogenesis to compliment tumor angiogenesis. This study examines the constitutive role of bone marrow-derived cells in this process. METHODS: Rat glioma cells were implanted into brains of T-cell-depleted knockout mice. At various timepoints after tumor implantation, naïve bone marrow cells from ubiquitous transgenic mice expressing green fluorescent protein (GFP) were infused into these animals. The incorporation of GFP-positive cells into the vascular architecture was visualized by fluorescence confocal microscopy in conjunction with the transcription profiles of vascular endothelial growth factor (VEGF) and angiopoietin-1 and -2 (Ang-1 and Ang-2). RESULTS: Of the cells infused, 8 days after tumor implantation, 0.49% were found exclusively sequestered in the vicinity of tumor vessels. This coincided with a decline in the expression of Ang-1 and a rise in the expression of VEGF and Ang-2. A few of these cells (0.66 of the 0.49%) localized onto the vascular wall. They resembled endothelial cells and expressed vWF. CONCLUSION: The incorporation of bone marrow-derived unpurified endothelial cells into the tumor vascular bed is both time-limited and infrequent. These cells may play a supportive rather than a constitutive role in tumor neovascularization.

The temporal-spatial expression of VEGF, angiopoietins-1 and 2, and Tie-2 during tumor angiogenesis and their functional correlation with tumor neovascular architecture.

Angiopoietins play a pivotal role in tumor angiogenesis by modulating vascular endothelial proliferation and survival. The expression of angiopoietins 1 and 2 (Ang-1 and Ang-2) and vascular endothelial growth factor (VEGF) has been documented in human malignant glioma. The expression of Ang-1, Ang-2, VEGF, and Tie-2, a member of the receptor tyrosine kinases and the natural receptor for both Ang-1 and Ang-2, follows a distinct transcriptional profile in vivo. Ang-2 and VEGF were expressed early in tumor formation and their levels increased throughout tumor growth. Their expression coincided with the expansion of the tumor mass and the formation of the vascular tree. There was no significant change in the expression of Tie-2 and Ang-1. The expression of Ang-1 and Tie-2 was more noticeable at the periphery of the tumor. The expression of Ang-2 was more robust at the periphery and within the tumor mass, and VEGF was more concentrated within the center of the tumor. This distinct expression profile may explain the morphology of the newly formed vessels at various times and regions of the tumor. The lack of concomitant expression of Ang-1 may underscore the unopposed endovascular induction by Ang-2 and VEGF resulting in the chaotic appearance and fragility of tumor vessels.

Olfactory ensheathing cells: time lapse imaging of cellular interactions, axonal support, rapid morphologic shifts, and mitosis.

Olfactory ensheathing cells (OECs) have considerable potential for facilitating axonal growth across regions of spinal cord and brain injury but in this context have been studied primarily in static images of fixed tissue from the olfactory system or after transplantation. In the present work, we studied the behavior of live OECs, and their interactions with neurons, Schwann cells, and astrocytes by using cells that express the reporter gene coding for green fluorescent protein (GFP); the work is based on combinations of fluorescence, phase contrast, digital time lapse imaging, and P75 immunocytochemical identification. Cultures, explants, and regions of olfactory system slices rich in OECs enhanced axonal growth of cerebellar granule cells or hippocampal neurons; axons grew parallel to the long axis of fusiform OECs. Neuron cell bodies and axons preferred OECs over artificial substrates. Axons and neuron cell bodies can take active or passive roles in extension and migration on underlying motile OECs and move from one OEC to another. Axon extension was facilitated to a similar degree by OECs and Schwann cells, whereas astrocytes were more likely to integrate with existing OECs than with Schwann cells. OECs showed a dramatic ability to rapidly change shape, size, and direction of migration and to undergo mitosis. Mitosis was characterized by a quick retraction of all processes, thereby forming a sphere that divided into spherical daughter cells within minutes. Progeny OECs might take on the parental or a non-parental morphotype, with both daughter cells showing robust expression of GFP. Together these OEC data demonstrated a substantial plasticity and capability for relatively rapid changes in structure and support the view that OECs have multiple attributes favorable for enhancing axonal extension and neuronal migration after central nervous system injury.

Enhanced cytomegalovirus infection of developing brain independent of the adaptive immune system.

Cytomegalovirus (CMV) has been suggested as the most prevalent infectious agent causing neurological dysfunction in the developing brain; in contrast, CMV infections are rare in the adult brain. One explanation generally given for the developmental susceptibility to the virus is that the developing immune system is too immature to protect the central nervous system from viral infection, but as the immune system develops it can protect the brain. We suggest an alternate view: that developing brain cells are inherently more susceptible to CMV infection, independent of the immune system. We used a recombinant mouse CMV that leads to green fluorescent protein expression in infected cells. Control experiments demonstrated a high correlation between the number of cells detected with the viral GFP reporter gene and with immunocytochemical detection of the virus. After intracerebral inoculation, the number of CMV-infected cells in neonatal brains was many times greater than in mature control or mature immunodepressed SCID mice, and the mortality rate of neonates was substantially greater than SCID or control adults. Parallel experiments with live brain slices inoculated in vitro, done in the absence of the systemic immune system, generated similar data, with immature hippocampus, hypothalamus, cortex, striatum, and cerebellum showing substantially greater numbers of infected cells (100-fold) than found in adult slices in these same regions. Interestingly, in the cerebellar cortex, CMV-infected cells were more prevalent in the postmitotic Purkinje cell layer than in the mitotic granule cell layer, suggesting a selective infection of some cell types not dependent on cell division. Together, these data support the view that CMV has an intrinsic preference for infection of developing brain cells, independent, but not mutually exclusive, of the developmental status of the systemic immune system in controlling CMV infection.