Cerebrospinal Venous Fistula Presenting with Cognitive Decline: Systematic Literature Review and Report of Two Cases.

OBJECTIVE: A cerebrospinal fluid (CSF) venous fistula (CVF) is an aberrant connection between the subarachnoid space and a vein resulting in CSF loss. The presentation and management of CVF with cognitive decline is incompletely understood. METHODS: A systematic review was completed following the PRISMA guidelines. Articles that included at least 1 case of imaging-confirmed CVF with details on patient treatment were included. A separate review of cases of patients with spontaneous intracranial hypotension (SIH) with frontotemporal dementia (FTD) or dementia symptoms was also completed. RESULTS: Ten CVF articles (69 patients; average age, 51.5 years) and 5 SIH with FTD or dementia articles (n = 41; average age, 55.9 years) were identified. Only 1 patients with CVF with cognitive abnormalities was identified. The most common symptom was headache in both reviews. Brain sag was identified in all patients, whereas CSF leak was identified in only 2 patients with SIH with FTD or dementia (4.9%). An epidural blood or fibrin glue patch was used in all patients with CVF and in 33 patients with SIH with FTD or dementia. Fifty-five patients with CVF (79.7%) and 27 patients with SIH with FTD or dementia (65.9%) had surgery. CONCLUSIONS: The 2 cases and literature reviews show the difficulty in diagnosis and treatment of CVF with cognitive decline. Novel imaging techniques should be used in patients with cognitive decline in whom a CSF leak is suspected. Transvenous embolization or surgery should be considered before patching for treatment of CVF-induced brain sag and resulting dementia.

Correction to: inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness.

Following publication of the original article [1], we have been notified that the tagging of one of the author names was done incorrectly in the XML version of the paper. The online and pdf versions of this paper are not affected by the change. Original and corrected tagging can be seen below. The original article has been corrected.

Inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness.

BACKGROUND: The circadian clock is the basis for biological time keeping in eukaryotic organisms. The clock mechanism relies on biochemical signaling pathways to detect environmental stimuli and to regulate the expression of clock-controlled genes throughout the body. MAPK signaling pathways function in both circadian input and output pathways in mammals depending on the tissue; however, little is known about the role of p38 MAPK, an established tumor suppressor, in the mammalian circadian system. Increased expression and activity of p38 MAPK is correlated with poor prognosis in cancer, including glioblastoma multiforme; however, the toxicity of p38 MAPK inhibitors limits their clinical use. Here, we test if timed application of the specific p38 MAPK inhibitor VX-745 reduces glioma cell invasive properties in vitro. METHODS: The levels and rhythmic accumulation of active phosphorylated p38 MAPK in different cell lines were determined by western blots. Rhythmic luciferase activity from clock gene luciferase reporter cells lines was used to test the effect of p38 MAPK inhibition on clock properties as determined using the damped sine fit and Levenberg-Marquardt algorithm. Nonlinear regression and Akaike's information criteria were used to establish rhythmicity. Boyden chamber assays were used to measure glioma cell invasiveness following time-of-day-specific treatment with VX-745. Significant differences were established using t-tests. RESULTS: We demonstrate the activity of p38 MAPK cycles under control of the clock in mouse fibroblast and SCN cell lines. The levels of phosphorylated p38 MAPK were significantly reduced in clock-deficient cells, indicating that the circadian clock plays an important role in activation of this pathway. Inhibition of p38 MAPK activity with VX-745 led to cell-type-specific period changes in the molecular clock. In addition, phosphorylated p38 MAPK levels were rhythmic in HA glial cells, and high and arrhythmic in invasive IM3 glioma cells. We show that inhibition of p38 MAPK activity in IM3 cells at the time of day when the levels are normally low in HA cells under control of the circadian clock, significantly reduced IM3 invasiveness. CONCLUSIONS: Glioma treatment with p38 MAPK inhibitors may be more effective and less toxic if administered at the appropriate time of the day.

NIK/MAP3K14 Regulates Mitochondrial Dynamics and Trafficking to Promote Cell Invasion.

Although the role of NF-κB-inducing kinase (NIK) in immunity is well established, its relevance in cancer is just emerging. Here we describe novel functions for NIK in regulating mitochondrial dynamics and motility to promote cell invasion. We show that NIK is localized to mitochondria in cancer cell lines, ex vivo tumor tissue, and mouse embryonic fibroblasts (MEFs). NIK promotes mitochondrial fission, velocity, and directional migration, resulting in subcellular distribution of mitochondria to the periphery of migrating cells. Moreover, NIK is required for recruitment of Drp1 to mitochondria, forms a complex with Drp1, and regulates Drp1 phosphorylation at Ser-616 and dephosphorylation at Ser-637. Consistent with a role for NIK in regulating mitochondrial dynamics, we demonstrate that Drp1 is required for NIK-dependent, cytokine-induced invasion. Importantly, using MEFs, we demonstrate that the established downstream mediators of NIK signaling, IκB kinase α/ß (IKKα/ß) and NF-κB, are not required for NIK to regulate cell invasion, Drp1 mitochondrial localization, or mitochondrial fission. Our results establish a new paradigm for IKK-independent NIK signaling and significantly expand the current dogma that NIK is predominantly cytosolic and exclusively regulates NF-κB activity. Overall, these findings highlight the importance of NIK in tumor pathogenesis and invite new therapeutic strategies that attenuate mitochondrial dysfunction through inhibition of NIK and Drp1.

MicroRNA-145 Promotes the Phenotype of Human Glioblastoma Cells Selected for Invasion.

BACKGROUND/AIM: Novel treatment strategies aiming to eliminate or attenuate the invasive phenotype of glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, could offer a profound therapeutic benefit to patients. We previously demonstrated one method to create invasive sub-populations of GBM cells (IM3 cells) and a positive regulatory role for the miR-143/-145 locus in enhancing the invasion of GBM cells. Herein, we investigated the correlation between miR-145 and srGAP1 (SLIT-ROBO Rho GTPase-activating protein1) that is purported to be a target of miR-145 and involved in migration and invasion. MATERIALS AND METHODS: IM3 cells were created by a serial selection by using Boyden chambers®. Antisense-miR-145 was transfected into IM3 cells by using lipofectamine 2000. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were employed to analyze the expression of srGAP1. RESULTS: The invasiveness of U87-IM3 and U251-IM3 is attenuated by transfection of antisense miR-145. In addition, srGAP1 was down-regulated in U87-IM3 and U251-IM3 cells compared to parental cells. CONCLUSION: The elevated miR-145 present in invasive glioblastoma cells (IM3 cells) targets and down-regulated srGAP1, thereby allowing downstream G-proteins to remain in their active state and promote the observed invasive phenotype.

What is the utility of postoperative antihelminthic therapy after resection for intraventricular neurocysticercosis?

BACKGROUND: Neurocysticercosis (NCC) is the most common worldwide parasitic infection of the central nervous system, and ventricular cysts are particularly problematic, carrying the risk of acute obstructive hydrocephalus. Herein, we present a typical case in which complete resection was possible and explore the evidence supporting the use of postoperative oral antihelminthic therapy. METHODS: We performed a systematic review of the medical literature. Articles were included if they provided: 1) documentation of intraventricular disease, 2) discussion of management strategy, and 3) a presentation of outcomes. Available data were analyzed based on the primary therapy for NCC. RESULTS: Data from 264 patients were abstracted from 32 references. Of all patients undergoing surgical resection of an isolated neurocysticercal cyst, 33.5% received postoperative antihelminthic therapy, most commonly albendazole. Among patients who had undergone surgical resection of a single intraventricular lesion (as was the case with our own patient), those who received postoperative antihelminthic therapy had a significantly lower risk of developing delayed hydrocephalus (18.8%, compared to 59.1% for those who received no medical therapy) (P = 0.02). The total mortality rate in our review was 3%. CONCLUSIONS: This review produced surprising results: 1) the generous proportion of patients who underwent medical therapy as first-line treatment for intraventricular NCC (20.8%), and 2) the significant overall mortality. The data found in this review also provided for a strong consensus for the use of postresection antihelminthic therapy, and thus we elected to treat our index case with albendazole, assuming the risk to be low and the potential benefit meaningful.

Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion.

BACKGROUND: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant to local therapy in part because of their ability to invade the normal brain parenchyma surrounding these tumors. Animal models capable of recapitulating glioblastoma invasion may help identify mediators of this aggressive phenotype. METHODS: Patient-derived glioblastoma lines have been propagated in our laboratories and orthotopically xenografted into the brains of immunocompromized mice. Invasive cells at the tumor periphery were isolated using laser capture microdissection. The mRNA expression profile of these cells was compared to expression at the tumor core, using normal mouse brain to control for host contamination. Galectin-1, a target identified by screening the resulting data, was stably over-expressed in the U87MG cell line. Sub-clones were assayed for attachment, proliferation, migration, invasion, and in vivo tumor phenotype. RESULTS: Expression microarray data identified galectin-1 as the most potent marker (p-value 4.0 x 10-8) to identify GBM cells between tumor-brain interface as compared to the tumor core. Over-expression of galectin-1 enhanced migration and invasion in vitro. In vivo, tumors expressing high galectin-1 levels showed enhanced invasion and decreased host survival. CONCLUSIONS: In conclusion, cells at the margin of glioblastoma, in comparison to tumor core cells, have enhanced expression of mediators of invasion. Galectin-1 is likely one such mediator. Previous studies, along with the current one, have proven galectin-1 to be important in the migration and invasion of glioblastoma cells, in GBM neoangiogenesis, and also, potentially, in GBM immune privilege. Targeting this molecule may offer clinical improvement to the current standard of glioblastoma therapy, i.e. radiation, temozolomide, anti-angiogenic therapy, and vaccinotherapy.

Serial selection for invasiveness increases expression of miR-143/miR-145 in glioblastoma cell lines.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary central nervous system malignancy and its unique invasiveness renders it difficult to treat. This invasive phenotype, like other cellular processes, may be controlled in part by microRNAs - a class of small non-coding RNAs that act by altering the expression of targeted messenger RNAs. In this report, we demonstrate a straightforward method for creating invasive subpopulations of glioblastoma cells (IM3 cells). To understand the correlation between the expression of miRNAs and the invasion, we fully profiled 1263 miRNAs on six different cell lines and two miRNAs, miR-143 and miR-145, were selected for validation of their biological properties contributing to invasion. Further, we investigated an ensemble effect of both miR-143 and miR-145 in promoting invasion. METHODS: By repeated serial invasion through Matrigel®-coated membranes, we isolated highly invasive subpopulations of glioma cell lines. Phenotypic characterization of these cells included in vitro assays for proliferation, attachment, and invasion. Micro-RNA expression was compared using miRCURY arrays (Exiqon). In situ hybridization allowed visualization of the regional expression of miR-143 and miR-145 in tumor samples, and antisense probes were used investigate in vitro phenotypic changes seen with knockdown in their expression. RESULTS: The phenotype we created in these selected cells proved stable over multiple passages, and their microRNA expression profiles were measurably different. We found that two specific microRNAs expressed from the same genetic locus, miR-143 and miR-145, were over-expressed in our invasive subpopulations. Further, we also found that combinatorial treatment of these cells with both antisense-miRNAs (antimiR-143 and -145) will abrogated their invasion without decreasing cell attachment or proliferation. CONCLUSIONS: To best of our knowledge, these data demonstrate for the first time that miR-143 and miR-145 regulate the invasion of glioblastoma and that miR-143 and -145 could be potential therapeutic target for anti-invasion therapies of glioblastoma patients.

Occipitocervical fusion in elderly patients.

BACKGROUND: Occipitocervical disease (OCD) in elderly patients will become increasingly common as the population ages. Our experience with occipitocervical fusions (OCF) in this population suggests mixed outcomes. METHODS: Twenty consecutive patients over 65 years old underwent OCF between 1995 and 2005. A retrospective review of demographic, presentation, surgical and outcome data was performed. RESULTS: Twenty patients averaging 75.3 years of age (range 65 to 91) were identified. All patients had evidence of myelopathy; however, the primary surgical indications were progressive spinal cord dysfunction (15), brainstem compression (3), and pain (2). Surgical approach was isolated posterior (9), or anterior transoral odontoidectomy followed by posterior stabilization (11). Overall, surgery improved function modestly; average modified Japanese Orthopedic Association functional score (improved 0.9 grades), average Ranawat Myelopathy Score (improved 0.4 grades), and average Nurick Myelopathy Grade (improved 0.6 grades). However, patients with poor preoperative functional assessment (Ranawat grade ≥ III) had greater neurologic improvement than those with good preoperative function, measured by Nurick grade improvement (1 vs. -0.28; P = .03) and Ranawat grade improvement (0.7 vs. -0.2; P = .03). Additionally, the posterior approach demonstrated significant improvement in Japanese Orthopedic Association functional assessment over patients with anterior/posterior approaches (2.2 vs. -0.3; P = .03), with fewer complications (posterior: 1 minor; anterior/posterior: 1 death, 2 major, 8 minor). Perioperative mortality occurred in 5%, and major morbidity in 10% of patients. CONCLUSIONS: Preventing or stabilizing neurologic deficit in patients with OCD may require OCF, despite the patient's age. In the elderly population, our data favor using the posterior approach when possible, and demonstrate greater neurologic improvement in patients with poor preoperative function.

Disseminated enterogenous cells at the cervicomedullary junction causing communicating hydrocephalus.

The authors present a unique case of a patient with communicating hydrocephalus and repeated ventriculoperitoneal shunt obstructions resulting from mucin-secreting enterogenous cell deposits at the cervicomedullary junction. Pathological examinations revealed that these cellular deposits lacked characteristic cystic architecture and the patient had no history of previous cyst with dissemination. Because of the repeated shunt obstructions and inability to surgically resect the lesion in its entirety, the authors elected radiation therapy to the cervicomedullary junction, encompassing the radiological abnormality. As of this writing, the patient has remained at neurological baseline and has not required further shunt revisions for obstruction.

Hemorrhagic complications of ventriculostomy placement: a meta-analysis.

INTRODUCTION: The reported intracerebral hemorrhage rate due to ventriculostomy placement varies widely. As studies emerge regarding alternative techniques of ventriculostomy placement, and placement by non-neurosurgeons, further definition of the true intracerebral hemorrhage rate associated with ventriculostomy is warranted. We performed a meta-analysis of the existing literature to further elucidate the incidence of intracerebral hemorrhage due to ventriculostomy. METHODS: We performed an extensive literature search using Ovid MEDLINE and PubMed for relevant studies published after 1970. Only studies with more than 25 ventriculostomy procedures were included. Data were extracted regarding number of hemorrhages, clinically significant hemorrhages, and the use of routine post-ventriculostomy CT scanning. We performed subgroup analyses based on the use of routine post-ventriculostomy CT scanning. Chi-squared test was used to determine statistical significance. RESULTS: Overall, 102 hemorrhagic complications from 1,790 ventriculostomies were reported, a hemorrhage rate of 5.7%. Of the 102 hemorrhages, 11 were clinically significant (clinically significant hemorrhage rate = 0.61%). In studies that used routine post-placement CT scans, the hemorrhage rate was 10.06%, compared to a hemorrhage rate of 1.53% in studies in which routine CT scans were not performed (P < 0.001). Eight clinically significant hemorrhages (0.91%) were identified in the studies utilizing routine post-procedural CT scanning, compared to three clinically significant hemorrhages (0.33%) in studies without routine CT scans (P = 0.113). CONCLUSION: The overall hemorrhage risk associated with ventriculostomy placement based on the existing literature is 5.7%. Clinically significant hemorrhage due to ventriculostomy is less than 1%. Modifications of technique that might reduce hemorrhage risk, and the utility of routine post-procedural CT scanning, merit further investigation.

Survival of cardiac arrest after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Survival of cardiac arrest (CA) after aneurysmal subarachnoid hemorrhage (SAH) is poorly characterized. We analyzed the clinical course and outcome of patients who survived resuscitation for CA after aneurysmal SAH. METHODS: Medical records of all patients with acute SAH treated at Mayo Clinic between 1990 and 1997 were reviewed. Three hundred five consecutive patients with angiographically proven aneurysmal SAH presenting within 7 days of ictus were analyzed. CA was defined as a pulseless state, documented by medical personnel, for which resuscitation was performed. Outcome was measured with the Glasgow Outcome Scale score at longest follow-up (mean, 16 mo). RESULTS: Data from 11 patients (3.6%) who had 14 episodes of CA were analyzed. Six patients had CA before reaching the hospital and were successfully resuscitated. Nine of 14 CA episodes occurred at hemorrhage or rehemorrhage. No patient with in-hospital CA failed to be resuscitated. Overall mortality in patients who had CA (46%) was higher than that of patients without CA (15%; P = 0.019). Outcome for all patients who had CA (mean Glasgow Outcome Scale score, 2.5) was worse than for patients without CA (mean Glasgow Outcome Scale score, 3.9; P = 0.005). However, half of the survivors of CA after SAH were living independently with limited deficit at longest follow-up. CONCLUSION: Most cases of CA occur at the time of initial or recurrent SAH. Resuscitation for in-hospital CA is likely to be successful. Although CA after aneurysmal SAH is associated with significantly higher mortality, the outcome of survivors of CA is not worse than that for other patients after aneurysmal SAH.

Influence of aspirin on outcome following aneurysmal subarachnoid hemorrhage.

OBJECT: Previous studies have indicated an increased incidence of death in patients with subarachnoid hemorrhage (SAH) who are currently receiving anticoagulation therapy. The significance of previous aspirin use in patients with SAH is unknown. The authors analyzed the effects of prior aspirin use on clinical course and outcomes following aneurysmal SAH. METHODS: The medical records of 305 patients with angiogram-confirmed aneurysmal SAH who consecutively presented to our institution between 1990 and 1997 within 7 days of ictus were analyzed. Twenty-nine (9.5%) of these patients had a history of regular aspirin use before onset of the SAH. The Glasgow Outcome Scale (GOS) was used to measure patient outcome at the longest available follow up. Aspirin users were older on average than nonusers (59 years of age compared with 53 years; p = 0.018). The mean admission Hunt and Hess grades of patients with and without aspirin use were similar (2 compared with 2.3; p = 0.51). Two trends, which did not reach statistical significance, were observed. 1) The rebleeding rate in aspirin users was 14.3%, compared with a 4.7% rebleeding rate in nonusers (p = 0.06). 2) Permanent disability from vasospasm was less common among aspirin users (23% compared with 50%; p = 0.069). Outcomes did not differ between aspirin users and nonusers (mean GOS Score 3.83 compared with GOS Score 3.86, respectively; p = 0.82). CONCLUSIONS: Despite trends indicating increased rebleeding rates and a lower incidence of permanent disability due to delayed ischemic neurological deficits, there was no significant effect of previous aspirin use on overall outcome following aneurysmal SAH. Based on these preliminary data, the presence of an intracranial aneurysm is not a strict contraindication to aspirin use.

Serum magnesium levels as related to symptomatic vasospasm and outcome following aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Recent evidence suggests that magnesium may be neuroprotective in the setting of cerebral ischemia, and therapeutic magnesium infusion has been proposed for prophylaxis and treatment of delayed ischemic neurological deficit (DIND) resulting from vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). We studied the association between serum magnesium levels, the development of DIND, and the outcomes of patients with SAH. METHODS: We studied 128 consecutive patients with aneurysmal SAH treated at our institution between 1990 and 1997 who had a serum magnesium level measured at least once during the acute phase of their hospitalization. Delayed ischemic neurological deficit was defined as severe (major focal deficit or coma), moderate (incomplete focal deficit or decreased sensorium without coma), or none. RESULTS: There was no significant difference in mean, minimum, or maximum serum magnesium levels between patients with and without DIND (1.93, 1.83, 2.02 versus 1.91, 1.84, 1.97 mg/dL, respectively). Similarly, no difference was found in mean serum magnesium levels among patients with severe (1.94 mg/dL), moderate (1.92 mg/dL), or no DIND (1.91 mg/dL). Analyses of serum magnesium levels before (0-4 days following SAH), during (4-14 days following SAH), and after (greater than 14 days following SAH) the period of highest risk for vasospasm revealed no association with the development or severity of DIND. Permanent deficit or death resulting from vasospasm and Glasgow Outcome Scale score at longest follow-up were similarly unaffected by serum magnesium levels overall or during any time interval. Forty (31.5%) patients were hypomagnesemic (less than 1.7 mg/dL) during hospitalization, but no difference in outcome (p = 0.185) or development of DIND (p = 0.785) was found when compared to patients with normal (1.7-2.1 mg/dL) or high (greater than 2.1 mg/dL) magnesium serum levels. CONCLUSION: We identified no relationship between serum magnesium levels and the development of DIND or outcome following aneurysmal SAH. Based on these data, magnesium supplementation to normal or high-normal physiological ranges seems unlikely to be beneficial for DIND resulting from vasospasm. However, no inference can be made regarding the value of therapeutic infusion of magnesium to supraphysiological levels.

Pulmonary complications of aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Pulmonary complications challenge the medical management of patients who have sustained aneurysmal subarachnoid hemorrhage (SAH). We assessed the frequency and types of pulmonary complications after aneurysmal SAH and analyzed the impact of pulmonary complications on patient outcome. METHODS: We reviewed the records of all patients with acute SAH treated at our institution between 1990 and 1997. Three hundred five consecutive patients with an aneurysmal hemorrhage source documented by angiography and treated within 7 days of ictus were analyzed. Outcomes at longest follow-up (mean, 16 mo) were measured by use of the Glasgow Outcome Scale. RESULTS: Pulmonary complications were documented in 66 patients (22%). The pulmonary complications were nosocomial pneumonia in 26 patients (9%), congestive heart failure in 23 (8%), aspiration pneumonia in 17 (6%), neurogenic pulmonary edema in 5 (2%), pulmonary embolus in 2 (<1%), and other pulmonary disorders in 4 (1%); 11 patients had two pulmonary complications. The incidence of symptomatic vasospasm was greater in patients with pulmonary complications (63%) than in patients without pulmonary complications (31%) (P = 0.001), and this association was independent of age and clinical grade at admission (odds ratio, 3.68; P < 0.001). Overall clinical outcomes were worse in patients with pulmonary complications (mean Glasgow Outcome Scale score, 3.3) than in patients without pulmonary complications (mean Glasgow Outcome Scale score, 4.0; P = 0.0001), but pulmonary complications were not an independent predictor of worse outcome when adjusted for age and clinical grade at admission (odds ratio, 1.38; P = 0.315). CONCLUSION: Patients who experience pulmonary complications after aneurysmal SAH have a higher incidence of symptomatic vasospasm than do patients without pulmonary complications. This most likely reflects both the failure to maintain aggressive hypervolemic and hyperdynamic therapy in patients with pulmonary compromise and the possible precipitation of congestive heart failure by hypervolemic therapy in patients with preexisting delayed ischemic neurological deficit. Although patients with pulmonary complications have worse overall clinical outcomes than do patients without pulmonary complications, this is attributable to older age and worse clinical grades at admission.

Guglielmi detachable coil treatment of ruptured saccular cerebral aneurysms: retrospective review of a 10-year single-center experience.

BACKGROUND AND PURPOSE: We retrospectively analyzed our results with Guglielmi detachable coils (GDCs) for the endovascular occlusion of acutely ruptured saccular cerebral aneurysms over 10 years. METHODS: Between 1991-2000, 83 patients (mean age, 56.1 years) with aneurysmal subarachnoid hemorrhage were treated with endovascular GDCs. Patients with aneurysms due to trauma or dissection and those with mycotic or fusiform aneurysms were excluded. Mean follow-up in survivors was 19.1 months, and the mean Hunt-Hess grade at admission was 2.2. Angiographic follow-up was performed in 93% of surviving patients (mean interval, 11.6 months). The basilar caput (34 patients) and anterior communicating artery complex (19 patients) were most commonly treated. RESULTS: Sixty-four patients (77%) had a Glasgow Outcome Scale score (GOS) of 4 or 5, nine (11%) had a score of 2 or 3, and 10 (12%) died. At follow-up, 24 patients (35%) had complete aneurysm occlusion, 18 (26%) had a dog-ear remnant, 24 (35%) had a residual neck, and two (3%) had residual aneurysm filling. No treated aneurysm rebled. Three patients required surgical repair after incomplete endovascular treatment. Two or more GDC occlusion procedures were required in 28 patients (34%). Major procedural complications occurred in two patients (2%), resulting in serious neurologic disability or death. CONCLUSION: Endovascular treatment of ruptured cerebral aneurysms with GDCs has low morbidity, and it facilitates good overall outcomes in patients after subarachnoid hemorrhage. The short-term effectiveness of GDC occlusion in preventing aneurysmal rebleeding was excellent. Durability of the treatment in preventing long-term rebleeding as compared with direct surgical clipping warrants further study. Advances in device technology and technique may improve future outcomes.

Symptomatic vasospasm and outcomes following aneurysmal subarachnoid hemorrhage: a comparison between surgical repair and endovascular coil occlusion.

OBJECT: The authors studied patients with aneurysmal subarachnoid hemorrhage (SAH) to determine whether the incidence of symptomatic vasospasm or overall clinical outcomes differed between patients treated with craniotomy and clip application and those treated by endovascular coil occlusion. METHODS: The authors reviewed 415 consecutive patients with aneurysmal SAH who had been treated with either craniotomy and clip application or endovascular coil occlusion at a single institution between 1990 and 2000. Three hundred thirty-nine patients underwent surgical clip application procedures, whereas 76 patients underwent endovascular coil occlusion. Symptomatic vasospasm occurred in 39% of patients treated with clip application, 30% of patients treated with endovascular coil occlusion, and 37% of patients overall. Compared with patients treated with clip application, patients treated with endovascular coil occlusion were more likely to suffer acute hydrocephalus (50 compared with 34%, p = 0.008) and were more likely to harbor aneurysms in the posterior circulation (53 compared with 20%, p < 0.001). Logistic regression models controlling for patient age, admission World Federation of Neurosurgical Societies (WFNS) grade, acute hydrocephalus, aneurysm location, and day of treatment revealed that, among patients with an admission WFNS grade of I to III, endovascular coil occlusion carried a lower risk of symptomatic vasospasm (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.14-0.8) and death or permanent neurological deficit due to vasospasm (OR 0.28, 95% CI 0.08-1) compared with craniotomy and clip application. Similar models revealed no difference in the likelihood of a Glasgow Outcome Scale score of 3 or less at the longest follow-up review (median 6 months) between treatment groups (OR 0.58, 95% CI 0.28-1.21). CONCLUSIONS: Patients with better clinical grades (WFNS Grades I-III) at hospital admission were less likely to suffer symptomatic vasospasm when treated by endovascular coil occlusion, compared with craniotomy and clip application. Nevertheless, there was no significant difference in overall outcome at the longest follow-up examination between the two treatment groups.

Preoperative ventriculostomy and rebleeding after aneurysmal subarachnoid hemorrhage.

OBJECT: Despite the widespread use of ventriculostomy in the treatment of acute hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH), there is no consensus regarding the risk of rebleeding associated with ventriculostomy before aneurysm repair. This present study was conducted to assess the risk of rebleeding after preoperative ventriculostomy in patients with aneurysmal SAH. METHODS: The authors reviewed the records of all patients with acute SAH who were treated at a single institution between 1990 and 1997. Thus, the records of 304 consecutive patients in whom an aneurysmal SAH source was documented on angiographic studies and who had presented to the authors' institution within 7 days of ictus were analyzed. Re-bleeding was confirmed by evidence of recurrent hemorrhage on computerized tomography scans in all cases. Forty-five patients underwent ventriculostomy for acute hydrocephalus after aneurysmal SAH at least 24 hours before aneurysm repair. Ventriculostomy was performed within 24 hours of SAH in 38 patients, within 24 to 48 hours in three patients, and more than 48 hours after SAH in four patients. The mean time interval between SAH and surgery in patients who did not undergo ventriculostomy was no different from the mean interval between ventriculostomy and surgery in patients who underwent preoperative ventriculostomy (3.6 compared with 3.8 days, p = 0.81). Fourteen (5.4%) of the 259 patients who did not undergo ventriculostomy suffered preoperative aneurysm rebleeding, whereas two (4.4%) of the 45 patients who underwent preoperative ventriculostomy had aneurysm rebleeding. CONCLUSIONS: No evidence was found that preoperative ventriculostomy performed after aneurysmal SAH is associated with an increased risk of aneurysm rebleeding when early aneurysm surgery is performed.

Volumetric quantification of Fisher Grade 3 aneurysmal subarachnoid hemorrhage: a novel method to predict symptomatic vasospasm on admission computerized tomography scans.

OBJECT: Predicting which patients with aneurysmal subarachnoid hemorrhage (SAH) will develop delayed ischemic neurological deficit (DIND) due to vasospasm remains subjective and unreliable. The authors analyzed the utility of a novel software-based technique to quantify hemorrhage volume in patients with Fisher Grade 3 aneurysmal SAH. METHODS: Patients with aneurysmal SAH in whom a computerized tomography (CT) scan was performed within 72 hours of ictus and demonstrated Fisher Grade 3 SAH were analyzed. Severe DIND was defined as new onset complete focal deficit or coma. Moderate DIND was defined as new onset partial focal deficit or impaired consciousness without coma. Fifteen consecutive patients with severe DIND, 13 consecutive patients with moderate DIND, and 12 consecutive patients without DIND were analyzed. Software-based volumetric quantification was performed on digitized admission CT scans by a single examiner blinded to clinical information. There was no significant difference in age, sex, admission Hunt and Hess grade, or time to admission CT scan among the three groups (none, moderate, or severe DIND). Patients with severe DIND had a significantly higher cisternal volume of hemorrhage (median 30.5 cm3) than patients with moderate DIND (median 12.4 cm3) and patients without DIND (median 10.3 cm3; p < 0.001). Intraparenchymal hemorrhage and intraventricular hemorrhage were not associated with DIND. All 13 patients with cisternal volumes greater than 20 cm3 developed DIND, compared with 15 of 27 patients with volumes less than 20 cm3 (p = 0.004). CONCLUSIONS: The authors developed a simple and potentially widely applicable method to quantify SAH on CT scans. A greater volume of cisternal hemorrhage on an admission CT scan in patients with Fisher Grade 3 aneurysmal SAH is highly associated with DIND. A threshold of cisternal hemorrhage volume (> 20 cm3) may exist above which patients are very likely to develop DIND. Prospective application of software-based volumetric quantification of cisternal SAH may predict which patients will develop DIND.