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OBJECTIVE Spontaneous CSF leaks into the anterior skull base nasal sinuses are often associated with meningoencephaloceles and occur in patients with idiopathic intracranial hypertension (IIH). Endonasal endoscopic repair has become the primary method of choice for repair. The authors sought to evaluate the success rate of endoscopic closure and to identify predictive factors for CSF leak recurrence. METHODS A consecutive series of endonasally repaired anterior skull base meningoencephaloceles was drawn from a prospectively acquired database. Lumbar punctures were not performed as part of a treatment algorithm. All patients had at least 5 months of follow-up. Chart review and phone calls were used to determine the timing and predictors of recurrence. Demographic information and details of operative technique were correlated with recurrence. Two independent radiologists reviewed all preoperative imaging to identify radiographic markers of IIH, as well as the location and size of the meningoencephalocele. RESULTS From a total of 54 patients there were 5 with recurrences (9.3%), but of the 39 patients in whom a vascularized nasoseptal (n = 31) or turbinate (n = 8) flap was used there were no recurrences (p = 0.0009). The mean time to recurrence was 24.8 months (range 9–38 months). There was a trend to higher BMI in patients whose leak recurred (mean [± SD] 36.6 ± 8.6) compared with those whose leak did not recur (31.8 ± 7.4; p = 0.182). Although the lateral recess of the sphenoid sinus was the most common site of meningoencephalocele, the fovea ethmoidalis was the most common site in recurrent cases (80%; p = 0.013). However, a vascularized flap was used in significantly more patients with sphenoid (78.3%) defects than in patients with fovea ethmoidalis (28.6%) defects (Fisher’s exact test, p = 0.005). Radiographic signs of IIH were equally present in all patients whose leak recurred (75%) compared with patients whose leak did not recur (63.3%); however, an enlarged Meckel cave was present in 100% (2/2) of patients whose leaks recurred compared with 13.3% (4/30) of patients whose leaks did not recur (p = 0.03). The average meningoencephalocele diameter tended to be larger (1.73 ± 1.3 cm) in patients with recurrence compared to those without recurrence (1.2 ± 0.66 cm; p = 0.22). A ventriculoperitoneal shunt was already in place in 3 patients, placed perioperatively in 5, and placed at recurrence in 2, none of whose leaks recurred. CONCLUSIONS Recurrence after endonasal repair of spontaneous CSF leaks from meningoencephaloceles can be dramatically reduced with the use of a vascularized flap. Although failures of endonasal repair tend to occur in patients who have higher BMI, larger brain herniations, and no CSF diversion, the lack of vascularized flap was the single most important risk factor predictive of failure.

OBJECTIVEDecompressive craniectomy (DC) is an emergency neurosurgical procedure used in cases of severe intracranial hypertension or impending intracranial herniation. The procedure is often lifesaving, but it exposes the brain to atmospheric pressure in the subsequent rehabilitation period, which changes intracranial physiology and probably leads to complications such as hydrocephalus, hygromas, and “syndrome of the trephined.” The objective of the study was to study the effect of cranioplasty on intracranial pressure (ICP), postural ICP changes, and intracranial pulse wave amplitude (PWA).METHODSThe authors performed a prospective observational study including patients who underwent DC during a 12-month period. Telemetric ICP sensors were implanted in all patients at the time of DC. ICP was evaluated before and after cranioplasty during weekly measurement sessions including a standardized postural change program.RESULTSTwelve of the 17 patients enrolled in the study had cranioplasty performed and were included in the present investigation. Their mean ICP in the supine position increased from –0.5 ± 4.8 mm Hg the week before cranioplasty to 6.3 ± 2.5 mm Hg the week after cranioplasty (p < 0.0001), whereas the mean ICP in the sitting position was unchanged (–1.2 ± 4.8 vs –1.1 ± 3.6 mm Hg, p = 0.90). The difference in ICP between the supine and sitting positions was minimal before cranioplasty (1.1 ± 1.8 mm Hg) and increased to 7.4 ± 3.6 mm Hg in the week following cranioplasty (p < 0.0001). During the succeeding 2 weeks of the follow-up period, the mean ICP in the supine and sitting positions decreased in parallel to, respectively, 4.6 ± 3.0 mm Hg (p = 0.0003) and –3.9 ± 2.7 mm Hg (p = 0.040), meaning that the postural ICP difference remained constant at around 8 mm Hg. The mean intracranial PWA increased from 0.7 ± 0.7 mm Hg to 2.9 ± 0.8 mm Hg after cranioplasty (p < 0.0001) and remained around 3 mm Hg throughout the following weeks.CONCLUSIONSCranioplasty restores normal intracranial physiology regarding postural ICP changes and intracranial PWA. These findings complement those of previous investigations on cerebral blood flow and cerebral metabolism in patients after decompressive craniectomy.

OBJECTIVECSF dynamics after transcallosal resection of intraventricular lesions can be altered, and the need for shunt implantation complicates the management of these patients. Because the pathophysiological mechanism and contributing factors are poorly understood and the incidence has largely not been described, the authors conducted a study to elucidate these factors.METHODSThe authors retrospectively reviewed data from patients who had been operated on at their institution via a transcallosal approach between March 2002 and December 2016. They evaluated the need for a shunt implantation up to 3 months after surgery by assessing clinical variables. These variables were age at surgery, the need for perioperative external CSF drainage, histology of the lesion, and the following radiological parameters: pre- and postoperative Evans index, maximal postoperative extension of subdural effusions (SDEs) measured on axial images, and maximal interhemispheric fissure (IHF) width measured on coronal images assessed at 4 different points in time (preoperatively, day 1, days 2–4, and days 4–8 after surgery). To identify potential risk factors, univariate and multivariate regression models were constructed. Receiver operating characteristic (ROC) curves for significant predictors, as well as the area under the curve (AUC), were calculated.RESULTSSeventy-four patients (40 female and 34 male) were identified; their median age at surgery was 17.6 years (range 4 months to 76 years). Shunt implantation was necessary in 13 patients (ventriculoperitoneal [VP] shunt, n = 7; subdural peritoneal [SDP] shunt, n = 6) after a median interval of 24 days (range 10 days to 3 months). Univariate logistic regression models revealed a significant effect of IHF width on days 4–8 (OR 1.31, 95% CI 1.03–1.66; p = 0.027), extension of SDE on days 2–4 (OR 1.33, 95% CI 1.11–1 0.60; p = 0.003), and age (OR 0.932, 95% CI 0.88–0.99; p = 0.02). In the multiple regression model, the effect of the independent variable extension of the SDE remained significant. ROC curves for the predictors IHF width on days 4–8 and extension of SDE on days 2–4 revealed an AUC equal to 0.732 and 0.752, respectively. Before shunt implantation, the ventricles were smaller compared to the preoperative size in 9 of the 13 patients (SDP shunt, n = 5; VP shunt, n = 4).CONCLUSIONSThe rate of shunt-dependent hydrocephalus 3 months after surgery in this heterogeneous group of patients was 17.6% (95% CI 9.7%–28.2%). The authors identified as predictive factors the variables extension of the convexity space, IHF 1 week after surgery, and younger age.

OBJECTIVEPrevious studies have demonstrated that human CSF contains membrane particles carrying the stem cell antigenic marker CD133 (prominin-1). Here, the authors analyzed the variation of the amount of these CD133-positive particles in the CSF of patients with subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH).METHODSConsecutive CSF samples from 47 patients with SAH or ICH were compared to 14 healthy control patients. After differential ultracentrifugation of CSF, the membrane particle fraction was separated on gel electrophoresis and its CD133 content was probed by immunoblotting using the mouse monoclonal antibody 80B258 directed against human CD133. The antigen-antibody complexes were detected by chemiluminescence reagents and quantified using human Caco-2 cell extract as positive control with a standardized curve.RESULTSAs compared to healthy controls (6.3 ± 0.5 ng of bound CD133 antibody; n = 14), the amount of membrane particle–associated CD133 immunoreactivities was significantly elevated in patients with SAH and ICH (38.2 ± 6.6 ng and 61.3 ± 11.0 ng [p < 0.001] for SAH [n = 18] and ICH [n = 29], respectively). In both groups the CD133 level dropped during the first 7 days (i.e., day 5–7: SAH group, 24.6 ± 10.1 ng [p = 0.06]; ICH group, 25.0 ± 4.8 ng [p = 0.002]). Whereas changes in the amount of CD133-positive membrane particles between admission and day 5–7 were not associated with clinical outcomes in patients with ICH (modified Rankin Scale [mRS] scores 0–3, −30.9 ± 12.8 ng vs mRS scores 4–6, −21.8 ± 10.7 ng; p = 0.239), persistent elevation of CD133 in patients with SAH was related to impaired functional outcome 3 months after ictus (mRS scores 0–2, −29.9 ± 8.1 ng vs mRS scores 3–6, 7.6 ± 20.3 ng; p = 0.027). These data are expressed as the mean ± standard error of the mean (SEM).CONCLUSIONSLevels of membrane particle–associated CD133 in the CSF of patients with SAH and ICH are significantly increased in comparison to healthy patients, and they decline during the hospital stay. Specifically, the persistent elevation of CD133-positive membrane particles within the first week may represent a possible surrogate measure for impaired functional outcome in patients with SAH.

OBJECTIVEIntracranial pressure (ICP), outflow resistance (Rout), and amplitude of cardiac-related ICP pulsations (AMPs) are established parameters to describe the CSF hydrodynamic system and are assumed, but not confirmed, to be disturbed in idiopathic normal pressure hydrocephalus (INPH). The aim of this study was to compare the CSF hydrodynamic profile between patients with INPH and healthy volunteers.METHODSSixty-two consecutive INPH patients (mean age 74 years) and 40 healthy volunteers (mean age 70 years) were included. Diagnosis was made by two independent neurologists who assessed patients’ history, neurological status, and MRI studies. A CSF dynamic investigation through the lumbar route was performed: ICP and other CSF dynamic variables were blinded to the neurologists during the diagnostic process and were not used for establishing the diagnosis of INPH.RESULTSRout was significantly higher in INPH (Rout 17.1 vs 11.1; p < 0.001), though a substantial number of INPH subjects had normal Rout. There were no differences between INPH patients and controls regarding ICP (mean 11.5 mm Hg). At resting pressure, there was a trend that AMP in INPH was increased (2.4 vs 2.0 mm Hg; p = 0.109). The relationship between AMP and ICP was that they shared the same slope, but the curve was significantly shifted to the left for INPH (reduced P0 [p < 0.05]; i.e., higher AMP for the same ICP).CONCLUSIONSThis study established that the CSF dynamic profile of INPH deviates from that of healthy volunteers and that INPH should thus be regarded as a disease in which intracranial hydrodynamics are part of the pathophysiology.Clinical trial registration no.: NCT01188382 (clinicaltrials.gov)

OBJECTIVEIn patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration.METHODSIn this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures.RESULTSTwenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119).CONCLUSIONSPreliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

OBJECTIVEThe authors aimed to describe the natural history of ventriculostomy-related infections (VRIs) under appropriate treatment and to assess risk factors for poor outcome.METHODSAll patients older than 18 years in whom an external ventricular drain (EVD) had been implanted and who had developed a VRI requiring treatment were included in this retrospective study. D0 was defined as the first day of antibiotic administration. Clinical and biological parameters were compared each day beginning with D1 and ending with D10 to those of D0. The authors defined D0 in a control group as the day a CSF culture came back positive, without any sign of infection. The authors then searched for poor prognostic factors in the VRI group.RESULTSAmong 567 patients requiring an EVD between January 2007 and October 2017, 39 developed a VRI. Most were monomicrobial infections, and 47 microbes were responsible (45% were gram-positive cocci). Clinical parameters differed significantly from the control group during the first 2 days and then returned to baseline. The CSF parameters differed significantly from the control group for a longer period, returning to baseline after 5 days. CSF sterilization occurred in a median time of 2 days. An intrathecal route or EVD exchange was not associated with a poor outcome. No clinical or biological parameter between D3 and D5 was linked to outcome.CONCLUSIONSClinical status improved faster than CSF parameters (before and after D5, respectively). Some CSF parameters remained abnormal until D10. Body temperature and microbiological cultures normalized faster than other parameters.

OBJECTIVEPerioperative visual loss (POVL) is a rare but serious complication in surgical disciplines, especially in spine surgery. The exact pathophysiology of POVL remains unclear, but elevated intraocular pressure (IOP) is known to be part of it. As POVL is rarely described in patients undergoing intracranial or intradural surgery, the aim of this study was to investigate the course of IOP during neurosurgical procedures with opening of the dura mater and loss of CSF.METHODSIn this prospective, controlled trial, 64 patients fell into one of 4 groups of 16 patients each. Group A included patients undergoing spine surgery in the prone position, group B patients had intracranial procedures in the prone position, and group C patients were treated for intracranial pathologies in a modified lateral position with the head rotated. In groups A–C, the dura was opened during surgery. Group D patients underwent spine surgeries in the prone position with an intact dura. IOP was measured continuously pre-, peri-, and postoperatively.RESULTSIn all groups, IOP decreased after induction of anesthesia and increased time dependently after final positioning for the operation. The maximum IOP in group A prior to opening of the dura was 28.6 ± 6.2 mm Hg and decreased to 23.44 ± 4.9 mm Hg directly after dura opening (p < 0.0007). This effect lasted for 30 minutes (23.5 ± 5.6 mm Hg, p = 0.0028); after 60 minutes IOP slowly increased again (24.5 ± 6.3 mm Hg, p = 0.15). In group B, the last measured IOP before CSF loss was 28.1 ± 5.0 mm Hg and decreased to 23.5 ± 6.1 mm Hg (p = 0.0039) after dura opening. A significant IOP decrease in group B lasted at 30 minutes (23.6 ± 6.0 mm Hg, p = 0.0039) and 60 minutes (23.7 ± 6.0 mm Hg, p = 0.0189). In group C, only the lower eye showed a decrease in IOP up to 60 minutes after loss of CSF (opening of dura, p = 0.0007; 30 minutes, p = 0.0477; 60 minutes, p = 0.0243). In group D (control group), IOP remained stable throughout the operation after the patient was prone.CONCLUSIONSThis study is the first to demonstrate that opening of the dura with loss of CSF during neurosurgical procedures results in a decrease in IOP. This might explain why POVL predominantly occurs in spinal but rarely in intracranial procedures, offers new insight to the pathophysiology of POVL, and provides the basis for further research and treatment of POVL.German Clinical Trials Register (DRKS) no.: DRKS00007590 (drks.de)

OBJECTIVEDelayed ischemic neurological deficit (DIND) is a leading cause of mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Arginine vasopressin (AVP) is a hormone released by the posterior pituitary. It is known to cause cerebral vasoconstriction and has been implicated in hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Direct measurement of AVP is limited by its short half-life. Copeptin, a cleavage product of the AVP precursor protein, was therefore used as a surrogate marker for AVP. This study aimed to investigate the temporal relationship between changes in copeptin concentrations and episodes of DIND and hyponatremia.METHODSCopeptin concentrations in cerebrospinal fluid were quantified using enzyme-linked immunosorbent assay in 19 patients: 10 patients with DIND, 6 patients without DIND (no-DIND), and 3 controls.RESULTSCopeptin concentrations were higher in DIND and no-DIND patients than in controls. In hyponatremic DIND patients, copeptin concentrations were higher compared with hyponatremic no-DIND patients. DIND was associated with a combination of decreasing sodium levels and increasing copeptin concentrations.CONCLUSIONSIncreased AVP may be the unifying factor explaining the co-occurrence of hyponatremia and DIND. Future studies are indicated to investigate this relationship and the therapeutic utility of AVP antagonists in the clinical setting.

OBJECTIVE The effect of CSF on blood coagulation is not known. Enhanced coagulation by CSF may be an issue in thrombotic complications of ventriculoatrial and ventriculosinus shunts. This study aimed to assess the effect of CSF on coagulation and its potential effect on thrombotic events affecting ventriculovenous shunts. METHODS Two complementary experiments were performed. In a static experiment, the effect on coagulation of different CSF mixtures was evaluated using a viscoelastic coagulation monitor. A dynamic experiment confirmed the amount of clot formation on the shunt surface in a roller pump model. RESULTS CSF concentrations of 9% and higher significantly decreased the activated clotting time (ACT; 164.9 seconds at 0% CSF, 155.6 seconds at 9% CSF, and 145.1 seconds at 32% CSF). Increased clot rates (CRs) were observed starting at a concentration of 5% (29.3 U/min at 0% CSF, 31.6 U/min at 5% CSF, and 35.3 U/min at 32% CSF). The roller pump model showed a significantly greater percentage of shunt surface covered with deposits when the shunts were infused with CSF rather than Ringer’s lactate solution (90% vs 63%). The amount of clot formation at the side facing the blood flow (impact side) tended to be lower than that at the side facing away from the blood flow (wake side; 71% vs 86%). CONCLUSIONS Addition of CSF to blood accelerates coagulation. The CSF-blood–foreign material interaction promotes clot formation, which might result in thrombotic shunt complications. Further development of the ventriculovenous shunt technique should focus on preventing CSF-blood–foreign material interaction and stagnation of CSF in wake zones.

OBJECTIVEStereotactic radiosurgery (SRS) is characterized by high levels of conformity and steep dose gradients from the periphery of the target to surrounding tissue. Clinical studies have backed up the importance of these factors through evidence of symptomatic complications. Available data suggest that there are threshold doses above which the risk of symptomatic radionecrosis increases with the volume irradiated. Therefore, radiosurgical treatment plans should be optimized by minimizing dose to the surrounding tissue while maximizing dose to the target volume. Several metrics have been proposed to quantify radiosurgical plan quality, but all present certain weaknesses. To overcome limitations of the currently used metrics, a novel metric is proposed, the efficiency index (η50%), which is based on the principle of calculating integral doses: η50% = integral doseTV/integral dosePIV50%.METHODSThe value of η50% can be easily calculated by dividing the integral dose (mean dose × volume) to the target volume (TV) by the integral dose to the volume of 50% of the prescription isodose (PIV50%). Alternatively, differential dose-volume histograms (DVHs) of the TV and PIV50% can be used. The resulting η50% value is effectively the proportion of energy within the PIV50% that falls into the target. This value has theoretical limits of 0 and 1, with 1 being perfect. The index combines conformity, gradient, and mean dose to the target into a single value. The value of η50% was retrospectively calculated for 100 clinical SRS plans.RESULTSThe value of η50% for the 100 clinical SRS plans ranged from 37.7% to 58.0% with a mean value of 49.0%. This study also showed that the same principles used for the calculation of η50% can be adapted to produce an index suitable for multiple-target plans (Gη12Gy). Furthermore, the authors present another adaptation of the index that may play a role in plan optimization by calculating and minimizing the proportion of energy delivered to surrounding organs at risk (OARη50%).CONCLUSIONSThe proposed efficiency index is a novel approach in quantifying plan quality by combining conformity, gradient, and mean dose into a single value. It quantifies the ratio of the dose “doing good” versus the dose “doing harm,” and its adaptations can be used for multiple-target plan optimization and OAR sparing.

OBJECTIVEThe clinical course of high-grade central nervous system gliomas is occasionally complicated by hydrocephalus. The risks of shunt placement and clinical outcome following CSF diversion in this population are not well defined.METHODSThe authors retrospectively reviewed the outcomes of patients with pathologically confirmed WHO grade III or IV gliomas with shunt-treated hydrocephalus at their institution. Outcomes of patients in this cohort were compared with those of patients who underwent shunt treatment for normal pressure hydrocephalus (NPH). Hospital-reported outcomes in a national database for malignant primary brain tumor patients undergoing a ventricular shunt procedure were also reviewed.RESULTSForty-one patients undergoing CSF shunting between 2001 and 2016 at the authors’ institution were identified. Noncommunicating and communicating hydrocephalus occurred at similar rates (51.2% vs 48.8%). Symptomatic improvement after shunting was observed in 75.0% of patients. A major complication occurred in 17.1% of cases, with 2 patients suffering an intracranial hemorrhage. Prior administration of bevacizumab was significantly associated with the incidence of hemorrhage (p = 0.026). Three patients (7.3%) died during admission, and 8 (19.5%) died within 30 days of shunt placement. The presence of ependymal or leptomeningeal enhancement was more common in patients who died within 30 days (75.0% vs 11.1%, p = 0.001). Six patients (18.1%) required readmission to the hospital within 30 days of discharge. Revision surgery was necessary in 7 patients (17.1%). The median time from shunt placement to death was 150.5 days. In comparison with patients with NPH, shunt-treated high-grade glioma patients had increased in-hospital (7.3% vs 0.5%, p = 0.008) and 30-day (19.5% vs 0.8%, p < 0.001) mortality but no difference in the incidence of revision surgery (17.1% vs 17.5%, p = 0.947). Similarly, in the national Vizient Clinical Database Resource Manager, shunt-treated patients with malignant primary brain tumors had an increased length of stay (6.9 vs 3.5 days, p < 0.001), direct cost of admission ($15,755.80 vs $9871.50, p < 0.001), and 30-day readmission rates (20.6% vs 2.4%, p < 0.001) compared with patients without brain tumors who received a shunt for NPH.CONCLUSIONSShunting can be an effective treatment for the symptoms of hydrocephalus in patients with high-grade gliomas. However, the authors’ results suggest that this procedure carries a significant risk of complications in this patient population.

OBJECTIVE Cerebrospinal fluid (CSF) shunting in idiopathic intracranial hypertension (IIH) is associated with high complication rates, primarily because of the technical challenges that are related to small ventricles and a large body habitus. In this study, the authors report the benefits of a standardized protocol for CSF shunting in patients with IIH as relates to shunt revisions. METHODS This was a retrospective study of consecutive patients with IIH who had undergone primary insertion of a CSF shunt between January 2014 and December 2020 at the authors’ hospital. In July 2019, they implemented a surgical protocol for shunting in IIH. This protocol recommended IIH shunt insertion by neurosurgeons with expertise in CSF disorders, a frontal ventriculoperitoneal (VP) shunt with an adjustable gravitational valve and integrated intracranial pressure monitoring device, frameless stereotactic insertion of the ventricular catheter, and laparoscopic insertion of the peritoneal catheter. Thirty-day revision rates before and after implementation of the protocol were compared in order to assess the impact of standardizing shunting for IIH on shunt complications. RESULTS The 81 patients included in the study were predominantly female (93%), with a mean age of 31 years at primary surgery and mean body mass index (BMI) of 37 kg/m2. Forty-five patients underwent primary surgery prior to implementation of the protocol and 36 patients after. Overall, 12 (15%) of 81 patients needed CSF shunt revision in the first 30 days, 10 before and 2 after introduction of the protocol. This represented a significant reduction in the early revision rate from 22% to 6% after the protocol (p = 0.036). The most common cause of shunt revision for the whole cohort was migration or misplacement of the peritoneal catheter, occurring in 6 of the 12 patients. Patients with a higher BMI were significantly more likely to have a shunt revision within 30 days (p = 0.022). CONCLUSIONS The Birmingham standardized IIH shunt protocol resulted in a significant reduction in revisions within 30 days of primary shunt surgery in patients with IIH. The authors recommend standardization for shunting in IIH as a method for improving surgical outcomes. They support the notion of subspecialization for IIH shunts, the use of a frontal VP shunt with sophisticated technology, and laparoscopic insertion of the peritoneal end.

OBJECTIVE In patients presenting within 6 hours after signs and symptoms of suspected subarachnoid hemorrhage (SAH), CSF examination is judged to be no longer necessary if a noncontrast CT (NCCT) scan rules out SAH. In this study, the authors evaluated the performance of NCCT to rule out SAH in patients with positive CSF findings. METHODS Between January 2006 and April 2018, 1657 patients were admitted with a nontraumatic SAH. Of these patients, 1546 had positive SAH findings on the initial NCCT and 111 patients had an NCCT scan that was reported as negative in the acute setting, but with positive CSF examination for subarachnoid blood. Demographic data, World Federation of Neurosurgical Societies grade, and SAH time points (ictus, time of NCCT, and time of lumbar puncture) were collected. All 111 NCCT scans were reevaluated by an experienced neuroradiologist. RESULTS Of the 111 patients with positive CSF findings, SAH was initially missed on NCCT in 25 patients (23%). Reevaluation of 21 patients presenting within 6 hours of symptom onset confirmed NCCT negative findings in 12 (5 aneurysms), an aneurysmal SAH (aSAH) pattern in 8 (7 aneurysms), and a perimesencephalic pattern in 1 patient. Reevaluation of 90 patients presenting after 6 hours confirmed negative NCCT findings in 74 patients (37 aneurysms), aSAH pattern in 10 (4 aneurysms), and a perimesencephalic pattern in 6 (2 aneurysms). CONCLUSIONS CSF examination is still mandatory to rule out SAH as NCCT can fail to show blood, even within 6 hours after symptom onset. In addition, the diagnosis SAH was frequently missed during initial reporting.

OBJECTIVECompetency in endoscopic endonasal approaches (EEAs) to repair high-flow cerebrospinal fluid (CSF) leaks is an essential component of the neurosurgical training process. The objective of this study was to demonstrate the feasibility of a simulation model for EEA repair of anterior skull base CSF leaks.METHODSHuman cadaveric specimens were utilized with a perfusion system to simulate a high-flow CSF leak. Neurological surgery residents (postgraduate year 3 or greater) performed a standard EEA to repair a CSF leak using a combination of fat, fascia lata, and pedicled nasoseptal flaps. A standardized 5-point Likert questionnaire was used to assess the knowledge gained, techniques learned, degree of safety, benefit of CSF perfusion during repair, and pre- and posttraining confidence scores.RESULTSIntrathecal perfusion of fluorescein-infused saline into the ventricular/subarachnoid space was successful in 9 of 9 cases. The addition of CSF reconstitution offered the residents visual feedback for confirmation of intraoperative CSF leak repair. Residents gained new knowledge and a realistic simulation experience by rehearsing the psychomotor skills and techniques required to repair a CSF leak with fat and fascial grafts, as well as to prepare and rotate vascularized nasoseptal flaps. All trainees reported feeling safer with the procedure in a clinical setting and higher average posttraining confidence scores (pretraining 2.22 ± 0.83, posttraining 4.22 ± 0.44, p < 0.001).CONCLUSIONSPerfusion-based human cadaveric models can be utilized as a simulation training model for repairing CSF leaks during EEA.

OBJECTIVE The objectives of this study were to evaluate levels of inflammasome-signaling proteins in serum and CSF of patients with traumatic brain injury (TBI), and to correlate these protein levels with intracranial pressure (ICP) and clinical outcomes at 6 months after injury. METHODS This is a prospective and observational study in patients with moderate and severe TBI who required an external ventricular drain as part of their treatment. Serum and CSF samples were collected 3 times a day for the first 5 days after TBI. The authors have determined the protein concentration of caspase-1 in the CSF and serum of patients with TBI by using commercially available enzyme-linked immunosorbent assays. The ICP value was recorded hourly. The 6-month outcome was assessed using the Glasgow Outcome Scale–Extended. RESULTS A total of 21 patients were included in this study, and a total of 234 paired serum-CSF samples were analyzed. The area under the curve (AUC) value of caspase-1 in CSF during the 5-day period was 2452.9 pg/mL·hr in the group of patients with high ICP vs 617.6 pg/mL·hr in the patients with low ICP. The differences were mainly on day 2 (19.7 pg/mL vs 1.8 pg/mL; p = 0.06) and day 3 (13.9 pg/mL vs 1 pg/mL; p = 0.05). The AUC value of caspase in CSF during the 5-day period was 1918.9 pg/mL·hr in the group of patients with poor outcome versus 924.5 pg/mL·hr in the patients with good outcome. The protein levels of caspase-1 in CSF were higher in patients with unfavorable outcomes during the first 96 hours after TBI. CONCLUSIONS In this cohort of patients with TBI who were admitted to the neurosurgical ICU, the inflammasome protein caspase-1 is increased in the CSF of patients with high ICP, especially on days 2 and 3 after TBI. Also the protein levels of caspase-1 in CSF were higher in patients with poor outcome during the first 96 hours after TBI. Moreover, not only the absolute value of caspase-1 in CSF but also its trend is associated with poor outcomes.

OBJECTIVENormal pressure hydrocephalus is not simply the result of a disturbance in CSF circulation, but often includes cardiovascular comorbidity and abnormalities within the cerebral mantle. In this study, the authors have examined the relationship between the global autoregulation pressure reactivity index (PRx), the profile of disturbed CSF circulation and pressure-volume compensation, and their possible effects on outcome after surgery.METHODSThe authors studied a cohort of 131 patients in whom a clinical suspicion of normal pressure hydrocephalus was investigated. Parameters describing CSF compensation and circulation were calculated during the CSF infusion test, and PRx was calculated from CSF pressure and mean arterial blood pressure (MAP) recordings. A simple scale was used to mark the patients’ outcome 6 months after surgery (improvement, temporary improvement, and no improvement).RESULTSThe PRx was negatively correlated with resistance to CSF outflow (R = −0.18; p = 0.044); patients with normal CSF circulation tended to have worse autoregulation. The correlation for patients who were surgically treated (n = 83) was R = −0.28; p = 0.01, and it was stronger in patients who experienced sustained improvement after surgery (n = 48, R = −0.43; p = 0.002). In patients who did not improve, the correlation was not significantly different from zero (n = 19, R = −0.07; p = 0.97). There was a trend toward higher values for PRx in nonresponders than in responders (0.16 ± 0.04 vs 0.09 ± 0.02, respectively; p = 0.061), associated with higher MAP values (107.2 ± 8.2 in nonresponders vs 89.5 ± 3.5 in responders; p = 0.195). The product of MAP × (1 + PRx), which was proposed as a measure of combined arterial hypertension and deranged autoregulation, showed a significant association with outcome (greater value in nonresponders; p = 0.013).CONCLUSIONSAutoregulation proves to associate with CSF circulation and appears strongest in shunt responders. Outcome following CSF diversion is possibly most favorable when CSF outflow resistance is increased and global cerebral autoregulation is intact, in combination with arterial normotension.

OBJECTIVERecent studies have indicated that a signal intensity increase of the fluid within the resection cavity on FLAIR images may predict tumor recurrence after glioma surgery. The aim of this study was to assess the increase in FLAIR signal intensity in a large patient cohort and in subgroups to assess its prognostic value for early tumor recurrence in glioma patients.METHODSA total of 212 patients (213 cases) who had undergone surgery for an intracranial glioma (WHO Grade IV [n = 103], WHO Grade III [n = 57], and WHO Grade II [n = 53]) were included in this retrospective study. FLAIR signal within the resection cavity at the time of tumor recurrence/last contact and on the previous MRI study was assessed qualitatively and quantitatively. Appearance of FLAIR signal increase was studied over time using Kaplan-Meier estimates in subgroups.RESULTSPatients with WHO Grade II glioma and connection of the resection cavity to CSF who did not undergo radiotherapy did not regularly develop this sign and were excluded from further analysis. For the remaining 87 cases, FLAIR signal intensity increase was observed in 27 cases. Recurrent disease was found in 26 of these 27 cases, resulting in a specificity of 80.0%, a sensitivity of 31.7%, and positive and negative predictive values of 96.3% and 6.7%, respectively. In 4 cases this sign had been observed prior (range 2.8–8.5 months) to tumor recurrence defined by standard criteria. Quantitative analysis underlined the results of qualitative analysis, but it did not add a diagnostic value.CONCLUSIONSSignal intensity increase of the fluid within the resection cavity on FLAIR images is a rare but highly specific and early sign for tumor recurrence/tumor progression in completely and incompletely resected high-grade glioma without connection of the resection cavity to CSF and with radiotherapy.

OBJECTIVESyringogenesis in Chiari malformation type I (CM-I) is thought to occur secondary to impaction of the cerebellar tonsils within the foramen magnum (FM). However, the correlation between the CSF area and syringogenesis has yet to be elucidated. The authors sought to determine whether the diminution in subarachnoid space is associated with syringogenesis. Further, the authors sought to determine if syrinx resolution was associated with the degree of expansion of subarachnoid spaces after surgery.METHODSThe authors performed a retrospective review of all patients undergoing posterior fossa decompression for CM-I from 2004 to 2016 at the University of Virginia Health System. The subarachnoid spaces at the FM and at the level of the most severe stenosis were measured before and after surgery by manual delineation of the canal and neural tissue area on MRI and verified through automated CSF intensity measurements. Imaging and clinical outcomes were then compared.RESULTSOf 68 patients, 26 had a syrinx at presentation. Syrinx patients had significantly less subarachnoid space at the FM (13% vs 19%, p = 0.0070) compared to those without syrinx. Following matching based on degree of tonsillar herniation and age, the subarachnoid space was significantly smaller in patients with a syrinx (12% vs 19%, p = 0.0015). Syrinx resolution was associated with an increase in patients’ subarachnoid space after surgery compared with those patients without resolution (23% vs 10%, p = 0.0323).CONCLUSIONSSyrinx development in CM-I patients is correlated with the degree to which the subarachnoid CSF spaces are diminished at the cranial outlet. Successful syrinx reduction is associated with the degree to which the subarachnoid spaces are increased following surgery.

OBJECTIVEAlthough rates of postoperative morbidity and mortality have become relatively low in patients undergoing transnasal transsphenoidal surgery (TSS) for pituitary adenoma, cerebrospinal fluid (CSF) fistulas remain a major driver of postoperative morbidity. Persistent CSF fistulas harbor the potential for headache and meningitis. The aim of this study was to investigate whether neural network–based models can reliably identify patients at high risk for intraoperative CSF leakage.METHODSFrom a prospective registry, patients who underwent endoscopic TSS for pituitary adenoma were identified. Risk factors for intraoperative CSF leaks were identified using conventional statistical methods. Subsequently, the authors built a prediction model for intraoperative CSF leaks based on deep learning.RESULTSIntraoperative CSF leaks occurred in 45 (29%) of 154 patients. No risk factors for CSF leaks were identified using conventional statistical methods. The deep neural network–based prediction model classified 88% of patients in the test set correctly, with an area under the curve of 0.84. Sensitivity (83%) and specificity (89%) were high. The positive predictive value was 71%, negative predictive value was 94%, and F1 score was 0.77. High suprasellar Hardy grade, prior surgery, and older age contributed most to the predictions.CONCLUSIONSThe authors trained and internally validated a robust deep neural network–based prediction model that identifies patients at high risk for intraoperative CSF. Machine learning algorithms may predict outcomes and adverse events that were previously nearly unpredictable, thus enabling safer and improved patient care and better patient counseling.

OBJECTIVE The aim of the study was to analyze the diagnostic and predictive values of clinical tests, CSF dynamics, and intracranial pulsatility tests, compared with external lumbar drainage (ELD), for shunt response in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS Sixty-eight consecutive patients with suspected iNPH were prospectively evaluated. Preoperative assessment included clinical tests, overnight intracranial pressure (ICP) monitoring, lumbar infusion test (LIFT), and ELD for 24–72 hours. Simple and multiple linear regression analyses were conducted to identify predictive parameters concerning the outcome after shunt therapy. RESULTS Positive response to ELD correctly predicted improvement after CSF diversion in 87.9% of the patients. A Mini–Mental State Examination (MMSE) value below 21 was associated with nonresponse after shunt insertion (specificity 93%, sensitivity 67%). Resistance to outflow of CSF (ROut) > 12 mm Hg/ml/min was false negative in 21% of patients. Intracranial pulsatility parameters yielded different results in various parameters (correlation coefficient between pulse amplitude and ICP, slow wave amplitude, and mean ICP) but did not correlate to outcome. In multiple linear regression analysis, a calculation of presurgical MMSE versus the value after ELD, ROut, and ICP amplitude quotient during LIFT was significantly associated with outcome (p = 0.04). CONCLUSIONS Despite a multitude of invasive tests, presurgical clinical testing and response to ELD yielded the best prediction for improvement of symptoms following surgery. The complication rate of invasive testing was 5.4%. Multiple and simple linear regression analyses indicated that outcome can only be predicted by a combination of parameters, in accordance with a multifactorial pathogenesis of iNPH.

OBJECTIVE Since its revival in the early 1990s, neuroendoscopy has become an integral component of modern neurosurgery. Endoscopic stent placement for treatment of CSF pathway obstruction is a rarely used and underestimated procedure. The authors present the first series of neuroendoscopic intracranial stenting for CSF pathway obstruction in adults with associated results and complications spanning a long-term follow-up of 20 years. METHODS The authors retrospectively reviewed a prospectively maintained clinical database for endoscopic stent placement performed in adults between 1993 and 2013. RESULTS Of 526 endoscopic intraventricular procedures, stents were placed for treatment of CSF disorders in 25 cases (4.8%). The technique was used in the management of arachnoid cysts (ACs; n = 8), tumor-related CSF disorders (n = 13), and hydrocephalus due to stenosis of the foramen of Monro (n = 2) or aqueduct (n = 2). The mean follow-up was 87.1 months. No deaths or infections occurred that were related to endoscopic placement of intracranial stents. Late stent dislocation or migration was observed in 3 patients (12%). CONCLUSIONS Endoscopic intracranial stent placement in adults is rarely required but is a safe and helpful technique in select cases. It is indicated when reliable and long-lasting restoration of CSF pathway obstructions cannot be achieved with standard endoscopic techniques. In the treatment of tumor-related hydrocephalus, it is a good option to avoid reclosure of the restored CSF pathway by tumor growth. Currently, routine stent placement after endoscopic fenestration of ACs is not recommended. Stent placement for treatment of CSF disorders due to tumor is a good option for avoiding CSF shunting. To avoid stent migration and dislocation, and to allow for easy removal if needed, the device should be fixed to a bur hole reservoir.

OBJECT Brain abscesses could lead to cerebral symptoms through tissue destruction, edema, changes in brain architecture, and increased intracranial pressure. However, the possibility that the pus itself could contribute to symptoms has received little attention. Brain abscesses are areas of tissue destruction, proteolysis, and formation of free amino acids, which are energy substrates for bacteria and possible sources of ammonia. Ammonia is neurotoxic, may cause brain edema, and could contribute to the symptoms of brain abscesses. METHODS The authors analyzed the extracellular phase of pus from 14 patients with brain abscesses with respect to ammonia and amino acids. For comparison, CSF from 10 patients undergoing external ventricular drainage was included. The ammonia-forming ability of Streptococcus intermedius and Staphylococcus aureus, two common microbial isolates in brain abscesses, was studied in vitro. RESULTS In brain abscesses ammonia was 15.5 mmol/L (median value; range 1.7–69.2 mmol/L). In CSF ammonia was 29 μmol/L (range 17–55 μmol/L; difference from value in pus: p < 0.001). The total concentration of amino acids in brain abscesses was 1.12–16 times higher than the ammonia concentration (p = 0.011). The median glucose value in pus was 0 mmol/L (range 0–2.1 mmol/L), lactate was 21 mmol/L (range 3.3–26.5 mmol/L), and pH was 6.8 (range 6.2–7.3). In vitro, S. intermedius and S. aureus formed ammonia at 6–7 mmol/L in 24 hours when incubated with 20 proteinogenic amino acids plus g-aminobutyric acid (GABA), taurine, and glutathione at 1 mmol/L. CONCLUSIONS Intracerebral abscesses contain toxic levels of ammonia. At the concentrations found in pus, ammonia could contribute to the brain edema and the symptoms of brain abscesses.

OBJECT Diagnosis of ventriculostomy-related infections (VRIs) is challenging due to the lack of rapid, sensitive assays for pathogen detection. The authors report the development of a multiplex polymerase chain reaction (PCR) assay for differential diagnosis of common VRI pathogens. METHODS MassTag PCR was used to develop a multiplex assay for detection of 11 VRI pathogens. The assay was established and optimized using cloned template standards and spiked samples and was then evaluated on CSF specimens from ventricular drains. Subjects were grouped into definite VRI, possible VRI, or no VRI based on conventional microbiology, CSF evaluation, and clinical parameters. RESULTS CSF specimens were obtained from 45 subjects (median age 49 years, interquartile range 32–63 years; 51% were male). The assay detected 10–100 genome copies. It detected a pathogen in 100% (6 of 6) of definite VRI cases in which a pathogen targeted by the assay was present; these represented 67% of all definite VRIs (6 of 9). Among subjects with a possible VRI, the assay detected a pathogen in 29% (5 of 17). In subjects without overt infection the presence of a pathogen was detected in 32% of subjects (6 of 19), albeit with lower signal compared with the VRI group. CONCLUSIONS MassTag PCR enabled parallel testing of CSF specimens for 11 pathogens of VRI. The high sensitivity of PCR combined with possible device colonization, specimen contamination, and concurrent antibiotic treatments limit the clinical value of the assay, similar to other current diagnostic approaches. With further optimization, multiplex PCR may provide timely identification of multiple possible VRI pathogens and guide management, complementing classic culture approaches.

Cadaveric surgical simulation carries the advantage of realistic anatomy and haptic feedback but has been historically difficult to model for intraventricular approaches given the need for active flow of CSF. This feasibility study was designed to simulate intraventricular neuroendoscopic approaches and techniques by reconstituting natural CSF flow in a cadaveric model. In 10 fresh human cadavers, a simple cervical laminectomy and dural opening were made, and a 12-gauge arterial catheter was introduced. Saline was continuously perfused at physiological CSF pressures to reconstitute the subarachnoid space and ventricles. A neuroendoscope was subsequently inserted via a standard right frontal bur hole. In 8 of the 10 cadavers, adequate reconstitution and endoscopic access of the lateral and third ventricles were achieved. In 2 cadavers, ventricular access was not feasible, perhaps because of a small ventricle size and/or deteriorated tissue quality. In all 8 cadavers with successful CSF flow reconstitution and endoscopic access, identifying the foramen of Monro was possible, as was performing septum pellucidotomy and endoscopic third ventriculostomy. Furthermore, navigation of the cerebral aqueduct, fourth ventricle, prepontine cistern, and suprasellar cistern via the lamina terminalis was possible, providing a complementary educational paradigm for resident education that cannot typically be performed in live surgery. Surgical simulation plays a critical and increasingly prominent role in surgical education, particularly for techniques with steep learning curves including intraventricular neuroendoscopic procedures. This novel model provides feasible and realistic surgical simulation of neuroendoscopic intraventricular procedures and approaches.

OBJECTIVEWhile cerebrospinal fluid (CSF) shunt surgery plays an essential role in the treatment of hydrocephalus, postoperative infection due to the implantation of foreign materials is still one of the most common and potentially serious complications of this procedure. Because no previously reported protocol has been proven to prevent postoperative infection after CSF shunt surgeries in adults, the authors investigated the effectiveness of a protocol introduced in their institution.METHODSA detailed standardized surgical protocol to prevent infection in patients undergoing CSF shunt surgeries was introduced in the authors’ institution in December 2011. The protocol included a series of detailed rules regarding the surgical procedure, the surgical environment to minimize contamination from air, double gloving, local injection of antibiotics, and postoperative management. The rate of CSF shunt infection during the 3 years after surgery before and after implementation of the protocol was compared in patients undergoing their first CSF shunt surgeries. The inclusion periods were from January 2006 to November 2011 for the preprotocol group and from December 2011 to December 2014 for the postprotocol group.RESULTSThe study included 124 preprotocol patients and 52 postprotocol patients. The mean patient age was 59 years in both groups, ranging from 40 days to 88 years. Comparison of patient background factors, including known risk factors for surgical site infections, showed no significant difference between the patient groups before and after implementation of the protocol. While 9 patients (7.3%) developed shunt infections before protocol implementation, no shunt infections (0%) were observed in patients who underwent surgery after protocol implementation. The difference was statistically significant (p = 0.047).CONCLUSIONSThe authors’ detailed protocol for CSF shunt surgeries was effective in preventing postoperative infection regardless of patient age.

OBJECTIVEEven though heme-induced cerebral inflammation contributes to many of the adverse sequelae seen in patients with subarachnoid hemorrhage (SAH), little is known about the mechanism; mouse models have shown a critical role for macrophages/microglia. Macrophage CD163 is a hemoglobin scavenger receptor involved in blood clearance after SAH. The authors hypothesized that the modified Fisher score is independently associated with cerebrospinal fluid (CSF) macrophage CD163 expression on postictal day 1, and that CSF macrophage CD163 expression is associated with 1-month neurological outcome.METHODSCSF macrophages from 21 SAH and 28 unruptured aneurysm patients (control) were analyzed for CD163 expression using flow cytometry and confocal microscopy on postictal day 1. Significant associations with modified Fisher scale grades or modified Rankin Scale scores were determined using linear regression and a matched case control analysis.RESULTSCSF macrophage CD163 expression was significantly increased in SAH patients compared with controls (p < 0.001). The modified Fisher scale (mF) grades (β = 0.407, p = 0.005) and CSF bilirubin concentrations (β = 0.311, p = 0.015) were positively and independently associated with CSF macrophage CD163 expression when the analysis was controlled for age and sex. CSF macrophages from an SAH patient with a high mF grade had increased co-localization of CD163 and glycophorin A (CD235a, an erythrocyte marker) compared with those from an SAH patient with a low mF grade. The controls had no co-localization. CSF macrophage CD163 expression (p = 0.003) was inversely associated with 1-month neurological outcome, when SAH patients were matched based on mF grade.CONCLUSIONSThis early study suggests that CSF macrophage CD163 expression, as measured by flow cytometry, may have some neuroprotective function given its inverse association with outcome and provides unique insights into the neuroinflammatory process after SAH.

OBJECTIVEPlacental alkaline phosphatase (PLAP) in CSF can provide a very high diagnostic value in cases of intracranial germ cell tumors (GCTs), especially in pure germinomas, to the level of not requiring histological confirmation. Unlike other tumor markers, reliable data analysis with respect to the diagnostic value of PLAP serum or CSF levels has not been available until now. This is the first systematic and comprehensive study examining the diagnostic value of CSF PLAP in patients with intracranial GCTs.METHODSFrom 2004 to 2014, 74 patients (average age 19.6 ± 10.6 years) with intracranial GCTs were evaluated using PLAP from their CSF and histological samples. Chemiluminescent enzyme immunoassay was utilized to measure CSF PLAP in the following tumor sites: pineal (n = 32), pituitary stalk, suprasellar (n = 16), basal ganglia (n = 15), intraventricular (n = 9), and cerebellar (n = 5) regions. In addition to classifying GCT cases, all patients underwent tumor biopsy for correlation with tumor marker data.RESULTSPLAP in combination with other tumor markers resulted in extremely high sensitivity and specificity of the diagnostic value of intracranial GCTs. Intracranial GCT cases were classified into 1) germinomas, both “pure” and syncytiotrophoblastic giant cell types (n = 38); 2) nongerminomatous GCTs, choriocarcinomas (n = 9) and teratomas (n = 4); and 3) nongerminomas, other kinds of tumors (n = 23). Consequently, all patients received chemoradiation therapy based on elevation of PLAP and the histopathological results. It was also speculated that the level of PLAP could show the amount of intracranial germ cell components of a GCT. PLAP was 100% upregulated in all intracranial germinoma cases. The absence of CSF PLAP proved that the tumor was not a germinoma.CONCLUSIONSThe current study is the first systematic and comprehensive examination of the diagnostic value of the tumor marker PLAP in pediatric patients with intracranial GCT. Using the level of PLAP in CSF, we were able to detect the instances of intracranial germinoma with very high reliability, equivalent to a pathological diagnosis.

OBJECT Brain deformation can be seen in hydrocephalus and idiopathic intracranial hypertension (IIH) via medical images. The phenomenology of local effects, brain shift, and raised intracranial pressure and herniation are textbook concepts. However, there are still uncertainties regarding the specific processes that occur when brain tissue is subject to the mechanical stress of different temporal and spatial profiles of the 2 neurological disorders. Moreover, recent studies suggest that IIH and hydrocephalus may be diseases with opposite pathogenesis. Nevertheless, the similarities and differences between the 2 subjects have not been thoroughly investigated. METHODS An anatomical porohyperelastic finite element model was used to assess the brain tissue responses associated with hydrocephalus and IIH. The same set of boundary conditions, with the exception of brain loading for development of the transmantle pressure gradient, was applied for the 2 models. The distribution of stress and strain during tissue distortion is described by the mechanical parameters. RESULTS The results of both the hydrocephalus and IIH models correlated with pathological characteristics. For the hydrocephalus model, periventricular edema was associated with the presence of positive volumetric strain and void ratio in the lateral ventricle horns. By contrast, the IIH model revealed edema across the cerebral mantle, including the centrum semiovale, with a positive void ratio and volumetric strain. CONCLUSIONS The model simulates all the clinical features in correlation with the MR images obtained in patients with hydrocephalus and IIH, thus providing support for the role of the transmantle pressure gradient and capillary CSF absorption in CSF-related brain deformation. The finite element methods can be used for a better understanding of the pathophysiological mechanisms of neurological disorders associated with parenchymal volumetric fluctuation.

OBJECT The authors completed a prospective, institutional review board–approved study using intraoperative MRI (iMRI) in patients undergoing posterior fossa decompression (PFD) for Chiari I malformation. The purpose of the study was to examine the utility of iMRI in determining when an adequate decompression had been performed. METHODS Patients with symptomatic Chiari I malformations with imaging findings of obstruction of the CSF space at the foramen magnum, with or without syringomyelia, were considered candidates for surgery. All patients underwent complete T1, T2, and cine MRI studies in the supine position preoperatively as a baseline. After the patient was placed prone with the neck flexed in position for surgery, iMRI was performed. The patient then underwent a bone decompression of the foramen magnum and arch of C-1, and the MRI was repeated. If obstruction was still present, then in a stepwise fashion the patient underwent dural splitting, duraplasty, and coagulation of the tonsils, with an iMRI study performed after each step guiding the decision to proceed further. RESULTS Eighteen patients underwent PFD for Chiari I malformations between November 2011 and February 2013; 15 prone preincision iMRIs were performed. Fourteen of these patients (93%) demonstrated significant improvement of CSF flow through the foramen magnum dorsal to the tonsils with positioning only. This improvement was so notable that changes in CSF flow as a result of the bone decompression were difficult to discern. CONCLUSIONS The authors observed significant CSF flow changes when simply positioning the patient for surgery. These results put into question intraoperative flow assessments that suggest adequate decompression by PFD, whether by iMRI or intraoperative ultrasound. The use of intraoperative imaging during PFD for Chiari I malformation, whether by ultrasound or iMRI, is limited by CSF flow dynamics across the foramen magnum that change significantly when the patient is positioned for surgery.

Object Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients. Methods Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase–1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed. Results The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883–0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 μM, with higher values predicting unfavorable outcome (82.4% accuracy). Conclusions The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.

Object Postoperative pneumocephalus is a common occurrence after endoscopic endonasal skull base surgery (ESBS). The risk of cerebrospinal fluid (CSF) leaks can be high and the presence of postoperative pneumocephalus associated with serosanguineous nasal drainage may raise suspicion for a CSF leak. The authors hypothesized that specific patterns of pneumocephalus on postoperative imaging could be predictive of CSF leaks. Identification of these patterns could guide the postoperative management of patients undergoing ESBS. Methods The authors queried a prospectively acquired database of 526 consecutive ESBS cases at a single center between December 1, 2003, and May 31, 2012, and identified 258 patients with an intraoperative CSF leak documented using intrathecal fluorescein. Postoperative CT and MRI scans obtained within 1–10 days were examined and pneumocephalus was graded based on location and amount. A discrete 0–4 scale was used to classify pneumocephalus patterns based on size and morphology. Pneumocephalus was correlated with the surgical approach, histopathological diagnosis, and presence of a postoperative CSF leak. Results The mean follow-up duration was 56.7 months. Of the 258 patients, 102 (39.5%) demonstrated pneumocephalus on postoperative imaging. The most frequent location of pneumocephalus was frontal (73 [71.5%] of 102), intraventricular (34 [33.3%]), and convexity (22 [21.6%]). Patients with craniopharyngioma (27 [87%] of 31) and meningioma (23 [68%] of 34) had the highest incidence of postoperative pneumocephalus compared with patients with pituitary adenomas (29 [20.6%] of 141) (p < 0.0001). The incidence of pneumocephalus was higher with transcribriform and transethmoidal approaches (8 of [73%] 11) than with a transsellar approach (9 of [7%] 131). There were 15 (5.8%) of 258 cases of postoperative CSF leak, of which 10 (66.7%) had pneumocephalus, compared with 92 (38%) of 243 patients without a postoperative CSF leak (OR 3.3, p = 0.027). Pneumocephalus located in the convexity, interhemispheric fissure, sellar region, parasellar region, and perimesencephalic region was significantly correlated with a postoperative CSF leak (OR 4.9, p = 0.006) and was therefore termed “suspicious” pneumocephalus. In contrast, frontal or intraventricular pneumocephalus was not correlated with postoperative CSF leak (not significant) and was defined as “benign” pneumocephalus. The amount of convexity pneumocephalus (p = 0.002), interhemispheric pneumocephalus (p = 0.005), and parasellar pneumocephalus (p = 0.007) (determined using a scale score of 0–4) was also significantly related to postoperative CSF leaks. Using a series of permutation-based multivariate analyses, the authors established that a model containing the learning curve, the transclival/transcavernous approach, and the presence of “suspicious” pneumocephalus provides the best overall prediction for postoperative CSF leaks. Conclusions Postoperative pneumocephalus is much more common following extended approaches than following transsellar surgery. Merely the presence of pneumocephalus, particularly in the frontal or intraventricular locations, is not necessarily associated with a postoperative CSF leak. A “suspicious” pattern of air, namely pneumocephalus in the convexity, interhemispheric fissure, sella, parasellar, or perimesencephalic locations, is significantly associated with a postoperative CSF leak. The presence and the score of “suspicious” pneumocephalus on postoperative imaging, in conjunction with the learning curve and the type of endoscopic approach, provide the best predictive model for postoperative CSF leaks.

OBJECTIVECerebrospinal fluid (CSF) rhinorrhea is among the most common complications following transsphenoidal surgery for sellar region lesions. The aim of this study was to review the authors’ institutional experience in identifying, repairing, and treating CSF leaks associated with direct endonasal transsphenoidal operations.METHODSThe authors performed a retrospective review of cases involving surgical treatment of pituitary adenomas and other sellar lesions at the University of Southern California between December 1995 and March 2016. Inclusion criteria included all pathology of the sellar region approached via a direct microscopic or endoscopic endonasal transsphenoidal approach. Demographics, pathology, intraoperative and postoperative CSF leak rates, and other complications were recorded and analyzed. A literature review of the incidence of CSF leaks associated with the direct endonasal transsphenoidal approach to pituitary lesions was conducted.RESULTSA total of 1002 patients met the inclusion criteria and their cases were subsequently analyzed. Preoperative diagnoses included pituitary adenomas in 855 cases (85.4%), Rathke’s cleft cyst in 94 (9.4%), and other sellar lesions in 53 (5.2%). Lesions with a diameter ≥ 1 cm made up 49% of the series. Intraoperative repair of an identified CSF leak was performed in 375 cases (37.4%) using autologous fat, fascia, or both. An additional 92 patients (9.2%) underwent empirical sellar reconstruction without evidence of an intraoperative CSF leak. Postoperative CSF leaks developed in 26 patients (2.6%), including 13 (1.3% of the overall group) in whom no intraoperative leak was identified. Among the 26 patients who developed a postoperative CSF leak, 13 were noted to have intraoperative leak and underwent sellar repair while the remaining 13 did not have an intraoperative leak or sellar repair. No patients who underwent empirical sellar repair without an intraoperative leak developed a postoperative leak. Eight patients underwent additional surgery (0.8% reoperation rate) for CSF leak repair, and 18 were successfully treated with lumbar drainage or lumbar puncture alone. The incidence of postoperative CSF rhinorrhea in this series was compared with that in 11 other reported series that met inclusion criteria, with incidence rates ranging between 0.6% and 12.1%.CONCLUSIONSIn this large series, half of the patients who developed postoperative CSF rhinorrhea had no evidence of intraoperative CSF leakage. Unidentified intraoperative CSF leaks and/or delayed development of CSF fistulas are equally important sources of postoperative CSF rhinorrhea as the lack of employing effective CSF leak repair methods. Empirical sellar reconstruction in the absence of an intraoperative CSF leak may be of benefit following resection of large tumors, especially if the arachnoid is thinned out and herniates into the sella.

OBJECTIVEInitiation of external CSF drainage has been associated with a significant increase in rebleeding probability after aneurysmal subarachnoid hemorrhage (aSAH). However, the implications for acute management are uncertain. The purpose of this study was to evaluate the role of the amount of drained CSF on aneurysmal rebleeding.METHODSConsecutive patients with aSAH were analyzed retrospectively. Radiologically confirmed cases of aneurysmal in-hospital rebleeding were identified and predictor variables for rebleeding were retrieved from hospital records. Clinical predictors were identified through multivariate analysis, and logistic regression analysis was performed to ascertain the cutoff value for the rebleeding probability.RESULTSThe study included 194 patients. Eighteen cases (9.3%) of in-hospital rebleeding could be identified. Using multivariate analysis, in-hospital rebleeding was significantly associated with initiation of CSF drainage (p = 0.001) and CSF drainage volume (63 ml [interquartile range (IQR) 55–69 ml] vs 25 ml [IQR 10–35 ml], p < 0.001). Logistic regression showed that 58 ml of CSF drainage within 6 hours results in a 50% rebleeding probability. The relative risk (RR) for rebleeding after drainage of more than 60 ml in 6 hours was 5.4 times greater compared with patients with less CSF drainage (RR 5.403, 95% CI 2.481–11.767; p < 0.001, number needed to harm = 1.687).CONCLUSIONSVolume of CSF drainage was highly correlated with the probability of in-hospital aneurysmal rebleeding. These findings suggest that the rebleeding probability can be affected in acute management should the placement of an external ventricular catheter be necessary. This finding necessitates meticulous control of the amount of drained CSF and the development of a definitive treatment protocol for this group of patients.

Object Primary empty sella syndrome (ESS) results from herniation of arachnoid mater into the pituitary fossa. It has been suggested to have a negative effect on pituitary surgery; however, outcomes in this cohort have not been defined. This study was performed to determine the effect of ESS on immediate and long-term biochemical outcome after pituitary surgery for Cushing's disease (CD). Methods Using a matched cohort study design, the authors followed patients treated with pituitary surgery for CD with and without ESS. Complete ESS was defined as pituitary gland height ≤ 2 mm, whereas partial ESS was defined as pituitary gland height > 2 mm but less than three-quarters of the total sellar depth. The primary end points were immediate and long-term biochemical outcome. Cerebrospinal fluid leaks were recorded as a secondary end point. Results Seventy-eight patients with CD and primary ESS were identified and matched with 78 patients with CD without ESS. After surgical management, immediate biochemical remission was achieved in 69 patients (88%) with ESS and 75 controls (96%, p = 0.10). Long-term remission was achieved in most patients in both groups (5-year cure: 85% vs 92%, p = 0.10). Among patients with ESS, the presence of complete ESS predicted a worse long-term outcome (p = 0.04). Intraoperative CSF leaks were significantly more frequent with ESS (54% vs 24%, p < 0.001), and despite sellar floor repair, the rate of postoperative CSF leaks was also increased (6% vs 3%, p = 0.27). Conclusions Biochemical outcome after pituitary surgery for CD was worse in patients with complete ESS, and the risk of a CSF leak was increased with both partial and complete ESS. However, as outcome remains superior to those following alternative therapies and the biology of these tumors is unchanged in the setting of ESS, pituitary surgery should remain the initial treatment of choice.

Object When patients present to the emergency department (ED) with acute headache concerning for subarachnoid hemorrhage (SAH) and a lumbar puncture (LP) shows blood in the CSF, it is difficult to distinguish the results of a traumatic LP from those of SAH. CT angiography (CTA) is often performed, but the long-term outcome for patients with a positive LP and normal neurovascular imaging remains uncertain. The primary objective of this study was to determine whether patients who presented to the ED with acute headache and had red blood cells (RBCs) in their CSF on LP but negative cerebrovascular imaging suffered subsequent SAH. Methods A case series study of consecutive adult ED patients who incurred charges for LP between 2001 and 2009 was performed from 2010 through 2011. Inclusion criteria were: headache, > 5 RBCs/mm3 in CSF, noncontrast head CT with no evidence of hemorrhage, and cerebrovascular CTA or MRA without aneurysm or vascular lesion within 2 weeks of the ED visit. Patients with less than 6 months of available follow-up were excluded. The primary outcomes were 1) subsequent nontraumatic SAH and 2) new vascular lesion. Secondary outcomes were complications related to SAH, or LP or angiography. Results Of 4641 ED patients billed for an LP, 181 patients (mean age 42 years) were included in this study. Over a median follow-up of 53 months, 0 (0%) of 181 patients (95% CI 0%–2.0%) had a subsequent SAH or new vascular lesion identified. Although not the primary outcome, there was 1 patient who was ultimately diagnosed with vasculitis. Eighteen (9.9%) of 181 patients (95% CI 6.0%–15.3%) had an LP-related complication and 0 (0%) of 181 patients (95% CI 0%–2.0%) had an angiography-related complication. Conclusions Patients who present to the ED with acute headache concerning for SAH and have a finding of bloody CSF on LP but negative findings on cerebrovascular imaging are at low risk for subsequent SAH and thus are likely to be safe for discharge. Replacement of the CT/LP with a CT/CTA diagnostic algorithm merits further investigation.

Object In this study the authors compare the efficacy of endoscopic third ventriculostomy (ETV) versus CSF shunting for resolution of papilledema in hydrocephalus. Methods This comparative case series study recruited 12 patients (24 eyes) with hydrocephalus who underwent either an ETV (Group 1, 6 patients [12 eyes]) or CSF shunt treatment (Group 2, 6 patients [12 eyes]). A complete ophthalmological examination including retinal nerve fiber layer (RNFL) evaluation by optical coherence tomography was provided for all patients before surgery and in the 1st week, 1st month, and 3rd month postoperatively. The 2 groups were compared for quantitative changes in RNFL thickness and, thereby, resolution of papilledema. Statistical evaluation was performed using the Mann-Whitney U-test with the aid of SPSS version 16.0. Results The mean preoperative RNFL thickness was 259.7 ± 35.8 μm in Group 1 and 244.5 ± 53.4 μm in Group 2 (p = 0.798). The mean decrease in RNFL thickness was 101.3 ± 38.8 μm, 141.2 ± 34.6 μm, and 162.0 ± 35.9 μm in Group 1 versus 97.0 ± 44.6 μm, 143 ± 45.6 μm, and 130.0 ± 59.8 μm in Group 2 for the postoperative 1st week, 1st month, and 3rd month, respectively. There was no significant difference between the two groups with respect to decrease in RNFL thickness during the 1st week, 1st month, and 3rd month (p = 0.563, p = 0.753, and p = 0.528, respectively). Conclusions This is the first study to quantitatively evaluate papilledema in assessing the success of ETV and CSF shunting. The authors' results indicated that ETV is as effective as CSF shunting with respect to decreasing intracranial pressure and resolution of papilledema.

ObjectNew approaches for understanding CSF motion in healthy individuals and patients with hydrocephalus and Chiari malformation are presented. The velocity and the pressure gradient of CSF motion were determined using phase contrast (PC) MRI.MethodsThe authors examined 11 healthy control subjects and 2 patients (1 with hydrocephalus and 1 with Chiari malformation), using 4-dimensional PC (4D-PC) MRI and a newly developed computer analysis method that includes calculation of the pressure gradient from the velocity field. Sagittal slices including the center of the skull and coronal slices of the foramen of Monro and the third ventricle were used.ResultsIn the ventricular system, mixing and swirling of the CSF was observed in the third ventricle. The velocity images showed that the CSF was pushed up and back down to the adjacent ventricle and then returned again to the third ventricle. The CSF traveled bidirectionally in the foramen of Monro and sylvian aqueduct. Around the choroid plexus in the lateral ventricle, the CSF motion was stagnant and the CSF pressure gradient was lower than at the other locations. An elevated pressure gradient was observed in the basal cistern of the subarachnoid space. Sagittal imaging showed that the more prominent pressure gradients originated around the cisterna magna and were transmitted in an upward direction. The coronal image showed a pressure gradient traveling from the central to the peripheral subarachnoid spaces that diminished markedly in the convexity of the cerebrum. The 2 patients, 1 with secondary hydrocephalus and 1 with Chiari malformation, were also examined.ConclusionsThe observed velocity and pressure gradient fields delineated the characteristics of the CSF motion and its similarities and differences among the healthy individuals and between them and the 2 patients. Although the present results did not provide general knowledge of CSF motion, the authors' method more comprehensively described the physiological properties of the CSF in the skull than conventional approaches that do not include measurements of pressure gradient fields.

Object To date, reports on the clinical efficacy of intraventricularly and intrathecally administered antibiotics for the treatment of neurosurgical ventriculitis and meningitis in adults are limited. The authors aimed to evaluate the efficacy and safety of the intraventricular (IVT) and lumbar intrathecal (IT) administration of antibiotics in critically ill neurosurgical patients. Methods Thirty-four postneurosurgical patients with meningitis and ventriculitis were studied. Intraventricular/lumbar intrathecal antibiotics were administered due to positive CSF cultures persisting despite the use of intravenous antibiotics. The time period until CSF sterilization, changes in clinical state, and efficacy of different routes of antibiotic administration were evaluated. Results The mean time necessary to obtain CSF sterilization was 2.9 ± 2.7 days (range 1–12 days). The CSF cultures became negative within 24 hours after the administration of IVT/IT antibiotics in 17 patients (50%) and up to 48 hours in a further 6 patients (18%). The clinical outcome of patients assessed by the modified Rankin Scale improved in 17 patients (50%), stayed unchanged in 10 patients (29%), and was impaired in 1 patient (3%). Six patients (18%) died; however, 2 of them died due to reasons not directly related to meningitis or ventriculitis, so the overall mortality rate for meningitis and/or ventriculitis was 11.8% in this group of patients. All patients with ventriculitis (n = 4) were treated by antibiotics administered via the IVT route. The average time to CSF sterilization was 6.5 days in the patients with ventriculitis. Thirty patients had clinical signs of meningitis without ventriculitis. Despite the higher ratio of unfavorable Gram-negative meningitis in the subgroup of patients treated via lumbar drainage, the mean duration of CSF sterilization was 2.2 days compared with 2.6 days in the subgroup treated via external ventricular drainage, a difference that was not statistically significant (p = 0.3). Adverse effects of IVT/IT antibiotics appeared in 3 of 34 patients and were of low clinical significance. Conclusions Intraventricular/lumbar intrathecal antibiotics can lead to very quick CSF sterilization in postneurosurgical patients with meningitis and ventriculitis. The relapse rate of meningitis and/or ventriculitis is also very low among patients treated by IVT/IT antibiotics. Intraventricular/lumbar intrathecal administration of antibiotics appears to be an effective and safe treatment for infections of the CNS caused by multidrug-resistant organisms. In patients with signs of ventriculitis, the authors prefer the IVT route of antibiotics. This study did not prove a lower efficacy of administration of antibiotics via lumbar drainage compared with the ventricular route in patients with meningitis.

ObjectBaicalein has been shown to offer neuroprotection in the ischemic brain, but its effect in subarachnoid hemorrhage (SAH) is unknown. The authors used a double-hemorrhage model to study the role of early baicalein treatment in SAH.MethodsSubarachnoid hemorrhage was induced in male Wistar rats through a repeat injection of autologous blood at a 48-hour interval. Rats subjected or not subjected to SAH received a 30-mg/kg baicalein injection 3 hours after SAH and daily for 6 consecutive days, and results were compared with those obtained in vehicle-treated control rats. Mortality of the rats was recorded. Neurological outcome was assessed daily. Cerebrospinal fluid dialysates were collected and examined for glutamate concentrations. Cerebral vasospasm (CVS), brain water content, neuron variability, expression of glutamate transporter–1 (GLT-1), immunoreactivity of astrocyte, and level of malondialdehyde, activities of superoxide dismutase (SOD), and catalase in brain tissues content were determined on post-SAH Day 7.ResultsMortality rate, neuronal degeneration, brain water content, and CVS were decreased and neurological function improved in the baicalein-treated rats. Baicalein increased astrocyte activity and preserved GLT-1, which attenuated the glutamate surge after SAH. Baicalein also provided antioxidative stress by preserving activities of SOD and catalase and decreased malondialdehydelevel after SAH. The glutamate, body weight, neurological scores, and glial fibrillary acidic protein activity were significantly correlated. The CVS was correlated with neuronal degeneration, and GLT-1 was correlated with oxidative stress.ConclusionsEarly baicalein treatment attenuated CVS and limited neurological injury following SAH. These data may indicate clinical utility for baicalein as an adjunct therapy to reduce brain injury and improve patient outcomes.

Object Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (Aβ) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. Methods Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3–8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecular-weight β-amyloid oligomers were measured using Western blot analysis. Results Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = −0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = −0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. Conclusions Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.

Object The pathogenesis of syringomyelia in association with Chiari malformation Type I (CM-I) is unclear. Studies of patients with CM-I have shown alterations in the CSF velocity profile using cardiac-gated cine phase-contrast MRI, and computational simulations have demonstrated that temporal features of the CSF pulse could contribute to syrinx development or enlargement. Few studies have reported temporal characteristics of the CSF profile, and few studies have reported on CM-I patients with and without syringomyelia separately. This study was performed to determine whether specific temporal features of the CSF flow profile may underlie the development or enlargement of a syrinx in patients with CM-I. Methods Ten healthy volunteers and 18 patients with CM-I with (8 patients) and without (10 patients) syringomyelia were studied using cardiac-gated cine phase-contrast MRI, measuring the maximum CSF velocities in the cranial and caudal directions, the timing of these maximums relative to the cardiac cycle time, the timing of caudal flow onset, timing of cranial flow onset, and the duration of caudal flow. Results The caudal CSF flow was significantly faster (p ≤ 0.01) and earlier (p < 0.02) in patients without syringomyelia than in healthy volunteers and patients with syringomyelia. There were no significant differences in the CSF velocities between patients with syringomyelia and healthy volunteers. Patients with CM-I who had syringomyelia had a significantly later start of caudal CSF flow (p < 0.01) and earlier maximum cranial velocity (p = 0.03) than healthy volunteers, but the relative durations of caudal and cranial flow were not significantly different between any of the groups. Conclusions The significantly earlier arrival and earlier peak velocity of caudal CSF flow may underlie the development of syringomyelia in patients with CM-I, and after a syrinx develops the CSF flow profile appears to stabilize.

Object Increased plasma nuclear and mitochondrial DNA levels have been reported in critically ill patients, and extracellular DNA may originate from damaged tissues having undergone necrosis. This study tested the hypothesis that nuclear and mitochondrial DNA levels in CSF and plasma are substantially increased in patients with acute spontaneous aneurysmal subarachnoid hemorrhage (SAH) and decrease thereafter, such that nuclear and mitochondrial DNA levels may be predictive of treatment outcomes. Methods Serial nuclear and mitochondrial DNA levels in CSF and plasma from 21 adult patients with spontaneous aneurysmal SAH and 39 healthy volunteers who received myelography examinations during the study period were evaluated. Results Data showed that circulating plasma nuclear DNA concentrations and both nuclear and mitochondrial DNA levels in CSF significantly increased in patients with aneurysmal SAH on admission compared with the volunteers. In patients with poor outcome, the CSF nuclear and mitochondrial DNA levels were significantly higher on Days 1 and 4, and plasma nuclear DNA levels were significantly higher from Day 8 to Day 14. Higher CSF nuclear (> 85.1 ng/ml) and mitochondrial DNA levels (> 31.4 ng/ml) on presentation were associated with worse outcome in patients with aneurysmal SAH. Conclusions Higher CSF DNA levels on presentation, rather than plasma DNA levels, are associated with worse outcomes in patients with acute spontaneous aneurysmal SAH. More prospective multicenter investigations are needed to confirm the predictive value of CSF and plasma DNA levels on outcome.

OBJECTIntracranial pressure (ICP) pulsations are generally considered a passive result of the pulsatility of blood flow. Active experimental modification of ICP pulsations would allow investigation of potential active effects on blood and CSF flow and potentially create a new platform for the treatment of acute and chronic low blood flow states as well as a method of CSF substance clearance and delivery. This study presents a novel method and device for altering the ICP waveform via cardiac-gated volume changes.METHODSThe novel device used in this experiment (named Cadence) consists of a small air-filled inelastic balloon (approximately 1.0 ml) implanted into the intracranial space and connected to an external programmable pump, triggered by an R-wave detector. Balloons were implanted into the epidural space above 1 of the hemispheres of 19 canines for up to 10 hours. When activated, the balloons were programed to cyclically inflate with the cardiac cycle with variable delay, phase, and volume. The ICP response was measured in both hemispheres. Additionally, cerebral blood flow (heat diffusion and laser Doppler) was studied in 16 canines.RESULTSThis system, depending on the inflation pattern of the balloon, allowed a flattening of the ICP waveform, increase in the ICP waveform amplitude, or phase shift of the wave. This occurred with small mean ICP changes, typically around ± 2 mm Hg (15%). Bilateral ICP effects were observed with activation of the device: balloon inflation at each systole increased the systolic ICP pulse (up to 16 mm Hg, 1200%) and deflation at systole decreased or even inverted the systolic ICP pulse (−0.5 to −19 mm Hg, −5% to −1600%) in a dose-(balloon volume) dependent fashion. No aphysiological or deleterious effects on systemic pressure (≤ ±10 mm Hg; 13% change in mean pressure) or cardiac rate (≤ ± 17 beats per minute; 16% change) were observed during up to 4 hours of balloon activity.CONCLUSIONSThe results of these initial studies using an intracranially implanted, cardiac-gated, volume-oscillating balloon suggest the Cadence device can be used to modify ICP pulsations, without physiologically deleterious effects on mean ICP, systemic vascular effects, or brain injury. This device and technique may be used to study the role of ICP pulsatility in intracranial hemo- and hydrodynamic processes and introduces the creation of a potential platform of a cardiac-gated system for treatment of acute and chronic low blood flow states, and diseases requiring augmentation of CSF substance clearance or delivery.

OBJECTIVE MicroRNAs (miRNAs) regulate gene expression and therefore play important roles in many physiological and pathological processes. The aim of this pilot study was to determine the feasibility of extraction and subsequent profiling of miRNA from CSF samples in a pilot population of aneurysmal subarachnoid hemorrhage patients and establish if there is a distinct CSF miRNA signature between patients who develop cerebral vasospasm and those who do not. METHODS CSF samples were taken at various time points during the clinical management of a subset of SAH patients (SAH patient samples without vasospasm, n = 10; SAH patient samples with vasospasm, n = 10). CSF obtained from 4 patients without SAH was also included in the analysis. The miRNA was subsequently isolated and purified and then analyzed on an nCounter instrument using the Human V2 and V3 miRNA assay kits. The data were imported into the nSolver software package for differential miRNA expression analysis. RESULTS From a total of 800 miRNAs that could be detected with each version of the miRNA assay kit, a total of 691 miRNAs were communal to both kits. There were 36 individual miRNAs that were differentially expressed (p < 0.01) based on group analyses, with a number of miRNAs showing significant changes in more than one group analysis. The changes largely reflected differences between non-SAH and SAH groups. These included miR-204-5p, miR-223-3p, miR-337-5p, miR-451a, miR-489, miR-508-3p, miR-514-3p, miR-516-5p, miR-548 m, miR-599, miR-937, miR-1224-3p, and miR-1301. However, a number of miRNAs did exclusively differ between the vasospasm and nonvasospasm SAH groups including miR-27a-3p, miR-516a-5p, miR-566, and miR-1197. CONCLUSIONS The findings indicate that temporal miRNA profiling can detect differences between CSF from aneurysmal SAH and non-SAH patients. Moreover, the miRNA profile of CSF samples from patients who develop cerebral vasopasm may be distinguishable from those who do not. These results provide a foundation for future research at identifying novel CSF biomarkers that might predispose to the development of cerebral vasospasm after SAH and therefore influence subsequent clinical management.