J. Gordon McComb

Ventriculostomy-related infections: a critical review of the literature

OBJECTIVE To provide a critical evaluation of the published literature describing risk factors for ventriculostomy-related infections (VRIs) and the efficacy of prophylactic catheter exchange. METHODS A MEDLINE literature search was performed, and data were extracted from studies published from 1941 through 2001. RESULTS Published criteria for diagnosing VRIs are highly variable. Intraventricular hemorrhage, subarachnoid hemorrhage, cranial fracture with cerebrospinal fluid leak, craniotomy, systemic infections, and catheter irrigation all predispose patients to the development of VRIs. Extended duration of catheterization is correlated with an increasing risk of cerebrospinal fluid infections during the first 10 days of catheterization. Prophylactic catheter exchange does not modify the risk of developing later VRIs in retrospective studies. CONCLUSION Categorizing suspected cerebrospinal fluid infections as contaminants, colonization, suspected or confirmed VRIs, or ventriculitis more accurately describes the patients clinical condition and may indicate different management strategies. A prospective, randomized clinical trial is required to further evaluate the efficacy of prophylactic catheter exchange in limiting the incidence of VRIs during prolonged catheterization. Although prophylactic catheter exchange remains a practice option, the available data suggest that this procedure is not currently justified.

Isoform-Specific Effects of Apolipoproteins E2, E3, and E4 on Cerebral Capillary Sequestration and Blood-Brain Barrier Transport of Circulating Alzheimer's Amyloid β

Abstract: Cerebral capillary sequestration and blood‐brain barrier (BBB) permeability to apolipoproteins E2 (apoE2), E3 (apoE3), and E4 (apoE4) and to their complexes with sAβ1–40, a peptide homologous to the major form of soluble Alzheimers amyloid β, were studied in perfused guinea pig brain. Cerebrovascular uptake of three apoE isoforms was low, their blood‐to‐brain transport undetectable, but uptake by the choroid plexus significant. Binding of all three isoforms to sAβ1–40 in vitro was similar with a KD between 11.8 and 12.9 nM. Transport into brain parenchyma and sequestration by BBB and choroid plexus were negligible for sAβ1–40‐apoE2 and sAβ1–40‐apoE3, but significant for sAβ1–40‐apoE4. After 10 min, 85% of sAβ1–40‐apoE4 taken up at the BBB remained as intact complex, whereas free sAβ1–40 was 51% degraded. Circulating apoE isoforms have contrasting effects on cerebral capillary uptake of and BBB permeability of sAβ. ApoE2 and apoE3 completely prevent cerebral capillary sequestration and blood‐to‐brain transport of sAβ1–40. Conversely, apoE4, by entering brain microvessels and parenchyma as a stable complex with sAβ, reduces peptide degradation and may predispose to cerebrovascular and possibly enhance parenchymal amyloid formation under pathological conditions.

Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice.

OBJECTIVETo determine the effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth and associated angiogenesis in the brains of nude mice. METHODSHuman glioblastoma cells (105 U87MG cells) in 1 μl of medium were stereotactically injected during a 20-minute period into the caudate/putamen of nude mice. The mice were intraperitoneally treated daily with Cilengitide or solvent (control) beginning 5 days after tumor injection. The mice were sacrificed from 1 hour to 63 days after tumor implantation and examined for tumor size, vascularity, apoptosis, and cell replication. RESULTSThis injection technique resulted in a highly reproducible, localized, spherical tumor cell placement in the parenchyma without reflux into the subarachnoid space or penetration into the ventricle. Serial brain sections showed the tumor size remained unchanged at 1 to 2 mm3 for approximately 30 to 40 days. Thereafter, the control tumors showed exponential growth to a volume of 120 mm3, with death of the mice at approximately 8 to 9 weeks. Serial staining for Ki-67, a marker for cell replication, and CD31, an indicator for angiogenesis, demonstrated an increase in proportion to the growth of the tumor. In contrast, the tumor volume in Cilengitide-treated mice stayed unchanged at 1 to 2 mm3 during the entire length of the experiment, with staining for Ki-67 and CD31 remaining low. CONCLUSIONThis standardized brain tumor model is highly reproducible and useful for testing new treatment regimens. Cilengitide is highly effective in suppressing blood vessel growth, thereby controlling orthotopic growth of this glioblastoma cell line.

Visualization of Cerebrospinal Fluid Movement with Spin Labeling at MR Imaging: Preliminary Results in Normal and Pathophysiologic Conditions

Institutional review board approval and informed consent were obtained for this study. This study was HIPAA compliant. The purpose of this study was to visualize the movement of cerebrospinal fluid (CSF) noninvasively by using an unenhanced magnetic resonance imaging technique. A time-spatial labeling inversion pulse (SLIP) technique was applied to label, or tag, CSF in a region of interest. The tagged CSF was clearly visualized at inversion times of 1500-4500 msec after pulse labeling in both intracranial and intraspinal compartments. Noninvasive visualization of CSF movement, including bulk and turbulent flow, in normal (n = 7) and altered (n = 2) physiologic conditions was possible by using the unenhanced time-SLIP technique.

KINETICS OF ARGININE-VASOPRESSIN UPTAKE AT THE BLOOD-BRAIN BARRIER

Uptake of arginine-vasopressin, VP, at the luminal side of the blood-brain barrier (BBB) was studied by means of an in situ brain perfusion technique in the guinea-pig. Kinetic experiments revealed a saturable peptide influx into the parietal cortex, caudate nucleus and hippocampus with Km between 2.1 and 2.7 microM, and Vmax ranging from 4.9 to 5.6 pmol.min-1.g-1. The non-saturable component, Kd, was not significantly different from zero. Influx of VP into the brain was not altered by the presence of the peptide fragments: VP-(1-8), pressinoic acid and [pGlu4,Cyt6]VP-(4-9) at 4.5 microM, nor yet by the aminopeptidase inhibitor, bestatin (0.5 mM) and the L-amino acid transport system substrates, L-tyrosine and L-phenylalanine at 5 mM. At a perfusate concentration of 4.5 microM, the V1-vasopressinergic receptor antagonist, d(CH2)5[Tyr(Me)2]VP, reduced VP influx; regional Ki values, assuming that the observed inhibitions were purely competitive, ranged between 4.7 and 8.5 microM. It is concluded that there is an apparent cerebrovascular permeability to circulating VP due to the presence of a carrier-mediated transport system for the peptide located at the luminal side. The mechanism for VP BBB uptake exhibits no affinity for peptide fragments and large neutral amino acids, but requires reception of the intact molecule, which may be the same initial step for both the BBB VP transporter and the V1-receptor.

Correction of Large (>25 cm2) Cranial Defects with “Reinforced” Hydroxyapatite Cement: Technique and Complications

INTRODUCTIONHydroxyapatite cement is both biocompatible and osteoconductive, and it lacks significant toxic or immunogenic properties, making it an ideal substrate for the repair of cranial defects. However, with its putty-like composition, the repair of large cranial defects can be difficult because significant settling occurs as the cement hardens. We describe a technique in which we use hydroxyapatite cement, reinforced with tantalum mesh and titanium miniplates, for the repair of large (>25 cm2) cranial defects. METHODSAfter the margins of the cranioplasty are delineated, tantalum mesh is placed under the edges of the defect. Titanium miniplate single-hole bars are used to criss-cross the defect and are then secured to the surrounding bone with screws. The mesh is secured to the bars with 28-gauge stainless steel wire. Hydroxyapatite cement is applied in the defect and contoured appropriately. RESULTSWe performed nine cranioplasties in eight patients ranging in age from 1.5 to 35 years (mean, 12.2 ± 10.1 yr). The reasons for cranioplasty included cranial defect from prior trauma (n = 4), fibrous dysplasia (n = 2), infected bone flaps (n = 2), and tumor (n = 1). The cranioplasties ranged in size from 40 to 196 cm2 (mean, 128.3 ± 56.9 cm2). Follow-up ranged from 2 to 33 months (mean, 11.4 ± 12.8 mo). Two cranioplasty constructs were removed at 1 and 3 months postoperatively owing to infection. CONCLUSIONThe use of hydroxyapatite cement with mesh and miniplates provides internal structural support and increased stability of the construct. Although this technique provides an excellent cosmetic result and no evidence to date of bony resorption, the rate of infection is alarmingly high in these large constructs.

Blood-brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer's amyloid β in guinea pigs

An intracarotid brain infusion/capillary depletion technique was used in guinea pigs to examine cerebral capillary sequestration and transport into brain parenchyma of sA beta 1-40 and sA beta 1-42, synthetic peptides identical to two forms of the amyloid beta peptide found in Alzheimers disease lesions: the 40 residue form, found primarily in vascular deposits, and the 42 residue form, found primarily in senile plaques. The peptides crossed well into the brain parenchyma via a specific transport mechanism for which sA beta 1-40 had an approximately two-fold greater affinity than sA beta 1-42. There was significant capillary sequestration of sA beta 1-40, but retention by the microvasculature of sA beta 1-42 was negligible. These data suggest that the level of the 40 residue peptide in cerebral vasculature and of the 42 residue peptide in parenchyma could be regulated by blood-brain barrier sequestration and transport of their respective circulating precursors.

Benign Cerebellar Astrocytomas of Childhood

Benign cerebellar astrocytomas of childhood are potentially surgically curable lesions. Histologically, these neoplasms can be divided into pilocytic and diffuse astrocytomas. Whether there is a difference in the recurrence rate between these two tumor types after a surgical resection is not clear. In addition, the role of immediate postoperative imaging in predicting a recurrence has not been established. To answer these questions, we have reviewed the charts of 23 patients with benign cerebellar astrocytomas treated at Childrens Hospital of Los Angeles over a 10-year period (1977-1987). Of the 23 tumors, 15 were pilocytic and 8 were diffuse. All patients underwent an attempted gross total surgical removal of the tumor, and all patients had a postoperative computed tomographic (CT) scan with and without intravenously administered contrast material performed within 72 hours of the operation. Based on the postoperative CT scan, 12 patients had residual tumors. Seven of the subtotally resected tumors were pilocytic (7 of 15), and 5 were diffuse (5 of 8). Interestingly, the surgeon believed that a gross total resection had been obtained in 9 of these patients. There have been 4 recurrences in these 23 patients, with a mean follow-up of 4.9 years. All recurrences were in patients with subtotal resections. Of the 11 patients with a total resection of the tumor, 7 developed a small rim of enhancement on subsequent scans an average of 5 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome For Preterm Infants with Germinal Matrix Hemorrhage and Progressive Hydrocephalus

OBJECTIVE An analysis of 76 preterm infants with Grade III or IV intracranial hemorrhage and surgically treated progressive hydrocephalus was undertaken to determine mortality, intellectual impairment, and motor deficit. METHODS The variables examined were degree of prematurity, birth weight, sex, Apgar scores, extent of intracranial hemorrhage, seizures, age at time of initial placement of a ventricular catheter reservoir to control hydrocephalus, need to convert the reservoir to a ventriculoperitoneal shunt, timing of the conversion of the reservoir to a ventriculoperitoneal shunt, and number of shunt revisions. Outcome was assessed for statistical significance using hierarchical linear regression and logistic regression analyses. RESULTS Linear regression analysis determined that mortality was best predicted, in order of importance, by extent of intracranial hemorrhage, number of shunt revisions, and birth weight (P < 0.0001, R = 0.79). Grade of hemorrhage, weight at birth, and presence of seizure activity were the most important determinants of motor outcome (P < 0.001, R = -0.78). CONCLUSIONS Logistic regression analysis of the 41 long-term survivors determined that grade of hemorrhage was the most important variable in determining cognitive outcome (P < 0.0001), motor function (P < 0.0001), and presence of seizure activity (P < 0.001). A logistic model of survival determined that grade of hemorrhage and multiple shunt revisions (more than five) were the most important determinants (P < 0.0001) of survival. In conclusion, the overwhelming factor in determining outcome in this patient group was the extent of intracranial hemorrhage.

Outcome, Cost Analysis, and Long-term Follow-up in Preterm Infants with Massive Grade IV Germinal Matrix Hemorrhage and Progressive Hydrocephalus

OBJECTIVE The benefit of aggressive management and surgical intervention in preterm infants with massive Grade IV intracranial hemorrhage has been questioned based on the poor outcome of this group of patients despite such therapy. To further delineate this problem, we reviewed the records of premature neonates in this category as to outcome and initial hospital cost. METHODS We performed a retrospective review of the medical records at our institution from 1977 to 1987 to identify premature neonates who had sustained massive hemorrhagic infarction of one hemisphere in addition to having blood in both ventricles and progressive hydrocephalus. RESULTS During the study, a total of 52 such patients were identified, only 19 (6 female and 13 male patients) of whom survived. Intellectual function was observed to be greater than 2 standard deviations below the mean in 15 of the 19 patients, between 1 and 2 standard deviations below the mean in 1 of 19, and 1 standard deviation below the mean in 3 of 19. Motor function was as follows: 12 of 19 had marked spastic quadriparesis, 2 of 19 had moderate spastic quadriparesis, 3 of 19 had spastic hemiplegia, 1 of 19 had spastic diplegia, and 1 of 19 had mild spastic hemiparesis. Eleven of 19 had chronic seizure disorders. The first hospitalization cost for the group of patients exceeded, on the average,