The First Examination of Diagnostic Performance of Automated Measurement of the Callosal Angle in 1856 Elderly Patients and Volunteers Indicates That 12.4% of Exams Met the Criteria for Possible Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Many patients with dementia may have comorbid or misdiagnosed normal pressure hydrocephalus, a treatable neurologic disorder. The callosal angle is a validated biomarker for normal pressure hydrocephalus with 93% diagnostic accuracy. Our purpose was to develop and evaluate an algorithm for automatically computing callosal angles from MR images of the brain. MATERIALS AND METHODS: This article reports the results of analyzing callosal angles from 1856 subjects with 5264 MR images from the Open Access Series of Imaging Studies and the Alzheimer's Disease Neuroimaging Initiative databases. Measurement variability was examined between 2 neuroradiologists (n = 50) and between manual and automatic measurements (n = 281); from differences in simulated head orientation; and from real-world changes in patients with multiple examinations (n = 906). We evaluated the effectiveness of the automatic callosal angle to differentiate normal pressure hydrocephalus from Alzheimer disease in a simulated cohort. RESULTS: The algorithm identified that 12.4% of subjects from these carefully screened cohorts had callosal angles of <90°, a published threshold for possible normal pressure hydrocephalus. The intraclass correlation coefficient was 0.97 for agreement between neuroradiologists and 0.90 for agreement between manual and automatic measurement. The method was robust to different head orientations. The median coefficient of variation for repeat examinations was 4.2% (Q1 = 3.1%, Q3 = 5.8%). The simulated classification of normal pressure hydrocephalus versus Alzheimer using the automatic callosal angle had an accuracy, sensitivity, and specificity of 0.87 each. CONCLUSIONS: In even the most pristine research databases, analyses of the callosal angle indicate that some patients may have normal pressure hydrocephalus. The automatic callosal angle measurement can rapidly and objectively screen for normal pressure hydrocephalus in patients who would otherwise be misdiagnosed.

Current and emerging MR imaging techniques for the diagnosis and management of CSF flow disorders: a review of phase-contrast and time-spatial labeling inversion pulse.

This article provides an overview of phase-contrast and time-spatial labeling inversion pulse MR imaging techniques to assess CSF movement in the CNS under normal and pathophysiologic situations. Phase-contrast can quantitatively measure stroke volume in selected regions, notably the aqueduct of Sylvius, synchronized to the heartbeat. Judicious fine-tuning of the technique is needed to achieve maximal temporal resolution, and it has limited visualization of CSF motion in many CNS regions. Phase-contrast is frequently used to evaluate those patients with suspected normal pressure hydrocephalus and a Chiari I malformation. Correlation with successful treatment outcome has been problematic. Time-spatial labeling inversion pulse, with a high signal-to-noise ratio, assesses linear and turbulent motion of CSF anywhere in the CNS. Time-spatial labeling inversion pulse can qualitatively visualize whether CSF flows between 2 compartments and determine whether there is flow through the aqueduct of Sylvius or a new surgically created stoma. Cine images reveal CSF linear and turbulent flow patterns.

A case of rudimentary lateral parietal cephalocele: extracranial meningothelial and glial tissue without intracranial communication or bony defect.

The authors report a case of a 7-month-old infant with a right lateral parietal scalp lesion intermittently leaking fluid similar to cerebrospinal fluid that histologically demonstrated meningothelial and glial cells. At surgical removal, however, no fibrous stalk or bony defect could be identified connecting the lesion with the intracranial compartment. While the embryologic mechanism of this lesion is unclear, the prognosis for normal neurological development appears excellent.

Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization.

PURPOSE: Our aims were to evaluate the metabolic profiles of pediatric brain tumors with short echo time (TE) MR spectroscopy and absolute quantitation of metabolite concentrations (in mmol/kg of tissue) and to describe metabolic features that distinguish individual tumor types and that may help to improve preoperative diagnosis of specific tumors. METHODS: MR imaging examinations of 60 patients with untreated brain tumors (14 medulloblastomas, 5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was performed and absolute metabolite concentrations were determined by using fully automated quantitation. RESULTS: Taurine (Tau) was significantly elevated in medulloblastomas (P < .00001) compared with all other tumors pooled (All Other). Tau was also observed consistently, at lower concentration, in pineal germinomas. Creatine (Cr) was significantly reduced in pilocytic astrocytomas, distinguishing them from All Other (P < .000001). The MR spectra of choroid plexus papillomas exhibited low Cr (P < .01) concentrations; however, myoinositol was elevated (P < .01) and total choline (tCho) (P < .0001) was reduced relative to All Other. Choroid plexus carcinomas had low Cr (P < .01 versus All Other) and the lowest Cr/tCho ratio (P < .0001 versus All Other) among all tumors studied. Guanidinoacetate was reduced in low-grade astrocytomas and anaplastic astrocytomas (P < .00001) versus All Other, whereas ependymoma and anaplastic ependymomas exhibited particularly low N-acetylaspartate (P < .00001 versus All Other). CONCLUSION: Quantitative proton MR spectroscopy reveals features of pediatric brain tumors that are likely to improve preoperative diagnoses.

Injuries from falls in the pediatric population: an analysis of 729 cases.

BACKGROUND/PURPOSE: Falls are classified as low or high level for triage purposes. Because triage criteria dictate less urgency for low-level falls, this classification scheme has important implications for pediatric emergency care. METHODS: Retrospective analysis was conducted of 729 (393 low-level and 336 high-level) pediatric patients treated for fall-related trauma (1992 through 1998). Falls were classified as low (<15 feet) or high-level (> or =15 feet). All falls were reported as accidental or unintentional. RESULTS: The overall mortality rate was 1.6% (2.4% for high-level falls compared with 1.0% for low-level falls). All 4 patients who died of a low-level fall had an abnormal head computed tomography (CT) scan and intracranial hypertension. Half of deaths from high-level falls were attributable to intracranial injuries, and half were caused by severe extracranial injuries. Common extracranial injuries were upper extremity fracture (6.2%), lower extremity fracture (5.6%), pulmonary contusion (1.8%), pneumothorax (1.1%), liver laceration (1.1%), bowel injury (1.0%), and splenic injury (2.1%). Orthopedic and thoracic injuries resulted more commonly from high-level falls, whereas abdominal injuries were as likely to occur after a low-level fall. CONCLUSIONS: Intracranial injury accounts for the majority of deaths from falls. Children suffering low-level falls were at similar risk for intracranial and abdominal injuries compared with those who fell from greater heights. Pediatric trauma triage criteria should account for these findings.

Maternal lung adenocarcinoma metastatic to the scalp of a fetus. Case report.

Maternal malignancy metastatic to the fetus is a rare event, with most neoplasms being either melanocytic or hematopoietic in origin. This report is the first known case of a maternal lung adenocarcinoma metastatic to a fetus. At 2 months of age, this male infant developed multiple scalp masses that were locally resected but rapidly recurred. The histology of the scalp lesions and that of a biopsy of the mother's tumor were both adenocarcinoma and were remarkably similar in appearance. In situ hybridization of tumor cells from this male infant found many large nuclei with XX signals indicating that the tumor was of maternal origin. This patient is alive, well and free of malignancy 5 years after a wide local resection of the scalp and skin grafting.

Vagus nerve stimulation for control of intractable seizures in childhood.

Vagus nerve stimulation (VNS) is gaining increasing popularity and credibility as a treatment option for children with intractable epilepsy. VNS offers several advantages over extant treatments. Its efficacy is maintained during prolonged stimulation, and seizure control actually improves with time. There is no associated cognitive impairment and no adverse drug interactions. Unlike cerebral surgery, VNS is a potentially reversible form of therapy. The computer-controlled characteristic of the device permits complete and involuntary treatment compliance. VNS is safe and well-tolerated. Its side effects are generally transient and mild, and no physiologic perturbations have been reported despite extensive monitoring. Serious adverse events are rare, and no deaths have been attributed to VNS therapy itself or to the technique of surgical insertion. In this article, we discuss the theoretical background behind VNS and review the clinical studies that substantiate its long-term safety, feasibility, tolerability and potential efficacy in children with refractory epilepsy.

Choroid plexus tumors in children: significance of stromal invasion.

OBJECTIVE: A group of choroid plexus tumors fit the cellular criteria for choroid plexus papilloma (CPP) except for invasion into the adjacent parenchyma, with associated loss of the normal villus architecture at the site of invasion. These tumors retain a benign cellular appearance. In the existing literature, it is unclear whether these tumors are classified as choroid plexus carcinomas or as CPPs. In our experience, although evidence of invasion is present, these tumors tend to exhibit benign behavior. We suggest that stromal invasion of this type remains consistent with a benign clinical course, although surgical results may demonstrate higher morbidity rates, given the invasive nature of the tumors. The failure to classify these tumors as CPPs may explain some of the variability in outcomes reported for various studies. METHODS: To study this question, clinical and histological data for children diagnosed with CPPs (either with or without stromal invasion) between 1985 and 1995 were examined. Only cases with pre- and postoperative magnetic resonance imaging data were included in the series. RESULTS: A total of 12 patients with CPPs were identified, with 4 tumors being notable for stromal invasion. After gross total tumor removal, none of the eight children with CPPs received adjuvant therapy at our institution; all are alive without evidence of tumor recurrence after surgical excision (mean, 108 mo). Of the four patients with stromal invasion, three underwent gross total resection. The one patient who underwent subtotal resection received chemotherapy at another facility. All four of these patients are alive, after a mean of 100 months of follow-up monitoring. CONCLUSION: It is recommended that CPPs with a benign cellular appearance but with evidence of local parenchymal invasion and loss of the normal villus architecture at the site of invasion be classified as CPPs. Patients with these tumors respond to surgical therapy alone, without the need for adjuvant treatment.

The delta valve: how does its clinical performance compare with two other pressure differential valves without antisiphon control?

OBJECTIVE: The Delta valve is a pressure differential valve with a siphon control device. The valve mechanism is normally closed, but is designed to open in response to positive ventricular pressure, thereby avoiding overdrainage of cerebrospinal fluid (CSF). As a result, the incidence of subdural fluid collections as well as postural symptoms is purportedly reduced. In addition, the valve might reduce the number of obstructions as there would be no negative pressure sucking tissue and debris into the shunt system. In order to assess whether use of the Delta valve reduced the number of shunt-related problems as compared with two other pressure differential valves without an antisiphon component, we performed a retrospective review of all children undergoing CSF diversion procedures at our institution. METHODS: We reviewed the charts of 1, 193 patients. Cases included 2,325 ventriculoperitoneal (V-P) shunt insertions or revisions from January 1, 1985, to December 31, 1994, performed at our institution. The Delta valve and two pressure differential valves without antisiphon function were exclusively inserted during the following time periods: Holter-Hausner (H-H): January 1, 1985, to August, 1987; Heyer-Schulte (H-S): August, 1987, to June, 1991, and Delta: June, 1991, to December 31, 1994. RESULTS: Of the cases reviewed, 475 patients underwent insertion of a V-P shunt at the Childrens Hospital of Los Angeles and had a total of 686 shunt operations. Median follow-up was 3 years and ranged up to 10 years. Kaplan-Meier analysis documented that 67% of H-H, 71% of H-S and 70% of the Delta valves were functioning at 1-year follow-up. At 2-year follow-up, 66% of H-H, 64% of H-S and 65% of the Delta valves were functioning. The difference was not statistically significant. The occurrence rate for symptomatic subdural fluid collections was 0.7% (1/130) for H-H, 2.2% (3/139) for H-S and 1.0% (2/206) for the Delta valve (p = 0.52). The combined breakage/obstruction rate for the series was 7.7% (10/130) for H-H, 2.9% (4/139) for H-S and 4.9% (10/206) for the Delta valve (p = 0.19). No Delta valves malfunctioned secondary to fibrous capsule affecting the antisiphon device. CONCLUSIONS: In conclusion, it appears that performance of the Delta valve was not significantly different from the H-H and H-S valves, two valves without an antisiphon device. There was no significant difference in the occurrence of symptomatic subdural fluid collections based upon valve type, or in the combined valve breakage/obstruction rates based upon valve type.

Long-term outcome of terminal myelocystocele patients.

INTRODUCTION: A terminal myelocystocele, a closed form of a neural tube defect (NTD), can present as a large, fully epithelialized, cystic lumbosacral mass containing fat, cerebrospinal fluid (CSF) and neural tissue. The spinal cord terminates at a neural placode wherein the central canal opens into a CSF-filled cavity that is distinct from fluid in the subarachnoid space surrounding the spinal cord. This form of NTD, in our experience, was only associated with major caudal cell mass abnormalities, as these patients often have maldevelopment of the lower spine, pelvis, genitalia, bowel, bladder, kidney and the abdominal wall. This study will describe the clinical manifestations, surgical management and long-term outcome of our terminal myelocystocele patients. METHODS: To characterize this rare entity, a 13-year retrospective review was undertaken at our institution. RESULTS: Nine patients with terminal myelocystoceles were identified. In all cases, there were multiple congenital defects including cloacal exstrophy, imperforate anus, omphalocele, pelvic deformity, equinovarus or renal abnormality. Only 1 out of 9 patients has required a shunt for hydrocephalus. The main goal of neurosurgical intervention was to reduce the size of the mass, which can slowly enlarge over time. The spinal cord was also untethered, although these patients have no chance of bowel or bladder control. With a mean follow-up of 63 months, all patients remained neurologically stable. Impairment of lower extremity function is usually severe. However, some patients were ambulatory with the aid of a walker or orthotic device. All patients required a prolonged hospital stay as well as multiple operations prior to initial discharge. CONCLUSION: Experienced, multispecialty care is needed to optimize the long-term outcome of these complex patients.

A prospective population-based study of pediatric trauma patients with mild alterations in consciousness (Glasgow Coma Scale score of 13-14).

OBJECTIVE: Considerable controversy surrounds the appropriate evaluation of children with mild alterations in consciousness after closed head trauma (Glasgow Coma Scale [GCS] score of 13-14). The objective of the current study was to determine the incidence of intracranial lesions in pediatric patients with a field GCS score of 13 or 14 after closed head injuries. METHODS: The current study is a population-based, multicenter prospective study of all patients to whom emergency medical services responded during a 12-month period. The setting was urban Los Angeles County, encompassing a patient population of 2.3 million children, 13 designated trauma centers, and 94 receiving hospitals. RESULTS: In the pediatric age group (<15 yr old), 8488 patients were transported by emergency medical services for injuries. Of these, 209 had a documented field GCS score of 13 or 14. One hundred fifty-seven patients were taken to trauma centers, and 135 (86%) underwent computed tomography. Forty-three patients (27.4%) had abnormal results on computed tomographic scans, 30 (19.1%) had an intracranial hemorrhage, and 5 required an operative neurosurgical procedure for hematoma evacuation. Positive and negative predictive values of deteriorating mental status (0.500 and 0.844, respectively), loss of consciousness (0.173 and 0.809), cranial fracture (0.483 and 0.875, and extracranial injuries (0.205 and 0.814) were poor predictors of intracranial hemorrhage. CONCLUSION: Pediatric patients who have mild alterations in consciousness in the field have a significant incidence of intracranial injury. The great majority of these patients will not require operative intervention, but the implications of missing these hemorrhages can be severe for this subgroup of head-injured patients. Because clinical criteria and cranial x-rays are poor predictors of intracranial hemorrhage, it is recommended that all children with a GCS score of 13 or 14 routinely undergo screening via non-contrast-enhanced computed tomography.

Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration.

OBJECT: The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors. METHODS: After optimal repeated tumor resection, multiple injections of murine vector-producing cells shedding murine replication-defective retroviral vectors coding the herpes simplex virus thymidine kinase type 1 (HSV-Tk1) gene were made into the rim of the resection cavity. Fourteen days after the vector-producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed HSV-Tk1 in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2-15 years). Treated brain tumors included seven malignant gliomas, two ependyminomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings. CONCLUSIONS: This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector-producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.

Tissue plasminogen activator (tPA) deficiency exacerbates cerebrovascular fibrin deposition and brain injury in a murine stroke model: studies in tPA-deficient mice and wild-type mice on a matched genetic background.

Although the serine protease, tissue plasminogen activator (tPA), is approved by the US Food and Drug Administration for therapy to combat focal cerebral infarction, the basic concept of thrombolytic tPA therapy for stroke was challenged by recent studies that used genetically manipulated tPA-deficient (tPA-/-) mice, which suggested that tPA mediates ischemic neuronal damage. However, those studies were potentially flawed because the genotypes of tPA-/- and wild-type control mice were not entirely clear, and ischemic neuronal injury was evaluated in isolation of tPA effects on brain thrombosis. Using mice with appropriate genetic backgrounds and a middle cerebral artery occlusion stroke model with nonsiliconized thread, which does lead to microvascular thrombus formation, in the present study we determined the risk for cerebrovascular thrombosis and neuronal injury in tPA-/- and genetically matched tPA+/+ mice subjected to transient focal ischemia. Cerebrovascular fibrin deposition and the infarction volume were increased by 8.2- and 6. 7-fold in tPA-/- versus tPA+/+ mice, respectively, and these variables were correlated with reduced cerebral blood flow up to 58% (P<0.05) and impaired motor neurological score by 70% (P<0.05). Our findings indicate that tPA deficiency exacerbates ischemia-induced cerebrovascular thrombosis and that endogenous tPA protects the brain from an ischemic insult, presumably through its thrombolytic action. In addition, our study emphasizes the importance of appropriate genetic controls in murine stroke research.

Integration of a variable action suction adapter into ultrasonic aspirators.

PURPOSE: Use of ultrasonic aspirators has become a mainstay in the neurosurgical armamentarium. The handpiece design and ultrasonic parameters have evolved to maximize its safe and efficacious use. Despite these modifications, continuous suction through the tip of the aspirator can result in neurovascular damage, especially when the aspirator is working in the cavernous sinus region or cerebellopontine angle. CONCEPT: We describe the integration of a variable suction adapter into the existing handpiece of an ultrasonic aspirator to minimize potential injury from the continuous forceful suction normally associated with the use of these devices. RATIONALE: The integration of such an adapter can reduce the potential for suction injury to cranial nerves or microvascular structures or smaller-caliber arteries and veins. DISCUSSION: This variable action suction adapter can decrease suction injuries to cranial nerves or the microvasculature.

Retroviral vector-mediated transfer and expression of human tissue plasminogen activator cDNA in bovine brain endothelial cells.

OBJECTIVES: Gene transfer of thrombolytic enzymes to vascular endothelial cells may influence the kinetics of intravascular thrombosis. This study defines the potential for gene transfer of tissue plasminogen activator (tPA) into bovine brain endothelial cells (BBEC). METHODS: The retroviral vectors derived from murine leukemia virus (MuLV) were used to transfer human tPA cDNA to BBEC. The tPA activity, tPA antigen and tPA inhibitor 1 (PAI-1) antigen were determined in the supernatant of transduced (BBEC/tPA) cell cultures by an immunoassay. RESULTS: The tPA antigen and enzymatic activity in cell culture supernatants of BBEC/tPA transduced cells were 75 ng/ml and 14 IU/ml after 4 days, that was 25 and 28-fold higher compared to the respective values in control cells. The PAI-1 antigen was not affected by tPA cDNA transfer. The Western blot assay of cell lysates confirmed that the majority of tPA in BBEC/tPA transduced cells was in the form of free tPA. While the maximal transduction efficiency of BBEC with an amphotropic MuLV vector was about 15%, a MuLV pseudotyped with vesicular stomatitis virus G glycoprotein envelope achieved high > 90% maximal transduction efficiency. CONCLUSIONS: The fibrinolytic activity of brain endothelial cells can be enhanced by transferring human tPA cDNA. These findings provide an initial step in implementation of future studies that investigate the use of this technology as an adjunctive treatment for cerebrovascular disease.

Does age or other factors influence the incidence of ventriculoperitoneal shunt infections?

Some studies indicate that infants, especially those less than 1 month of age have a higher incidence of ventriculoperitoneal shunt infections. To look at age as well as other variables that might relate to the rate of shunt infection, we reviewed the records of all patients undergoing a ventriculoperitoneal shunt insertion or revision at our institution from January 1, 1985, to December 31, 1994. There were a total of 2,325 ventriculoperitoneal shunting procedures performed on 1,193 patients with a male:female ratio of 678:515. The overall infection rate was 3.2% (74 infections). Analyzed by age, the infection rates were as follows: <1 month 9/223 (4.0%), 1-6 months 16/449 (3.6%), 6-12 months 13/297 (4.4%), 12-18 months 3/122 (2.5%), 18-24 months 7/116 (6.0%) and 24+ months 26/1, 118 (2.3%). There was no statistically significant difference between age groups (p > 0.05). Upon selectively examining premature neonates who developed hydrocephalus secondary to intraventricular hemorrhage from the figures given above, one finds that 2/44 (4.5%) of neonates became infected, which was also not significant. The infection rate was the same irrespective of whether the procedure was to insert or revise the shunt, or whether another operative procedure was done under the same anesthesia. The etiology of the hydrocephalus was not a factor, nor was the presence of an open neural tube defect. The presence of fluid accumulation along the shunt tract or at another neurological operative site was associated with a significant increase in incidence of infection 15/168 (8.9%) when compared to those with no fluid accumulation (p < 0.001). The type of infecting organism was divided roughly in thirds, with relatively equal representation from Staphylococcus epidermidis/coagulase negative and Staphylococcus aureus. The remaining third was comprised of a wide variety of organisms.

A prospective analysis of the use of octylcyanoacrylate tissue adhesive for wound closure in pediatric neurosurgery.

OBJECTIVE: Cyanoacrylate monomers have been developed for use as skin adhesives. Previous studies have demonstrated that using this skin adhesive for the closure of traumatic lacerations results in excellent cosmesis, decreased procedure-related pain and timesavings. SURGICAL TECHNIQUE: Octylcyanoacrylate skin adhesive is applied after the placement of deep fascial sutures with close approximation of the skin edges. The adhesive is applied in liquid form and polymerizes rapidly to solid form. Multiple layers are applied forming a hard impenetrable barrier. RESULTS: This technique was prospectively evaluated in the closure of 102 elective neurosurgical operations with 142 incisions: ventriculoperitoneal shunt insertion/revision (53%) and craniotomy for tumors (10%) were the commonest procedures. There were a total of 83 scalp, 36 abdominal, 8 neck, 6 chest and 6 lumbar incisions. The mean incision length was 5.1 cm (range 0.25-50 cm). Fifty-nine percent of the wounds had previous areas of operative incisions. Complications included 1 poor cosmetic result and 4 cerebrospinal fluid (CSF) leaks. Of the 4 patients with CSF leaks, 2 required operative wound revision, and 1 required ventriculoperitoneal shunting for hydrocephalus. CONCLUSION: Cyanoacrylate skin adhesive is a viable means of obtaining cosmetic wound closure. Its use requires attention to proper skin approximation and hemostasis. In our experience, propensity for CSF leakage especially in reoperative procedures is a relative contraindication.