Suresh N. Magge

Packed red blood cell transfusion increases local cerebral oxygenation.

Objective:To determine a) whether packed red blood cell transfusion (RBCT) increases local brain tissue oxygen partial pressure (Pbto2) in a neurocritical care population; and b) what (if any) demographic, clinical, or physiologic variables mediate the assumed change. Design:Prospective observational study. Setting:A neurosurgical intensive care unit at a university-based level I trauma center and tertiary care hospital. Patients:Thirty-five consecutive volume-resuscitated patients with subarachnoid hemorrhage or traumatic brain injury, without cardiac disease, requiring Pbto2 monitoring and receiving RBCT were studied between October 2001 and December 2003. Interventions:None. Measurements and Main Results:The following physiologic variables were measured and compared 1 hr before and after RBCT: Pbto2, intracranial pressure, cerebral perfusion pressure, hemoglobin oxygen saturation (Sao2), Fio2, hemoglobin, and hematocrit. An increase in Pbto2 was observed in 26 of the 35 patients (74%). In nine patients, Pbto2 decreased after RBCT. The mean (±sd) increase in Pbto2 for all patients was 3.2 ± 8.8 mm Hg (p = .02), a 15% change from baseline (1 hr before RCBT). This Pbto2 increase was associated with a significant mean increase in hemoglobin and hematocrit after RBCT (1.4 ± 1.1 g/dL and 4.2% ± 3.3%, respectively; both p < .001). Cerebral perfusion pressure, Sao2, and Fio2 were similar before and after RBCT. Among the 26 patients whose Pbto2 increased, the mean increase in Pbto2 was 5.1 ± 9.4 mm Hg or a 49% mean increase (p < .01). Conclusions:RBCT is associated with an increase in Pbto2 in most patients with subarachnoid hemorrhage or traumatic brain injury. This mean increase appears to be independent of cerebral perfusion pressure, Sao2, and Fio2. Further study is required to determine why Pbto2 decreases in some patients after RBCT.

Role of monocyte chemoattractant protein-1 (MCP-1/CCL2) in migration of neural progenitor cells toward glial tumors.

Neural progenitor cells (NPCs) have been investigated as potential vehicles for brain tumor therapy because they have been shown to migrate toward central nervous system gliomas and can be genetically engineered to deliver cytotoxic agents to tumors. The mechanisms that regulate migration of NPCs to tumors are not fully understood. By means of microarray analysis, polymerase chain reaction, enzyme‐linked immunosorbent assay, and immunohistochemistry, we found that monocyte chemoattractant protein‐1 (MCP‐1/CCL‐2) was expressed in experimental brain tumor cells in vivo and in vitro. CCR2, the receptor for MCP‐1, was expressed on C17.2 NPCs. We used a modified Boyden chamber assay and found increased migration of NPCs in vitro in response to MCP‐1. By means of an in vivo model for NPC migration, we found evidence of NPC migration toward areas of MCP‐1 infusion in rat brains. An understanding of NPC migration mechanisms may be used to enhance delivery of cytotoxic agents to brain tumor cells.

Association of a younger age with an increased risk of angiographic and symptomatic vasospasms following subarachnoid hemorrhage

OBJECT Vasospasm is a leading cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). It is important to predict which patients are at risk for vasospasm so that interventions can be made. There are several potential risk factors for vasospasm, one of which is age. However, the effect of age on vasospasm, particularly symptomatic vasospasm, remains controversial. METHODS Three hundred ninety-one patients were retrospectively identified from a prospective observational database of patients with SAH who had been admitted to a single center. Demographic and clinical data were recorded, and cerebral angiograms obtained at admission and between 5 and 10 days later were compared. The relationship between age and angiographic and symptomatic vasospasms was examined using logistic regression techniques. RESULTS Mild (86 patients), moderate (69 patients), severe (56 patients), and no angiographic vasospasms (180 patients) were documented by comparing admission and follow-up angiograms in each patient. Symptomatic vasospasm was identified in 69 patients (17.6%). Angiographic vasospasm was more frequent as age decreased. Except in patients < 30 years old, the frequency of symptomatic vasospasm also increased with decreasing age (p = 0.0001). After adjusting for variables known to be associated with vasospasm, an advanced age was associated with a reduced incidence of any angiographic vasospasm (OR 0.96, 95% CI 0.94-0.97), severe angiographic vasospasm (OR 0.96, 95% CI 0.95-0.98), and symptomatic vasospasm (OR 0.98, 95% CI 0.96-0.99). CONCLUSIONS Results in this study show that a younger age is associated with an increased incidence of angiographic and symptomatic vasospasm.

Neurotrophin-mediated neuroprotection of hippocampal neurons following traumatic brain injury is not associated with acute recovery of hippocampal function

Traumatic brain injury (TBI) causes selective hippocampal cell death which is believed to be associated with the cognitive impairment observed in both clinical and experimental settings. The endogenous neurotrophin-4/5 (NT-4/5), a TrkB ligand, has been shown to be neuroprotective for vulnerable CA3 pyramidal neurons after experimental brain injury. In this study, infusion of recombinant NT-4/5 increased survival of CA2/3 pyramidal neurons to 71% after lateral fluid percussion brain injury in rats, compared with 55% in vehicle-treated controls. The functional outcome of this NT-4/5-mediated neuroprotection was examined using three hippocampal-dependent behavioral tests. Injury-induced impairment was evident in all three tests, but interestingly, there was no treatment-related improvement in any of these measures. Similarly, injury-induced decreased excitability in the Schaffer collaterals was not affected by NT-4/5 treatment. We propose that a deeper understanding of the factors that link neuronal survival to recovery of function will be important for future studies of potentially therapeutic agents.

Idiopathic syrinx in the pediatric population: a combined center experience

OBJECT Discovery of a syrinx in a child, without a readily identifiable proximate cause such as a Chiari malformation, tumor, or site of tethering, is often a cause of concern for families and a source of consternation for clinicians. There is a paucity of data describing the natural history of an idiopathic syrinx in the pediatric population. The authors present the combined data of 2 major pediatric neurosurgical centers to describe their experience with this condition. METHODS Data were collected at Childrens Hospital Boston and St. Louis Childrens Hospital according to institutional review board-approved protocols and captured visits over a 2.5-year interval (October 2006-March 2009), with records reviewed if the patient had a preexisting diagnosis of syrinx. Patients were identified by ICD-9 codes derived from departmental databases. All pediatric patients (age < 19 years) in whom idiopathic syrinx had been diagnosed, as defined by MR imaging findings (dilated central canal in the spinal cord of ≥ 1 mm in axial dimension and extending over at least 2 vertebral levels), were included. RESULTS Forty-eight patients met the criteria for idiopathic syrinx during this period, and in 32 of them detailed follow-up imaging was available. Discovery of a syrinx was incidental in 6 patients, whereas the others were referred for imaging because of the presence of pain, neurological symptoms, scoliosis, or skin markings. The average age at the first MR imaging session was 9.7 years, with a mean syrinx size of 4 mm (range 1.2-9.4 mm). The majority (52%) of patients had a thoracic syrinx, with the average lesion spanning 7.1 vertebral levels. The average follow-up was 23.8 months (range 2-64 months), and subgroups of patients with < 3 years and ≥ 3 years of follow-up were independently reviewed. Overall, symptoms improved in 34% and worsened in 9%; 57% of the patients remained asymptomatic or stable. Radiographically (in the subgroup of 32 patients with detailed follow-up imaging), syrinx size decreased in 25% of patients, increased in 12.5%, and remained unchanged in 62.5%, with no apparent correlation between change in syrinx size and clinical symptoms. CONCLUSIONS Clinically, children with an idiopathic syrinx remained asymptomatic, stable, or improved in 91% of cases. The majority of syringes (87.5%) remained stable or shrank over time, with no apparent correlation between changes in size and changes in symptoms. Although longer follow-up is needed, these data suggest that the natural history of an idiopathic syrinx in children is benign, and that repeated imaging may not be necessary.

Dislocation of the mandible into the middle cranial fossa

Dislocation of the mandibular condyle into the middle cranial fossa is a rare event due to anatomical and biomechanical factors. The authors report the case of a 12-year-old girl who presented with this condition after colliding with a classmate. One day after her injury, the patient demonstrated an inability to close her mouth completely, and she had minor tenderness to palpation anterior to the tragus, without neurological deficits. Imaging studies demonstrated a fractured glenoid fossa with intrusion of the mandible into the cranial cavity. Open reduction of the mandibular condyle was performed, and the glenoid fossa was reconstructed with a split-thickness bone graft and titanium screws. Several dural tears noted at the time of surgery were repaired primarily. Mandibular condyle dislocation into the middle cranial fossa is often misdiagnosed initially because of its low incidence and nonspecific symptoms. Computed tomography scanning is the most sensitive diagnostic study for detecting this injury. Closed reduction after induction of general anesthesia has been recommended in recently suffered injuries without neurological deficits, but this approach may overlook damage to intracranial structures. Surgical repair is recommended if neurological injury is suspected. Treatment options should be tailored to the individual factors of each case.

The influence of lesion volume, perilesion resection volume, and completeness of resection on seizure outcome after resective epilepsy surgery for cortical dysplasia in children.

OBJECT Focal cortical dysplasia (FCD) is one of the most common causes of intractable epilepsy leading to surgery in children. The predictors of seizure freedom after surgical management for FCD are still unclear. The objective of this study was to perform a volumetric analysis of factors shown on the preresection and postresection brain MRI scans of patients who had undergone resective epilepsy surgery for cortical dysplasia and to determine the influence of these factors on seizure outcome. METHODS The authors reviewed the medical records and brain images of 43 consecutive patients with focal MRI-documented abnormalities and a pathological diagnosis of FCD who had undergone surgical treatment for refractory epilepsy. Preoperative lesion volume and postoperative resection volume were calculated by manual segmentation using OsiriX PRO software. RESULTS Forty-three patients underwent first-time surgery for resection of an FCD. The age range of these patients at the time of surgery ranged from 2 months to 21.8 years (mean age 7.3 years). The median duration of follow-up was 20 months. The mean age at onset was 31.6 months (range 1 day to 168 months). Complete resection of the area of an FCD, as adjudged from the postoperative brain MR images, was significantly associated with seizure control (p = 0.0005). The odds of having good seizure control among those who underwent complete resection were about 6 times higher than those among the patients who did not undergo complete resection. Seizure control was not significantly associated with lesion volume (p = 0.46) or perilesion resection volume (p = 0.86). CONCLUSIONS The completeness of FCD resection in children is a significant predictor of seizure freedom. Neither lesion volume nor the further resection of perilesional tissue is predictive of seizure freedom.

Surgical management of pediatric brain tumors

Brain tumors are the most common cause of cancer-related death and the second most common form of cancer in pediatric patients. Many of these tumors are treated primarily with surgery, either alone or in combination with radiation or chemotherapy. Recent advances have lead to greater survival and decreased morbidities in childhood brain tumor patients. A full understanding of the biology and primary treatment modalities for the particular tumor are essential for any professional treating these patients, including the neurosurgeon. Each tumor type has features in common with, and unique from, other tumors that need to be understood prior to undertaking a rational treatment plan. This article summarizes some of these features.

Evaluation of the ShuntCheck noninvasive thermal technique for shunt flow detection in hydrocephalic patients.

BACKGROUND:ShuntCheck (Neuro Diagnostic Devices, Inc., Trevose, Pennsylvania) is a new device designed to detect cerebrospinal fluid (CSF) flow in a shunt by sensing skin temperature downstream from a region of CSF cooled by an ice cube. OBJECTIVE:To understand its accuracy and utility, we evaluated the use of this device during routine office visits as well as during workup for suspected shunt malfunction. METHODS:One hundred shunted patients were tested, including 48 evaluated during possible shunt malfunction, of whom 24 went on to surgical exploration. Digitally recorded data were blindly analyzed and compared with surgical findings and clinical follow-up. RESULTS:Findings in the 20 malfunctioning shunts with unambiguous flow or absence of flow at surgery were strongly correlated with ShuntCheck results (sensitivity and specificity to flow of 80% and 100%, respectively, P = .0007, Fishers exact test, measure of agreement κ = 0.8). However, the thermal determination did not distinguish patients in the suspected malfunction group who received surgery from those who were discharged without surgery (P = .248 by Fishers exact test, κ = 0.20). Half of the patients seen in routine office visits did not have detectable flow, although none required shunt revision on clinical grounds. Intermittent flow was specifically demonstrated in one subject who had multiple flow determinations. CONCLUSION:Operative findings show that the technique is sensitive and specific for detecting flow, but failure to detect flow does not statistically predict the need for surgery. A better understanding of the normal dynamics of flow in individual patients, which this device may yield, will be necessary before the true clinical utility of non-invasive flow measurement can be assessed.

Cervical chordoma in a patient with tuberous sclerosis presenting with shoulder pain.

The patient was taken to the operating room for a C3–C6 laminectomy for biopsy and subtotal debulking. She was fused posteriorly from C3 to C7 using lateral mass screws and rods. The frozen section was non-diagnostic but felt to be consistent with a benign tumor. The fi nal pathologic diagnosis was chordoma. She returned to the operating room for a neck dissection, a C4–C6 corpectomy, gross total resection of tumor, and a fusion with a Synthes SynexTM cage and plate from C3 to C7 ( fi g. 2 ) The postoperative MRI ( fi g. 3 ) showed no evidence of We present the case of a 16-year-old girl with a history of tuberous sclerosis. She had previously undergone a craniotomy to remove a hamartoma for seizures, which were now well controlled. She was admitted to the hospital because of worsening right shoulder pain that had been present for several months. On examination, she had normal strength but had a slight decrease of her right biceps refl ex. MRI scans ( fi g. 1 ) revealed a large mass in the spinal canal that was growing out of several foramina.