Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors.

Gangliogliomas are generally low grade neoplasms composed of mixtures of neoplastic glial and neuronal elements whose origin and exact nature are still controversial. We studied a series of 60 intracranial gangliogliomas looking for coexistent cortical architectural abnormalities (cortical dysplasia, microdysgenesis) and to determine if tumor behavior correlates with MIB1 (marker of cellular proliferation) labeling. The patients included 34 males and 26 females who ranged in age from 6 months to 55 years (mean 20 years). Thirty-eight tumors (63%) were located in the temporal lobe and 6 (10%) in the frontal lobe. Fifty-four patients (90%) presented with seizures (most with intractable epilepsy) and the duration of seizures ranged from 1 to 38 years (mean 14 years). In all cases, the predominant glioma component resembled a low grade fibrillary astrocytoma. In 14 tumors (23%), an oligodendroglial component was present. In one case, the glial component resembled an anaplastic astrocytoma. The tumors were characterized variously by perivascular chronic inflammation (N = 45, 75%), vascular proliferation (N = 36, 60%), granular bodies (N = 54, 90%), binucleated neurons (N = 36, 60%), calcification (N = 28, 47%), and cystic degeneration (N = 26, 43%). Meningeal involvement by tumor was observed in five (8%) cases. In 38 patients, sufficient tissue was resected to evaluate for the presence of concomitant cortical architectural abnormalities. Cortical architectural abnormalities were identified near to but clearly separate from the tumor in 19 (50%) patients. Only four patients including the anaplastic tumor died with tumor progression. MIB1 indices (positive tumor cells/1,000 tumor cells counted) in 54 cases ranged from 0 to 10.2 (mean 1.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemorrhage detected using MR imaging in the setting of acute stroke: an in vivo model.

BACKGROUND AND PURPOSE: The treatment algorithm for acute cerebrovascular accidents has traditionally sorted these accidents as either hemorrhagic or nonhemorrhagic, and MR imaging, with its ability to allow expeditious assessment of vascular substrates and regional blood volume, is well suited for this purpose. Our purpose was to delineate the accuracy of MR imaging in acute, hemorrhagic forms of stroke during the time frame considered beneficial for intervention in an animal model. METHODS: Eighteen dogs with small, iatrogenic parenchymal, subarachnoid hemorrhage (SAH), or both were serially scanned over the initial 6-hour postictal period. Confirmatory pathologic specimens and 3-hour postictal CT scans were obtained in all animals. The MR and CT studies were then interpreted in a blinded fashion by two neuroradiologists for the presence of hemorrhage. The results were subjected to receiver operating characteristic analysis. RESULTS: MR imaging depicted acute parenchymal hemorrhage and SAH with a high degree of accuracy at 1.5 T. This finding was independent of each of the time points studied during the 6-hour window. For SAH, the MR accuracy for reader 1 was 0.86 (95% CI, 0.76-0.97); for reader 2, accuracy was 0.85 (95% CI, 0.71-0.99). The CT accuracy for the two readers was 0.42 (95% CI, 0.26-0.58) and 0.66 95% CI, 0.43-0.89), respectively. Fluid-attenuated inversion-recovery images improved the conspicuity of SAH on MR images and, along with spin-density-weighted spin-echo sequences, helped to establish the hemorrhagic nature. For parenchymal hemorrhage, the MR accuracy for reader 1 was 0.90 (95% CI, 0.81-0.99); for reader 2, accuracy was 0.93 (95% CI, 0.84-1.00). With CT, the accuracy of reader 1 was 0.91 (95% CI, 0.85-0.97) whereas for reader 2 accuracy was 0.76 (95% CI, 0.69-.83). Parenchymal hemorrhage detection and diagnosis was best with T2*-weighted gradient-echo images. CONCLUSION: MR imaging with appropriately selected sequences appears able to provide information regarding the presence (or absence) of hemorrhage in an acute stroke model requisite to the initiation of treatment.

Prevention of chronic cerebral vasospasm in dogs with milrinone.

OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of morbidity and death in patients with aneurysmal subarachnoid hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a powerful inotrope and vasodilator, but it has little effect on heart rate or blood pressure. Because of these properties, milrinone is an attractive potential therapy after subarachnoid hemorrhage. The purpose of the present study was to investigate the effect of milrinone on chronic experimental cerebral vasospasm. METHODS: A double-hemorrhage canine model of vasospasm was used to study the efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were compared in a treatment group of animals that received a loading dose of milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05 microgram/kg/min) milrinone pellets (n = 10) and a control group that received placebo pellets (n = 9), over an 8-day period after the initial subarachnoid hemorrhage. The hemorrhage was created by injection of 4 ml of autologous, nonheparinized, arterial blood into the cisterna magna on Days 1 and 3. Hemodynamic measurements, including cardiac output determinations, were made on Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS: Treatment with milrinone caused no significant changes in systemic hemodynamics. Angiographic vasospasm, however, was significantly reduced in the Day 8 angiograms for the treated group, compared with the control group (98.28 +/- 14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area, respectively; P < 0.001). CONCLUSION: Milrinone is effective in preventing chronic cerebral vasospasm in a canine model of experimental chronic cerebral vasospasm. This effect is independent of changes in systemic hemodynamics. Milrinone and related drugs warrant further investigation for the treatment of cerebral vasospasm.

Surgical management of pediatric tumor-associated epilepsy.

Brain tumors are a common cause of seizures in children. Early surgical treatment can improve seizure outcome, but controversy exists regarding the most appropriate type of surgical intervention. Some studies suggest tumor resection alone is sufficient, while others recommend mapping and resection of the surrounding epileptogenic foci to optimize seizure outcome. To address this issue, we reviewed the charts of 34 pediatric patients aged 18 months to 20 years with medically intractable epilepsy and primary brain tumors. The average age at operation was 12.6 years, and patients had seizures for an average of 6.4 years. The majority of tumors were located in the temporal lobe. Seventeen patients, because of tumor location near an eloquent area, underwent extraoperative mapping using subdural electrode grids prior to definitive tumor resection. Fourteen of these patients had a gross total tumor resection, yet only two had a distinct zone of ictal onset identified and resected. The remaining 17 patients had tumors either in the nondominant hemisphere or far removed from speech-sensitive areas, and therefore did not undergo extraoperative subdural electroencephalograph mapping. Fourteen of these patients also had a gross total tumor resection, while none had intraoperative electrocorticography to guide the resection of additional nontumoral tissue. Overall, of the 28 patients treated with a gross total tumor resection, 24 (86%) are seizure free, while the other four are significantly improved. Of the six patients who had a subtotal tumor removal, five have persistent seizures. The mean follow-up was 3.6 years. We conclude that in children and adolescents, completeness of tumor resection is the most important factor in determining seizure outcome. The routine mapping and resection of epileptogenic foci might not be necessary in the majority of patients. As a corollary, the use of subdural electrode grids in pediatric patients with tumor-associated epilepsy should be limited to cases requiring extraoperative cortical stimulation for localization of nearby eloquent cortex.

Childhood ganglioglioma and medically intractable epilepsy. A clinicopathological study of 15 patients and a review of the literature.

Gangliogliomas are an increasingly recognized cause of epilepsy in children. Several studies have shown that early surgical treatment is beneficial, but controversy exists regarding the type of surgical treatment required for optimal seizure control and to prevent tumor recurrence. To address this issue, we performed a retrospective review of 15 children operated on at the Cleveland Clinic during a 7-year period with medically intractable epilepsy who were found to harbor a ganglioglioma during the course of their work-up. Nine patients with mostly nondominant hemisphere tumors underwent tumor resection without the use of electrocorticography to guide additional resection of epileptogenic foci, while 6 other patients with dominant hemisphere tumors had subdural electrode grids placed to extraoperatively map zones of ictal onset and eloquent areas. The extent of tumor resection was then correlated to seizure outcome and tumor recurrence. Of the 11 patients who received a gross total resection, 9 are seizure-free while 2 have a greater than 90% reduction in their seizure frequency (100% 'good' outcome). There was no tumor recurrence in this group. Of the 4 patients who underwent a subtotal tumor resection, 1 is seizure-free while 3 have persistent seizures (25% 'good' outcome). All patients in this group have stable disease on follow-up magnetic resonance imaging. In those patients who received subdural electrode grids, the extent of resection of the zones of ictal onset did not correlate with seizure outcome. The mean follow-up was 42 months. We conclude that complete tumor resection is the most important factor for optimal seizure control and to prevent tumor recurrence.