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Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. It is characterized by destruction and lymphocytic infiltration of the pituitary gland, probably by an autoimmune process, leading to a pituitary mass lesion and/or various degrees of hypopituitarism. The lesion is usually confined to the adenohypophysis. Posterior pituitary gland or stalk involvement is rare, although patients presenting with diabetes insipidus have been reported. We describe a girl aged 13 years 9 months with lymphocytic hypophysitis who presented with diabetes insipidus and secondary amenorrhea. MRI of the brain revealed a 1 cm enhancing mass in the pituitary stalk. A biopsy of the mass by right pterional craniotomy showed lymphocytic infiltration without neoplastic cells or granuloma formation. To our knowledge, this is the youngest reported patient with a diagnosis of lymphocytic hypophysitis. In this case report, her clinical presentation is discussed along with a review of the literature.We present the first childhood case of lymphocytic hypophysitis which is an autoimmune inflammatory disorder of the pituitary gland. Although this is a rare condition in adults, it also needs to be considered in the pediatric population. Conservative management is preferred unless there are signs of increased intracranial pressure. Most importantly, close monitoring for multiple hormone deficiencies is indicated in this condition.

Low doses of thrombin are neuroprotective while high doses are neurotoxic and lead to brain injury. However, evidence suggests that low doses of thrombin cause brain injury when infused concomitantly with tissue plasminogen activator (tPA), which is used clinically to facilitate evacuation of intracerebral hematomas. In this study, we examined the effects of intracerebral infusion of tPA and thrombin, individually and in combination. Rats were infused in the right basal ganglia with 50 microL saline solutions containing thrombin, tPA, or thrombin + tPA. In the first experiment, rats were used for blood-brain barrier (BBB) permeability measurements at 24 h after infusion. In the second experiment, animals were euthanized 3 days after infusion, and brain sections were stained with Fluoro-Jade to measure neuronal cell death. Behavioral tests were carried out before and after surgery. Infusion of thrombin + tPA markedly increased Evans blue tissue content in ipsilateral brain samples (p0.05). Fluoro-Jade-stained sections from thrombin + tPA group demonstrated significantly higher cell death counts (p0.01). Significant neurological deficit was revealed in thrombin + tPA group in forelimb-placing and corner-turn tests (p0.01). This study shows that tPA potentiates the neurotoxic effects of thrombin and leads to increased BBB permeability, neuronal cell death, and neurological deficit. Our results suggest that using tPA to lyse intracerebral hematomas has potential to produce neuronal cell death and disruption of BBB.

Our previous studies showed that intracerebral infusion of argatroban, a specific thrombin inhibitor, reduces brain edema and neurological deficits in a C6 glioma model. The present study investigated whether systemic argatroban administration can reduce glioma mass and neurological deficits and extend survival time in C6 and F98 gliomas. Rat C6 or F98 glioma cells were infused into the right caudate of adult male Fischer 344 rats. Osmotic minipump loaded with argatroban (0.3 mg/hour) or vehicle was implanted into abdomen immediately after glioma implantation. Tumor mass was determined at day 9. Over the period of the experiment, the animals underwent behavioral testing (forelimb placing and forelimb use asymmetry). In addition, survival time was tested in the F98 glioma model. In C6 glioma, argatroban reduced glioma mass (p0.05) and neurological deficits (p0.05) at day 9. In F98 glioma, agratroban prolonged the survival time (p0.05) and reduced the body weight loss (84 +/- 15 gram vs. 99 +/- 2 gram in the vehicle group, P0.05). In conclusion, systemic use of argatroban reduced tumor mass and neurological deficits, and prolonged survival time. These results suggest that thrombin plays a key role in glioma growth and thrombin inhibition with argatroban may be a novel treatment for gliomas.

Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial tumor formation, multiplicity or to measure growth rates, it is difficult to test compounds for their interventional or preventional capabilities. In this study Fisher-334 rats, treated transplacentally with ENU, underwent magnetic resonance imaging (MRI) examination in order to evaluate this approach for detection of tumor formation and growth. ENU-induced intracranial cerebral tumors were first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 +/- 0.112 months. These tumors were found histologically to be predominately mixed gliomas. Two therapeutic interventions were evaluated using MRI, vitamin A (all-trans retinol palmitate, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month (P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compared to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against the ENU-induced tumor model.

It is our hypothesis that low grade gliomas are the glial counterparts of other precancerous lesions such as colon polyps and, therefore, suitable targets for chemoprevention. Steps in the molecular progression of gliomas have been described, indicating that an accumulation of abnormalities is required for progression to a high grade and interruption of this progression might be possible. An animal model of chemical glial carcinogenesis was used to test this hypothesis. Pregnant rats were injected intravenously with ENU (ethylnitrosourea) on the 18th day of gestation to induce gliomas in the offspring, which were randomized to receive control diet, diet supplemented with vitamin A palmitate, or diet supplemented with N-acetylcysteine. Animals exposed to ENU and receiving a control diet developed brain tumors and had a shortened life expectancy compared with rats unexposed to ENU. The animals treated with NAC showed no statistically significant delay in the time to tumor and no change in the histologic grade of the tumors when compared with animals receiving control diet, but the time to death from any cause of NAC treated animals differed significantly from untreated animals. Animals receiving high dose VA had statistically significantly prolonged time to tumor, survived significantly longer than untreated animals, but had no reduction in the total number of tumors or change in the histologic grade of their tumors. The theoretical basis of these results is likely due to the putative mechanism of action of these agents. These data indicate that glioma chemoprevention is possible and deserves further exploration.

PURPOSE: To determine whether a relationship exists between water diffusion coefficients or diffusion anisotropy and MR-defined regions of normal or abnormal brain parenchyma in patients with cerebral gliomas. METHODS: In 40 patients with cerebral gliomas, diffusion was characterized in a single column of interest using a motion-insensitive spin-echo sequence that was applied sequentially at two gradient strength settings in three orthogonal directions. Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes at 128 points along the column. An average ADC and an index of diffusion anisotropy (IDA = diffusion coefficientmax-min/diffusionmean) was than calculated for any of nine MR-determined regions of interest within the tumor or adjacent parenchyma. RESULTS: In cerebral edema, mean ADC (all ADCs as 10(-7) cm2/s) was 138 +/- 24 (versus 83 +/- 6 for normal white matter) with mean IDA of 0.26 +/- 0.14 (versus 0.45 +/- 0.17 for normal white matter). Solid enhancing central tumor mean ADC was 131 +/- 25 with mean IDA of 0.15 +/- 0.10. Solid enhancing tumor margin mean ADC was 131 +/- 25, with IDA of 0.25 +/- 0.20. Cyst or necrosis mean ADC was 235 +/- 35 with IDA of 0.07 +/- 0.04. CONCLUSION: In cerebral gliomas ADC and IDA determinations provide information not available from routine MR imaging. ADC and IDA determinations allow distinction between normal white matter, areas of necrosis or cyst formation, regions of edema, and solid enhancing tumor. ADCs can be quickly and reliably characterized within a motion-insensitive column of interest with standard MR hardware.

Analysis of intermediate- and long-term results of surgical treatment of metopic synostosis is lacking. We therefore retrospectively studied 23 patients with metopic synostosis (14 males, 9 females) who have been followed from 3 months to 8.1 years (mean 42.5 months) after operation. Age at first operation ranged from 2 to 56 months (mean 8.2 months), with 15 patients operated on before 6 months and 8 after 7 months. Fronto-orbital remodeling and calvarial vault reshaping with floating forehead techniques were carried out in all patients. Stabilization of bony segments was accomplished with microplates and screws in 7 patients (30 percent), wires in 15 (65 percent), and absorbable sutures in 1. Complications included minor wound dehiscence (n = 1), seizures (n = 1), and increased intracranial pressure (n = 1). Postoperative photographic documentation of surgical results was available in 17 of the 23 patients. Aesthetic outcome in these 17 patients was graded (I = none or minor contour irregularities; II = moderate; and III = severe) by one of the authors (Cohen) and by a lay panel (n = 3) according to the degree of residual cranio-orbital deformity. Judged by the surgeon, grade I results were present in 53 percent, grade II in 35 percent, and grade III in 12 percent. To date, total reoperation (reoperative fronto-orbital remodeling and calvarial vault reshaping) was necessary in 2 patients (9 percent), one of whom had signs of increased intracranial pressure 3 years after the original craniofacial procedure, while partial reoperation (temporal cranioplasty) was carried out (n = 2) or recommended (n = 3) in another 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Although myxopapillary ependymomas are generally benign with a tendency for slow growth and local recurrence, they are capable of spread within the nervous system and of extraneural metastasis. Histologic features have not been helpful in determining which patients are at risk for recurrence or dissemination, making management decisions difficult.A retrospective review was conducted of 14 cases of myxopapillary ependymoma. The nucleolar organizing region (NOR) staining method was used to determine if this technique was useful in the management of these tumors.Five patients had total resections of encapsulated lesions, four had total resections of adherent tumors, and four had subtotal resections. Twelve received postoperative radiation therapy. With a mean follow-up of 80 months, 12 patients are well and disease-free. Two patients have had recurrences after surgery and irradiation, leading to death in one and disability in the other. The mean number of NOR per cell in eight specimens ranged from 0.4-1.64. The patient who died with intracranial spread had the highest number of NOR per cell.Based on these data and a review of the literature, it is recommended that radiation be delayed until recurrence in tumors that have been totally resected. Local radiation therapy may be indicated in subtotally resected tumors. NOR staining shows promise in predicting the likelihood of spread of tumor. Patients with myxopapillary ependymomas should be followed indefinitely because of the potential for late recurrence, even after aggressive therapy.

The efficacy and cytotoxic properties of immunotoxin conjugates directed against the transferrin receptor were examined in cell lines and operative specimens from pediatric brain tumors. Dose-response relationships were assessed for immunotoxin-mediated inhibition of protein synthesis for two immunotoxins, 454A12-rRA and anti-tfnR-CRM 107. Three target medulloblastoma cell lines (DAOY, D283MED, and D341MED), a glioblastoma (U373), and a neuroblastoma (SH-SY5Y) cell line exhibited similar sensitivity to both immunotoxins with IC50s in the 10(-9)-10(-10) M range. The time course of protein synthesis inhibition by the immunotoxins in DAOY cells showed that inhibition by anti-tfnR-CRM 107 was rapid and apparent by 6 h of incubation. In contrast, a response to 454A12-rRA was not observed until 16 h. Cell viability was decreased 30-40% by 24 h after removing 454A12-rRA (1 x 10(-9) M) and was maximally decreased 70-80% after 3 days. The efficacy of the immunotoxins on a variety of fresh specimens of pediatric brain tumors was also examined. The more aggressive and malignant tumor types such as glioblastoma multiforme and medulloblastoma had low IC50 values (10(-12) M), indicating that these tumors were extremely sensitive to transferrin receptor-targeted immunotoxins. In general, protein synthesis in slow-growing and benign tumors was not as greatly affected by immunotoxins. Immunoblots showed expression of transferrin receptors on the cell lines and tumors which correlated with in vitro sensitivity to immunotoxin. The results demonstrate that two immunotoxins targeted to the transferrin receptor are efficacious in killing brain tumor cell lines and primary tumor cultures at very low concentrations and that highly malignant tumors are especially sensitive to this cytotoxic response.

Current techniques of diagnosis and treatment allow for earlier detection, precise delineation of the vascular anatomy, and, most important, successful treatment of most patients with spinal AVMs. Magnetic resonance imaging is useful in the initial assessment of patients with progressive myelopathy but cannot replace myelography or arteriography in screening patients who may have a spinal AVM. The most common variety of spinal AVM is a dural arteriovenous fistula. Dural arteriovenous fistulas cause cord injury by producing venous congestion, and symptoms can be reversed by elimination of venous congestion of the spinal cord. Dural arteriovenous fistulas can be treated successfully by interrupting the arteriovenous fistula either in the dura or by disconnecting the dural fistula from the coronal venous plexus in the subarachnoid space. This can be done by interrupting the medullary vein that drains the arterial blood from the dural fistula into the coronal venous plexus of the spinal cord. Stripping of the engorged venous network on the surface of the spinal cord is unwarranted and may cause further cord injury. In dural arteriovenous fistulas embolization is often beneficial in patients with acute neurologic deterioration, to permit time for stabilization and improvement in spinal cord hemodynamics and in cord function before neurosurgical intervention is undertaken. Embolization also may be indicated in patients with intradural spinal AVMs in which surgery cannot be performed safely. Although embolic occlusion does not permanently occlude most intradural AVMs, it often permits stabilization of neurologic function and may be repeated later if neurologic dysfunction returns or progresses. Although the outcome after treatment is dependent on the type and location of the spinal AVM, as in most treatable neurologic disorders the functional outcome of patients with spinal AVMs is directly related to their neurologic condition at the time of treatment. Patients with minimal dysfunction, and with easily accessible AVMs, such as dural arteriovenous fistulas, have the greatest chance for useful recovery or stabilization. Since these patients represent the largest number of patients with spinal AVMs, they must be diagnosed and treated early to achieve the best possible outcome.

Four cases of hemangiopericytoma of the spine are reported. These are rare tumors that arise from the pericytes. Due to their invasive nature and marked vascularity, a detailed radiological work-up including computed tomography and spinal angiography should be obtained before a direct surgical attack is performed. Embolization of the tumor may also be quite helpful before surgical excision and has allowed a gross total removal of the tumor in two of the cases.