Jamshid Ahmadi

Long-Term Administration of Mifepristone (RU486): Clinical Tolerance During Extended Treatment of Meningioma

Background: Mifepristone (RU486) is an oral antiprogestational and, to a lesser extent, antiglucocorticoid agent commonly used for short-term (single-day) therapy. However, treatment of neoplasms or chronic conditions will require long-term administration. Meningioma is a benign central nervous system tumor that is often progesterone-but not estrogen-receptor positive, making long-term antiprogestational therapy a logical treatment strategy. Methods: Patients with unresectable meningioma were treated with oral mifepristone 200 mg/day. This dose was selected to provide significant antiprogestational but not antiglucocorticoid activity. Patients also received oral dexamethasone 1 mg/day for the first 14 days. Serial follow-up allowed evaluation for tolerability and side effects of long-term therapy as well as observation for efficacy (tumor shrinkage or improvement in visual fields). Results: Twenty-eight patients received daily oral mifepristone for a total of 1,626 patient-months of treatment. The median duration of therapy was 35 months (range 2–157 months). Repeated oral administration was well tolerated with mild fatigue (22 patients), hot flashes (13 patients), and gynecomastia/breast tenderness (6 patients) being the most common side effects. However, endometrial hyperplasia or polyps were documented in 3 patients and one patient developed peritoneal adenocarcinoma after 9 years of therapy. Minor responses (improved automated visual field examination or improved CT or MRI scan) were noted in 8 patients, 7 of whom were male or premenopausal female. Conclusions: Long-term administration of mifepristone is feasible and clinically well tolerated, with generally mild toxicity. However, endometrial hyperplasia was noted in several patients. In view of the association between long-term treatment with tamoxifen (another agent that can induce an unopposed estrogen effect) and endometrial cancer, this observation will require further investigation and screening. Minor regression of meningioma that can result in significant clinical benefit is suggested in the male and premenopausal female subgroups of patients.

MR Imaging of Neurocysticercosis

Magnetic resonance (MR) was performed in 50 patients with neurocysticercosis. Comparison was made with other neuroradiological imaging modalities including CT, myelography, CT ventriculography, and CT myelocisternography. Eighteen patients were found to have intraventricular cysts. In several patients, these were multiple and 22 intraventricular cysts were discovered. Although 4 of the 22 ventricular cysts were missed by MR, T1-weighted images can play a significant role in the early detection of intraventricular cysticercosis cysts, showing the cyst wall (9 of 22), a high intensity mural nodule (6 of 22), and increased signal intensity of the cyst fluid (5 of 22). Cisternal cysts (14 cysts in 10 patients) could be identified; they appear similar to intraventricular cysts, but mural nodules are infrequently seen (1 of 14). Twenty-nine patients had 69 parenchymal cysts. An attempt was made to assess the viability of these parenchymal lesions by matching the CT and MR findings with the Escobar pathologic staging system. Neuroimaging findings seemed compatible with early parenchymal lesions in the vesicular stage in 11 instances. Findings in cases with later stage cysts tend to support the concept that a dying larva provokes pronounced inflammatory reaction in the adjacent brain. Computed tomography remains the superior modality for depicting parenchymal calcifications within dead larvae. A case of a spinal cysticercosis cyst demonstrated with MR (in a patient with extensive intracranial cisternal cysts and a fourth ventricular cyst) is described.

MR IMAGING OF PINEAL REGION NEOPLASMS

Twenty-eight patients with tumor of the pineal region underwent magnetic resonance (MR) examination. Gadolinium DTPA was given to 13 patients. Histologic confirmation was obtained in all patients, including 10 germinomas, 4 pineocytomas, 4 pineoblastomas, 5 astrocytomas, 2 teratomas, 1 choriocarcinoma, 1 mixed germ cell tumor, and 1 metastasis from breast carcinoma. Pineal region neoplasms have remarkable heterogeneity in both histopathologic and MR appearances. Gadolinium DTPA enhanced MR increases the specificity of diagnosing pineal region neoplasms. In addition, Gd-DTPA provides better delineation of the tumor margin and demonstrates cystic components of the neoplasm. Our approach to pineal region neoplasms is to make a decision about whether stereotaxic biopsy or surgery should be performed on a certain patient. When a pineal region neoplasm is diagnosed as benign, such as a benign teratoma, on the basis of imaging, surgery is performed to resect the entire lesion. When a definitive diagnosis is not possible, sterotaxic biopsy is performed to obtain histological diagnosis for treatment planning. Gadolinium DTPA enhanced MR plays an extremely important role in target selection in stereotaxic biopsy of pineal region neoplasms and is also useful in the early detection of intracranial seeding. Spinal seeding is demonstrated on MR as well, thus alleviating the need for a contrast myelogram. Finally, Gd-DTPA enhanced MR can be used to monitor the effects of the various treatment modalities employed for pineal region neoplasms.

Imaging of the pituitary and parasellar region

The pituitary is part of a chain of enormous biologic amplification, which is regulated by a small amount of releasing factors in the portal blood from the hypothalamus. The pituitary is a master gland that regulates a number of hormones. A subtle abnormality in the pituitary can cause significant changes in body metabolism. Because the pituitary glands are small structures, high-resolution imaging techniques are required to satisfactorily evaluate the gland. It is imperative for the radiologist to be familiar with the anatomy, physiology, and pathology of the pituitary gland, which provides a solid foundation for accurate interpretation of the imaging studies of the pituitary gland.

Monitoring of Infectious Intracranial Aneurysms by Sequential Computed Tomographic/Magnetic Resonance Imaging Studies

To monitor the course of infectious intracranial aneurysms, repeated cerebral angiography has been recommended every 2 weeks during intravenous antibiotic therapy until the aneurysm has resolved or an operation has been performed. However, serial cerebral angiograms are not without some risk to the patient. We have prospectively studied five patients harboring a total of six infectious intracranial aneurysms by sequential computed tomography (CT) and/or magnetic resonance imaging (MRI) studies. All infectious aneurysms were initially identified by cerebral angiography and were treated with 6 to 8 weeks of intravenous antibiotics. The aneurysm size ranged from 4 to 10 mm. Sequential CT scans and/or MRI studies were obtained at 2- to 3-week intervals to monitor the course of the aneurysms. Three aneurysms enlarged during antibiotic therapy, and one remained unchanged in size. These four aneurysms were treated surgically. The two remaining aneurysms resolved with intravenous antibiotic therapy. Cerebral angiograms were obtained routinely preoperatively and were used to verify the resolution of the infectious aneurysms when they were no longer visible on CT or MRI. On the basis of this prospective study, we conclude that sequential thin-slice CT and/or MRI can effectively and safely monitor the course of infectious intracranial aneurysms once identified by cerebral angiography. This may reduce the need for serial angiography and reduce the ultimate risk in the management of infectious intracranial aneurysms.

MRI of intraventricular cysticercosis : surgical implications

Objective Our goal was to evaluate the role of Gd-enhanced MR in the diagnosis and surgical planning of intraventricular cysticercosis cysts. Materials and Methods Thirty-three patients with intraventricular cysticercosis were evaluated with Gd-enhanced MRI including follow-up studies ranging over time periods from 6 months to 8 years. The patient age ranged from 17 to 65 years. All had lived in Mexico or Central America. Results Twenty patients had surgical removal of the cysts. The majority of patients (18 of 20) who had surgical removal of the cyst showed improvement with resolution of hydrocephalus. Two of 20 patients required additional shunting to alleviate hydrocephalus. In these two patients, Gd-enhanced MR showed cyst wall enhancement. Ependymitis with adhesion was found at surgery in these two patients. Nine patients had shunt placement; one of nine patients showed cyst enlargement 2.5 years later that required surgical removal. Of the remaining eight patients, four showed irregular, thick, ring-like enhancement mimicking a neoplasm on follow-up imaging studies. Four patients with cysts in the lateral ventricle did not require treatment. Two of the four patients showed irregular, thick, ring-like enhancement on follow-up imaging studies. Conclusion Gadolinium-enhanced MR is more sensitive than contrastenhanced CT for detecting ependymitis, which is essential in deciding whether surgical removal of the cyst or shunt placement is indicated. A degenerating intraventricular cysticercosis cyst may present as an irregular, thick, ring-like enhancing lesion or a nodular enhancing lesion with varying degrees of surrounding edema, mimicking a neoplasm.

Evaluation of cerebrospinal fluid rhinorrhea by metrizamide computed tomographic cisternography.

Seven interesting and instructive cases of cerebrospinal fluid rhinorrhea evaluated by metrizamide computed tomographic cisternography are presented. The rhinorrhea was spontaneous in three patients and was related to previous head trauma or surgical procedures in four patients. The anatomical site and the extent of the fistula were demonstrated precisely by directly showing metrizamide passing through the bony defect. A combination of bone dehiscence and metrizamide within the adjacent paranasal sinuses or the nasal cavity is also useful in localization. Distortion of the interhemispheric fissure, sylvian fissure, or basal sulci indicates the probability of brain herniation through the defect.

Double-Blind Phase III Randomized Trial of the Antiprogestin Agent Mifepristone in the Treatment of Unresectable Meningioma: SWOG S9005.

PURPOSE Progesterone receptors are expressed in approximately 70% of meningiomas. Mifepristone is an oral antiprogestational agent reported to have modest activity in a phase II study. This multicenter, prospective, randomized, placebo-controlled phase III trial conducted by SWOG was planned to define the role of mifepristone in the treatment of unresectable meningioma. PATIENTS AND METHODS Eligible patients were randomly assigned to receive either mifepristone or placebo for 2 years unless disease progressed. Patients who were stable or responding to protocol therapy after 2 years had the option to continue with the same blinded therapy. Serial follow-up allowed assessment of efficacy and toxicity. Time to treatment failure and overall survival were ascertained for all randomly assigned patients. On progression, patients receiving placebo could cross over and receive active drug. RESULTS Among 164 eligible patients, 80 were randomly assigned to mifepristone and 84 to placebo. Twenty-four patients (30%) were able to complete 2 years of mifepristone without disease progression, adverse effects, or other reasons for discontinuation. Twenty-eight patients (33%) in the placebo arm completed the 2-year study. There was no statistical difference between the arms in terms of failure-free or overall survival. CONCLUSION Long-term administration of mifepristone was well tolerated but had no impact on patients with unresectable meningioma.

Intracranial Arterial Aneurysms in Childhood: More Recent Considerations:

Nineteen children with congenital, mycotic, traumatic and tumoral arterial aneurysms were studied neuroradiologically. The important role of computed tomography (CT) was shown in two traumatic aneurysm cases where bleeding was clinically inapparent. Among the unique cases described was a boy with a pituitary tumor in whom an aneurysm was discovered incidentally; coexistence of these lesions in childhood has not been documented previously. Nor has a tumoral aneurysm been mentioned (the case reported had a surrounding primary anaplastic sarcoma). Rare cases included a cavernous carotid mycotic aneurysm and infants with hemorrhage from congenital distal middle cerebral artery aneurysms. Marked cellular responses within the aneurysm walls, believed to be a reaction to hemorrhage, were noted in both infants. (J Child Neurol 1986; 1:99-114)

MR imaging of cerebral toxoplasmosis: correlation of computed tomography and pathology

A case of cerebral toxoplasmosis in a patient with acquired immune deficiency syndrome who was evaluated by both CT and magnetic resonance is reported. Magnetic resonance proved to be far more sensitive in detecting the intracranial lesions than CT.