Diagnosis and Treatment of Brain Stem Hemorrhage Caused by Angiographically Occult Vascular Malformation(AOVM)

In cases of symptomatic AOVM of the brainstem, there is a great risk of progressive morbidity caused by repetitive hemorrhage, and the condition can even be fatal. To establish the optimum method of management of this condition, we investigated 15 patients treated between January 1991 and January 1996. Seven lesions were located in the pons, three in the medulla, three in the midbrain, and one each at the pontomedullary and pontomesencephalic junction. Surgery was performed in six cases in which the lesions were close to the dorsal pial surface of the brainstem ; the histological diagnosis was five cases of cavernous angioma and one of arteriovenous malformation. Nine patients with surgically inaccessible lesions, deep seated or located in the midbrain, were treated by gamma knife radiosurgery. All patients who underwent surgery showed neurologic improvement, and among those who underwent radiosurgery, the outcome was favorable. For symptomatic lesions located in the dorsal pial surface of the pons or medulla, surgical resection is the treatment of choice, and prevents further neurological disability and rehemorrhage. For the best possible outcome, intraoperative sonography and electrophysiologic monitoring are mandatory. Gamma knife radiosurgery can be employed in selected cases in which lesions are deep-seated and inaccessible and associated with repeated hemorrhage and progressive neurologic deficit.

Effect of High-Dose Tamoxifen on Malignant Gliomas

In vitro studies have shown that the nonsteroidal antiestrogen tamoxifen can suppress deoxyribonucleic acid(DNA) synthesis and cell proliferation in cultured human gliomas. This growth suppression is independent on its antiestrogenic properties. Tamoxifen may act through the inhibition of the enzyme protein kinase C(PKC), which transduces mitogenic signals from the cell surface to the nucleus. In order to evaluate the therapeutic response and side effect of high-dose tamoxifen, we performed a clinical study of 28 patients with malignant gliomas who were treated with high-dose tamoxifen in our hospital between February 1991 and January 1993. An effect was defined as a statistically improved survival times/rates. In patients who were assigned to receive high-dose tamoxifen, it was first administered at standard antiestrogen doses(20mg orally bid/day) to observe for any side effect and if tolerated, the dose was increased weekly to achieve target doses(100mg orally bid/day) over a 1 month period. We compared the survival times/rates between anaplastic astrocytomas and glioblastoma mutiformes. Although the median survival time was slightly longer in anaplastic astrocytomas than that of glioblastoma multiformes, there was no statistical difference of survival curves between two groups at the p=0.05 level. We also examined the survival times/rates of malignant gliomas according to treatment modalities(radiotherapy alone, radiotherapy plus ACNU, and radiotherapy plus tamoxifen). Although the survival rate and time were slightly higher in radiotherapy plus tamoxifen group than those of another treatment groups, we could not find the statistical significance of survival curves between three treatment groups(p>0.05). High-dose oral tamoxifen appeared to be well tolerated in most patients. Five patients developed anorexia following dose escalation of tamoxifen. Another complications were amenorrhea, nausea/vomiting, and constipation. There were no changes in hematological studies that could be attributed to tamoxifen. We think that high-dose tamoxifen cah be administered safely to malignant gliomas patients. Our results were not impressive. We conclude that the definition of the true efficacy of high-dose tamoxifen in patients harboring malignant gliomas is not possible from this limited study, and a further large scale, randomized trial of this agent is necessary.