1/132. Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies.erythema multiforme major (EMM; stevens-johnson syndrome) is a cutaneous disorder associated with a wide variety of factors including ingestion of drugs such as phenytoin and exposure to intracranial radiation therapy. Based on observations of a 47-year-old black man with brain metastases who developed EMM after combined phenytoin and radiation therapy, we conducted a medline literature search for articles on similar cases from 1966 to the present. Twenty cases were identified that support the hypothesis that EMM is associated with combined phenytoin and radiation therapy. The reaction, or its severity, has no relationship to the phenytoin or radiation therapy dosage, or to the histologic type of brain tumor. Also, EMM has no apparent age or gender predisposition in association with phenytoin-radiation therapy. Thus this is a clinical phenomenon that occurs with unusual frequency in patients with brain tumor who undergo radiation therapy while taking phenytoin. phenytoin and other anticonvulsants such as phenobarbital and carbamazepine induce cytochrome P450 3A and produce oxidative reactive intermediates that may be implicated in hypersensitivity reactions such as EMM. Both carbamazepine and barbiturates have shown cross-sensitivity with phenytoin; furthermore, a case of EMM in a patient receiving carbamazepine and whole brain radiation therapy has been reported. As carbamazepine, valproate, and barbiturates have been associated with EMM, gabapentin may be considered as alternative anticonvulsant therapy when appropriate.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
2/132. stevens-johnson syndrome in patients on phenytoin and cranial radiotherapy.The use of phenytoin as a prophylactic anticonvulsant after brain surgery, particularly for brain tumors, is a common practice, regardless of whether the patient has a previous history of convulsions. This treatment policy assumes that the benefits exceed the risks. Four cases are described of adverse reactions to phenytoin during the concomitant use of cranial radiotherapy. In one patient this proved fatal. There is increasing anecdotal support in the literature for a synergistic effect between phenytoin therapy and cranial radiotherapy that can result in the life-threatening stevens-johnson syndrome. While the association is uncommon, four cases within 24 months in one department suggest that the routine use of postoperative phenytoin as a prophylactic anticonvulsant in the absence of a history of seizures may not be warranted, particularly if the patient is to receive cranial radiotherapy.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
3/132. Cerebral "radiation necrosis": vascular and glial features.Glial and vascular abnormalities in brain, simulating intracranial neoplasia, are described in a patient who received radiation to the pituitary region for treatment of an adenoma, 13 months before death. In addition to the expected changes of cerebral radionecrosis, four interesting features are cited: 1. Diffuse hyperplasia of capillaries in the cerebral cortex with marked endothelial hypertrophy; 2. abundant, large multipolar bizarre cells in the perivascular connective tissues; 3. focal astrocytic proliferation with many cells resembling either Alzheimer type I astrocytes or neoplastic cells, and 4. radiation changes in the non-irradiated brain.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
4/132. dementia following treatment of brain tumors with radiotherapy administered alone or in combination with nitrosourea-based chemotherapy: a clinical and pathological study.A retrospective clinical and pathological study of 4 patients who developed the syndrome of radiation induced dementia was performed. All patients fulfilled the following criteria: (1) a history of supratentorial irradiation; (2) no evidence of symptomatic recurrent tumor; (3) no other cause of progressive cerebral dysfunction and dementia. The clinical picture consisted of a progressive "subcortical" dementia occurring 3-12 months after a course of cerebral radiotherapy. Examination revealed early bilateral corticospinal tract involvement in all patients and dopa-resistant Parkinsonian syndrome in two. On CT scan and MRI of the brain, the main features consisted of progressive enlargement of the ventricles associated with a diffuse hypodensity/hyperintensity of the white matter best seen on T2 weighted images on MRI. The course was progressive over 8-48 months in 3 patients while one patient had stabilization of his condition for about 28 years. Treatment with corticosteroids or shunting did not produce sustained improvement and all patients eventually died. Pathological examination revealed diffuse white matter pallor with sparing of the arcuate fibers in all patients. Despite a common pattern on gross examination, microscopic studies revealed a variety of lesions that took two basic forms: (1) a diffuse axonal and myelin loss in the white matter associated with tissue necrosis, particularly multiple small foci of necrosis disseminated in the white matter which appeared different from the usual "radionecrosis"; (2) diffuse spongiosis of the white matter characterized by the presence of vacuoles that displaced the normally-stained myelin sheets and axons. Despite a rather stereotyped clinical and radiological course, the pathological substratum of radiation-induced dementia is not uniform. Whether the different types of white matter lesions represent the spectrum of a single pathological process or indicate that the pathogenesis of this syndrome is multifactorial with different target cells, remains to be seen.- - - - - - - - - - ranking = 1.25keywords = brain (Clic here for more details about this article) |
5/132. Stereotactic radiosurgery. VI. Posterior displacement of the brainstem facilitates safer high dose radiosurgery for clival chordoma.The current 'best treatment method' for clival chordoma is regarded as radical surgical resection followed by radiation therapy; radiosurgery usually plays a major part in the radiation therapy programme. From primate radiation biology studies and from clinical observations, the brainstem is known to be the most radiosensitive part of the central nervous system. The tolerance of the brainstem to high single radiosurgical doses of radiation is limited (all the more so in programmes such as our own where conventionally fractionated radiotherapy precedes radiosurgery or the patient has relapsed after conventional radiotherapy--as in the patient reported here). In this report we describe the operative displacement of the brainstem posteriorly at time of resection such that the proportion of the prescribed postoperative radiosurgical dose received by the brainstem is greatly reduced (by the order of 50%). The gains perceived to accrue from this technique are quantified from isodosimetric considerations not only in dose sparing to the brainstem, but importantly in that the dose to the clival chordoma may be highly significantly increased without exceeding current accepted tolerance brainstem dose limits. Two patients have received this joint surgical/radiosurgical approach to date; the second case is presented here in detail.- - - - - - - - - - ranking = 2.6382309701235keywords = brain, central nervous system, nervous system (Clic here for more details about this article) |
6/132. Stereotactic radiosurgery. VIII. The classification of postradiation reactions.Postradiation reactions in the CNS are well described and catalogued in the conventional radiotherapy literature; acute, subacute and late CNS reactions are recognized. Tumours predispose to these normal tissue reactions by the oedema and pressure epiphenomena that occur in their environs, and probably by other mechanisms associated with tissue breakdown. That late normal tissue reactions (particularly permanent late sequelae--universally referred to as 'necrosis') occur in the normal nervous system is in the complication list of every radiosurgery centre. This article, for the first time, places postradiosurgery observations within or without the existing classification of reactions, and draws attention to the fact that previous 'radiosurgery risk factor' papers in the literature may be wrong to pool different 'reactions' in the formulation of risk formulae for normal brain damage following single shot radiotherapy. Acute reactions occur in the same manner as described for conventional radiotherapy, being a transient swelling phenomenon that occurs 12-48 h after therapy; they are fully reversible and do not usually augur late problems; routine administration of short duration steroids around the time of radiosurgery may prevent or delay the clinical signs. Subacute reactions occur 3-10 months later (a later time than the subacute reactions following conventionally fractionated radiotherapy), and may prove fully or partially reversible, or progress to permanent sequelae; the difference between these and late sequelae (which tend to be permanent themselves) then becomes blurred. That tumour swelling occurs in the subacute phase and is associated with oedema in the surrounding normal brain is an interesting observation (occurring in extra- and intra axial slow-growing tumours); it denotes tumour damage and has not been encountered in the conventionally-fractionated radiotherapy literature. Tumour shrinkage occurs later, with subsidence of the surrounding oedema, and this phenomenon may therefore be regarded (paradoxically) as a good prognostic sign, a point about which the referring clinician should be made aware. Similarly, contrast enhancement in the tumour perimeter at this time reflects a host reactive response and not tumour activity. Persistent clinical neurological signs and MRI changes (best seen on the T2 weighted sequences) beyond 2 years, indicate late damage or reaction. Usually, this represents scarring or coagulative necrosis without mass effect, but if there is a low signal area with mass effect and considerable surrounding oedema, liquefactive necrosis has occurred and (as in the brachytherapy literature) surgical decompression is very occasionally needed.- - - - - - - - - - ranking = 0.53888499616043keywords = brain, nervous system (Clic here for more details about this article) |
7/132. Enhanced accuracy in differential diagnosis of radiation necrosis by positron emission tomography-magnetic resonance imaging coregistration: technical case report.OBJECTIVE AND IMPORTANCE: To demonstrate the usefulness of positron emission tomography-magnetic resonance imaging (MRI) coregistration for differentiation of radiation necrosis and recurrent tumor in stereotactic planning. CLINICAL PRESENTATION: T1-weighted MRI scans of a 43-year-old woman revealed a contrast-enhancing lesion 4 years after open removal of a recurrent, right parieto-occipital Grade II oligodendroglioma and subsequent external radiation therapy. The suspected contrast-enhancing lesion revealed only moderate tracer uptake (1.3 times the uptake in the contralateral normal cortex) in a coregistered [11C]methionine positron emission tomographic scan. Approximately 15 mm posterior and mesial to the center of the contrast-enhancing lesion, however, an area of higher tracer uptake was found (1.8 times that of the contralateral normal cortex), which exhibited only very minor contrast enhancement on MRI. TECHNIQUE: The coregistered images were used for planning stereotactic serial biopsies, from the contrast-enhancing lesion as well as from the area with higher methionine uptake. Histological examination demonstrated that the contrast-enhancing lesion with low methionine uptake was necrotic tissue, and the nonenhancing area with high methionine uptake was recurrent tumor. CONCLUSION: High-resolution positron emission tomography and modern coregistration techniques allow differentiation of contrast enhancement and methionine uptake in irradiated brain tissue within small areas. High methionine uptake is typical for recurrent tumor tissue and can be differentiated from minor tracer accumulation resulting from disruption of the blood-brain barrier or macrophage activity within the necrotic area.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
8/132. radiation-induced blood-brain barrier damage in astrocytoma: relation to elevated gelatinase B and urokinase.Successful management of brain tumors prolongs life, raising the risk of delayed injury secondary to the treatment. radiation therapy, a mainstay of brain tumor treatment, can damage the cerebral blood vessels. Acutely a breakdown of the blood-brain barrier (BBB) may be seen, but fibrosis complicates radiation injury in the chronic phase. matrix metalloproteinases (MMPs) and plasminogen activators are two matrix-degrading proteolytic enzymes, which are induced by radiation. They disrupt the basal lamina around cerebral capillaries and open the BBB. We report a patient with an astrocytoma managed by partial resection and external beam irradiation to maximal tolerable doses. The patient later developed malignant brain edema shortly after stereotactic radiosurgery. Tissue obtained during surgical debulking to control the edema showed very high levels of gelatinase B (92 kDa type IV collagenase) and urokinase-type plasminogen activator (uPA). Tumor cells were absent from the biopsy and subsequent autopsy specimens, but necrosis with fibrosis of the blood vessels was seen. If abnormal matrix enzyme function participates in the expression of radiation injury, then inhibitors to such enzymes may provide one strategy for controlling cerebrovascular damage after therapeutic brain radiation.- - - - - - - - - - ranking = 2.25keywords = brain (Clic here for more details about this article) |
9/132. Enhanced in vitro radiosensitivity of skin fibroblasts in two patients developing brain necrosis following AVM radiosurgery: a new risk factor with potential for a predictive assay.PURPOSE: radiosurgery is an effective treatment for arteriovenous malformations (AVM) with a low risk of developing brain necrosis. Models have been developed to predict the risk of complications. We postulated that genetic differences in radiosensitivity may also be a risk factor. methods AND MATERIALS: Fibroblast cultures were established from skin biopsies in two AVM patients developing radiation necrosis. The results of clonogenic survival assays were compared to a parallel study with two groups of cancer patients treated with radiation: 1) patients without late side effects; 2) patients experiencing severe late sequelae. RESULTS: The survival fraction at 2 Gy (SF2) of the 2 AVM patients was 0.17 (0.14-0.19) and 0.18 (0.14-0.22). The SF2's of the cancer patients ranged between 0.25-0.38 (mean = 0.31) for the control group, and between 0. 10-0.20 (mean = 0.17) for the hypersensitive group. The SF2's of the AVM patients who developed brain necrosis were comparable to that of the hypersensitive group (p = 0.85) but significantly lower than the control group (p = 0.05). CONCLUSION: The two patients who developed radiation necrosis demonstrate increased fibroblast radiosensitivity. The SF2 of skin fibroblasts may potentially be used as a predictive assay to detect patients at risk for brain necrosis.- - - - - - - - - - ranking = 1.75keywords = brain (Clic here for more details about this article) |
10/132. Functional magnetic resonance image-guided surgery of tumors in or near the primary visual cortex.OBJECTIVE: To assess the accuracy of functional magnetic resonance imaging (fMRI) of the primary visual cortex in patients undergoing surgery for tumors in the occipital lobe. methods: Two patients with nondominant occipital lobe tumors were studied, one with a solitary lung metastasis and another with radiation necrosis after radiosurgery for a low-grade astrocytoma. At surgery, visual evoked potentials (VEPs) were stimulated using light-emitting-diode goggles and recorded using cortical grids placed immediately after brain exposure. The location of the peak VEP was compared to that predicted by the registered functional scan. RESULTS: In each case, the epicenter of visual activation as represented on the registered fMRI corresponded to the site of peak VEP recording. Prediction error for the visual cortex, measured in patient 1, was 1.0 mm. Visual confirmation showed the registration in the second patient to be accurate as well. CONCLUSION: As previously demonstrated for sensorimotor fMRI, visual fMRI accurately predicts the location of the primary visual cortex. Additional confirmation is expected with more clinical experience.- - - - - - - - - - ranking = 0.25keywords = brain (Clic here for more details about this article) |
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