Acetazolamide therapy for symptomatic plateau waves in patients with brain tumors

2002 ◽  
Vol 97 (1) ◽  
pp. 224-226 ◽  
Author(s):  
Christopher J. Watling ◽  
J. Gregory Cairncross
Keyword(s):  
Intracranial Pressure ◽  
Carbonic Anhydrase ◽  
Brain Tumors ◽  
Neurological Disorder ◽  
Malignant Gliomas ◽  
Effective Therapy ◽  
Content Type ◽  
Plateau Waves ◽  
Dexamethasone Therapy ◽  
Fine Print

✓ In this report, the authors describe three patients with malignant gliomas who experienced paroxysmal neurological symptoms triggered by standing. The symptoms were attributed to acute elevations of intracranial pressure, an uncommon phenomenon called “plateau waves.” In each instance, the attacks occurred despite the fact that the patient was receiving dexamethasone therapy and stopped promptly with the addition of acetazolamide. Acetazolamide, an orally administered carbonic anhydrase inhibitor, appears to be a specific and effective therapy for this uncommon neurological disorder.

Uptake of tritiated methotrexate by mouse brain tumors after intravenous or intrathecal administration

1974 ◽  
Vol 40 (6) ◽  
pp. 706-716 ◽  
Author(s):  
Yukitaka Ushio ◽  
Toru Hayakawa ◽  
Heitaro Mogami
Keyword(s):  
Brain Tumors ◽  
Brain Tissue ◽  
Intravenous Injection ◽  
Malignant Gliomas ◽  
Intrathecal Administration ◽  
Drug Dosage ◽  
Content Type ◽  
Radioactive Assay ◽  
The Brain ◽  
Fine Print

✓ Malignant gliomas were induced in strain ddN mice by intracerebral implantation of a 20-methylcholanthrene pellet. The uptake and distribution of tritiated methotrexate (MTX-3H) in the tumor were investigated by radioactive assay and radioautography after single intravenous or intrathecal injections. By either route, a large amount of MTX-3H was taken up by gliomas, and a significantly higher concentration was observed in tumor than in the brain tissue. At 24 hours after intrathecal administration, the uptake of MTX-3H by gliomas exceeded that achieved after intravenous injection, although the drug dosage in the latter was 10 times that in the former.

Camptothecin analogs in malignant gliomas: comparative analysis and characterization

2003 ◽  
Vol 98 (3) ◽  
pp. 570-577 ◽  
Author(s):  
Prakash Sampath ◽  
Eric Amundson ◽  
Monroe E. Wall ◽  
Betty M. Tyler ◽  
Mansukh C. Wani ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Cell Lines ◽  
Topoisomerase I ◽  
Glioma Cell ◽  
Malignant Gliomas ◽  
Sodium Dodecyl ◽  
Local Therapy ◽  
Content Type ◽  
Glioma Cell Lines ◽  
Fine Print

Object. The authors compared and characterized several new classes of camptothecin (CPT) analogs (a total of 22 drugs) directed against human and murine glioma cell lines in vitro, trying to identify CPT analogs that can be used for local therapy in future clinical trials. Camptothecin is a naturally occurring alkaloid that inhibits the DNA-replicating enzyme topoisomerase I. Moreover, CPT and its analogs have shown promising antitumor activity against both systemic and intracranial neoplasms. Because the CPTs have poor bioavailability and are unable to cross the blood—brain barrier, they may best be delivered to the central nervous system by polymers. The authors have previously shown that local delivery of Na-CPT by implantable polymers prolongs survival in a rat intracranial glioma model. In recent years, a number of newly synthesized CPT analogs have been developed that exhibit more potency and stability than Na-CPT. Methods. Cytotoxicities of the drugs were tested using modified clonogenic and monotetrazolium assays in three glioma cell lines. A potassium chloride—sodium dodecyl sulfate coprecipitation assay was used to determine the frequency of drug-stabilized cleavable complexes. Of the CPT analogs analyzed, the 10,11-methylenedioxy (MD) class consistently demonstrated the greatest cytotoxicity. Three of these analogs, 10,11-MD-20(RS)-CPT, 10,11-MD-20(S)-CPT-glycinate ester (Gly).HCl, and 9-amino-10,11-MD-20(S)-CPT-Gly, exhibit significantly greater antiproliferative activities than CPT, Na-CPT, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against all three glioma cell lines. In addition, the 10,11-MD20(RS)-CPT analog induces more cleavable complexes than Na-CPT at every concentration. Conclusions. The increased potency and greater stability of CPT analogs hold promise for more effective local antitumor treatments against malignant intracranial brain tumors. The greater cytotoxicity of 10,11-MD CPTs in comparison with other CPT analogs as well as CPT, BCNU, or Na-CPT, may present an ideal candidate drug class for development against both primary and metastatic brain tumors.

Lack of neural control and reactivity to vasoactive agents in malignant glioma arteries

1991 ◽  
Vol 74 (4) ◽  
pp. 633-635 ◽  
Author(s):  
Jan-Erik Hardebo ◽  
Jan Kåahrström ◽  
Leif G. Salford
Keyword(s):  
Brain Tumors ◽  
Malignant Glioma ◽  
Blood Brain Barrier ◽  
Neural Control ◽  
Malignant Gliomas ◽  
Brain Barrier ◽  
Vasoactive Agents ◽  
Tumor Vessels ◽  
Content Type ◽  
Fine Print

✓ Vessels in malignant brain tumors have a defective blood-brain barrier. It is important to know if tumor vessels respond to vasoactive agents, since systemic administration of vasodilatory agents together with chemotherapy could increase the access of these drugs to the tumor. It was found that arteries in human malignant gliomas have no neural control and are totally nonreactive to various vasoactive agents. The vessels lose their reactivity within 1 to 2 mm outside the visible tumor front.

Postoperative intracranial pressure in patients operated on for cerebral aneurysms following subarachnoid hemorrhage

1981 ◽  
Vol 54 (6) ◽  
pp. 726-732 ◽  
Author(s):  
Andrew H. Kaye ◽  
David Brownbill
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Pressure ◽  
Postoperative Period ◽  
Cerebral Aneurysms ◽  
Anterior Communicating Artery ◽  
Antifibrinolytic Agents ◽  
Content Type ◽  
Plateau Waves ◽  
Arterial Vasospasm ◽  
Fine Print

✓ The postoperative intracranial pressure (ICP) in 36 patients operated on for cerebral aneurysm following subarachnoid hemorrhage was studied. Not only was the baseline ICP significantly lower in patients whose outcome was assessed as “good” as compared with those patients with a worse outcome at 1 month after surgery, but also the height of the plateau waves and B-waves was significantly less in the patients who did well. The baseline ICP and the height of the B-wave formation were unrelated to the position of the aneurysm. Plateau waves were marginally significantly higher in aneurysms of the anterior communicating artery complex. Neither preoperative hypertension nor the use of antifibrinolytic agents made any difference to postoperative ICP. In patients with cerebral arterial vasospasm found preoperatively on the angiograms, the ICP tended to be lower in the postoperative period than in those without spasm.

Hemodynamic characterization of intracranial pressure plateau waves in head-injured patients

1999 ◽  
Vol 91 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Marek Czosnyka ◽  
Piotr Smielewski ◽  
Stefan Piechnik ◽  
Eric A. Schmidt ◽  
Pippa G. Al-Rawi ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Flow Velocity ◽  
Reduced Pressure ◽  
Content Type ◽  
Plateau Waves ◽  
Compensatory Reserve ◽  
Head Injured ◽  
Clinical Consequences ◽  
Injured Patients ◽  
Fine Print

Object. Plateau waves of intracranial pressure (ICP) are often recorded during intensive care monitoring of severely head injured patients. They are traditionally interpreted as meaningful secondary brain insults because of the dramatic decrease in cerebral perfusion pressure (CPP). The aim of this study was to investigate both the hemodynamic profile and the clinical consequences of plateau waves.Methods. One hundred sixty head-injured patients were studied using continuous monitoring of ICP; almost 20% of these patients exhibited plateau waves. In 96 patients arterial pressure, ICP, and transcranial Doppler (TCD) blood flow velocity were studied daily for 20 minutes to 3 hours. Sixteen episodes of plateau waves in eight patients were recorded and analyzed.The dramatic increase in ICP was followed by a profound fall in CPP (by 45%). In contrast, flow velocity fell by only 20%. Autoregulation was documented to be intact both before and after plateau but was disturbed during the wave (p < 0.05). Pressure-volume compensatory reserve was always depleted before the wave. Cerebrovascular resistance decreased during the wave by 60% (p <0.05) and TCD pulsatility increased (p <0.05). Plateau waves did not increase the probability of an unfavorable outcome following injury.Conclusions. The authors have confirmed that the plateau waves are a hemodynamic phenomenon associated with cerebrovascular vasodilation. They are observed in patients with preserved cerebral autoregulation but reduced pressure-volume compensatory reserve.

The integration of metabolic imaging in stereotactic procedures including radiosurgery: a review

2002 ◽  
Vol 97 ◽  
pp. 542-550 ◽  
Author(s):  
Marc Levivier ◽  
David Wikler ◽  
Nicolas Massager ◽  
Philippe David ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Treatment Planning ◽  
Target Volume ◽  
Emission Tomography ◽  
Low Grade ◽  
Content Type ◽  
Positron Emission ◽  
Pet Scanning ◽  
Fine Print

Object. The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS). Methods. Techniques have been developed for the routine use of stereotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography—guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas. Conclusions. Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.

Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non—small cell carcinoma

2002 ◽  
Vol 97 ◽  
pp. 484-488 ◽  
Author(s):  
Toru Serizawa ◽  
Junichi Ono ◽  
Toshihiko Iichi ◽  
Shinji Matsuda ◽  
Makoto Sato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Tumors ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Small Cell ◽  
Metastatic Brain Tumors ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
Significant Difference ◽  
Fine Print

Object. The purpose of this retrospective study was to evaluate the effectiveness of gamma knife radiosurgery (GKS) for the treatment of metastatic brain tumors from lung cancer, with particular reference to small cell lung carcinoma (SCLC) compared with non-SCLC (NSCLC). Methods. Two hundred forty-five consecutive patients meeting the following five criteria were evaluated in this study: 1) no prior brain tumor treatment; 2) 25 or fewer lesions; 3) a maximum of three tumors with a diameter of 20 mm or larger; 4) no surgically inaccessible tumor 30 mm or greater in diameter; and 5) more than 3 months of life expectancy. According to the same treatment protocol, large tumors (≥ 30 mm) were surgically removed and the other small lesions (< 30 mm) were treated with GKS. New lesions were treated with repeated GKS. Chemotherapy was administered, according to the primary physician's protocol, as aggressively as possible. Progression-free, overall, neurological, qualitative, and new lesion—free survival were calculated with the Kaplan—Meier method and were compared in the SCLC and NSCLC groups by using the log-rank test. The poor prognostic factors for each type of survival were also analyzed with the Cox proportional hazard model. Conclusions. Tumor control rate at 1 year was 94.5% in the SCLC group and 98% in the NSCLC group. The median survival time was 9.1 months in the SCLC group and 8.6 months in the NSCLC group. The 1-year survival rates in the SCLC group were 86.5% for neurological survival and 68.9% for qualitative survival; those in the NSCLC group were 87.9% for neurological and 78.9% for qualitative survival. The estimated median interval to emergence of a new lesion was 6.9 months in the SCLC group and 9.8 months in the NSCLC group. There was no significant difference between the two groups for any type of survival; this finding was verified by multivariate analysis. The results of this study suggest that GKS appears to be as effective in treating brain metastases from SCLC as for those from NSCLC.

Does gamma knife surgery stimulate cellular immune response to metastatic brain tumors? A histopathological and immunohistochemical study

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 180-184 ◽  
Author(s):  
György T. Szeifert ◽  
Isabelle Salmon ◽  
Sandrine Rorive ◽  
Nicolas Massager ◽  
Daniel Devriendt ◽  
...  
Keyword(s):  
Immune Response ◽  
Brain Tumors ◽  
Gamma Knife ◽  
Cellular Immune Response ◽  
Lymphocytic Infiltration ◽  
Gamma Knife Surgery ◽  
Metastatic Brain Tumors ◽  
Content Type ◽  
Cellular Immune ◽  
Fine Print

Object. The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS). Methods. Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery. Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration. Conclusions. Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.

Thymidine kinase-mediated killing of rat brain tumors

1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Wild Type ◽  
Cns Disorders ◽  
Content Type ◽  
Potential Applications ◽  
Ganciclovir Treatment ◽  
The Brain ◽  
Fine Print

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

Flushing in relation to a possible rise in intracranial pressure: documentation of an unusual clinical sign

2000 ◽  
Vol 92 (6) ◽  
pp. 1040-1044 ◽  
Author(s):  
Gregory W. Hornig
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Intraventricular Hemorrhage ◽  
Pneumococcal Meningitis ◽  
Clinical Importance ◽  
Neurological Deterioration ◽  
Content Type ◽  
Transient Nature ◽  
Fine Print

✓ This report documents clinical features in five children who developed transient reddening of the skin (epidermal flushing) in association with acute elevations in intracranial pressure (ICP). Four boys and one girl (ages 9–15 years) deteriorated acutely secondary to intracranial hypertension ranging from 30 to 80 mm Hg in the four documented cases. Two patients suffered from ventriculoperitoneal shunt malfunctions, one had diffuse cerebral edema secondary to traumatic brain injury, one was found to have pneumococcal meningitis and hydrocephalus, and one suffered an intraventricular hemorrhage and hydrocephalus intraoperatively. All patients were noted to have developed epidermal flushing involving either the upper chest, face, or arms during their period of neurological deterioration. The response was transient, typically lasting 5 to 15 minutes, and dissipated quickly. The flushing reaction is postulated to be a centrally mediated response to sudden elevations in ICP. Several potential mechanisms are discussed. Flushing has clinical importance because it may indicate significant elevations in ICP when it is associated with neurological deterioration. Because of its transient nature, the importance of epidermal flushing is often unrecognized; its presence confirms the need for urgent treatment.

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