RESUMO
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 (p < 0.05). Fluoro-Jade-stained sections from thrombin + tPA group demonstrated significantly higher cell death counts (p < 0.01). Significant neurological deficit was revealed in thrombin + tPA group in forelimb-placing and corner-turn tests (p < 0.01). 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.
Assuntos
Lesões Encefálicas/induzido quimicamente , Doenças do Sistema Nervoso/etiologia , Trombina , Ativador de Plasminogênio Tecidual , Animais , Gânglios da Base/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Contagem de Células , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Azul Evans , Fluoresceínas , Masculino , Exame Neurológico , Compostos Orgânicos , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Neoplasias Encefálicas/patologia , Imunotoxinas/farmacologia , Receptores da Transferrina/imunologia , Ricina/farmacologia , Neoplasias Encefálicas/terapia , Sobrevivência Celular/efeitos dos fármacos , Criança , Glioma/patologia , Glioma/terapia , Humanos , Imunotoxinas/uso terapêutico , Meduloblastoma/patologia , Meduloblastoma/terapia , Proteínas de Neoplasias/biossíntese , Neuroblastoma/patologia , Neuroblastoma/terapia , Receptores da Transferrina/análise , Ricina/uso terapêutico , Células Tumorais CultivadasRESUMO
Immunotoxins have been suggested as possible therapeutic agents in patients with leptomeningeal carcinomatosis. The pharmacokinetics, stability, and toxicity of immunotoxins injected into the i.t. space were examined in rats and rhesus monkeys. Monoclonal antibodies specific for the human (454A12 and J1) and rat (OX26) transferrin receptors were coupled to recombinant ricin A chain. In monkeys, the maximally tolerated dose of the anti-human transferrin receptor immunotoxin (454A12-rRA) was a dose that yielded a nominal cerebrospinal fluid (CSF) concentration of approximately 1.2 x 10(-7) M. In rats, the 10% lethal dose (LD10) of the anti-human transferrin receptor immunotoxin was a dose yielding a nominal CSF concentration of 8.8 x 10(-7) M whereas the LD10 of the anti-rat transferrin receptor immunotoxin (OX26-rRA) was a dose yielding a nominal CSF concentration of 1.2 x 10(-7) M. Thus, the species-relevant antibody resulted in toxicity at a concentration one-seventh that of the immunotoxin with the irrelevant antibody. A comparison of the area under the concentration curve at the LD10 for rats with the area under the concentration curve at the maximally tolerated dose in monkeys and humans shows that the species-relevant immunotoxin was a better predictor of the toxic dose of the anti-transferrin receptor immunotoxin in humans than the irrelevant immunotoxin. The pharmacokinetics of the 454A12-rRA immunotoxin within the CSF of monkeys showed a biphasic clearance with an early-phase half-life of 1.4 h and a late phase half-life of 10.9 h. The clearance was 4.4 ml/h or approximately twice the estimated clearance due to bulk flow of CSF. Loss by degradation was ruled out because immunoblot analysis showed that the immunotoxin was stable for up to 24 h after administration. Possible losses in addition to sampling include diffusion into brain tissue and transcapillary permeation. The apparent volume of distribution was 10.1 ml or approximately three-fourths the total CSF volume of the monkey. Dose limiting toxicity corresponded with the selective elimination of Purkinje cells in both rats and monkeys and was manifested clinically as ataxia and lack of coordination. The onset of ataxia in monkeys occurred within 5 days and, in the more mild form, was reversible with time. There was evidence of only minimal inflammation within the CSF, and there were no signs of systemic toxicity. Immunotoxins injected into the subarachnoid space may have potential for treatment of leptomeningeal carcinomatosis.
Assuntos
Receptores da Transferrina/imunologia , Ricina/líquido cefalorraquidiano , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/líquido cefalorraquidiano , Ataxia/induzido quimicamente , Meia-Vida , Injeções Espinhais , Macaca fascicularis , Macaca mulatta , Ratos , Ratos Sprague-Dawley , Ricina/administração & dosagem , Ricina/efeitos adversos , Especificidade da EspécieRESUMO
PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% +/- 4% at 3 years and 79% +/- 7% at 5 years. Sites of relapse for the 14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma.
Assuntos
Neoplasias Cerebelares/radioterapia , Irradiação Craniana/métodos , Meduloblastoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Irradiação Craniana/efeitos adversos , Intervalo Livre de Doença , Humanos , Lomustina/administração & dosagem , Meduloblastoma/tratamento farmacológico , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Estadiamento de Neoplasias , Doses de Radiação , Taxa de Sobrevida , Estados Unidos/epidemiologia , Vincristina/administração & dosagemRESUMO
BACKGROUND: In a previous study we found that intracerebral infusion of argatroban, a specific thrombin inhibitor, reduces brain edema and neurologic deficits in a C6 glioma model. OBJECTIVES: To examine the role of thrombin in gliomas and whether systemic argatroban administration can reduce glioma mass and neurologic deficits and extend survival time in C6 and F98 gliomas. METHODS: The presence of thrombin in human glioblastoma samples and rat C6 glioma cells (in vitro and in vivo) was assessed using immunohistochemistry. The effect of thrombin on C6 cell proliferation in vitro was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The role of thrombin in vivo was assessed in rat C6 and F98 glioma cell models using argatroban, a thrombin inhibitor. The effects of argatroban on tumor mass, neurologic deficits and survival time were investigated. RESULTS: Thrombin immunoreactivity was found in cultured rat C6 glioma cells and human glioblastomas. Thrombin induced C6 cell proliferation in vitro. In C6 glioma, argatroban reduced glioma mass (P < 0.05) and neurologic deficits (P < 0.05) at day 9. In F98 glioma, argatroban prolonged survival time (P < 0.05). CONCLUSION: These results suggest that thrombin plays an important role in glioma growth. Thrombin may be a new therapeutic target for gliomas.
Assuntos
Glioma/etiologia , Trombina/fisiologia , Animais , Arginina/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Glioma/química , Glioma/patologia , Humanos , Masculino , Atividade Motora/efeitos dos fármacos , Ácidos Pipecólicos/administração & dosagem , Ácidos Pipecólicos/farmacologia , Ratos , Ratos Endogâmicos F344 , Sulfonamidas , Taxa de Sobrevida , Trombina/análise , Trombina/antagonistas & inibidores , Carga Tumoral/efeitos dos fármacosRESUMO
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 (p < 0.05) and neurological deficits (p < 0.05) at day 9. In F98 glioma, agratroban prolonged the survival time (p < 0.05) and reduced the body weight loss (84 +/- 15 gram vs. 99 +/- 2 gram in the vehicle group, P < 0.05). 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.
Assuntos
Edema Encefálico/prevenção & controle , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Transtornos Mentais/prevenção & controle , Ácidos Pipecólicos/administração & dosagem , Animais , Anticoagulantes/administração & dosagem , Antineoplásicos/administração & dosagem , Arginina/análogos & derivados , Encéfalo/efeitos dos fármacos , Edema Encefálico/etiologia , Neoplasias Encefálicas/complicações , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glioma/complicações , Injeções Intraventriculares , Masculino , Transtornos Mentais/etiologia , Ratos , Ratos Endogâmicos F344 , Sulfonamidas , Taxa de Sobrevida , Resultado do TratamentoRESUMO
In three cases of desmoplastic medulloblastoma, MR findings were varied. We report the unusual appearance of this tumor in two children and one adult.
Assuntos
Neoplasias Cerebelares/diagnóstico , Imageamento por Ressonância Magnética , Meduloblastoma/diagnóstico , Adulto , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Cerebelo/patologia , Cerebelo/cirurgia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Meduloblastoma/patologia , Meduloblastoma/cirurgiaRESUMO
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.
Assuntos
Água Corporal/metabolismo , Neoplasias Encefálicas/diagnóstico , Encéfalo/metabolismo , Glioma/diagnóstico , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Anisotropia , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Criança , Pré-Escolar , Difusão , Glioma/metabolismo , Humanos , Pessoa de Meia-IdadeRESUMO
Having encountered a number of thick-walled or mobile symptomatic intracranial cysts that have resisted stereotactic puncture with standard blunt-ended ventricular catheters, the authors have designed a cyst puncture catheter that has a number of features helpful in overcoming this problem. The catheter and its use are described, and examples of difficult-to-puncture cysts are given.
Assuntos
Encefalopatias/cirurgia , Cateteres de Demora , Cistos/cirurgia , Punções/instrumentação , Elastômeros de Silicone , Encefalopatias/diagnóstico por imagem , Cistos/diagnóstico por imagem , Desenho de Equipamento , Humanos , Técnicas Estereotáxicas/instrumentação , Tomografia Computadorizada por Raios XRESUMO
Isolated segments from the feeding arteries to arteriovenous malformations (AVMs) from 24 patients were studied in vitro. In a perfusion chamber, isometric contraction of these arterial rings to various vasoactive substances was recorded and correlated with the following: spontaneous activity, spasm as seen in the operating room; radiographic evidence of ectasia preoperatively and postoperatively; and postoperative course. Of the 24 patients studied, four patients had nonreactive AVM nutrient vessels upon in vitro testing. In addition, these vessel segments displayed no spontaneous activity although all of the other vessels tested developed spontaneous activity while in the perfusion chamber. The patients with "unreactive vessels" had an increased incidence of postoperative edema and hemorrhage in the surrounding brain, consistent with the symptoms of normal perfusion pressure breakthrough. Thus, our study utilizes an in vitro technique to evaluate a specific segment of the AVM complex, the feeding vessel, which permitted us to assess abnormalities of reactivity in these vessel segments. This method may be useful for future evaluations of the pathophysiology of AVMs.
Assuntos
Artérias Cerebrais/fisiopatologia , Malformações Arteriovenosas Intracranianas/fisiopatologia , Animais , Artérias Cerebrais/efeitos dos fármacos , Cães , Feminino , Humanos , Técnicas In Vitro , Masculino , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: We report our experience with a previously undescribed method of myelomeningocele closure, which is the use of bilateral lumbar periosteal flaps as an additional tissue layer in complex cases. These flaps reinforce the dural repair, act to protect the spinal cord, and may help to contain any potential cerebrospinal fluid leak from the primary repair of the cord, thereby preventing pseudomeningocele formation. METHODS: The repair involves the development of bilateral thoracolumbar fascial flaps in conjunction with periosteal flaps, which are elevated from adjacent lumbar pedicles and transverse processes, thus forming a composite tissue flap. These periosteally based flaps may be closed in a "pants over vest" fashion to completely cover the spinal defect, reinforcing the neurosurgical repair. The flap anatomy and dissection are detailed. RESULTS: Two representative cases in which the lumbar periosteal turnover flap procedure was used are reported. One patient was operated on during the early neonatal period for primary myelomeningocele repair; the other was operated on at age 5 years after a tethered cord release. Durable, stable soft tissue coverage of the spinal cord was obtained in both patients, with a postoperative follow-up period of at least 12 months. There was no recurrence of the pseudomeningocele noted preoperatively in the second patient. CONCLUSION: The lumbar periosteal turnover flap may be used to reinforce tenuous spinal cord and dural repairs in the myelomeningocele patient. This method provides a secure and watertight closure over the primary repair of the cord, may help to contain potential cerebrospinal fluid leaks, and adds an additional autologous tissue layer to standard skin or muscle flap repairs.
Assuntos
Meningomielocele/cirurgia , Retalhos Cirúrgicos/métodos , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Exame Neurológico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Espinha Bífida Oculta/cirurgia , Técnicas de SuturaRESUMO
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, and 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.
Assuntos
Hemangiopericitoma/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Angiografia , Criança , Embolização Terapêutica , Feminino , Hemangiopericitoma/irrigação sanguínea , Hemangiopericitoma/diagnóstico por imagem , Humanos , Masculino , Mielografia , Recidiva Local de Neoplasia/cirurgia , Compressão da Medula Espinal/diagnóstico por imagem , Neoplasias da Coluna Vertebral/irrigação sanguínea , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The goals of this clinical trial of intraventricular 454A12-rRA therapy were to identify dose-limiting toxicities, to evaluate the pharmacokinetics of single-dose intraventricular 454A12-rRA, and to detect antitumor activity. METHODS: We performed a pilot study of intraventricular therapy with the immunotoxin 454A12-rRA in eight patients with leptomeningeal spread of systemic neoplasia. The immunotoxin 454A12-rRA is a conjugate of a monoclonal antibody against the human transferrin receptor and recombinant ricin A chain, the enzymatically active subunit of the protein toxin ricin. Patients were treated with single doses of 454A12-rRA ranging from 1.2 to 1200 micrograms. RESULTS: The early phase half-life of 454A12-rRA in ventricular cerebrospinal fluid (CSF) averaged 44 +/- 21 minutes, and the late phase half-life averaged 237 +/- 86 minutes. The clearance of the immunotoxin was faster than the clearance of coinjected technetium-99m-diethylenetriamine penta-acetic acid, averaging approximately 2.4-fold greater. No 454A12-rRA degradation was detected by Western blot analysis of ventricular CSF for a period of 24 hours, and bioactivity was retained in CSF paralleling the concentration of immunotoxin. No acute or chronic drug toxicity was identified in patients who received less than or equal to 38 micrograms of 454A12-rRA by intraventricular injection. Doses more than or equal to 120 micrograms caused a CSF inflammatory response that was associated with transient headache, vomiting, and altered mental status. This acute syndrome was responsive to steroids and CSF drainage. No systemic toxicity was detected. In four of the eight patients, a greater than 50% reduction of tumor cell counts in the lumbar CSF occurred within 5 to 7 days after the intraventricular dose of 454A12-rRA; however, no patient had their CSF cleared of tumor, and clinical or magnetic resonance imaging evidence of tumor progression was demonstrated in seven of the eight patients after treatment. CONCLUSION: Tumoricidal concentrations of the immunotoxin 454A12-rRA can be attained safely in the CSF of patients with leptomeningeal tumor spread.
Assuntos
Imunotoxinas/farmacocinética , Imunotoxinas/uso terapêutico , Neoplasias Meníngeas/tratamento farmacológico , Ricina/uso terapêutico , Neoplasias da Medula Espinal/tratamento farmacológico , Adulto , Idoso , Animais , Anticorpos Monoclonais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ventrículos Cerebrais , Feminino , Meia-Vida , Humanos , Imunotoxinas/administração & dosagem , Infusões Parenterais , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/secundário , Taxa de Depuração Metabólica , Camundongos , Pessoa de Meia-Idade , Projetos Piloto , Receptores da Transferrina/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Ricina/administração & dosagem , Ricina/farmacocinética , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/secundário , Pentetato de Tecnécio Tc 99mRESUMO
The mechanisms previously proposed for the progression of syringomyelia associated with Chiari I malformation of the cerebellar tonsils are controversial, leave many clinical observations unexplained, and underlie the prevalence of different operations currently used as initial treatment. To explore the mechanism of syringomyelia progression in this setting, the authors used anatomical and dynamic (phase-contrast and phase-contrast cine) magnetic resonance (MR) imaging, and intraoperative ultrasonography to examine the anatomy and dynamics of movement of the cerebellar tonsils, the wall of the spinal cord surrounding the syrinx, and the movement of cerebrospinal fluid (CSF) and syrinx fluid at rest, during the respiratory and cardiac cycles, and during Valsalva maneuver in seven affected patients. In all patients the cerebellar tonsils occluded the subarachnoid space at the level of the foramen magnum. Syringomyelia extended from the cervical to the lower thoracic segment of the spinal cord. No patient had evidence of a patent communication between the fourth ventricle and the syrinx on anatomical MR images, dynamic MR images, or intraoperative ultrasound studies. Dynamic MR images of three patients revealed abrupt downward movement of the spinal CSF and the syrinx fluid during systole and upward movement during diastole, but limited movement of CSF across the foramen magnum during the cardiac cycle. Intraoperative ultrasound studies demonstrated abrupt downward movement of the cerebellar tonsils during systole that was synchronous with sudden constriction of the spinal cord and syrinx. Decompression of the foramen magnum was achieved via suboccipital craniectomy, laminectomy of C-1 and C-2, and dural grafting, leaving the arachnoid intact. Immediately after surgery, the pulsatile downward thrust of the tonsils and constriction of the spinal cord and syrinx disappeared. Syringomyelia resolved within 1 to 6 months after surgery in all patients. Observations by the authors suggest the following previously unrecognized mechanism for progression of syringomyelia associated with occlusion of the subarachnoid space at the foramen magnum. The brain expands as it fills with blood during systole, imparting a systolic pressure wave to the intracranial CSF that is accommodated in normal subjects by sudden movement of CSF from the basal cisterns to the upper portion of the spinal canal. With obstruction to rapid movement of CSF at the foramen magnum, the cerebellar tonsils, which plug the subarachnoid space posteriorly, move downward with each systolic pulse, acting as a piston on the partially isolated spinal CSF and producing a systolic pressure wave in the spinal CSF that acts on the surface of the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Malformação de Arnold-Chiari/complicações , Siringomielia/etiologia , Adolescente , Adulto , Criança , Humanos , Período Intraoperatório , Imageamento por Ressonância Magnética , Cuidados Pré-Operatórios , Siringomielia/líquido cefalorraquidiano , Siringomielia/diagnóstico , Siringomielia/cirurgia , Resultado do TratamentoRESUMO
Although proliferative arteriopathy has been postulated to play a role in the etiology of vasospasm after subarachnoid hemorrhage (SAH), histological and morphological studies examining cerebral vasospasm have produced conflicting results. To help settle this controversy, the authors used an in vivo label of cell division, bromodeoxycytidine, to assess cell proliferation in a primate model of SAH. Fifteen cynomolgus monkeys received a clot of either whole blood (11 animals) or red blood cells (four animals) placed around the right middle cerebral artery (MCA). On the day of surgery continuous intravenous infusion of bromodeoxycytidine was begun and continued until the animal was sacrificed immediately after arteriography on Day 7, 12, or 27 following surgery. Sections from the right and left MCA's were stained with a monoclonal antibody against bromodeoxcytidine, and labeled cells were counted. Arteriographic evidence of vasospasm occurred in nine monkeys on Day 7. On Day 12 and Day 27 no monkeys had persistent vasospasm. Placement of subarachnoid clot around the right MCA increased proliferative activity across all layers of the arterial wall. Most of the labeled cells were in the adventitia and the endothelium. Although there were more dividing cells in all layers of the right MCA than the left MCA (p < 0.01), the number of stained cells per section was limited (range 0.1 to 21.2, mean 8) and the occurrence of vasospasm was not associated with the number of dividing cells in the right MCA on Day 7, 12, 27, or for all days combined (p > 0.6). Cerebral vasospasm after SAH was not associated with the extent of proliferation of cells in the vessel wall, nor could the intensity of the limited proliferative changes have been responsible for narrowing of the vessel diameter.
Assuntos
Artérias Cerebrais/patologia , Ataque Isquêmico Transitório/patologia , Animais , Bromodesoxicitidina , Divisão Celular , Angiografia Cerebral , Endotélio Vascular/patologia , Feminino , Imuno-Histoquímica , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/etiologia , Macaca fascicularis , Masculino , Músculo Liso Vascular/patologia , Hemorragia Subaracnóidea/complicaçõesRESUMO
Four patients who developed increased intracranial pressure from ventricular shunt failure suffered a delay in diagnosis because magnetic resonance imaging of the brain did not show ventriculomegaly and because ophthalmic findings were initially overlooked or misinterpreted. None of the patients had the conventional manifestations of shunt failure: severe headache, nausea, vomiting, and depressed consciousness. Three patients suffered marked, permanent vision loss from chronic papilledema. These cases affirm that increased intracranial pressure may occur in shunt dependency without producing either conventional clinical symptoms or signs on imaging of the brain. Because ophthalmic manifestations may be the major clues to diagnosis, and because irreversible loss of vision is possible if these clues are overlooked, consideration should be given to periodic ophthalmological examination of shunt-dependent patients.
Assuntos
Ventrículos Cerebrais/patologia , Papiledema/etiologia , Derivação Ventriculoperitoneal/efeitos adversos , Transtornos da Visão/etiologia , Adolescente , Adulto , Ventriculografia Cerebral , Criança , Doença Crônica , Diagnóstico Diferencial , Feminino , Cefaleia/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Hipertensão Ocular/etiologia , Atrofia Óptica/etiologia , Tomografia Computadorizada por Raios X , Acuidade Visual , Campos VisuaisRESUMO
The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p less than 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH.
Assuntos
Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/líquido cefalorraquidiano , Neuropeptídeo Y/sangue , Neuropeptídeo Y/líquido cefalorraquidiano , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Análise de Variância , Animais , Angiografia Cerebral , Modelos Animais de Doenças , Feminino , Ataque Isquêmico Transitório/etiologia , Macaca fascicularis , Masculino , Radioimunoensaio , Hemorragia Subaracnóidea/complicaçõesRESUMO
Pituitary adenomas represent the only true adenomas of the cranial cavity. In 1000 asymptomatic pituitary glands examined at autopsy, there was a 22.4 per cent incidence of undetected microadenomas. Advances in diagnostic endocrinology, in radiologic imaging, and in surgical and medical treatments have brought many more patients to the attention of the authors. Over the last 10 years, their treatment approaches have evolved to those presented in this article.
Assuntos
Adenoma/terapia , Neoplasias Hipofisárias/terapia , Acromegalia/terapia , Bromocriptina/uso terapêutico , Síndrome de Cushing/terapia , Humanos , Síndrome de Nelson/terapia , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/metabolismo , Prolactina/metabolismoRESUMO
We report a unique case of histologically confirmed meningeal fibrosis in a child who had progressive ischemic neurologic symptoms before the delayed diagnosis of an intracranial primitive neuroectodermal tumor (PNET) was made > 1 year after initial presentation. This pathology has previously been described after neurosurgical procedures, subarachnoid hemorrhage, cranial irradiation, and with no known etiology, but has never been reported in association with a central nervous system neoplasm. In a 6-year-old boy with headaches of several months' duration MRI demonstrated hydrocephalus, a right cerebellopontine angle cyst, and dural enhancement. Biopsies of the thickened meninges taken when the cyst was surgically fenestrated demonstrated only fibrosis with no evidence of infection, hemorrhage, or neoplasm. In the next 6 months, the child had two acute stroke-like episodes with alternating hemiparesis that gradually improved. There were ischemic changes in the diencephalon on MRI. Repeat dural biopsies were unchanged. One year after the initial operation, a left hemiparesis recurred and MRI demonstrated multiple intracranial masses in the cerebral cortex, cerebellum, suprasellar area, and cauda equina. After surgical resection, the cortical mass was found to be a PNET. All the lesions regressed after treatment with radiation and chemotherapy. We hypothesize that the meningeal fibrosis represented a "desmoplastic" reaction to an occult PNET, similar to the fibrous proliferation with cerebellar desmoplastic medulloblastoma except for the extent of the meningeal involvement and the long undetected parenchymal tumor. The mechanism of the ischemic brain injury was most likely vascular involvement by the fibrotic process, either directly or by predisposition to vasoconstriction.
Assuntos
Neoplasias Encefálicas/diagnóstico , Meninges/patologia , Tumores Neuroectodérmicos Primitivos/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Córtex Cerebral/patologia , Córtex Cerebral/cirurgia , Criança , Terapia Combinada , Diagnóstico Diferencial , Fibrose , Humanos , Imageamento por Ressonância Magnética , Masculino , Tumores Neuroectodérmicos Primitivos/patologia , Tumores Neuroectodérmicos Primitivos/cirurgia , Síndromes Paraneoplásicas/patologia , Síndromes Paraneoplásicas/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: Selective dorsal rhizotomy (SDR) is associated with moderale to severe postoperative pain. Although the efficacy of epidural analgesia in this population has been demonstrated, it has not been compared with conventional intravenous (i.v.) analgesia. This prospective study compared the effects of epidural and i.v. morphine regarding postoperative analgesia, side effects, and outcomes in children following SDR. METHODS: Twenty-seven children were randomized to receive either epidural or i.v. analgesia. Children in the epidural group had a catheter placed by the neurosurgeon and received preservative-free morphine (Duramorph) 30 microg/kg, followed by an infusion of 3 microg/kg/h for 3 days. Children in the i.v. group received morphine 0.05-0.1 mg/kg intraoperatively, followed by 0.02 mg/kg doses postoperatively administered by nurses via a patient-controlled analgesia device. RESULTS: The epidural group experienced lower pain scores (P = .04) and fewer muscle spasms (P < or = .04), and tolerated activity better (P < or = .02) during the early postoperative period than the i.v. group. Side effects were similar between groups, with no respiratory depression in either group. Parents of children in both groups perceived an adequate level of comfort and were very satisfied with the analgesic technique. Additionally, parents believed that their child's postoperative pain was less than anticipated (P < or = .01). CONCLUSIONS: Both techniques provided effective postoperative analgesia with a similar incidence of side effects; however, our findings suggest that continuous infusions of epidural morphine improved overall comfort with lower pain scores, fewer muscle spasms, and improved tolerance of activity during the initial postoperative period.