Dynamic response of the intracranial system in the conscious dog to papaverine hydrochloride.
The influence of papaverine on the intracranial system of the dog was studied by measuring the pressure-depth-time response for the intact intracranial system, i.e., for the subarachnoid and subpial compartments. This was accomplished by a measurement system which provided an accurate pressure-depth determination and a uniform rate of transducer insertion. Distinct regions of the intracranial system (subarachnoid, transitional, and subpial) were identified from inflections in the pressure response curve. The test parameter, brain relative stiffness (BRS), was obtained by determining the slope of the pressure response values within the subpial region. This parameter is a measure of the "stiffness" or elasticity of bring tissue within the test configuration. A bolus injection of papaverine (1 mg per kilogram, i.v.) caused an increase in the transitional region, a compensatory reduction in the subarachnoid space, and an increase in BRS. It is postulated that at normotensive arterial blood pressure, cerebrovascular expansion caused by papaverine resulted in increased brain tissue elasticity, i.e., an increase in the pressure-depth response for the subpial region. Possible implications for this increase are discussed. Experiments should be conducted in which local blood flow studies are coupled with measurements of brain elastic response. (+info
Treatment of neoplastic meningitis with intrathecal temozolomide.
Neoplastic meningitis (NM) results from leptomeningeal dissemination of cancers arising within the central nervous system or metastasizing to the leptomeninges from systemic neoplasms. The inability to produce therapeutic drug levels intrathecally (i.t.) with systemic administration and the minimal efficacy of chemotherapeutic agents currently available for direct i.t. use limit therapy. Temozolomide [8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4([3H])-one] is a novel methylating agent with proven activity against intraparenchymal malignant gliomas (MGs). Insolubility of the standard formulation prevents its efficacious use as an i.t. agent, however. To overcome this obstacle, we have developed a unique microcrystalline formulation of temozolomide with greatly enhanced solubility. Treatment of athymic rats bearing subarachnoid MER- human MG xenografts with four doses of i.t. microcrystalline temozolomide over a 2-week period produced a 142% increase in median survival at individual doses of 2.2 micromol (P = 0.0073) and a >367% increase in median survival at individual doses of 6.8 micromol (P = 0.0015). At the higher dose tested, three of eight rats treated developed no neurological symptoms and had no evidence of residual tumor on histological examination after treatment. Use of this microcrystalline formulation in athymic rats bearing subarachnoid MER+ human MG xenografts increased median survival >132% (P < 0.0058) at both dose levels tested. Toxicity directly attributable to the i.t. administration of microcrystalline temozolomide was exhibited in the highest dose groups only and was limited to small patchy areas of focal demyelination involving <5% of spinal cord long tracks. (+info
Quinupristin/dalfopristin attenuates the inflammatory response and reduces the concentration of neuron-specific enolase in the cerebrospinal fluid of rabbits with experimental Streptococcus pneumoniae meningitis.
The inflammatory response following initiation of antibiotic therapy and parameters of neuronal damage were compared during intravenous treatment with quinupristin/dalfopristin (100 mg/kg as either a short or a continuous infusion) and ceftriaxone (10 mg/kg/h) in a rabbit model of Streptococcus pneumoniae meningitis. With both modes of administration, quinupristin/dalfopristin was less bactericidal than ceftriaxone. However, the concentration of proinflammatory cell wall components (lipoteichoic acid (LTA) and teichoic acid (TA)) and the activity of tumour necrosis factor (TNF) in cerebrospinal fluid (CSF) were significantly lower in the two quinupristin/dalfopristin groups than in ceftriaxone-treated rabbits. The median LTA/TA concentrations (25th/75th percentiles) were as follows: (i) 14 h after infection: 133 (72/155) ng/mL for continuous infusion of quinupristin/dalfopristin and 193 (91/308) ng/mL for short duration infusion, compared with 455 (274/2042) ng/mL for ceftriaxone (P = 0.002 and 0.02 respectively); (ii) 17 h after infection: 116 (60/368) ng/mL for continuous infusion of quinupristin/dalfopristin and 117 (41/247) ng/mL for short duration infusion, compared with 694 (156/2173) ng/mL for ceftriaxone (P = 0.04 and 0.03 respectively). Fourteen hours after infection the median TNF activity (25th/75th percentiles) was 0.2 (0.1/1.9) U/mL for continuous infusion of quinupristin/dalfopristin and 0.1 (0.01/3.5) U/mL for short duration infusion, compared with 30 (4.6/180) U/mL for ceftriaxone (P = 0.02 for each comparison); 17 h after infection the TNF activity was 2.8 (0.2/11) U/mL (continuous infusion of quinupristin/dalfopristin) and 0.1 (0.04/6.1) U/mL (short duration infusion), compared with 48.6 (18/169) U/mL for ceftriaxone (P = 0.002 and 0.001). The concentration of neuron-specific enolase (NSE) 24 h after infection was significantly lower in animals treated with quinupristin/dalfopristin: 4.6 (3.3/5.7) microg/L (continuous infusion) and 3.6 (2.9/4.7) microg/L (short duration infusion) than in those treated with ceftriaxone (17.7 (8.8/78.2) microg/L) (P = 0.03 and 0.009 respectively). In conclusion, antibiotic treatment with quinupristin/dalfopristin attenuated the inflammatory response within the subarachnoid space after initiation of antibiotic therapy. The concentration of NSE in the CSF, taken as a measure of neuronal damage, was lower in quinupristin/dalfopristin-treated rabbits than in ceftriaxone-treated rabbits. (+info
Brain parenchymal, subarachnoid racemose, and intraventricular cysticercosis in an Indian man.
The coexistence of brain parenchymal cysts at various stages of evolution, both intraventricular and subarachnoid racemose, is reported in a patient with neurocysticercosis. The condition has a variety of presentations, depending on the location of the cyst. This case is of particular interest because of the rarity of this condition in India. (+info
Sonographic nomogram of the leptomeninges (pia-glial plate) and its usefulness for evaluating bacterial meningitis in infants.
BACKGROUND AND PURPOSE: To our knowledge, the upper limits of the thickness of normal meninges on neurosonograms are not known. We therefore established a nomogram for sonographic measurements of the leptomeninges (pia-glial plate) and assessed its usefulness in neurosonographic examinations of children with bacterial meningitis. METHODS: The pia mater-cortical glia limitans complex on the surface of the brain and in the sulcus of a frontal gyrus was measured on neurosonograms in 100 infants without meningeal disease in order to establish a nomogram of the thickness of this pia-glial plate, referred to as the leptomeninx. Effects of prematurity, age, sex, and single-layer (surface) versus double-layer (sulcus) measurements were analyzed. Meningeal thicknesses derived from a retrospective analysis of the neurosonograms of 33 patients with purulent meningitis and a prospective study of 22 patients with bacterial meningitis were compared with the nomograms. Clinical outcomes of children with meningeal thickening were compared with those of affected children with normal meninges. RESULTS: The distribution of sulci measurements was significantly asymmetrical around the mean. Statistical data showed no influence of prematurity and sex, but showed surface measurements to be more consistent than sulcal measurements. Older chronological age was related to slightly larger sulci, but did not influence the surface measurements. In children with bacterial meningitis, the surface meninges were less frequently thickened than were the sulci. Sulcal enlargement occurred often in combination with echogenic deposits in the sub-arachnoid space. CONCLUSION: Leptomeninges are best measured on the surface of a gyrus rather than in a sulcus, as the normal thickness of the sulci shows much more variability. Clinical outcome of bacterial meningitis cannot be predicted by presence or absence of meningeal thickening as the only sonographic abnormality. (+info
Role of peroxynitrite as a mediator of pathophysiological alterations in experimental pneumococcal meningitis.
This study investigated the role of peroxynitrite in an adult rat model of pneumococcal meningitis. Immunohistochemically, nitrotyrosine residues, as a marker for peroxynitrite formation, were detected perivascularly and in proximity to inflammatory cells in the subarachnoid space. Nitrotyrosine immunoreactivity was colocalized with blood-brain barrier breaching, which was visualized by fluorescence microscopy after intravenous application of Evans blue. Treatment of infected rats with uric acid (300 mg/kg intraperitoneally), a scavenger of peroxynitrite, significantly attenuated intracranial pressure, cerebrospinal fluid white blood cell count, and blood-brain barrier leakage, as indicated by Evans blue concentration in the cerebrospinal fluid (21.6+/-9.3 mm Hg, 5776+/-1790 cells/microL, 9.7+/-6.4 microgram/mL in infected, untreated rats vs. 7.2+/-1.6 mm Hg, 2004+/-904 cells/microL, 1.1+/-1.0 microgram/mL infected, uric acid-treated rats, mean+/-SD, P<.05). These data suggest that peroxynitrite plays a central role in mediating pathophysiological alterations during bacterial meningitis. (+info
Spontaneous ventriculostomy: report of three cases revealed by flow-sensitive phase-contrast cine MR imaging.
Spontaneous ventriculostomy is a rare condition that occurs with the spontaneous rupture of a ventricle, resulting in a communication between the ventricular system and the subarachnoid space. Three cases of spontaneous ventriculostomy through the floor of the third ventricle that occurred in cases of chronic obstructive hydrocephalus are presented. The communication was identified via flow-sensitive phase-contrast cine MR imaging. Spontaneous ventriculostomy is probably a result of a rupture of the normally thin membrane that forms the floor of the third ventricle and, with long-standing obstructive hydrocephalus, creates an internal drainage pathway that spontaneously compensates for the hydrocephalus. (+info
Spinal oligodendroglioma with diffuse arachnoidal dissemination in a Japanese Black heifer.
A gelatinous focus with cystic spaces, was found in the posterior funiculus of the 2nd to 3rd lumbar levels of the spinal cord of a Japanese Black heifer, 2 years old, with clinical signs of severe dysstasia. Histopathological examination revealed that the spinal lesion consisted of multifocal and diffuse proliferation of round cells with abundant vacuolar cytoplasm and hyperchromatic nuclei. In the lesions there was a number of cystic spaces containing aggregates of small round cells. The neoplastic foci showed a honeycomb structure divided by thin blood vessels, representing typical lesions of oligodendroglioma. Diffuse and multifocal proliferation of these round cells were also recognized in the subarachnoidal space in the sacral spinal cord. Immunohistochemically, the proliferating round cells were negative for glial fibrillary acidic protein. Based on these morphological features, the case was diagnosed as lumbar spinal oligodendroglioma with diffuse arachnoidal dissemination. (+info