Effect of transforming growth factor-beta1 on microglial MHC-class II expression.

In the present report, the effects of IFN-gamma and transforming growth factor beta1 (TGF-beta1) on major histocompatibility complex class II (MHC-II) gene expression in isolated mouse brain microglial cells, in the MH-S macrophage cell line and in the primary mouse macrophage cultures were examined. IFN-gamma is a potent inducer of MHC-II gene and this induction was further elevated in microglia by TGF-beta1, while TGF-beta1 inhibited IFN-gamma, induction in macrophages. The enhancing effect of TGF-beta1 was also detected in microglia at the protein level. Transient transfection of microglia with 5' deletional mutants of the MHC-II IAalpha promoter linked to the chloramphenicol acetyltransferase reporter gene demonstrated that TGF-beta1 acts at the transcriptional level to enhance the MHC-II expression induced by IFN-gamma.

Prognostic significance of P53 histochemistry and DNA histogram parameters in head and neck malignancies.

BACKGROUND: The aim of the study was to determine the role of quantitative pathological parameters in prognosis of head and neck malignancies. MATERIALS AND METHODS: 51 head and neck squamous cell carcinoma patients were examined for mutant p53 gene expression (45 out of 51 patients) by immunohistochemistry and for cellular DNA-content (44 out of 51 patients) using digital picture analyzer. Statistical analysis was performed using BMDP package. RESULTS: No correlation with prognosis was found for age, sex, localization, T-classification and therapy. There was significant relationship between N-status and overall survival (p = 0.0008). No correlation was found with overall and disease-free survival for either histologic type or grading. P53: No significant correlation was detected with overall survival. A relationship was found between mutant p53 and metastasis-free time (p = 0.06). Ploidy: There were no significant differences between aneuploid and euploid tumors for either disease-free or overall survival. Synthetic (S)-phase fraction: A correlation was found for both survival rates (p = 0.029) and metastasis-free time (p = 0.05). Polyploid fraction (PF): correlation was shown for both overall survival (p = 0.0128) and metastasis-free time (p = 0.0038). CONCLUSION: There is correlation between p53 overexpression and metastatic potential and there is a significant relationship between SPF and PF value and prognosis (metastasis-free and overall survival) of head and neck cancer.

MRI in cerebral intraventricular hemorrhage: analysis of 50 consecutive cases.

MRI of intraventricular haemorrhage (IVH) has not been studied formally. We aimed to describe the degradation rate and patterns shown on 1.5 T MRI in IVH, comparing them to other coexisting brain hemorrhage. We studied 50 consecutive cases using T1-, proton-density, and T2-weighted images. IVH was seen in two forms: layered (free-flowing in ventricles) (37 cases) and/or clotted (31). Both were best shown by proton-density image. Layered IVH was seen in the dependent portions of the lateral ventricles with fluid ("blood-CSF") levels, degrading more slowly than both clotted IVH and intraparenchymal hemorrhages (IPH) (acute blood products persisting for several more days; P < 0.05). Clotted IVH degraded at a rate comparable to IPH. IVH cleared rapidly and did not form hemosiderin. Subarachnoid hemorrhage (SAH) cleared faster and was less conspicuous than IVH. Hypertensive (22), aneurysmal (11), traumatic (2), idiopathic (9), or vascular malformation-related (6) IVH were seen. IVH coexisted with IPH (30) or SAH (12), or both (12). The high rate of layering with blood-CSF levels in IVH is most likely due to different densities of blood components and CSF and the fibrinolytic capability of the latter. Delayed degradation of layered IVH probably reflects high intraventricular oxygen and glucose content. Further study is necessary to determine if MRI characteristics of IVH are helpful in excluding other intraventricular diseases such as neoplasia and pyocephalus.

Differential regulation of major histocompatibility complex class II expression and nitric oxide release by beta-amyloid in rat astrocyte and microglia.

Astrocytes and microglial cells were examined for expression of two immunologically important molecules, major histocompatibility complex class II (MHC-II) and nitric oxide (NO) following treatment with IFN-gamma and beta-amyloid (betaA) peptides, betaA(1-42) and betaA(25-35). IFN-gamma is a potent inducer of both MHC-II gene expression and NO production. The induction of MHC-II was inhibited by both betaA peptides in astrocytes but they had little or no effect in microglia. betaA peptides had no effect on NO release in astrocytes but on microglia betaA(1-42) synergistically induced NO release with IFN-gamma. Transient transfection of astrocytes with 5' deletional mutants of MHC-II IAalpha promoter linked to the chloramphenicol acetyl transferase reporter gene (IAalpha-CAT), demonstrated that betaA acts at the transcriptional level to downregulate IFN-gamma induced MHC-II gene expression in astrocytes. In previous studies, the induction of MHC-II on glial cells were suggested to be involved in the pathogenesis of neurodegenerative diseases and MHC-II(+) microglial cells were observed at much higher frequency than astrocytes. This study provides information on the regulation of the MHC-II gene expression in astrocytes and in microglial cells by betaA and this pathway may be critically involved in the immune/inflammatory regulation within the central nervous system.

MRI findings in lumbar puncture headache syndrome: abnormal dural-meningeal and dural venous sinus enhancement.

Intracranial hypotension (IH) is a treatable cause of persistent headaches. Persistent cerebrospinal fluid (CSF) leak at a lumbar puncture (LP) site may cause IH. We present postcontrast MRI of a patient with post-lumbar-puncture headache (LPHA) showing abnormal, intense, diffuse, symmetric, contiguous dural-meningeal (pachymeningeal) enhancement of the supratentorial and infratentorial intracranial dura, including convexities, interhemispheric fissure, tentorium, and falx. MRI also showed abnormal dural venous sinus enhancement, a new finding in LPHA, suggesting compensatory venous expansion. Thus, IH and venodilatation may play a role in the development of LPHA.

Fluid-attenuated inversion-recovery MR imaging in acute and subacute cerebral intraventricular hemorrhage.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion-recovery (FLAIR) MR imaging may show subarachnoid hemorrhage (SAH) with high sensitivity. We hypothesized that the FLAIR technique is effective and reliable in the diagnosis of cerebral intraventricular hemorrhage (IVH). METHODS: Two observers evaluated the 1.5-T MR fast spin-echo FLAIR images, T1- and T2-weighted MR images, and CT scans of 13 patients with IVH and the FLAIR images of 40 control subjects. RESULTS: IVH appeared bright on the FLAIR images obtained during the first 48 hours and was of variable appearance at later stages. FLAIR MR imaging detected 12 of 13 cases of IVH; no control subjects were falsely thought to have IVH (92% sensitivity, 100% specificity). However, IVH could not be fully excluded in the third ventricle (20%, n = 8) or in the fourth ventricle (28%, n = 11) on some control images because of CSF pulsation artifacts. Two cases had CT-negative IVH seen on FLAIR images. One case had FLAIR-negative IVH seen by CT. Although the sensitivities of conventional MR imaging (92%) and CT (85%) were also high, FLAIR imaging showed IVH more conspicuously than did standard MR imaging and CT in 62% of the cases (n = 8). FLAIR was as good as or better than CT in showing IVH in 10 cases (77%). FLAIR images showed all coexisting SAH. CONCLUSION: FLAIR MR imaging identifies acute and subacute IVH in the lateral ventricles with high sensitivity and specificity. In cases of subacute IVH, conventional MR imaging complements FLAIR in detecting IVH. The usefulness of the FLAIR technique for detecting third and fourth ventricular IVH may be compromised by artifacts. Blood hemoglobin degradation most likely causes the variable FLAIR appearance of IVH after the first 48 hours.

Cranial magnetic resonance imaging findings in bacterial endocarditis: the neuroimaging spectrum of septic brain embolization demonstrated in twelve patients.

Infective endocarditis (IE) is an elusive systemic disorder that is often associated with neurologic complications. The contribution of brain magnetic resonance imaging (MRI) to the diagnosis of IE and the spectrum of such findings has been only sparsely described previously. The authors report cranial MRI findings in 12 patients with IE. Each of the patients had MRI evidence of cerebral embolization, with multiple brain lesions noted in most patients (n = 10). Cortical branch infarction was the most common lesion (n = 8), which usually involved the distal middle cerebral artery tree. The next most common finding (n = 7) was numerous small embolic lesions which typically lodged in the supratentorial gray-white junction, some of which were clinically silent and many of which enhanced (probable microabscesses). Brain hemorrhages were noted in four patients, most commonly subarachnoid hemorrhage (n = 3). Two patients developed multiple frank parenchymal macroabscesses/cerebritis lesions. A previously unreported finding in septic embolization, a stroke that became infected with abscess formation ("septic infarction"), was noted in two patients. MRI showed orbital cellulitis in two patients. Most patients studied with gadolinium showed enhancement of lesions (n = 5/8). The authors conclude that cranial MRI may be a valuable tool in the evaluation of patients with IE. The presence of characteristic cranial MRI lesions, especially of multiple types, may prompt early diagnosis and treatment.

The cerebral intravascular enhancement sign is not specific: a contrast-enhanced MRI study.

The intravascular enhancement (IVE) sign, also known as the "arterial enhancement sign", is an abnormal finding in the brain on contrast-enhanced MRI studies. IVE has been described in arterial cerebrovascular disorders, most commonly in acute or subacute arterial ischemic infarcts. However, the specificity of this sign has not been established. We describe four patients with disorders other than arterial strokes in whom gadolinium-enhanced high-field (1.5 T) MRI suggested IVE. The conditions were herpes simplex viral encephalitis, idiopathic cerebellitis, pneumococcal meningitis, and superior sagittal sinus thrombosis with venous infarction. IVE in these cases may be due to multiple factors, including arterial, venous, perivascular, and leptomeningeal or sulcal contrast medium accumulation. Our observations suggest that arterial ischemia, previously described as the cardinal cause of IVE, probably does not explain all instances, and urge caution in interpreting this sign as a specific MRI manifestation of acute arterial infarction or ischemia.

Cerebral venous infarctions presenting as enhancing space-occupying lesions: MRI findings.

Cerebral venous thrombosis is an unusual form of cerebrovascular disease that may cause cerebral venous infarction (CVI). Magnetic resonance imaging (MRI) of the brain may improve the often elusive diagnosis of CVI. However, the sensitivity, specificity, and full spectrum of such MRI findings are poorly understood. The authors present the cases of three patients with CVI whose MRI scans showed abnormally enhancing tumor-like brain lesions. Two of the CVIs were hemorrhagic and exerted mass effect. One patient showed increasingly nodular and heterogeneous ring-like enhancement progressing from the single-dose to the triple-dose gadolinium contrast images. The CVI of a second patient also showed ring-like enhancement. Biopsy was performed on one of these patients and was strongly considered for the other two patients to exclude neoplastic disease. Careful examination of the MRI appearance of venous structures and the use of specialized MRI techniques improved the recognition of CVI for two patients and prevented biopsy. This represents the first description of abnormal triple-dose MRI contrast enhancement in CVI. Consideration of CVI in the care of patients with enhancing tumor-like masses may lead to earlier diagnosis and treatment, preventing unnecessary invasive diagnostic procedures. CVI should be added to the differential diagnosis of supratentorial ring-enhancing masses.

Occipital lobe seizures as the major clinical manifestation of reversible posterior leukoencephalopathy syndrome: magnetic resonance imaging findings.

PURPOSE: Reversible posterior leukoencephalopathy syndrome (RPLS) is an increasingly recognized brain disorder most commonly associated with malignant hypertension, toxemia of pregnancy, or the use of immunosuppressive agents. When associated with acute hypertension, RPLS typically occurs concurrently with the fulminant clinical syndrome of hypertensive encephalopathy. We describe occipital lobe seizures, in the setting of only moderate elevations of blood pressure, as the major clinical manifestation of RPLS. METHODS: Two patients from the Dent Neurologic Institute are presented with clinical and magnetic resonance imaging (MRI) correlation. RESULTS: New onset secondarily generalized occipital seizures were noted, with MRI findings consistent with RPLS. Both of the patients had chronic renal failure and a moderate acute exacerbation of chronic hypertension. Other features of hypertensive encephalopathy were lacking, such as headache, nausea, papilledema, and an altered sensorium. Magnetic resonance imaging (MRI) showed edematous lesions primarily involving the posterior supratentorial white matter and corticomedullary junction, consistent with RPLS. With lowered blood pressure, the MRI lesions resolved and the patients became seizure-free without requiring chronic anticonvulsant therapy. CONCLUSIONS: Occipital seizures may represent the only major neurologic manifestation of RPLS due to acute hypertension, especially in patients with renal failure. Other evidence of hypertensive encephalopathy, such as cerebral signs and symptoms, need not be present. Blood pressure elevations may be only moderate. Early recognition of this readily treatable cause of occipital seizures may obviate the need for extensive, invasive investigations. Despite the impressive lesions on MRI, prompt treatment of this disorder carries a favorable prognosis.

Magnetic resonance imaging findings in acute cerebellitis.

Cerebellitis, also known as acute cerebellar ataxia, is an inflammatory syndrome of cerebellar dysfunction that may reflect an infectious, post-infectious, or post-vaccination disorder. We present serial magnetic resonance imaging (MRI) findings in a partially reversible, idiopathic cerebellitis. Bilateral cerebellar parenchymal abnormalities were noted, including hyperintensities on T2-weighted images and cerebellar swelling. After contrast administration, the cerebellum showed abnormal bilateral enhancement. The authors state this represents the first report of abnormal contrast enhancement in this condition. The MRI lesions most likely reflect the reversible, inflammatory nature of the syndrome.

Spinal leptomeningeal hemangioblastomatosis in von Hippel-Lindau disease: magnetic resonance and pathological findings.

A 55-year-old man with von Hippel-Lindau disease presented with quadriparesis. Multiple enhancing cervical and thoracic spinal masses were seen on magnetic resonance imaging (MRI). A rim of diffuse, nodular enhancement linking all of the discrete masses was apparent on the surface of the cervical and thoracic regions of the cord. Surgical exploration revealed multiple extramedullary-intradural and intramedullary masses, extending to and infiltrating the cord; the leptomeninges contained numerous small tumor seeds at several levels. The excised spinal masses were diagnosed as capillary hemangioblastomas, which infiltrated the pia mater. Diffuse, intense, spinal leptomeningeal enhancement on MRI associated with multiple hemangioblastomas has not been previously reported and may be referred to as spinal "leptomeningeal hemangioblastomatosis."

Cerebral ventricular empyema associated with severe adult pyogenic meningitis: computed tomography findings.

Cerebral ventricular empyema (CVE), also known as pyocephalus, is a rare form of pyogenic ventriculitis. We present cranial computed tomography (CT) in an adult who developed a bilateral CVE associated with acute pyogenic meningitis. CT showed an obstructive ventriculomegaly and fluid-fluid levels layering in the lateral ventricles and the third ventricle. Frank neutrophilic pus was taken from the subarachnoid space. After antibiotic treatment, the pyocephalus resolved. CVE may be visualized on CT with pus layering in the ventricular CSF, creating a fluid level of intermediate hypodensity.

Multiple giant intracranial aneurysms associated with lymphomatoid granulomatosis. A magnetic resonance imaging and angiographic study.

Lymphomatoid granulomatosis is an uncommon lymphoproliferative disorder that frequently has central nervous system manifestations. Lymphomatoid granulomatosis has clinical features similar to both vasculitis and lymphoma. The pathological hallmarks of this disease include necrotic angiocentric and angiodestructive infiltrations of premalignant or malignant lymphoid cells. There are, to the authors' knowledge, only a few magnetic resonance imaging reports and no magnetic resonance angiographic reports of this disorder. Presented here is a case of lymphomatoid granulomatosis producing multiple giant fusiform and saccular aneurysms throughout the major intracerebral arteries, along with patterns of vascular beading typically seen with vasculitis demonstrated by magnetic resonance angiography.

Magnetic resonance imaging in demyelinating, infectious, metabolic, and congenital diseases.

A mere 5 to 7 years ago, the majority of literature on demyelinating, infectious, metabolic, and congenital diseases of the brain focused on comparison between computed tomography and magnetic resonance imaging (MRI). MRI has become not only the foremost diagnostic tool in imaging of the central nervous system, but also a key research instrument. This is displayed by the recent increase in papers concerning magnetic resonance spectroscopy. It is perhaps no better illustrated than in the study of multiple sclerosis. A review of neuroimaging in infectious diseases places a heavy emphasis on AIDS-related infections. The ongoing development of new scan sequences, contrast agents, and fast scanning techniques are broadening our image of the brain and, indeed, our understanding of pathophysiologic mechanisms of disease states. Excellent examples of this are the metabolic and congenital diseases where, based on the knowledge of metabolic pathways and embryology, MRI has become the modality of choice.

Cognitive impairment after acute supratentorial stroke: a 6-month follow-up clinical and computed tomographic study.

To document the occurrence, time course, and predictors of global cognitive impairment following a supratentorial stroke, we prospectively studied 41 consecutive patients with acute cerebral ischemia and no evidence of pre-existing intellectual disturbances. The Graded Neurologic Scale and Mattis Dementia Rating Scale were used to assess neurologic and cognitive deficits within the first week, 3 weeks and 6 months after the onset of symptoms. CT was performed at each examination and semiquantitative measurements of infarct volumes and brain atrophy were obtained. Sixty-one percent of patients were found to be cognitively impaired within the first week. After 6 months this deficit had resolved in 24%, but was still present in 37% of individuals. Initial findings associated with a high risk of long-term intellectual dysfunction were: 1. moderately severe cognitive impairment, 2. diminished alertness in the acute stroke stage, 3. infarction involving the temporal lobe, 4. evidence of multiple brain infarcts and 5. pronounced ventricular enlargement. Logistic regression analysis revealed temporal infarcts and evidence of multiple ischemic lesions as the most powerful predictors of persistent cognitive impairment. By these two factors alone, 85.4% of study participants could be correctly classified regarding their cognitive outcome. These results suggest cognitive dysfunction to be a frequent sequela of supratentorial stroke. Its long-term persistence may be predicted on the basis of certain features.

Intravenous carboplatin for recurrent malignant glioma: a phase II study.

Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate.

Quantitative effects of cetirizine and diphenhydramine on mental performance measured using an automobile driving simulator.

The purpose of this study was to assess the effects of cetirizine on objective measures of mental performance. Fifteen subjects were given single doses of cetirizine (20 mg, 10 mg, and 5 mg) diphenhydramine, 50 mg (positive control), and placebo (negative control) in this randomized, double-blinded, crossover study. An automobile driving simulator, digit symbol substitution, Trails B maze tracking and subjective feelings of drowsiness were measured at 0, 2, 4, 6, 8, and 24 hours after the dose. No differences between placebo and any of the three doses of cetirizine could be detected, however, diphenhydramine produced impaired mental performance and drowsiness. These data indicate that these doses of cetirizine produce little or no effect on cognitive function or mental performance.