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Central neurocytomas comprise nearly half of adult intraventricular neoplasms. The median age of onset is 34 years. It is typically a low-grade neoplasm (World Health Organization grade II), although some cases of malignant neurocytomas have been described. We present a rare case of an atypical central neurocytoma with craniospinal dissemination, including both imaging and pathologic findings., (Published by Elsevier Inc.)

We report a case of a 53-year-old man presenting with depressed alertness and severe excessive sleepiness in the setting of neurosarcoidosis. Neuroimaging demonstrated hypothalamic destruction due to sarcoidosis with a CSF hypocretin level of 0 pg/mL. The patient also experienced respiratory depression that presumably resulted from hypocretin-mediated hypothalamic dysfunction as a result of extensive diencephalic injury. This is a novel case, demonstrating both hypocretin deficiency syndrome, as well as respiratory dysfunction from destruction of hypocretin neurons and extensive destruction of key diencephalic structures secondary to the underlying neurosarcoidosis., (© 2015 American Academy of Sleep Medicine.)

Dementia with Lewy bodies (DLB) is the second most common diagnosis of dementia after Alzheimer disease (AD). The essential pathologic feature is the Lewy body, a neuronal inclusion containing α-synuclein, found in brainstem nuclei and the neocortex. Clinical features include early fluctuations in attention, hallucinations, and parkinsonism, with progression to a combined cortical and subcortical dementia. To distinguish it from Parkinson disease dementia, a time course of one year from cognitive changes to motor feature onset has been established. There is more severe impairment of verbal fluency, executive function, and visuospatial abilities in DLB patients. Both rapid eye movement sleep behavior disorder and neuroleptic sensitivity are notable in this patient group. Treatment is aimed at symptom management. Cholinesterase inhibitors can be beneficial for behavioral and cognitive issues, whereas dopaminergic agents may help motor symptoms. Survival is equivalent to AD when measured from symptom onset, though diagnosis in DLB may be delayed., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Patients with corticobasal degeneration (CBD) pathology present with diverse clinical syndromes also associated with other neuropathologies, including corticobasal syndrome, progressive nonfluent aphasia, and an Alzheimer's-type dementia. Some present with behavioral variant frontotemporal dementia (bvFTD), though this subtype still requires more detailed clinical characterization. All patients with CBD pathology and clinical assessment were reviewed (N = 17) and selected if they initially met criteria for bvFTD [bvFTD(CBD), N = 5]. Available bvFTD patients with Pick's [bvFTD(Pick's), N = 5] were selected as controls. Patients were also compared to healthy older controls [N = 53] on neuropsychological and neuroimaging measures. At initial presentation, bvFTD(CBD) showed few neuropsychological or motor differences from bvFTD(Pick's). Neuropsychiatrically, they were predominantly apathetic with less florid social disinhibition and eating disturbances, and were more anxious than bvFTD(Pick's) patients. Voxel-based morphometry revealed similar patterns of predominantly frontal atrophy between bvFTD groups, though overall degree of atrophy was less severe in bvFTD(CBD), who also showed comparative preservation of the frontoinsular rim, with dorsal > ventral frontal atrophy, and sparing of temporal and parietal structures relative to bvFTD(Pick's) patients. Despite a remarkable overlap between the two patient types, bvFTD patients with underlying CBD pathology show subtle clinical features that may distinguish them from patients with Pick's disease neuropathology.

Objective: To characterize cognitive and behavioral features, physical findings, and brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with known histopathology., Methods: We reviewed clinical and magnetic resonance imaging data in all patients evaluated at our center with either an autopsy diagnosis of CBD (n = 18) or clinical CBS at first presentation with known histopathology (n = 40). Atrophy patterns were compared using voxel-based morphometry., Results: CBD was associated with 4 clinical syndromes: progressive nonfluent aphasia (n = 5), behavioral variant frontotemporal dementia (n = 5), executive-motor (n = 7), and posterior cortical atrophy (n = 1). Behavioral or cognitive problems were the initial symptoms in 15 of 18 patients; less than half exhibited early motor findings. Compared to controls, CBD patients showed atrophy in dorsal prefrontal and perirolandic cortex, striatum, and brainstem (p < 0.001 uncorrected). The most common pathologic substrates for clinical CBS were CBD (35%), Alzheimer disease (AD, 23%), progressive supranuclear palsy (13%), and frontotemporal lobar degeneration (FTLD) with TDP inclusions (13%). CBS was associated with perirolandic atrophy irrespective of underlying pathology. In CBS due to FTLD (tau or TDP), atrophy extended into prefrontal cortex, striatum, and brainstem, whereas in CBS due to AD, atrophy extended into temporoparietal cortex and precuneus (p < 0.001 uncorrected)., Interpretation: Frontal lobe involvement is characteristic of CBD, and in many patients frontal, not parietal or basal ganglia, symptoms dominate early stage disease. CBS is driven by medial perirolandic dysfunction, but this anatomy is not specific to a single underlying histopathology. Antemortem prediction of CBD will remain challenging until clinical features of CBD are redefined, and sensitive, specific biomarkers are identified., (Copyright © 2011 American Neurological Association.)

Neural stem cells with astrocyte-like characteristics exist in the human brain subventricular zone (SVZ), and these cells may give rise to glioblastoma multiforme (GBM). We therefore analyzed MRI features of GBMs in specific relation to the SVZ. We reviewed the preoperative and serial postoperative MR images of 53 patients with newly diagnosed GBM. The spatial relationship of the contrast-enhancing lesion (CEL) with the SVZ and cortex was determined preoperatively. Classification was as follows: group I, CEL contacting SVZ and infiltrating cortex; group II, CEL contacting SVZ but not involving cortex; group III, CEL not contacting SVZ but involving cortex; and group IV, CEL neither contacting SVZ nor infiltrating cortex. Patients with group I GBMs (n = 16) were most likely to have multifocal disease at diagnosis (9 patients, 56%, p = 0.001). In contrast, group IV GBMs (n = 14) were never multifocal. Group II (n = 14) and group III (n = 9) GBMs were multifocal in 11% and 29% of cases, respectively. Group I GBMs always had tumor recurrences noncontiguous with the initial lesion(s), while group IV GBM recurrences were always bordering the primary lesion. Group I GBMs may be most related to SVZ stem cells; these tumors were in intimate contact with the SVZ, were most likely to be multifocal at diagnosis, and recurred at great distances to the initial lesion(s). In contrast, group IV GBMs were always solitary lesions; these may arise from non-SVZ, white matter glial progenitors. Our MRI-based classification of GBMs may further our understanding of GBM histogenesis and help predict tumor recurrence pattern.

Objective: Identifying the genetic alterations in gliomatosis cerebri (GC) may yield clinically useful prognostic markers and provide clues as to whether GC represents a distinct pathological entity or is an extreme form of diffusely infiltrative glioma., Methods: Clinical histories, treatment histories, magnetic resonance imaging, and pathological analysis of patients with GC treated at either the University of California San Francisco or the Mayo Clinic were reviewed. Degenerate oligonucleotide-primed polymerase chain reaction was performed on biopsy samples of GC. Comparative genomic hybridization was used to determine relative deoxyribonucleic acid copy number. We evaluated relationships of clinical and radiological treatment and comparative genomic hybridization data to survival after diagnosis with Cox regression analysis., Results: Radiographic analysis and biopsy specimens were available for study in 29 patients (17 men, 12 women). Comparative genomic hybridization was successfully performed in 22 patients. Contrast enhancement was the most significant predictor of poor survival (P = 0.0026). Loss of chromosomes 13q and 10q and gains of 7q were also independent significant predictors of poor survival (P = 0.0032, 0.0335, and 0.0487, respectively). Patients treated with temozolomide or with radiation therapy had improved survival, but this effect did not reach statistical significance (P = 0.180 and 0.124, respectively)., Conclusion: Chromosomal aberrations associated with aggressive astrocytomas are predictors of poor outcome in patients with GC. This suggests that GC may be an architectural variant of diffuse astrocytomas. The presence of these aberrations and the presence of any contrast enhancement on magnetic resonance imaging scans are possible stratifiers for patients with GC. Stratification of GC into higher- and lower-grade forms may be useful in tailoring treatments to patients with this disease.

Suspensions of transmissible gastroenteritis virus (TGEV), a porcine coronavirus, were nebulized at rates of 0.1-0.2 ml/min into moving air using a Collison nebulizer or a plastic medical nebulizer operating at pressures ranging from 7 to 15 psi. The airborne viruses were collected on heating, ventilating, and air conditioning (HVAC) filters in an experimental apparatus and also sampled upstream of these test filters using AGI-30 and BioSampler impinger samplers. To study the effects of relative humidity (RH) on TGEV collection by the filters and samplers, the virus was nebulized into air at 30, 50, 70, and 90% RH. There were no significant changes in virus titer in the nebulizer suspension before and after nebulization for either nebulizer at any of the pressures utilized. Aerosolization efficiency - the ratio of viable virus sampled with impingers to the quantity of viable virus nebulized - decreased with increasing humidity. BioSamplers detected more airborne virus than AGI-30 samplers at all RH levels. This difference was statistically significant at 30 and 50% RH. Nebulizer type and pressure did not significantly affect the viability of the airborne virus. Virus recovery from test filters relative to the concentration of virus in the nebulizer suspension was less than 10%. The most and the least virus were recovered from filter media at 30% and 90% RH, respectively. The results suggest that TGEV, and perhaps other coronaviruses, remain viable longer in an airborne state and are sampled more effectively at low RH than at high humidity., (© Springer Science+Business Media B.V. 2007.)

Introduction: Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that measures the degree of water diffusion in vivo. DWI abnormalities are frequently observed on immediate postoperative imaging following surgical resection of gliomas in adults. These abnormalities subsequently demonstrate contrast enhancement, which may be confused with lesion recurrence. The purpose of this study was to investigate the occurrence of these postoperative abnormalities in pediatric patients with intracranial mass lesions., Methods: Thirty-three consecutive patients

Object: Diffusion-weighted magnetic resonance (MR) imaging is an invaluable tool in the diagnosis of acute stroke and other types of brain injury. Abnormalities in and around the resection cavity on diffusion-weighted imaging have been observed following surgery for infiltrating glioma. The purpose of this study was to investigate prospectively the incidence, time course, and ultimate outcome of these abnormalities., Methods: Forty-four consecutive patients with newly diagnosed gliomas were prospectively observed using serial MR imaging including diffusion-weighted sequences. Clinical and surgical data were also collected. Immediately postoperatively neuroimaging identified 28 patients (64%) in whom areas of reduced diffusion appeared in or around the resection cavity (mean volume 8.2 +/- 1.5 cm3). Complete resolution of this reduced diffusion was demonstrated within 90 days in 24 patients (86%). On subsequent neuroimages these areas demonstrated Gd enhancement as early as postoperative Day 15 and as late as Day 198 and ultimately took on the appearance of encephalomalacia in 26 (93%) of 28 cases. Postoperative reduced diffusion was not predicted by the clinical or surgical parameters that were assessed. No clinical deficits were attributable to the reduced diffusion., Conclusions: An abnormality related to diffusion-weighted sequences on postoperative MR imaging can occur after resection of newly diagnosed gliomas. In this study the abnormality typically resolved and was replaced by contrast enhancement on follow-up imaging, ultimately demonstrating encephalomalacia on long-term follow up. Findings on neuroimaging during the period of enhancement could be confused with recurrent tumor and interpreted as early treatment failure. Based on the findings of this study the authors strongly suggest that the inclusion of diffusion-weighted sequences in postoperative MR imaging is essential, as is MR imaging immediately before radiation therapy to monitor disease progression. A new enhancement observed after glioma surgery should be interpreted in the context of the diffusion-weighted image obtained immediately postoperatively.

Background: X-linked dystonia-parkinsonism (XDP) or "lubag" is an X-linked recessive disorder that afflicts Filipino men, and rarely, women. Genetic confirmation is performed through haplotyping or detection of disease-specific changes in the DYT3 gene., Objective: To describe the phenotypes and molecular data of 8 symptomatic female patients with XDP from 5 kindreds., Methods: Case series., Results: The average age of onset of symptoms was 52 years (range, 26-75 years). Six of 8 patients had parkinsonism, whereas only 1 had dystonia. The initial symptom was focal tremor or parkinsonism in 4, chorea in 3, and focal dystonia (cervical) in 1. Seven of 8 patients had slow or no progression of their symptoms and required no treatment. The patient with disabling parkinsonism was responsive to carbidopa/levodopa. Seven were heterozygous for the XDP haplotype, whereas 1 was homozygous., Conclusions: The phenotypes of female patients with XDP may include parkinsonism, dystonia, myoclonus, tremor, and chorea. The dystonia, if present, is mild and usually nonprogressive. Similar to men with XDP, parkinsonism is a frequent symptom in women. In contrast to men, affected women have a more benign phenotype, older age of onset, and milder course. Extreme X-inactivation mosaic may be a cause of symptoms in women with XDP, but a homozygously affected woman has also been observed.

Each year in the United States, it is estimated that there will be 42,000 new cases of rectal cancer and 8,500 deaths.(1,2) Some patients present with an incurable rectal cancer but more often death follows development of recurrent rectal cancer after failed curative-intent therapy. Knowledge of the natural history of rectal cancer and limitations of treatment options coupled with sound clinical judgment and compassion are essential prerequisites for the clinician providing palliative care.

Background: Currently used antiplatelet drugs, including aspirin, ticlopidine, and others, are effective against certain but not all of the many endogenous platelet activators. Because of their limited efficacy, a significant number of serious thromboembolic complications still occur, highlighting the need for a more effective therapy. Thus, we have identified a systemically active peptide analogue (DMP 728) of the arginine-glycine-aspartic acid (RGD) recognition sequence that mediates the binding of ligands such as fibrinogen to the platelet glycoprotein (GP) IIb/IIIa receptors. The goals of the present study were to determine the antiplatelet and antithrombotic efficacies of DMP 728 in various arterial thrombosis models., Methods and Results: DMP 728 demonstrated antiplatelet efficacy in vitro in inhibiting ADP-induced human platelet aggregation (IC50, 46 +/- 2 nmol/L) and fibrinogen binding to human platelets (IC50, 2.3 +/- 0.8 nmol/L) or purified human GPIIb/IIIa receptors (IC50, 0.6 +/- 0.1 nmol/L). DMP 728 demonstrated high affinity and specificity for human platelet GPIIb/IIIa over other adhesion molecules. In anesthetized mongrel dogs, DMP 728 at 0.001 to 1.0 mg/kg IV produced dose-dependent antiplatelet effects in inhibiting ex vivo platelet aggregation induced by ADP and in prolonging template bleeding time. DMP 728 effects on bleeding time prolongation were more rapidly reversible than those on platelet aggregation inhibition. A maximal antiplatelet effect for DMP 728 was demonstrated at 0.01 mg/kg IV bolus. The antithrombotic efficacy of DMP 728 was examined in vitro and in vivo after IV administration at different doses in various models of arterial thrombosis. In the coronary artery Folts model in dogs, DMP 728 demonstrated maximal antithrombotic efficacy at 0.01 mg/kg IV bolus with an ED50 of 0.005 mg/kg IV bolus in inhibiting cyclic flow reductions. Additionally, DMP 728 demonstrated 100% prevention of primary thrombosis and rethrombosis (P < .01) after treatment with different thrombolytics, including tissue plasminogen activator and streptokinase, in an electrolytically induced femoral artery thrombosis model in dogs., Conclusions: Acute intravenous DMP 728 administration (0.001 to 1.0 mg/kg) has dose-dependent antiplatelet and antithrombotic effects in different arterial thrombosis models. These data suggest that DMP 728, a low-molecular-weight GPIIb/IIIa receptor antagonist, may have therapeutic potential as an effective antithrombotic agent in coronary and peripheral artery thromboembolic disorders.

Since thrombin plays an important role in platelet-mediated arterial thrombosis, we have examined the antiplatelet activity of a synthetic thrombin inhibitor, DuP 714 (Ac-(D)Phe-Pro-boroArg), in comparison with that of the naturally occurring inhibitor hirudin. Hirudin was slightly more potent than DuP 714 in inhibiting thrombin-induced aggregation in washed human platelets (IC50s of 72 nM and 150 nM, respectively) and in inhibiting the secretion of plasminogen activator inhibitor-I from human platelets (IC50s of 300 nM and 900 nM, respectively). In contrast, DuP 714 was more potent than hirudin in inhibiting thrombin-induced [125I]fibrinogen binding to gel purified platelets, and in inhibiting thrombin-induced intracellular calcium mobilization in washed platelets. These results indicate that the tripeptide DuP 714 has comparable antiplatelet activity to the 65 amino acid hirudin. We conclude that DuP 714 may have clinical utility in the prevention of platelet-dependent, arterial thrombotic processes.

The effect of different beta-adrenoceptor blockers on free radical-mediated cardiac membrane lipid peroxidation (CMLP) was compared to their beta-blocking potency (pA2). CMLP was determined by the measurement of malondialdehyde (MDA) formation in rat cardiac membrane homogenates exposed to a free radical generating system (FeCL3/ADP/DHF) in the presence or absence of the beta-adrenoceptor blockers (1-1,000 microM). beta-adrenoceptor blocking potency (pA2) was determined using guinea pig right atria stimulated with isoproterenol. The catechol containing beta-blocker (DCC-10255) was shown to be a potent inhibitor of CMLP via an iron-dependent mechanism. On the other hand, the non-catechol beta-adrenoceptor blocker, timolol, was shown to be a weak inhibitor of CMLP. Furthermore, dl- and d-propranolol were active and equipotent though less potent than DCC-10255 in inhibiting CMLP. The myocardial cytoprotective efficacy for catechol and non-catechol beta-adrenoceptor blockers was evaluated in an isolated rat myocyte model. It was demonstrated that catechol-containing agents with either strong or weak beta-adrenoceptor blockade possess a relatively potent in vitro antioxidant and myocardial cytoprotective efficacy against free radical mediated CMLP and myocyte injury, respectively. It is concluded that the inhibition of CMLP by beta-adrenoceptor blockers is independent of their beta-adrenoceptor blockade.

A rapid and convenient procedure for the quantitative determination of the fatty acid composition of plasma lipids is described. Human plasma was applied directly to the preadsorbent zones of thin-layer silica gel plates with added antioxidant, internal standards and carriers. The thin-layer chromatography (TLC) plates were partially developed with methanol followed by chloroform/methanol (1:1, v/v), and then they were fully developed in hexane/diethyl ether/acetic acid (80:20:1, v/v/v) to separate the major classes of lipids. Silica gel from regions containing the separated lipids was scraped into screw-capped tubes and treated with boron trifluoride-methanol prior to gas chromatography. The method of direct application to TLC plates gave yields and compositions of fatty acids very similar to the method of applying extracted plasma lipids. This relatively simple method is suitable for analyzing the fatty acids in plasma lipids from a 50 microliter finger-tip blood samples from an individual, and it may be useful in wide-scale screening of different individuals to estimate the relative amounts of ingested polyunsaturated fatty acids.