JOURNAL OF NEUROIMAGING, Issue 1 2001
Peterus Thajeb MD
ABSTRACT The authors report on cerebral and oculorhinal manifestations in a patient with a cytoplasmic pattern of antineutrophil cytoplasmic autoantibody (c-ANCA),associated vasculitis. Recurrent Tolosa-Hunt syndrome, cavernous sinus syndrome, Raeder's paratrigeminal neuralgia, and seizures were the major clinical manifestations. Brain MRI showed localized enhancing lesions initially in the cavernous sinus and later in the convexity pachymeninges. The lesions disappeared following 9 months of oral prednisolone (15 mg/day) and cyclophosphamide (100 mg/day) therapy. The presence of c-ANCA, demonstration of vasculitis, and depositions of immunoglobulin G (IgG) and fibrinogen in the vessel walls of pachymeninges of the patient confirmed an immune-mediated cause of the vasculitis. Cranial pathology without renal and pulmonary involvement suggests a variant of Wegener's granulomatosis, which is called the "limited" form of Wegener's granulomatosis. [source]

Cerebral and conjunctival haemorrhages associated with von Willebrand factor deficiency and canine angiostrongylosis

JOURNAL OF SMALL ANIMAL PRACTICE, Issue 2 2005
N. T. Whitley
A case of angiostrongylosis is described in a 14-month-old golden retriever bitch. Conjunctival haemorrhage and neurological signs, referable to a space-occupying cerebral lesion, were associated with defective primary haemostasis caused by low levels of von Willebrand factor. Full clinical recovery followed treatment with desmopressin, fresh whole blood transfusion, fenbendazole and supportive care. The magnetic resonance image of the suspected organising haematoma is described. Similarities to the human condition, acquired von Willebrand syndrome, and a possible role for aberrant larval migration in haematoma formation are suggested. [source]

Cerebral near infrared spectroscopy for the measurement of indocyanine green elimination in cirrhosis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2000
Therapondos
Background: Indocyanine green (ICG) clearance is a useful indicator of hepatic function but most measurement methods are invasive. Aim: To validate a less invasive technique using cerebral near infrared spectrophotometry (NIRS) to measure ICG elimination, and to compare it with the established methods for the determination of ICG clearance in a group of normal controls and patients with cirrhosis. Method: NIRS was used to measure ICG elimination in 41 cirrhotic patients and nine healthy volunteers. The first 13 of the cirrhotic patients also had their ICG clearance measured by the conventional spectrophotometric technique. Results: NIRS ICG elimination rate (ICG-k) and spectrophotometry ICG-k values correlated strongly (r= 0.828, P < 0.001, n=13). There was a significant reduction in the mean NIRS-k in cirrhotic patients and within Child,Pugh classes A, B, and C (P < 0.001). Conclusion: Measurement of ICG elimination by the NIRS method is at least as reliable as the conventional spectrophotometric technique in normals and in patients with cirrhosis. This technique merits further development for use as a bedside, less invasive liver function test. [source]

Proton transfer ratio, lactate, and intracellular pH in acute cerebral ischemia

MAGNETIC RESONANCE IN MEDICINE, Issue 4 2007
Kimmo T. Jokivarsi
Abstract The amide proton transfer ratio (APTR) from the asymmetry of the Z -spectrum was determined in rat brain tissue during and after unilateral middle cerebral artery occlusion (MCAo). Cerebral lactate (Lac) as determined by 1H NMR spectroscopy, water diffusion, and T1, were quantified as well. Lac concentrations were used to estimate intracellular pH (pHi) in the brain during the MCA occlusion. A decrease in APTR during occlusion indicated acidification from 7.1 to 6.79 ± 0.19 (a drop by 0.3 ± 0.2 pH units), whereas pHi computed from Lac concentration was 6.3 ± 0.2 (a drop by 0.8 ± 0.2 pH units). Despite the disagreement between the two methods in terms of the size of the change in the absolute pHi during ischemia, ,APTR and pHi (and Lac concentration) displayed a strong correlation during the MCAo. Diffusion and T1, indicated cytotoxic edema following MCA occlusion; however, APTR returned slowly toward the values determined in the contralateral hemisphere post-ischemia. These data argue that the APTR during ischemia is affected not only by pHi but by other physicochemical factors as well, and indicates different aspects of pathology in the post-ischemic brain compared to those that influence water diffusion and T1,. Magn Reson Med 57:647,653, 2007. © 2007 Wiley-Liss, Inc. [source]

The relationship between cerebral and somatic oxygenation and superior and inferior vena cava flow, arterial oxygenation and pressure in infants during cardiopulmonary bypass,

ANAESTHESIA, Issue 3 2009
M. C. White
Summary We investigated blood flow and regional oxygenation (rSO2) during cardiopulmonary bypass (CPB). Twenty infants (mean (SD) age 5 (3) months, weight 5.4 (1.6) kg) were prospectively studied. Total CPB and superior vena cava (SVC) flow were measured using Transonic Bypass Flowmeters, inferior vena cava (IVC) flow derived arithmetically and rSO2 measured using Near Infra-Red Spectroscopy. Mean SVC flow was 51.3 (14.8) ml.kg,1.min,1 and mean IVC flow 62.5 (19.0) ml.kg,1.min,1. Mean cerebral rSO2 was 71 (11)% and somatic rSO2 55 (13)%. Cerebral and somatic rSO2 showed no correlation with SVC and IVC flow. Cerebral rSO2 showed a positive correlation with Paco2, mean arterial pressure (MAP) and haematocrit (p < 0.0001). Somatic rSO2 showed a positive correlation with MAP and haematocrit (p = 0.01, p = 0.02). In conclusion, the distribution of blood flow during CPB varies. The most important factor affecting this is Paco2. Cerebral and somatic oxygenation are unaffected by flow but significantly influenced by MAP, haematocrit and Paco2. [source]

A response to ,Cerebral and extracerebral release of protein S100B in cardiac surgical patients', Snyder-Ramos SA, Gruhlke T, Bauer H, Bauer M, Luntz AP, Motsch J, Martin E, Vahl CF, Missler U, Wiesmann M and Bottiger BW, Anaesthesia 2004; 59: 344,9

ANAESTHESIA, Issue 11 2004
D. Janigro
No abstract is available for this article. [source]

Association of carotid artery atheromatous plaque types with cerebral perfusion

ANZ JOURNAL OF SURGERY, Issue 11 2009
Dong Yan Gao
Abstract Background:, In an attempt to define the association of internal carotid artery atheromatous plaque morphology with potential cerebral ischaemia, we have investigated the relationship of different carotid plaque types with defects in cerebral perfusion. Methods:, In 130 patients requiring surgical correction of internal carotid artery stenoses greater than 70%, defects in cerebral perfusion due to both haemodynamic insufficiency and intracerebral vessel occlusion were identified using single photon emission computed tomography scans (SPECT). Carotid artery plaques in these patients were classified as homogeneous or heterogeneous based on preoperative Doppler Duplex Scanning and on the macroscopic characteristics of the plaques recorded by the surgeon during carotid endarterectomy, with sub-classification into potentially embolus-generating and non- embolus-generating plaques. In individual patients, plaque types were then correlated with the perfusion defects found in the SPECT scans. Results:, Of 130 patients, 112 (86%) had cerebral perfusion defects. In 56 asymptomatic patients in the study, 48 (85.7%) had perfusion defects as did 64 (86.5%) of 74 symptomatic patients. Cerebral infarcts were seen in 41 (31.5%). Occlusive infarcts (66%) were twice as frequent as haemodynamic insufficiency infarcts (34%). Eighteen patients with small cerebral infarcts on SPECT scanning gave no medical history of cerebral symptoms. Statistical analysis of the results revealed that there was no statistically identifiable association between carotid plaque type and the generation of cerebral symptoms or infarction. Conclusion:, This study found that internal carotid plaque morphology has no statistically significant association with perfusion defects, symptoms or cerebral infarction in patients with significant internal carotid artery stenosis. Also, it is suggested that haemodynamic cerebral infarction may be more common that previously believed (34% of infarcts identified in the study). Further, it is suggested that plaque morphology alone is not an indication for carotid endarterectomy. [source]

Cerebral Microinfarcts Associated with Severe Cerebral ,-Amyloid Angiopathy

BRAIN PATHOLOGY, Issue 2 2010
Virawudh Soontornniyomkij
Abstract Cerebral amyloid angiopathy (CAA) is common in elderly individuals, especially those affected with Alzheimer's disease. Eighteen brains with severe SCAA (SCAA) were compared with 21 brains with mild CAA (MCAA) to investigate whether the presence of SCAA in the brains of demented patients was associated with a higher burden of old microinfarcts than those with MCAA. Immunohistochemistry for CD68 was employed to highlight old microinfarcts in tissue blocks from various brain regions. Old microinfarcts, manually counted by light microscopy, were present in 14 of 18 SCAA brains and in 7 of 21 MCAA brains (P = 0.01, two-tailed Fisher's exact test). The average number of old microinfarcts across geographic regions in each brain ranged from 0 to 1.95 (mean rank 24.94, sum of ranks 449) in the SCAA group, and from 0 to 0.35 (mean rank 15.76, sum of ranks 331) in the MCAA group (P = 0.008, two-tailed Mann,Whitney U-test). Frequent old microinfarcts in demented individuals with severe CAA may contribute a vascular component to the cognitive impairment in these patients. [source]

Cerebral and pulmonary nocardia in a bone marrow transplant patient

BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2005
A. D. Laurence
No abstract is available for this article. [source]

How to identify patients with vulnerable plaques

DIABETES OBESITY & METABOLISM, Issue 10 2008
Salim S. Virani
Multiple strategies are available for clinicians to identify patients at high risk for cardiovascular events. Two commonly discussed strategies are the identification of vulnerable plaques and the identification of vulnerable patients. The strategy of identifying vulnerable patients is less invasive, easy to implement and not restricted primarily to one vascular bed (e.g. coronary or cerebral). This review discusses the utility as well as the limitations of global risk assessment tools to identify such patients. The utility of biomarkers [C-reactive protein, lipoprotein-associated phospholipase A2 and lipoprotein(a)] and non-invasive measures of atherosclerosis burden (coronary artery calcium scores, carotid intima,media thickness and ankle,brachial index) in identifying patients at high risk for cardiovascular events are also discussed. [source]

Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures

EPILEPSIA, Issue 9 2010
Annelies Van Dycke
Summary Purpose:, Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug-related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods:, Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 ,l/h) (treatment). In 7 of 10 adenosine-treated rats, saline was also delivered during a washout period. Results:, During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine-treated rats (p < 0.01). Four rats had a seizure frequency reduction of at least 50%. Both nonconvulsive and convulsive seizures significantly decreased during the treatment period. In the saline-control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions:, This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures. [source]

Cerebral Damage in Epilepsy: A Population-based Longitudinal Quantitative MRI Study

EPILEPSIA, Issue 9 2005
Rebecca S. N. Liu
Summary:,Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community-based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex. Methods: One hundred seventy-nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times. Results: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy. Conclusions: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age-related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures. [source]

Functional approach to investigate Lp(a) in ischaemic heart and cerebral diseases

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2003
A. De La Peña-Díaz
Abstract Background Lp(a), a major cardiovascular risk factor, contains a specific apolipoprotein, apo(a), which by virtue of structural homology with plasminogen inhibits the formation of plasmin, the fibrinolytic enzyme. A number of clinical reports support the role of Lp(a) as a cardiovascular or cerebral risk factor, and experimental data suggest that it may contribute to atherothrombosis by inhibiting fibrinolysis. Design A well-characterized model of a fibrin surface and an apo(a)-specific monoclonal antibody were used to develop a functional approach to detect pathogenic Lp(a). The assay is based on the competitive binding of Lp(a) and plasminogen for fibrin, and quantifies fibrin-bound Lp(a). High Lp(a) binding to fibrin is correlated with decreased plasmin formation. In a transversal case,control study we studied 248 individuals: 105 had a history of ischaemic cardiopathy (IC), 52 had cerebro-vascular disease (CVD) of thrombotic origin, and 91 were controls. Results The remarkably high apo(a) fibrin-binding in CVD (0·268 ± 0·15 nmol L,1) compared with IC (0·155 ± 0·12 nmol L,1) suggests the existence of peculiar and poorly understood differences in pro- or anti-thrombotic mechanisms in either cerebral and/or coronary arteries. Conclusions Our results demonstrated that Lp(a) fibrin-binding and small Apo(a) isoforms are associated with athero-thrombotic disease. [source]

High prevalence of unrecognized cerebral infarcts in first-ever stroke patients with cardioembolic sources

EUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2009
A.-H. Cho
Background:, With magnetic resonance imaging (MRI) analysis, we investigated the prevalence, clinical significance, and factors related to the presence of unrecognized cerebral infarcts in patients with first-ever ischaemic stroke. Methods:, We consecutively included patients who were admitted with first-ever stroke. Unrecognized cerebral infarct was defined as an ischaemic infarction or primary intracerebral hemorrhage on MRI irrelevant to the index stroke, without acute lesions on diffusion-weighted image. Results:, Of the total 203 patients, 78 (39.4%) patients were observed as having unrecognized cerebral infarct. Patients with high-risk cardioembolic sources (e.g., atrial fibrillation) more frequently had unrecognized stroke than those without (P = 0.008, 21/36 [58.3%] vs. 57/167 [34.1%]). On univariate analysis, male sex (P = 0.027) and cardioembolic source (P = 0.008) were associated with the presence of unrecognized cerebral infarcts. After adjustment for gender, age and risk factors, the presence of cardioembolic sources independently increased the risk of unrecognized cerebral infarct (P = 0.002, odds ratio 3.56, 95% confidence interval 1.58,8.02). Regarding clinical outcome at 3 months, the presence of unrecognized cerebral infarct was not associated with the poor clinical outcome. Conclusion:, In our study, the presence of cardioembolic sources was an independent risk factor for the unrecognized cerebral infarct in patients with first-ever stroke. [source]

Cerebral vasomotor reactivity of bilateral severe carotid stenosis: is stroke unavoidable?

EUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2006
A. Y. Gur
We evaluated the cerebral hemodynamic features of severe bilateral carotid stenosis by assessing and comparing cerebral vasomotor reactivity (VMR) in the middle cerebral (MCA) and vertebral arteries (VA) by transcranial Doppler and the Diamox (1 g acetazolamide i.v.) test. VMR was evaluated by recording the percentage differences in peak systolic blood flow velocity in each MCA and VA at baseline and by the Diamox test. Twenty-eight symptomatic (SCAS) and 31 asymptomatic (ACAS) patients with bilateral severe (>70%) internal carotid artery stenosis were studied. The mean MCA VMR% was 29 ± 26.9% in SCAS and 43.2 ± 26.8% in ACAS patients (P < 0.01). Their respective mean VA VMR% was 30.2 ± 36.5% and 39.6 ± 24.4% (P = NS). VMR% of the symptomatic MCA side in SCAS patients was significantly lower than the opposite side (20.5 ± 31.1% and 39.2 ± 37.9% respectively; P < 0.03). In contrast, the VA VMR% of both sides in SCAS patients remained similar (28.1 ± 39.3% and 34.6 ± 47.9% respectively; P = NS). VMR% of the MCA and VA in ACAS patients was also similar for both sides of bilateral carotid stenosis. The cerebral hemodynamic features differ between SCAS and ACAS patients with bilateral carotid occlusive disease in the anterior part of the circle of Willis. An independent cerebral vascular reserve capacity of the posterior circulation is proposed. [source]

Iatrogenic Creutzfeldt,Jakob disease subsequent to dural graft: persisting risk after 1987

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2003
C. Boutoleau
The first case of Creutzfeldt,Jakob disease (CJD) related to the use of a dura mater graft of cadaveric origin was identified in 1987 and this procedure is now considered as one of the main causes of iatrogenic CJD. Although the decontamination procedure for the preparation of graft material was modified, the product was withdrawn from the market in many countries a few years later and replaced by synthetic material. In this context, two patients treated in our institution developed CJD following a cadaveric dural graft performed after cerebral and lumbar trauma. Their clinical presentation, showing predominant cerebellar symptoms, late deterioration and myoclonic jerks, and a rapid disease course until death, was similar to that of previously reported cases involving the iatrogenic form. As the graft for one of the patients was performed in 1991 (several years after modification of the decontamination procedure), this fourth reported case suggests that the risk of iatrogenic CJD may have persisted in some patients treated after 1987, when grafts of cadaveric origin were totally abandoned. [source]

Myotonic dystrophy type 2

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2002
J. Finsterer
Myotonic dystrophy type 2 (DM2) is a clinically but not genetically heterogeneous, multisystem disorder, that is clinically similar to, but distinct from myotonic dystrophy type 1 (DM1). Initially, different phenotypes of DM2 were described by Ricker (proximal myotonic myopathy, PROMM), Ranum (myotonic dystrophy 2, DM2) and Udd (proximal myotonic dystrophy, PDM). Clinical features these three phenotypes had in common were diffuse, proximal or distal weakness, wasting, myotonia, cataract, cerebral, endocrine and cardiac abnormalities. Initially, the clinical differences between DM1 and PROMM seemed unmistakable, but meanwhile it has become apparent that the clinical differences between these entities are blurring. In 1999, Day et al., Meola et al. and Ricker et al. mapped the mutated gene of all three phenotypes to chromosome 3q. In 2001, the three different phenotypes were found to rely on the same mutation in the ZNF9 gene on chromosome 3q21.3. Although DM2 may be clinically heterogeneous, it is by result of a mutation in a single gene. The mutation responsible for DM2 is a CCTG-repeat expansion of 75,11 000 repeats in intron 1 of the ZNF9 gene on chromosome 3q21.3. Because of the clinical heterogeneity, the diagnosis of DM2 should rely on DNA analysis alone. [source]

Genetic reductions of ,-site amyloid precursor protein-cleaving enzyme 1 and amyloid-, ameliorate impairment of conditioned taste aversion memory in 5XFAD Alzheimer's disease model mice

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2010
Latha Devi
Abstract Although transgenic mouse models of Alzheimer's disease (AD) recapitulate amyloid-, (A,)-related pathologies and cognitive impairments, previous studies have mainly evaluated their hippocampus-dependent memory dysfunctions using behavioral tasks such as the water maze and fear conditioning. However, multiple memory systems become impaired in AD as the disease progresses and it is important to test whether other forms of memory are affected in AD models. This study was designed to use conditioned taste aversion (CTA) and contextual fear conditioning paradigms to compare the phenotypes of hippocampus-independent and -dependent memory functions, respectively, in 5XFAD amyloid precursor protein/presenilin-1 transgenic mice that harbor five familial AD mutations. Although both types of memory were significantly impaired in 5XFAD mice, the onset of CTA memory deficits (,9 months of age) was delayed compared with that of contextual memory deficits (,6 months of age). Furthermore, 5XFAD mice that were genetically engineered to have reduced levels of ,-site amyloid precursor protein-cleaving enzyme 1 (BACE1) (BACE1+/,·5XFAD) exhibited improved CTA memory, which was equivalent to the performance of wild-type controls. Importantly, elevated levels of cerebral ,-secretase-cleaved C-terminal fragment (C99) and A, peptides in 5XFAD mice were significantly reduced in BACE1+/,·5XFAD mice. Furthermore, A, deposition in the insular cortex and basolateral amygdala, two brain regions that are critically involved in CTA performance, was also reduced in BACE1+/,·5XFAD compared with 5XFAD mice. Our findings indicate that the CTA paradigm is useful for evaluating a hippocampus-independent form of memory defect in AD model mice, which is sensitive to rescue by partial reductions of the ,-secretase BACE1 and consequently of cerebral A,. [source]

LPL polymorphism predicts stroke risk in men

GENETIC EPIDEMIOLOGY, Issue 3 2002
Alanna C. Morrison
Abstract Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE ,2- and ,4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23,15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24,5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors. Genet. Epidemiol. 22:233,242, 2002. © 2002 Wiley-Liss, Inc. [source]

Pharmacology of the Selective 5-HT1B/1D Agonist Frovatriptan

HEADACHE, Issue 2002
M.B. Comer BSc
Objective.,To determine the pharmacological profile of frovatriptan. Background.,Frovatriptan is a new 5-HT1B/1D agonist developed for the treatment of migraine. Methods.,Pharmacological studies were performed using in vitro and in vivo techniques. Results.,Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT1B and 5-HT1D receptors, and moderate affinity for 5-HT1A, 5-HT1F, and 5-HT7 receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT1B and 5-HT1D receptors, and as a moderately potent full agonist at 5-HT7 receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow. Conclusion.,The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects. [source]

Blood Flow Velocity and Pulsatility Index Differences in Patients With Unilateral Migraine

HEADACHE, Issue 7 2001
Oleg Y. Chernyshev MD
Objective.,To evaluate blood flow velocity and pulsatility in unilateral migraine without aura during the headache-free period using transcranial Doppler (TCD) sonography. Methods.,Patients with unilateral headache were recruited during the headache-free period. Maximum mean flow velocity (MFV) and pulsatility index (PI) were measured in the middle cerebral (MCA) and basilar arteries. Controls were headache-free individuals without cerebrovascular disease. Results.,Twenty-five patients with right-sided migraine, 25 patients with left-sided migraine, and 19 controls were studied. The MCA PI was higher on the right headache side versus the left headache side (0.97 ± 0.2 versus 0.86 ± 0.1 cm/s, P = .02) and versus controls (0.9 ± 0.2 cm/s, NS). The basilar artery MFV was higher in patients with right-sided headache versus left-sided headache (39.5 ± 5.6 versus 34.7 ± 8.2 cm/s, P = .02) and versus controls (38.2 ± 8 cm/s, NS). No decrease in MFV with age was observed in patients with migraine. Conclusions.,Middle cerebral artery flow pulsatility and basilar artery velocity are higher in patients with right-sided migraine compared with left-sided migraineurs, during the headache-free period. Although these parameters were similar to controls, the differences found during the headache-free period in migraineurs may indicate vascular involvement predisposing to the unilateral headache recurrence. [source]

Homocysteine Level and Cognitive Function in Patients with Arterial Disease: The Second Manifestations of ARTerial Disease Study

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2006
Fleur van A. Raamt MD
OBJECTIVES: To assess the relationship between total plasma homocysteine (tHcy) level and cognitive function in patients with manifest arterial disease. DESIGN: Cross-sectional. SETTING: Patients with symptomatic cerebrovascular disease, cardiovascular disease, peripheral arterial disease, or abdominal aortic aneurysm included in the Second Manifestations of ARTerial disease study, a single-center, longitudinal study with an extensive screening program at baseline. PARTICIPANTS: Three hundred forty-five consecutively included patients, mean age 59. MEASUREMENTS: The patients underwent an extensive neuropsychological test. The cognitive domains assessed were memory, executive function, attention, and visuoperception and construction. Each raw score was transformed into standardized z-scores, and a sum score for global cognitive function was determined. Risk factors and vascular damage were measured in detail. RESULTS: Linear regression showed that elevated levels of tHcy were related to lower global cognitive function (,=,0.065, 95% confidence interval (CI)=,0.116 to ,0.013) and, more specifically, lower performance on memory (,=,0.078, 95% CI=,0.155 to ,0.002), attention (,=,0.079, 95% CI=,0.163 to ,0.005), and visuoperception and construction (,=,0.125, 95% CI=,0.236 to ,0.014) per standard deviation increase in tHcy (SD=6.4 mol/L), after adjustment for age, sex, educational level, extent of atherosclerosis, and location of vascular disease. Silent cerebral infarcts did not influence this relationship. CONCLUSION: A relationship was found between tHcy levels and cognitive function that was independent of extent and location of arterial disease. The results suggest that vascular mechanisms are not responsible for the relationship between tHcy and cognitive function. [source]

Regular or "Super-Aspirins"?

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2001
A Review of Thienopyridines or Aspirin to Prevent Stroke
PURPOSE: To review the evidence for the effectiveness and safety of the thienopyridines (ticlopidine and clopidogrel) compared with aspirin for the prevention of vascular events among patients at high risk of vascular disease. BACKGROUND: Atherosclerosis and resultant cardiovascular disease are important causes of morbidity and mortality in older people. In particular, atherosclerosis of the cerebral arteries can lead to transient ischemic attacks (TIAs) and stroke. Stroke ranks as the third-leading cause of death in the United States and in 1997 was responsible for over 150,000 fatalities.1 In addition to the mortality associated with this disease, stroke is also a leading source of long-term disability in survivors. Nearly 4.5 million stroke survivors are alive today,1 highlighting the fact that primary, but also secondary, prevention are extremely important for minimizing the complications of this illness. DATA SOURCES: Specialized trial registers of the Cochrane Stroke Group and the Antithrombotic Trialist's Collaboration, MEDLINE, and Embase were searched. Additional unpublished information and data were sought from Sanofi, the pharmaceutical company that developed and manufactures ticlopidine and clopidogrel, as well as the principal investigators of the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial,7 the largest of the trials identified. STUDY SELECTION CRITERIA: All unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin among patients at high risk of vascular disease (those with symptoms of ischemia of the cerebral, coronary, or peripheral circulations) who were followed for at least 1 month for the recurrence of vascular events were included. DATA EXTRACTION: Data were extracted from four completed randomized trials completed in the past 20 years, which included 22,656 patients.7,10 Two authors independently extracted the data from these trials for the following information: the types of patients enrolled; the entry and exclusion criteria; the randomization method; the number of patients originally allocated to the treatment and control groups; the method and duration of follow-up; the number of patients in each group lost to follow-up; information on compliance with the treatment allocated; the definitions of outcome events; the number of outcome events in each treatment group; and any method used for blinding patients, treating clinicians, and outcome assessors to treatment allocation. MAIN RESULTS: Four completed trials involving a total of 22,656 patients were identified. Aspirin was compared with ticlopidine in three trials (3,471 patients)8,10 and with clopidogrel in one trial (19,185 patients).7 A recent TIA or ischemic stroke was the qualifying event in 9,840 patients, a recent myocardial infarction in 6,302 patients, and symptomatic peripheral arterial disease in 6,514 patients. The average age of the patients was approximately 63, with approximately two-thirds of the patients being male and white. The duration of follow-up ranged from 12 to 40 months. CONCLUSIONS: This systematic review demonstrates that, compared with aspirin, thienopyridines are only modestly more effective in preventing serious vascular events in high-risk patients. For patients who are intolerant of, or allergic to aspirin, the available safety and efficacy data suggest that clopidogrel is an appropriate, but more-expensive, alternative antiplatelet drug. It appears safer than ticlopidine and as safe as aspirin but it should not replace aspirin as the first-choice antiplatelet agent for all patients. Further studies are necessary to determine which, if any, particular types of patients would benefit most and least from clopidogrel instead of aspirin. [source]

Facial surface analysis by 3D laser scanning and geometric morphometrics in relation to sexual dimorphism in cerebral,craniofacial morphogenesis and cognitive function

JOURNAL OF ANATOMY, Issue 3 2005
Robin J. Hennessy
Abstract Over early fetal life the anterior brain, neuroepithelium, neural crest and facial ectoderm constitute a unitary, three-dimensional (3D) developmental process. This intimate embryological relationship between the face and brain means that facial dysmorphogenesis can serve as an accessible and informative index of brain dysmorphogenesis in neurological and psychiatric disorders of early developmental origin. There are three principal challenges in seeking to increase understanding of disorders of early brain dysmorphogenesis through craniofacial dysmorphogenesis: (i) the first, technical, challenge has been to digitize the facial surface in its inherent three-dimensionality; (ii) the second, analytical, challenge has been to develop methodologies for extracting biologically meaningful shape covariance from digitized samples, making statistical comparisons between groups and visualizing in 3D the resultant statistical models on a ,whole face' basis; (iii) the third, biological, challenge is to demonstrate a relationship between facial morphogenesis and brain morphogenesis not only in anatomical,embryological terms but also at the level of brain function. Here we consider each of these challenges in turn and then illustrate the issues by way of our own findings. These use human sexual dimorphism as an exemplar for 3D laser surface scanning of facial shape, analysis using geometric morphometrics and exploration of cognitive correlates of variation in shape of the ,whole face', in the context of studies relating to the early developmental origins of schizophrenia. [source]

Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures

JOURNAL OF ANATOMY, Issue 4 2005
Niall Patton
Abstract The retinal and cerebral microvasculatures share many morphological and physiological properties. Assessment of the cerebral microvasculature requires highly specialized and expensive techniques. The potential for using non-invasive clinical assessment of the retinal microvasculature as a marker of the state of the cerebrovasculature offers clear advantages, owing to the ease with which the retinal vasculature can be directly visualized in vivo and photographed due to its essential two-dimensional nature. The use of retinal digital image analysis is becoming increasingly common, and offers new techniques to analyse different aspects of retinal vascular topography, including retinal vascular widths, geometrical attributes at vessel bifurcations and vessel tracking. Being predominantly automated and objective, these techniques offer an exciting opportunity to study the potential to identify retinal microvascular abnormalities as markers of cerebrovascular pathology. In this review, we describe the anatomical and physiological homology between the retinal and cerebral microvasculatures. We review the evidence that retinal microvascular changes occur in cerebrovascular disease and review current retinal image analysis tools that may allow us to use different aspects of the retinal microvasculature as potential markers for the state of the cerebral microvasculature. [source]

Giant Aneurysm After Aortic Coarctation: Repair without Circulatory Arrest

JOURNAL OF CARDIAC SURGERY, Issue 5 2010
D.E.S.A., Gabor Erdoes M.D.
Using the hemi-clamshell approach, the entire aortic arch was replaced and the supraaortic branches were reimplanted. The applied surgical technique using hypothermic extracorporeal circulation without cardiac arrest allowed an uninterrupted cerebral and spinal cord perfusion due to stepwise clamping of the aortic arch during reconstruction and resulted in an excellent neurologic outcome at six-month follow-up.,(J Card Surg 2010;25:560-562) [source]

Erythrocytapheresis for Plasmodium falciparum infection complicated by cerebral malaria and hyperparasitemia

JOURNAL OF CLINICAL APHERESIS, Issue 1 2001
Y. Zhang
Abstract In malaria due to Plasmodium falciparum, life-threatening complications are in part related to the degree of parasitemia. Whole blood exchange and red blood cell exchange (RCE) have been used for the rapid removal of parasites from the circulation of patients with a high parasite load complicated by cerebral, pulmonary, and renal dysfunction. We have treated three 5,45-year-old patients with hyperparasitemia and end-organ dysfunction with red cell exchange by automated apheresis as an adjunct to specific anti-malarial chemotherapy. Parasitemia dropped more than 80% in all three patients immediately after the exchange, and all patients had an uneventful and full recovery. In combination with effective anti-malarial chemotherapy, apheresis RCE is a safe and rapid approach to treat complicated malaria due to P. falciparum. J. Clin. Apheresis. 16:15-18, 2001. © 2001 Wiley-Liss, Inc. [source]

A novel epidermal nevus syndrome with congenital cylindromatous turban tumor

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2003
Jacinto J. Regalado
Background:, Epidermal nevi (in the broad sense of epithelial nevi) may give rise to benign or malignant skin tumors. They may also be associated with anomalies of other organ systems in an epidermal nevus syndrome. Results:, This article describes a preterm infant with nevus sebaceus of the scalp and face, a large turban tumor with features of malignant cylindroma and multiple non-cutaneous defects. These included skeletal, hematopoietic, hepatobiliary, and urinary anomalies. Severe secondary lesions were present (pulmonary hypoplasia due to oligohydramnios; cerebral infarcts probably related to the turban tumor). Karyotype was normal, and family history was negative. Conclusions:, This unique case is unlike any reported epidermal nevus syndrome. Similarly, there is no prior report of a congenital cylindroma, certainly not as a turban tumor, which implies very rapid growth. The presence of both overgrowth and undergrowth phenomena (e.g. hypoplastic urinary tract and biliary atresia) may reflect dysregulation of paracrine growth factors, presumably due to genetic mutation. [source]

Forensic Considerations in Cases of Neurofibromatosis,An Overview

JOURNAL OF FORENSIC SCIENCES, Issue 5 2007
Roger W. Byard M.B.B.S.
Abstract:, Neurofibromatosis types 1 and 2 are inherited neurocutaneous disorders characterized by a variety of manifestations that involve the circulatory system, the central and peripheral nervous systems, the skin, and the skeleton. Significant reduction in lifespan occurs in both conditions often related to complications of malignancy and hypertension. Individuals with these conditions may also be the subject of medicolegal autopsy investigation if sudden death occurs. Unexpected lethal events may be associated with intracranial neoplasia and hemorrhage or brainstem compression. Vasculopathy with fibrointimal proliferation may result in critical reduction in blood flow within the coronary or cerebral circulations, and aneurysmal dilatation may be associated with rupture and life-threatening hemorrhage. An autopsy approach to potential cases should include review of the history/hospital record, liaison with a clinical geneticist (to include family follow-up), a full external examination with careful documentation of skin lesions and nodules, measurement of the head circumference in children, photography, possible radiologic examination, a standard internal autopsy examination, documentation of the effects of previous surgery and/or chemo/radiotherapy, examination for specific tumors, specific examination and sampling of vasculature (renal, cerebral, and cardiac), formal neuropathologic examination of brain and spinal cord, possible examination of the eyeballs, examination of the gastrointestinal tract, histology to include tumors, vessels, gut, and bone marrow, toxicological testing for anticonvulsants, and sampling of blood and tissue for possible cytogenetic/molecular evaluation if required. [source]

Who should receive a statin these days?

JOURNAL OF INTERNAL MEDICINE, Issue 4 2006
Lessons from recent clinical trials
Abstract. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1,2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease. [source]