Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Neuroinflammation in obesity: circulating lipopolysaccharide-binding protein associates with brain structure and cognitive performance.

BACKGROUND/OBJECTIVES: Growing evidence implicates neuroinflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Obesity is associated with reduced white matter integrity and cognitive decline. Circulating lipopolysaccharide binding protein (LBP) concentration is known to be increased in patients with obesity. Here, we aimed to evaluate whether circulating LBP is associated longitudinally with white matter structure and cognitive performance according to obesity status. SUBJECTS/METHODS: This longitudinal study analyzed circulating LBP (ELISA), DTI-metrics (axial diffusivity (L1), fractional anisotropy (FA) and radial diffusivity (RD)) in specific regions of the white matter of 24 consecutive middle-aged obese subjects (13 women) and 20 healthy volunteers (10 women) at baseline and two years later. Digit Span Test (DST) was used as a measure of working memory/short-term verbal memory. RESULTS: Circulating LBP concentration was associated with FA and L1 values of several white matter regions both at baseline and follow-up. The associations remained significant after controlling for age, BMI, fat mass and plasma high sensitivity C-reactive protein. Importantly, the increase in LBP over time impacted negatively on FA and L1 values and on DST performance. CONCLUSIONS: Circulating LBP associates with brain white matter integrity and working memory/short-term verbal memory in both obese and non-obese subjects.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Comparative study of whole-body MRI and bone scintigraphy for the detection of bone metastases.

AIM: To assess and compare the diagnostic accuracy of whole-body magnetic resonance imaging (MRI) and bone scintigraphy in the detection of metastases to bone. MATERIAL AND METHODS: Forty randomly selected patients with known malignant tumours were prospectively studied using bone scintigraphy and whole-body MRI. Two patients were excluded. Symptoms of bone metastasis were present in 29 (76%) patients and absent in nine (24%). Findings were classified into four categories according to the probability of bone metastasis: (1) negative, (2) probably negative, (3) probably positive, and (4) positive. Diagnostic accuracy was determined according to the area under the receiver operating characteristic (ROC) curve. The definitive diagnosis was reached using other imaging techniques, biopsy, or 12 months clinical follow-up. RESULTS: Metastases were present in 18 patients. The sensitivity, specificity, and diagnostic accuracy were 94, 90, and 92%, respectively, for whole-body MRI and 72, 75, and 74%, respectively, for bone scintigraphy. Diagnostic accuracy measured by the area under the ROC curve was significantly higher for whole-body MRI (96%) than for bone scintigraphy (77%; p<0.05). Interobserver agreement measured by the kappa index was significantly higher for whole-body MRI (0.895) than for bone scintigraphy (0.524; p<0.05). Whole-body MRI detected lesions in tissues other than bone in 17 (45%) patients. CONCLUSIONS: Whole-body MRI is more accurate and more objective than bone scintigraphy for the detection of bone metastases. Whole-body MRI can also detect lesions in tissues other than bone.

18F-FDG PET/CT in staging and delineation of radiotherapy volume for head and neck cancer. / 18F-FDG PET/TC para la estadificación y la delineación del volumen de radioterapia en el cáncer de cabeza y cuello.

PURPOSE: The aim is to investigate the use of 18F-FDG (fluorine-18 fluorodeoxyglucose) PET/CT in head and neck cancer (HNC) staging and its effect on the therapeutic strategy and radiotherapy (RT) planning. METHODS AND MATERIALS: One hundred patients with HNC were included. Primary tumor sites: 18% oral cavity, 20% oropharynx, 12% hypopharynx, 11% nasopharynx, 37% larynx, 2% paranasal sinuses. Patients were staged according to the American Joint Committee of Cancer 7th edition. Stage: 5% stage I, 7% stage II, 14% stage III, 61% stage IVA, 7% stage IVB and 6% stage IVC. A contrast-enhanced CT and a 18F-FDG PET/CT acquired under RT position were performed. Both exams were compared to analyze patients' staging reclassification. Changes in therapeutic strategy were analyzed. RESULTS: 18F-FDG PET/CT detected 6 distant metastases and treatment intention changed to palliative. Eight synchronous tumors were detected; one received palliative treatment. 18F-FDG PET/CT reclassified cTNM staging in 27patients. Tumor extension changed in 28 (14% up-staged; 14% down-staged), implying a change in GTV (Gross Tumor Volume) delineation. Nodal detection was reclassified in 47 patients: 8 patients down-staged (N2C to N2A/N2B/N1) and 2 were false positive. Nineteen patients were false negatives and 5 staged as N+(N1/N2A/N2B) turned out into N2C. These staging modifications imply adapting the nodal volume to be irradiated. CONCLUSIONS: 18F-FDG PET/CT reclassification was higher than 10% in almost all categories studied (cTNM, tumor extension and nodal disease) and detects more metastases and synchronous tumors than conventional studies, which has an impact on the therapeutic patient management and RT planning.

Predicting Motor Outcome in Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Predicting motor outcome following intracerebral hemorrhage is challenging. We tested whether the combination of clinical scores and DTI-based assessment of corticospinal tract damage within the first 12 hours of symptom onset after intracerebral hemorrhage predicts motor outcome at 3 months. MATERIALS AND METHODS: We prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. We assessed intracerebral hemorrhage and perihematomal edema location and volume, and corticospinal tract involvement. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage or/and the perihematomal edema. We also calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Motor impairment was graded by the motor subindex scores of the modified NIHSS. Motor outcome at 3 months was classified as good (modified NIHSS 0-3) or poor (modified NIHSS 4-8). RESULTS: Of 62 patients, 43 were included. At admission, the median NIHSS score was 13 (interquartile range = 8-17), and the median modified NIHSS score was 5 (interquartile range = 2-8). At 3 months, 13 (30.23%) had poor motor outcome. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively (area under the curve = 0.89; 95% CI, 0.78-1). CONCLUSIONS: Combined assessment of motor function and posterior limb of the internal capsule damage during acute intracerebral hemorrhage accurately predicts motor outcome.

Comparative overview of brain perfusion imaging techniques.

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.

MRI findings in Möbius syndrome: correlation with clinical features.

The authors studied the MRI findings of three patients with Möbius syndrome. Möbius syndrome is a rare congenital disorder characterized by complete or partial facial diplegia accompanied by other cranial nerve palsies. MRI demonstrated brainstem hypoplasia with straightening of the fourth ventricle floor, indicating an absence of the facial colliculus. These MRI features suggest the diagnosis of Möbius syndrome and correlate with the clinical and neurophysiologic findings.

Neuropsychological outcome in relation to the traumatic coma data bank classification of computed tomography imaging.

The Traumatic Coma Data Bank (TCDB) classification of CT (computed tomography) scan has been related to the general outcome and intracranial pressure evolution. Our aim was to analyse the relationship of this classification with neuropsychological outcome and late indices of ventricular dilatation. Fifty-seven patients with a moderate or severe head injury (mean admission Glasgow Coma Scale Score, 7.7) were studied from 122 consecutive cases. There were 49 males and 8 females (mean age, 27.7 years). Subjects were classified into TCDB categories on the basis of their most serious acute CT scan finding. From the last control CT scan image, performed at a mean of 6.12 months postinjury, several measures of ventricular dilatation were calculated. Neuropsychological assessment at 6-month included tests of verbal and visual memory, visuoconstructive functions, fine motor speed, and frontal lobe functions. Patients with diffuse injury type I showed better neuropsychological outcome than patients with more severe diffuse injuries and those with mass lesions. Within the diffuse injury groups, the degree of diffuse damage was related to measures of verbal memory and attention and cognitive flexibility. Ventricular enlargement was more evident in patients with mass lesions and it decreased in the remaining groups as the severity of diffuse injury diminished. These results show that there is a relationship between acute intracranial lesion diagnosis according to TCDB classification and neuropsychological results and ventricular dilatation indices at 6 months postinjury.

Cerebral hemodynamic effects of 7.2% hypertonic saline in patients with head injury and raised intracranial pressure.

The aim of the present study was to investigate the acute effects of 7.2% hypertonic saline (HS) on intracranial pressure (ICP), cerebral and systemic hemodynamics, serum sodium, and osmolality in 14 patients with moderate and severe traumatic brain injury (Glasgow Coma Scale < or =13) and raised ICP (>15 mm Hg) within the first 72 h postinjury. After CO2 reactivity and autoregulation were tested, each patient received a 15-min infusion of 7.2% HS (1,232 mEq/L, volume 1.5 mL/kg). ICP, serial hemodynamics, cerebral blood flow (CBF) estimated from cerebral arteriovenous oxygen content difference (AVDO2), and laboratory variables, including serum osmolality, electrolytes, urea, and creatinine were collected before infusion (T0) and at 5, 30, 60, and 120 min after (T5, T30, T60, T120). Urine output was measured 2 h before infusion and at T120. While CO2 reactivity was preserved in all patients, autoregulation was preserved in only four. ICP decreased to about 30% of base line (p = 0.0001) during the whole study period. During the first hour after infusion, cerebral perfusion pressure (p< or =0.04) and cardiac index (CI; p< or =0.01) increased, while systemic vascular resistance index fell (p< or =0.05). Heart rate increased (p< or =0.04) during the first 30 min. Pulmonary artery occlusion pressure (PAOP) increased (p = 0.004) at T5. There were no significant changes in mean arterial blood pressure (MABP), urine output, and estimated CBF. A significant positive correlation (r = 0.75; p = 0.02) between ICP and serum osmolality was found at T5. The administration of 7.2% HS in patients with traumatic brain injury significantly reduces ICP without significant changes in relative global CBF (expressed as 1/AVDO2), increases CI and transiently increases PAOP, without changing MABP and urine output. The correlation between changes in osmolality and ICP supports the hypothesis that HSS may in part decrease ICP by means of an osmotic mechanism.

Radiologic findings in two cases of acute Schmörl's nodes.

We describe two cases of atypical acute Schmörl's nodes, one benign, the other on a tumoral vertebra. In both cases, MR imaging showed a decreased vertebral T1 signal and a slightly increased T2 signal. These signal intensities are indistinguishable from tumoral disease or inflammatory lesions. The identification of endplate defects or intranuclear cleft bending of the disk by either CT or MR may be helpful for the correct diagnosis of acute Schmörl's nodes.

Magnetization transfer ratio values and proton MR spectroscopy of normal-appearing cerebral white matter in patients with liver cirrhosis.

BACKGROUND AND PURPOSE: Hepatic encephalopathy in cirrhotic patients may be the clinical manifestation of disturbed cerebral cell volume homeostasis. The aim of this study was to investigate the presence of significant changes in magnetization transfer ratio (MTR) values, which could reflect an increase in free water within the brain of patients with liver cirrhosis, and to correlate these findings with minimal hepatic encephalopathy and proton MR spectroscopy ((1)H-MRS) abnormalities. METHODS: Twenty-four patients with liver cirrhosis and eight healthy control volunteers were included in the study. MR imaging studies included conventional T1- and T2-weighted imaging, (1)H-MRS, and magnetization transfer imaging. MTR and (1)H-MRS values were obtained from normal-appearing white matter and were correlated with each other and with the presence of minimal hepatic encephalopathy. RESULTS: (1)H-MRS showed a decrease in choline and myo-inositol and an increase in glutamine + glutamate with respect to creatine + phosphocreatine. MTR values were significantly decreased in cirrhotic patients when compared with healthy control volunteers, although this decrease was not significantly higher in the patients with minimal hepatic encephalopathy. The decreases in MTR values correlated with increases in glutamine + glutamate. CONCLUSION: The MTR decrease in patients with liver cirrhosis may be caused by low-grade astrocytic swelling produced as a response to the osmotic stress occurring in these patients. However, in this cross-sectional study, we did not find a correlation between MTR decrease and the presence of minimal hepatic encephalopathy, probably because of limitations in MTR quantification techniques.

Evolution of multiple sclerosis lesions on serial contrast-enhanced T1-weighted and magnetization-transfer MR images.

BACKGROUND AND PURPOSE: Magnetization-transfer imaging is a technique that could provide indirect evidence of the characteristics of multiple sclerosis (MS) lesions. The purpose of this work was to study the evolution of MS lesions on T1-weighted MR images over time and to investigate changes in magnetization-transfer ratio (MTR) values of MS lesions with different initial appearances on contrast-enhanced T1-weighted images. METHODS: Eleven patients with relapsing-remitting MS were studied with MR imaging. The MTRs were calculated for 47 lesions that had been classified according to their appearance on contrast-enhanced T1-weighted images. Each patient was examined at four time points over a 1-year period. The MTR changes observed in the selected lesions were compared with their initial T1-weighted appearance. RESULTS: The lowest MTR values were initially found in hypointense nonenhancing lesions and in ring-enhancing lesions, with both types showing a hypointense center. Changes in MTR values were more dynamic and reversible in ring-enhancing than in hypointense nonenhancing plaques. Nodular-enhancing lesions had slightly lower initial MTRs than did isointense non-enhancing lesions. CONCLUSION: The absence or presence of contrast uptake may indicate a different pathologic basis for hypointense MS lesions on T1-weighted MR images. These differences should be kept in mind when considering T1 lesion load as a surrogate marker of disability in MS.

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.

Magnetic resonance anatomic study of iliocava junction and left iliac vein positions related to L5-S1 disc.

STUDY DESIGN: An in vivo anatomic study analyzing the venous anatomy in the lumbosacral area was performed. OBJECTIVES: To obtain in vivo data concerning iliocava junction and left common iliac vein positions at L5-S1. SUMMARY OF BACKGROUND DATA: The left common iliac vein and the iliocava junction are at risk during L5-S1 anterior lumbar interbody fusion. Anatomic studies have demonstrated great interindividual variability in this vascular anatomy. METHODS: Magnetic resonance angiography was used to study 134 patients. Image processing was carried out with maximum intensity projection algorithm and the maximum intensity projection and addition algorithm. Iliocava junction position was measured in the maximum intensity projection and addition image. Four groups of junction position were established: very high, high, low, and very low. The left common iliac vein position was measured in axial magnetic resonance images, and three groups were established: lateral, intermediate, and medial. To describe the operative window delimited by the venous structures at L5-S1, the study population was classified into 12 configurations by combining junction position and vein position values. RESULTS: Very high lateral included 3.76% of the patients, high lateral 48.12%, high intermediate 10.53%, high medial 0.75%, low lateral 15.04%, low intermediate 4.51%, low medial 6.77%, very low lateral 0.75%, very low intermediate 2.26%, and very low medial 7.52%. Medial vein position was significantly more frequent in men. CONCLUSIONS: In 18.05% of the study population, the venous structures overlapped the center of the L5-S1 disc, reducing the operative window.

Gastrointestinal helminths of Commerson's dolphins Cephalorhynchus commersonii from central Patagonia and Tierra del Fuego.

The stomachs and intestines of 9 Commerson's dolphins incidentally caught in trawl nets in central Patagonia and 23 stranded on beaches in Tierra del Fuego were surveyed for helminth parasites. A total of 267 individuals belonging to 4 species of parasites (1 nematode, 3 digeneans) were found in the dolphins from the first area: Anisakis sp. (larvae type 1 = A. simplex), Braunina cordiformis, Hadwenius sp. and Pholeter gastrophilus. In the Tierra del Fuego dolphins, 142 specimens belonging to 3 species (2 nematodes, 1 digenean, 1 cestode) were found: A. simplex, Hadwenius sp. and Strobilocephalus triangularis. Only 2 of the helminth species were shared in the 2 study areas, A. simplex and Hadwenius sp., and both were more common in central Patagonia. Among the species, A. simplex was most prevalent and abundant in both study areas. In Tierra del Fuego, adults of A. simplex appeared in only 1 host. Hadwenius sp., P. gastrophilus and S. triangularis are new host records for Commerson's dolphin. Species diversity and species richness were low in both study areas. Helminth communities were more diverse in central Patagonia (t = 1.97, df = 258, p < 0.05) and species richness was higher in central Patagonia (S = 4). No differences in diversity were observed between females and males of central Patagonia (t = 1.97, df = 139, p < 0.05) and between females of central Patagonia and Tierra del Fuego. The results may suggest some differences in habitat use, diet and sex between Commerson's dolphin populations in the 2 study areas.