82Rb and [15O]H2O myocardial perfusion PET imaging: a prospective head to head comparison.

BACKGROUND: 82Rb PET and [15O]H2O PET are both validated tracers for myocardical perfusion imaging but have not previously been compared clinically. During our site's transition from 82Rb to [15O]H2O PET, we performed a head-to-head comparison in a mixed population with suspected ischemic heart disease. METHODS: A total of 37 patients referred for perfusion imaging due to suspicion of coronary stenosis were examined with both 82Rb and [15O]H2O PET on the same day in rest and during adenosine-induced stress. The exams were rated by two blinded readers as normal, regional ischemia, globally reduced myocardial perfusion, or myocardial scarring. For [15O]H2O PET, regional ischemia was defined as two neighboring segments with average stress perfusion ≤ 2.3 mL/(min·g). Further, we evaluated a total perfusion deficit (TPD) of ≥ 10% as a more conservative marker of ischemia. RESULTS: [15O]H2O PET identified more patients with regional ischemia: 17(46%) vs 9(24%), agreement: 59% corresponding to a Cohen's kappa of .31 [95%CI .08-.53], (P < .001). Using the more conservative TPD ≥ 10%, the agreement increased to 86% corresponding to a kappa of .62 [95%CI .33-.92], (P = .001). For the subgroup of patients with no known heart disease (n = 18), the agreement was 94%. Interrater agreement was 95% corresponding to a kappa of .89 [95%CI .74-1.00] (P < .001). CONCLUSIONS: In clinical transition from 82Rb to [15O]H2O PET, it is important to take into account the higher frequency of patients with regional ischemia detected by [15O]H2O PET.

Identifying the central sulcus in patients with intra-axial lesions: a multicenter study comparing conventional presurgical MRI to topographical analysis and BOLD-fMRI.

OBJECTIVES: Identification of eloquent brain areas in patients with intra-axial lesions is important to minimize the risk of neurological deficit. We performed a multicenter study comparing conventional 2-dimensional magnetic resonance imaging (MRI) for identification of the central sulcus to topographical MRI and blood-oxygenation-level-dependent functional MRI (BOLD-fMRI). METHODS: Seventy-seven unoperated patients with brain lesions were imaged at 1.5 or 3 T. The central sulcus was identified by an experienced neuroradiologist on 2-dimensional MRI, by topographic analysis of 3-dimensional MRI in BrainVoyager, and by BOLD-fMRI analysis in BrainVoyager or SPM5. RESULTS: The central sulcus in the affected hemisphere was readily identified in a significantly higher percentage of patients by 2-dimensional MRI and topographical analysis (77/77 patients) compared to BOLD-fMRI (57 patients; P < 0.001). The topographical analysis identified a significantly larger portion of the total central sulcus than 2-dimensional MRI (P < 0.05). No differences were found between institutions, histological versus radiological diagnoses, MRI sequence parameters, age, or sex. CONCLUSIONS: Identification of the central sulcus is best performed using topographical analysis; however, 2-dimensional analysis may suffice for daily routine work.

A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia.

The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and rituximab combined (N = 32) or prednisolone monotherapy (N = 32). After 12 months, a satisfactory response was observed in 75% of the patients treated with rituximab and prednisolone but in a significantly smaller proportion (36%) of those given prednisolone alone (P = 0·003). Furthermore, relapse-free survival was significantly better after the combined therapy than after prednisolone monotherapy (P = 0·02). After 36 months, about 70% of the patients were still in remission in the rituximab-prednisolone group, whereas only about 45% were still in complete or partial remission in the prednisolone group. There was no significant difference between the two groups regarding adverse reactions to the studied medications. Likewise, serious adverse events were equally distributed, and no allergic reactions to rituximab were recorded. In conclusion, our data show that using rituximab and prednisolone combined rather than prednisolone alone as first-line treatment in WAIHA increases both the rate and the duration of the response.

Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia.

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding symptoms. A total of 133 patients were randomly assigned to either dexamethasone 40 mg/day for 4 days (n = 71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n = 62). Patients were allowed supplemental dexamethasone every 1 to 4 weeks for up to 6 cycles. Our primary end point, sustained response (ie, platelets ≥50×10(9)/L) at 6 months follow-up, was reached in 58% of patients in the rituximab + dexamethasone group vs 37% in the dexamethasone group (P = .02). The median follow-up time was 922 days. We found longer time to relapse (P = .03) and longer time to rescue treatment (P = .007) in the rituximab + dexamethasone group. There was an increased incidence of grade 3 to 4 adverse events in the rituximab + dexamethasone group (P = .04). In conclusion, rituximab + dexamethasone induced higher response rates and longer time to relapse than dexamethasone alone. This study is registered at http://clinicaltrials.gov as NCT00909077.

Volume and densities of chronic subdural haematoma obtained from CT imaging as predictors of postoperative recurrence: a prospective study of 107 operated patients.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common entity in neurosurgery with a considerable postoperative recurrence rate. Computerised tomography (CT) scanning remains the most important diagnostic test for this disorder. The aim of this study was to characterise the relationship between the recurrence of CSDH after treatment with burr-hole irrigation and closed-system drainage technique and CT scan features of these lesions to assess whether CT findings can be used to predict recurrence. METHODS: We investigated preoperative and postoperative CT scan features and recurrence rate of 107 consecutive adult surgical cases of CSDH and assessed any relationship with univariate and multivariate regression analyses. RESULTS: Seventeen patients (15.9 %) experienced recurrence of CSDH. The preoperative haematoma volume, the isodense, hyperdense, laminar and separated CT densities and the residual total haematoma cavity volume on the 1st postoperative day after removal of the drainage were identified as radiological predictors of recurrence. If the preoperative haematoma volume was under 115 ml and the residual total haematoma cavity volume postoperatively was under 80 ml, the probability of no recurrence was very high (94.4 % and 97.4 % respectively). CONCLUSIONS: These findings from CT imaging may help to identify patients at risk for postoperative recurrence.

Sampling requirements in DCE-MRI based analysis of high grade gliomas: simulations and clinical results.

PURPOSE: To investigate the effect of variations in temporal resolution and total measurement times on the estimations of kinetic parameters derived from dynamic contrast-enhanced (DCE) MRI in patients with high-grade gliomas (HGGs). MATERIALS AND METHODS: DCE-MRI with high temporal resolution (dynamic sampling time (T(s)) = 2.1 s and 3.4 s) and total sampling time (T(acq)) of 5.2 min was acquired in 101 examinations from 15 patients. Using the modified Tofts model K(trans), k(ep) v(e) and v(p) were estimated. The effects of increasing T(s) and reducing T(acq) on the estimated kinetic parameters were estimated through down-sampling and data truncation, and the results were compared with numerical simulations. RESULTS: There was an overall dependence of all four kinetic parameters on T(s) and T(acq). Increasing T(s) resulted in under-estimation of K(trans) and over-estimation of V(p), whereas k(ep) and V(e) varied in a less predictable manner. Reducing T(acq) resulted in over-estimation of K(trans) and k(ep) and under-estimation of v(p) and v(e). Increasing T(s) and reducing T(acq) resulted in increased relative error for all four parameters. CONCLUSION: Estimated K(trans), K(ep), and V(e) in HGGs were within 15% of the high sampling rate reference values for T(s) <20 s. Increasing T(s) and reducing T(acq) leads to reduced precision of the estimated values.

Comprehensive segmentation of subcortical brain volumes in early onset schizophrenia reveals limited structural abnormalities.

Structural brain abnormalities are well documented in adult schizophrenia, but there are few studies of brain structures in early onset schizophrenia (EOS) and findings are inconsistent. Most previous EOS studies have been limited to global morphometric measures, such as whole gray matter (GM) or cerebrospinal fluid (CSF), or to single brain structures. The purpose of this study was to compare specific volumes and hemispheric lateralization in a large number of subcortical brain structures, between EOS patients and a healthy control group. High-resolution structural magnetic resonance images (MRI) and automatic brain volume segmentation were performed on 18 EOS patients and 33 healthy controls (11-18 years). A total of 29 brain structures were studied. The patients showed marked bilateral enlargements of the lateral ventricles and of the fourth ventricle, and bilateral enlargement of the caudate nuclei compared to the controls. For all other subcortical brain structures, there were no significant differences between the EOS group and the healthy control group, contrary to findings from the majority of morphometric studies of childhood or adult onset schizophrenia.

Diphtheria outbreak in Norway: lessons learned.

We describe an outbreak of diphtheria in Norway that occurred in 2008 and affected 3 unvaccinated family members. The epidemic caught the public health system off-guard on most levels; the diagnosis was distrusted due to its rarity, no diphtheria anti-toxin was available, and notification procedures were not rigorously followed.

Increased theta and alpha EEG activity during nondirective meditation.

OBJECTIVES: In recent years, there has been significant uptake of meditation and related relaxation techniques, as a means of alleviating stress and maintaining good health. Despite its popularity, little is known about the neural mechanisms by which meditation works, and there is a need for more rigorous investigations of the underlying neurobiology. Several electroencephalogram (EEG) studies have reported changes in spectral band frequencies during meditation inspired by techniques that focus on concentration, and in comparison much less has been reported on mindfulness and nondirective techniques that are proving to be just as popular. DESIGN: The present study examined EEG changes during nondirective meditation. The investigational paradigm involved 20 minutes of acem meditation, where the subjects were asked to close their eyes and adopt their normal meditation technique, as well as a separate 20-minute quiet rest condition where the subjects were asked to close their eyes and sit quietly in a state of rest. Both conditions were completed in the same experimental session with a 15-minute break in between. RESULTS: Significantly increased theta power was found for the meditation condition when averaged across all brain regions. On closer examination, it was found that theta was significantly greater in the frontal and temporal-central regions as compared to the posterior region. There was also a significant increase in alpha power in the meditation condition compared to the rest condition, when averaged across all brain regions, and it was found that alpha was significantly greater in the posterior region as compared to the frontal region. CONCLUSIONS: These findings from this study suggest that nondirective meditation techniques alter theta and alpha EEG patterns significantly more than regular relaxation, in a manner that is perhaps similar to methods based on mindfulness or concentration.

[Eosinophilia--pathogenesis, classification and therapy]. / Eosinofili--patogenese, klassifikation og behandling.

Eosinophilia represents a complex clinical problem, the management of which is based on case history and clinical examination. Allergy, parasitic infection or inflammation may then be identified or malignancy suspected. In some cases, representing a haematologic disorder, clonality is demonstrated only by specific tests. The diagnostic and therapeutic approach, including a new classification for eosinophilia, is reviewed, and the importance of molecular biological technique is highlighted. Unexplained eosinophilia should be managed in collaboration with a haematology department.

Epidemic of poisoning caused by scopolamine disguised as Rohypnol tablets.

OBJECTIVE: An epidemic of scopolamine poisonings occurred in Oslo in 2008 among users of illicit drugs, caused by fake Rohypnol pills. The clinical features, diagnostic process, and handling of the epidemic are presented. METHODS: Suspected cases of scopolamine poisoning were extracted by reviewing registration forms from an ongoing prospective clinical study of acute poisonings in Oslo. Medical records of extracted contacts were examined and cases included according to specified clinical criteria. RESULTS: Forty-four cases of probable scopolamine poisoning were registered. Main clinical features were mydriasis, visual hallucinations, plucking behavior, agitation, and coma. No clinical diagnosis of anticholinergic syndrome was made prior to forensic analysis of the tablets, the most frequent diagnosis up to this point being unspecified drug-induced psychosis. Later in the epidemic, scopolamine poisoning became the dominating diagnosis. Ten patients were admitted to psychiatric hospitals, the rest recovered in medical units, or left health care against medical advice. DISCUSSION: Scopolamine poisonings are rare, but the resulting anticholinergic syndrome is well described. The syndrome was not recognized until the forensic analysis result strikingly changed how the patients were diagnosed and handled. A unique aspect of this epidemic was the intoxicating agent being scopolamine-containing tablets looking like Rohypnol, sold and used under the impression of being the latter. CONCLUSION: Recognizing the anticholinergic syndrome is important to provide proper treatment. Forensic analysis was the key to correct diagnosis in this outbreak, demonstrating its importance in verifying an epidemic of poisoning by fake drugs.

Simple dual tasking recruits prefrontal cortices in chronic severe traumatic brain injury patients, but not in controls.

The ability to carry out two tasks simultaneously, dual tasking, is specifically impaired after traumatic brain injury (TBI). The aim of the present study was to investigate the neuronal correlates to this increased dual cost in chronic severe TBI patients (n = 10) compared to healthy controls (n = 11) using functional magnetic resonance imaging (fMRI) at 3 Tesla (T). The tasks were a visual search and a simple two-fingers button press motor task. Performance data demonstrated similar and significant dual task interference in both TBI patients and controls using a linear mixed model. However, principal component analysis showed that TBI patients and controls could be classified into different categories based on motor activity in the single compared to the dual task condition, thus reflecting the increased variability in the performance in the TBI group. Random effects between-group analysis demonstrated significantly reduced activation in the TBI group in both single task conditions in the occipital and posterior cingulate cortices, and for the visual task also in the thalami. This pattern was reversed in the dual task condition with significantly increased activation of a predominantly left lateralized prefrontal-anterior midline-parietal network in the TBI group compared to the controls. The increase in activation occurred within regions described to be engaged in healthy volunteers as dual task cost increases. This finding points to substitution, functional reorganization within the primary network subserving the task, following TBI, and demonstrates more effortful processing. Recruitment of these additional prefrontal resources may be connected to serial rather than parallel processing in low level dual tasking in TBI. Thus, in severe TBI, low level dual task performance depends on increased attentional and executive guidance.

Mapping the primary motor cortex in healthy subjects and patients with peri-rolandic brain lesions before neurosurgery.

OBJECTIVE: The aim of this study was to establish a robust set of motor tasks that could be used to functionally delineate the motor cortex with blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) at 3 T and produce precise functional maps for pre-operative planning and functional neuronavigation. METHOD: Twelve male and four female control subjects were recruited for this study which examined six different motor tasks. Finger-, tongue-, lip- and toe-movements, as well as isometric upper arm- and thigh-contraction tasks were conducted during separate scans on a 3 T MRI scanner. Furthermore, patients that previously had undergone similar motor tasks were reviewed, to evaluate whether this set of tasks was able to be adopted for use in a population of patients with brain lesions. RESULTS: The results of this study indicated that the finger-, toe- and tongue-motor tasks were the most robust in identifying their respective primary motor area. Moreover, all three tasks activated regions at regular intervals along the convexity of the hemisphere, making it possible to functionally delineate the primary motor cortex in both healthy subjects and patients. DISCUSSION: The motor tasks described in this study (toe, finger and tongue) were effective at localizing the primary motor cortex for the purposes of neurosurgical planning. These three tasks produced the highest success rate and resulted in activations at regular intervals along the convexity of the hemisphere, allowing the delineation of the entire motor strip even in the presence of edema and anatomical distortions.

Fractal dimension analysis of MR images reveals grey matter structure irregularities in schizophrenia.

The fractal dimension (FD) was used to reveal brain structure irregularities in patients with schizophrenia. FD provides a unique way of quantifying the shape complexity of cortical folding of the human brain. MR images were obtained from seven patients with schizophrenia that were compared with six healthy control subjects. The MR images were first segmented, and the FD was calculated for the grey/white matter boundary for the whole brain and the hemispheres separately, using the box-counting and Minkowski-Bouligand methods. The results showed that the patients had larger FD values than the controls, for the whole brain volume and right hemisphere.

Diffuse axonal injury in severe traumatic brain injury visualized using high-resolution diffusion tensor imaging.

Traumatic brain injury (TBI) is the most common cause of death and disability in young people. The functional outcome in patients with TBI cannot be explained by focal pathology alone, and diffuse axonal injury (DAI) is considered a major contributor to the neurocognitive deficits experienced by this group. The aim of the present study was to investigate whether diffusion tensor imaging (DTI) offers additional information as to the extent of damage not visualized with standard magnetic resonance imaging (MRI) in patients with severe TBI. Nine chronic male TBI patients and 11 matched healthy controls were recruited. Results of the voxel-based analysis of fractional anisotropy (FA) maps and apparent diffusion coefficient (ADC) maps revealed significant differences in anisotropy in major white matter tracts, including the corpus callosum (CC), internal and external capsule, superior and inferior longitudinal fascicles, and the fornix in the TBI group. The FA and ADC measurements offered superior sensitivity compared to conventional MRI diagnosis of DAI. Region-of-interest (ROI) analyses confirmed these results in the investigated regions. The findings of this study support the hypothesis that severe TBI is accompanied by DAI. The DTI changes were more prominent on the right side that contained the focal pathology in most of the patients and accurately reflected differences in both hemispheres. In conclusion, DTI holds great promise as a diagnostic tool to identify and quantify the degree of white matter injury in TBI patients.

Computer-assisted 3D ultrasound-guided neurosurgery: technological contributions, including multimodal registration and advanced display, demonstrating future perspectives.

BACKGROUND: Navigation systems are now frequently being used for guiding surgical procedures. Existing neuronavigation systems suffer from the lack of updated images when tissue changes during surgery as well as from user-friendly displays of all essential images for accurate and safe surgery guidance. METHODS: We have developed various new technologies for improved neuronavigation. Using intraoperative 3D ultrasound (US) imaging, we have developed various registration algorithms for using and updating a complete multimodal and multivolume 3D map for navigation. RESULTS: We experienced that advanced multimodal visualization makes it easy to interpret information from several image volumes and modalities simultaneously. Using high quality intraoperative 3D ultrasound, essential preoperative information could be corrected due to brain shift. fMRI and other important preoperative data could then be used together with intraoperative ultrasound imaging for more accurate, safer and improved guidance of therapy. CONCLUSIONS: We claim that new features, as demonstrated in the present paper, using intraoperative 3D ultrasound in combination with advanced registration and display algorithms will represent important contributions towards more accurate, safer and more optimized future patient treatment.

Putting the brain in Jeopardy: a novel comprehensive and expressive language task?

OBJECTIVE: To develop and test a novel fMRI compatible comprehensive and expressive language task that reliably and predictably activates both Wernicke's and Broca's cortical brain regions, respectively, and has utility for the determination of hemispheric language dominance. METHODS: Ten healthy men (seven) and women (three) were administered a task based on the television game Jeopardy that was adapted for fMRI presentation. The task was programmed using E-PRIME software and designed to run as an event-related experiment. The study was conducted on 3 T MRI Phillips Intera scanner, and data was anlysed using Brain Voyager QX. All subjects provided written informed consent. RESULTS: The Jeopardy task produced robust left hemisphere activation in regions corresponding to Wernicke's and Broca's areas. CONCLUSION: This novel fMRI compatible task (Jeopardy) reliably maps both Broca's and Wernicke's areas with robust hemispheric lateralization. It is potentially useful in language localization studies as it offers advantages over conventional procedures and other fMRI tasks by virtue of being non-invasive and mapping both language areas in one experiment.

Brain activation measured using functional magnetic resonance imaging during the Tower of London task.

BACKGROUND: Individuals with traumatic brain injury (TBI) often suffer from a number of enduring cognitive impairments such as in attention, memory, speed of processing information and dual-task performance. OBJECTIVE: The aim of this study was to assess the patterns of regional brain activation in response to the Tower of London (ToL) task in a group of patients suffering from chronic TBI using functional magnetic resonance imaging (fMRI). METHODS: fMRI was performed during performance of the ToL planning task in 10 patients suffering from severe TBI and in 10 age- and sex-matched controls using a 3 T magnetic resonance scanner. RESULTS: Performance data showed no difference in response accuracy between the TBI group and the healthy control group. Statistical parametric brain maps showed that the TBI group activates larger and additional areas of the cerebral cortex than the healthy control group both for tasks and for a subtraction contrast between the tasks. CONCLUSIONS: The results of this study are interpreted as a cortical reorganization inside the executive system of vigilance and working memory in patients with TBI. Both parietal and frontal areas are recruited to compensate for damaged brain tissue.

Fibrinogen and other coronary risk factors.

The association between plasma fibrinogen concentration and other coronary risk factors diverged in previous studies, and the impact from complex lipoprotein patterns has not been studied. Our research involved 24 healthy subjects without coronary heart disease (control) and 22 patients who had survived having acute myocardial infarction before the age of 41 years (cases), overall 40 men and 6 women with age range of 34 to 54 years. In multiple linear regression analyses concerning control subjects, family disposition, social class, a score based on serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations, and fasting capillary blood glucose concentration were significantly associated with plasma fibrinogen concentration (P < .00005, R2 = 0.81). For case subjects, the ratio between serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations was significantly associated with plasma fibrinogen concentration (P = .0018, R2 = 0.39). Thus, for healthy subjects, 4 coronary risk factors explained three quarters of the variation of plasma fibrinogen concentration, and for patients with a previous acute myocardial infarction, another coronary risk factor explained one third of the variation. In conclusion, the pattern of coronary risk factors associated with plasma fibrinogen concentration differed between those without coronary heart disease and those with a previous acute myocardial infarction.