Attention-related potentials allow for a highly accurate discrimination of mild cognitive impairment subtypes.

The three most frequent forms of mild cognitive impairment (MCI) are single-domain amnestic MCI (sd-aMCI), single-domain dysexecutive MCI (sd-dMCI) and multiple-domain amnestic MCI (md-aMCI). Brain imaging differences among single domain subgroups of MCI were recently reported supporting the idea that electroencephalography (EEG) functional hallmarks can be used to differentiate these subgroups. We performed event-related potential (ERP) measures and independent component analysis in 18 sd-aMCI, 13 sd-dMCI and 35 md-aMCI cases during the successful performance of the Attentional Network Test. Sensitivity and specificity analyses of ERP for the discrimination of MCI subgroups were also made. In center-cue and spatial-cue warning stimuli, contingent negative variation (CNV) was elicited in all MCI subgroups. Two independent components (ICA1 and 2) were superimposed in the time range on the CNV. The ICA2 was strongly reduced in sd-dMCI compared to sd-aMCI and md-aMCI (4.3 vs. 7.5% and 10.9% of the CNV component). The parietal P300 ERP latency increased significantly in sd-dMCI compared to md-aMCI and sd-aMCI for both congruent and incongruent conditions. This latency for incongruent targets allowed for a highly accurate separation of sd-dMCI from both sd-aMCI and md-aMCI with correct classification rates of 90 and 81%, respectively. This EEG parameter alone performed much better than neuropsychological testing in distinguishing sd-dMCI from md-aMCI. Our data reveal qualitative changes in the composition of the neural generators of CNV in sd-dMCI. In addition, they document an increased latency of the executive P300 component that may represent a highly accurate hallmark for the discrimination of this MCI subgroup in routine clinical settings.

Maintenance of remission in Crohn's disease.

When remission of Crohn's disease is achieved, the next goal is to maintain long-term remission. Aminosalicylates may be recommended for maintenance remission, even though the results are less consistent than those observed in ulcerative colitis. The benefit is mainly observed in the post-surgical setting and in patients with ileitis, and with a prolonged disease duration. Corticosteroids are not effective in maintaining remission and should not be used for this indication. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn's disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Mycophenolate mofetil could be considered a therapy in patients who are either allergic to azathioprine or in whom azathioprine failed to induce remission. The use of infliximab may change the future approach to maintenance therapy for Crohn's disease. Patients who responded clinically to infliximab have maintained their clinical response when receiving repeat infusions at 8-week intervals. In patients refractory to other therapies, infliximab may be effective in maintaining remission.

Seizure semiology: an overview of the 'inverse problem'.

In clinical practice, a classification of seizures based on clinical signs and symptoms leads to an improved understanding of epilepsy-related issues and therefore strongly contributes to a better patient care. The inverse problem involves inferring the anatomical brain localization of a seizure from the scalp surface EEG, a concept we apply here to correlate seizure origin with seizure semiology. The spheres of sensorium, motor features, consciousness changes and autonomic alterations during ictal and postictal manifestations are reviewed, including several subdivisions used to better categorize particular features. Particular attention is given to behavioral features, as well as to features occurring in idiopathic generalized epileptic syndromes and psychogenic nonepileptic spells.

Diffusion tensor imaging shows structural remodeling of stroke mirror region: results from a pilot study.

Background: The role of the non-injured hemisphere in stroke recovery is poorly understood. In this pilot study, we sought to explore the presence of structural changes detectable by diffusion tensor imaging (DTI) in the contralesional hemispheres of patients who recovered well from ischemic stroke. Methods: We analyzed serial DTI data from 16 stroke patients who had moderate initial neurological deficits (NIHSS scores 3-12) and good functional outcome at 3-6 months (NIHSS score 0 or modified Rankin Score ≤1). We segmented the brain tissue in gray and white matter (GM and WM) and measured the apparent diffusion coefficient (ADC) and fractional anisotropy in the infarct, in the contralesional infarct mirror region as well as in concentrically expanding regions around them. Results: We found that GM and WM ADC significantly increased in the infarct region (p < 0.01) from acute to chronic time points, whereas in the infarct mirror region, GM and WM ADC increased (p < 0.01) and WM fractional anisotropy decreased (p < 0.05). No significant changes were detected in other regions. Conclusion: DTI-based metrics are sensitive to regional structural changes in the contralesional hemisphere during stroke recovery. Prospective studies in larger cohorts with varying levels of recovery are needed to confirm our findings.

Risk of mental disorders in children of parents with alcohol or heroin dependence: a controlled high-risk study.

Aim: To assess the specific effect of alcohol dependence (AD) or heroin dependence (HD) in patients and their spouses on the risk of psychopathology in their 276 6.0- to 17.9- year-old children (mean 11.3 years). Methods: The sample included 101 offspring of patients with AD, 23 of patients with HD, and 152 of medical controls, as well as their 2 parents. Participants were assessed using semistructured diagnostic interviews and family history reports by psychologists blind to patient diagnoses. Results: Children of HD and AD patients had largely elevated rates of recurrent major depressive disorder. Children of HD patients were also at an increased risk for attention deficit hyperactivity disorder and substance use disorders (SUD). There were interactions between SUD in the 2 parents to increase the risk of SUD in offspring. Conclusions: These results emphasize the need for prompt identification and treatment of these children and highlight the need to pay clinical attention not only to the patient, but also to the co-parent in order to optimize prevention in offspring.

Temporal distribution and magnitude of the vulnerability period around stroke depend on stroke subtype.

Background: We aimed to analyze the rate and time distribution of pre- and post-morbid cerebrovascular events in a single ischemic stroke population, and whether these depend on the etiology of the index stroke. Methods: In 2,203 consecutive patients admitted to a single stroke center registry (ASTRAL), the ischemic stroke that led to admission was considered the index event. Frequency distribution and cumulative relative distribution graphs of the most recent and first recurrent event (ischemic stroke, transient ischemic attack, intracranial or subarachnoid hemorrhage) were drawn in weekly and daily intervals for all strokes and for all stroke types. Results: The frequency of events at identical time points before and after the index stroke was mostly reduced in the first week after (vs. before) stroke (1.0 vs. 4.2%, p < 0.001) and the first month (2.7 vs. 7.4%, p < 0.001), and then ebbed over the first year (8.4 vs. 13.1%, p < 0.001). On daily basis, the peak frequency was noticed at day -1 (1.6%) with a reduction to 0.7% on the index day and 0.17% 24 h after. The event rate in patients with atherosclerotic stroke was particularly high around the index event, but 1-year cumulative recurrence rate was similar in all stroke types. Conclusions: We confirm a short window of increased vulnerability in ischemic stroke and show a 4-, 3- and 2-fold reduction in post-stroke events at 1 week, 1 month and 1 year, respectively, compared to identical pre-stroke periods. This break in the 'stroke wave' is particularly striking after atherosclerotic and lacunar strokes.

Dermoscopy of acral melanoma: a multicenter study on behalf of the international dermoscopy society.

Background: Most studies on dermoscopy of acral lesions were conducted in Asian populations. In this study, we analyzed these features in a predominantly Caucasian population. Objective: Estimate the prevalence of dermoscopic features in acral lesions, and assess their level of agreement between observers. Methods: In this retrospective multicenter study, 167 acral lesions (66 melanomas) were evaluated for 13 dermoscopic patterns by 26 physicians, via a secured Internet platform. Results: Parallel furrow pattern, bizarre pattern, and diffuse pigmentation with variable shades of brown had the highest prevalence. The agreement for lesion patterns between physicians was variable. Agreement was dependent on the level of diagnostic difficulty. Conclusion: Lesions with a diameter >1 cm were more likely to be melanoma. We found as well that a benign pattern can be seen in parts of melanomas. For this reason one should evaluate an acral lesion for the presence of malignant patterns first. © 2013 S. Karger AG, Basel.

Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection.

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9-90 kDa autologous proteins.

Treatment of eosinophilic esophagitis by dilation.

Treatment options for eosinophilic esophagitis (EoE) include drugs, diets and esophageal dilation. Esophageal dilation can be performed using either through-the-scope balloons or wire-guided bougies. Dilation can lead to long-lasting symptom improvement in EoE patients presenting with esophageal strictures. Esophageal strictures are most often diagnosed when the 8- to 9-mm outer diameter adult gastroscope cannot be passed any further or only against resistance. A defined esophageal diameter to be targeted by dilation is missing, but the majority of patients have considerable symptomatic improvement when a diameter of 16-18 mm has been reached. A high complication rate, especially regarding esophageal perforations, has been reported in small case series until 2006. Several large series were published in 2007 and later that demonstrated that the complication risk (especially esophageal perforation) was much lower than what was reported in earlier series. The procedure can therefore be regarded as safe when some simple precautions are followed. It is noteworthy that esophageal dilation does not influence the underlying eosinophil-predominant inflammation. Patients should be informed before the procedure that postprocedural retrosternal pain may occur for some days, but that it usually responds well to over-the-counter analgesics such as paracetamol. Dilation-related superficial lacerations of the mucosa should not be regarded and reported as complications, but instead represent a desired effect of the therapy. Patient tolerance and acceptance for esophageal dilation have been reported to be good.

Rise in plasma lactate concentrations with psychosocial stress: a possible sign of cerebral energy demand.

OBJECTIVE: It is known that exogenous lactate given as an i.v. energy infusion is able to counteract a neuroglycopenic state that developed during psychosocial stress. It is unknown, however, whether the brain under stressful conditions can induce a rise in plasma lactate to satisfy its increased needs during stress. Since lactate is i) an alternative cerebral energy substrate to glucose and ii) its plasmatic concentration is influenced by the sympathetic nervous system, the present study aimed at investigating whether plasma lactate concentrations increase with psychosocial stress in humans. METHODS: 30 healthy young men participated in two sessions (stress induced by the Trier Social Stress Test and a non-stress control session). Blood samples were frequently taken to assess plasma lactate concentrations and stress hormone profiles. RESULTS: Plasma lactate increased 47% during psychosocial stress (from 0.9 ± 0.05 to 1.4 ± 0.1 mmol/l; interaction time × stress intervention: F = 19.7, p < 0.001). This increase in lactate concentrations during stress was associated with an increase in epinephrine (R(2) = 0.221, p = 0.02) and ACTH concentrations (R(2) = 0.460, p < 0.001). CONCLUSION: Plasma lactate concentrations increase during acute psychosocial stress in humans. This finding suggests the existence of a demand mechanism that functions to allocate an additional source of energy from the body towards the brain, which we refer to as 'cerebral lactate demand'.

Diagnosis and management of chronic obstructive pulmonary disease: the swiss guidelines: official guidelines of the Swiss Respiratory Society.

The new Swiss Chronic Obstructive Pulmonary Disease (COPD) Guidelines are based on a previous version, which was published 10 years ago. The Swiss Respiratory Society felt the need to update the previous document due to new knowledge and novel therapeutic developments about this prevalent and important disease. The recommendations and statements are based on the available literature, on other national guidelines and, in particular, on the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. Our aim is to advise pulmonary physicians, general practitioners and other health care workers on the early detection and diagnosis, prevention, best symptomatic control, and avoidance of COPD as well as its complications and deterioration.

Use of duplex ultrasonography in the treatment of thromboangiitis obliterans with iloprost.

We present a 34-year-old patient with digital necrosis due to thromboangiitis obliterans. He was successfully treated with iloprost, a prostaglandin analogue. Duplex ultrasonography was performed during the perfusion of iloprost to optimize the doses and the treatment duration. A complete revascularization was observed after 10 days. Iloprost perfusions were stopped, and a slow regression of the necroses was observed in the subsequent days. With the use of duplex ultrasonography, unnecessary high doses of iloprost and long periods of treatment can be avoided reducing side effects and treatment costs.

Understanding Van Gogh's Night: bipolar disorder

Vincent Van Gogh (1853-1890) imparted in his art a deep essence of life, and in such a unique way that many would say it is possible to experience it vicariously by looking at his paintings even once. In 10 years, while exerting mental and physical efforts that may well have contributed to his premature death, he produced an impressive number of masterpieces. However, the specific neurological disorder Van Gogh suffered and how this may have influenced his art is still not clear. The combination of his eccentric personality, irascible temper, unstable moods and prolific creativity, makes the understanding of his illness a very complex endeavor and therefore poses a great challenge to those who investigate the relationships between the 'artistic mind', the brain and illness. In fact, most of the diagnoses (nearly 30) proposed for Van Gogh, during the last century, are not based on medical evidence but are ascertainable from analyses of his paintings and biographical data. Although no definitive diagnosis can be made based on such evidence, we conclude that according to DSM-IV criteria and findings extrapolated from his letters, Van Gogh is most likely to have suffered a bipolar disorder, affective or schizoaffective, which caused his death by suicide.

Interventions aiming at balance confidence improvement in older adults: an updated review.

BACKGROUND: Loss of balance confidence is a frequent condition that affects 20-75% of community-dwelling older persons. Although a recent fall is a common trigger, loss of balance confidence also appears independent of previous experience with falls. Maintaining or improving balance confidence is important to avoid unnecessary, self-imposed restrictions of activity and subsequent disability. Holding another person's hand or using an assistive device while walking are simple interventions that are used naturally to address poor balance confidence in daily life. However, more complex interventions have also been developed and tested to achieve more sustained improvement in balance confidence. OBJECTIVES: This review describes interventions that have been tested to improve balance confidence in older community-dwelling persons. METHODS: Based on 2 recent systematic reviews, an additional search for literature was performed to update current information on interventions aiming at balance confidence improvement. Interventions were classified as those directly aimed at increasing balance confidence or not, and further stratified into those using monofactorial or multifactorial approaches. RESULTS: A total of 46 randomized controlled trials were identified. Five of the 8 interventions that directly targeted balance confidence showed benefits. Among those, multicomponent behavioral group interventions provided the most robust evidence of benefits in improving balance confidence and in decreasing activity avoidance. Among interventions not directly aiming at balance confidence improvement (11/21 studies with benefits), exercise (including tai chi) appears as the most promising monofactorial intervention. Nine of the 17 multifactorial fall prevention programs showed an effect on balance confidence, exercise being a main component in 7 of these 9 studies. Interventions that targeted elderly persons reporting poor balance confidence and/or those at risk for falls seemed more likely to be beneficial. CONCLUSIONS: Positive and sometimes sustained improvement in balance confidence can be achieved by various interventions among community-dwelling elderly persons. The effect of these interventions on activity restriction associated with poor balance confidence have been less well studied, but some studies also suggest potential benefits.

Therapy of mild to moderate luminal Crohn's disease.

The management of luminal Crohn's disease, the most common form of initial presentation of the disease, depends on the location and the severity of the lesions. Mild to moderate disease represents a relatively large proportion of patients with a first flare of luminal disease, which may also be associated with perianal disease. As quality of life of these patients correlates with disease activity, adequate therapy is a central goal of the overall patient management. Treatment options include mainly sulfasalazine, budesonide and systemic steroids, while the role of mesalazine and antibiotics remains controversial. The role of biological therapies in mild to moderate disease has not been thoroughly evaluated and will not be discussed here.