The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale.

Fatigue and depression are frequent symptoms in multiple sclerosis (MS). Both are overlapping and shadowing each other and may impair the quality of life. For detection of depression symptoms in MS, the Multiple Sclerosis Depression Rating Scale (MSDRS) has been proposed recently. Here, we compare the performance of MSDRS in MS patients with and without fatigue to that of established rating scales, i.e. Hospital Anxiety and Depression Scale and Beck Depression Inventory. Twenty-nine MS patients were screened for fatigue and depression symptoms. Patients with fatigue showed significantly higher depression scores compared to patients without fatigue, whereas the number of depressed patients did not differ between the two groups. MSDRS seems to have higher sensitivity to detect severe depression than established rating scales. However, one should keep in mind that such a finding might be due to an increase in false positive cases when using MSDRS. Implementing this scale in future studies might be of help to enhance the understanding of its potential utility.

[Transcranial direct current stimulation (tDCS) for depression: Results of nearly a decade of clinical research]. / La stimulation transcrânienne à courant continu (tDCS) dans la dépression : bilan de près d'une décennie de recherche clinique.

OBJECTIVE: Since 2006 transcranial direct current stimulation (tDCS) has been investigated in the treatment of depression. In this review, we discuss the implications and clinical perspectives that tDCS may have as a therapeutic tool in depression from the results reported in this domain. METHODS: A comprehensive literature review has found nearly thirty articles - all in English - on this topic, corresponding to clinical studies, placebo-controlled or not, case reports and reviews. RESULTS: Several meta-analyses showed that the antidepressant effects of active tDCS are significant against placebo, but variable, mainly due to the heterogeneity of the patients included in the studies, for example regarding the resistance to antidepressant treatment. CONCLUSIONS: Specific recommendations for the use of tDCS in treating depression may not yet be available, but some elements of good practice can be highlighted. Of particular note is that anodal tDCS of the left prefrontal cortex at 2mA for 20 minutes per day has a potential therapeutic value without risk of significant side effects: tDCS offers safe conditions for clinical use in the treatment of depression.

[Transcranial direct current stimulation for depressive disorders]. / Transkranielle Gleichstromstimulation bei depressiven Störungen.

Major depressive disorders are one of the most prevalent psychiatric disorders worldwide but approximately 20-30 % of patients do not respond to standard guideline conform treatment. Recent neuroimaging studies in depressive patients revealed altered activation patterns in prefrontal brain areas and that successful cognitive behavioral therapy and psychopharmacological interventions are associated with a reversal of these neural alterations. Therefore, a direct modulation of prefrontal brain activation by non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) seems to be a promising and innovative approach for the treatment of depressive disorders. In addition, recent neuropsychological findings indicated an augmentation of positive tDCS effects by simultaneous external activation of the stimulated brain area, for example by cognitive training tasks. Based on these findings, the possibility to augment cognitive-emotional learning processes during cognitive behavioral therapy by simultaneous tDCS to increase antidepressive therapeutic effects is discussed in this article.

[Non-invasive brain stimulation for treatment of schizophrenic psychoses]. / Hirnstimulationsverfahren zur Behandlung schizophrener Psychosen.

Despite many different available pharmacological and psychosocial treatment options, an optimal control of symptoms is only partly possible for most schizophrenia patients. Especially, persistent auditory hallucinations, negative symptoms and cognitive impairment are difficult to treat symptoms. Several non-invasive brain stimulation techniques are increasingly being considered as new therapeutic add on options for the management of schizophrenia, targeting these symptom domains. The technique which has been available for the longest time and that is best established in clinical care is electroconvulsive therapy (ECT). New stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) allow a more pathophysiological-based approach. This review article introduces various non-invasive brain stimulation techniques and discusses recent treatment studies on schizophrenia. In total, the novel brain stimulation techniques discussed here can be considered relevant add on therapeutic approaches for schizophrenia. In this context, the best evidence is available for the application of rTMS for the treatment of negative symptoms and persistent auditory hallucinations; however, negative studies have also been published for both indications. Studies using other non-invasive brain stimulation techniques showed promising results but further research is needed to establish the clinical efficacy. Based on a growing pathophysiological knowledge, non-invasive brain stimulation techniques provide new treatment perspectives for patients with schizophrenia.

Transcranial Direct Current Stimulation (tDCS) in a Patient with PRES and Bipolar Depression.

Transcranial direct current stimulation (tDCS) is a non-invasive tool for brain stimulation and has proven efficacy in depressive disorders. Here, we report the case of a patient with recurrent bipolar depressive disorder and neurologic complications due to posterior reversible encephalopathy syndrome (PRES) due to parathyroid adenoma. During a long-term hospital stay, multiple drug regimens did not resolve depressive symptoms. Finally, an add-on therapy with tDCS brought improvement of symptoms. This case highlights the feasibility of tDCS in treatment-resistant depression and concomitant neurologic disorder.

[Mirtazapine and hyperemesis gravidarum]. / Mirtazapin bei Hyperemesis gravidarum.

The case of a 29-year-old patient in the 21st gestational week with severe hyperemesis gravidarum which did not respond to conventional antiemetic treatment is reported. Nausea and vomiting improved within 48 h after i.v. administration of 30 mg mirtazapine/day. The pathophysiological and therapeutic implications are discussed.

[Psychotic and non-psychotic denial of pregnancy]. / Psychotische und nicht psychotische Verleugnung der Schwangerschaft.

We report about two patients with denial of pregnancy. While the first patient was free of psychopathological symptoms besides denial of pregnancy until rupture of the membranes, and was able to accomodate the new born, the second patient with psychotic denial of pregnancy could not accomodate the child because of the schizophrenia, so that an adoption was necessary. On the basis of the two cases aetiological, epidemiological, clinical und prognostic implications of psychotic and non-psychotic denial of pregnancy are discussed.

Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: a standardized low resolution tomography (sLORETA) study.

Prefrontal transcranial direct current stimulation (tDCS) with the anode placed on the left dorsolateral prefrontal cortex (DLPFC) has been reported to enhance working memory in healthy subjects and to improve mood in major depression. However, its putative antidepressant, cognitive and behavior action is not well understood. Here, we evaluated the distribution of neuronal electrical activity changes after anodal tDCS of the left DLPFC and cathodal tDCS of the right supraorbital region using spectral power analysis and standardized low resolution tomography (sLORETA). Ten healthy subjects underwent real and sham tDCS on separate days in a double-blind, placebo-controlled cross-over trial. Anodal tDCS was applied for 20 min at 2 mA intensity over the left DLPFC, while the cathode was positioned over the contralateral supraorbital region. After tDCS, EEG was recorded during an eyes-closed resting state followed by a working memory (n-back) task. Statistical non-parametric mapping showed reduced left frontal delta activity in the real tDCS condition. Specifically, a significant reduction of mean current densities (sLORETA) for the delta band was detected in the left subgenual PFC, the anterior cingulate and in the left medial frontal gyrus. Moreover, the effect was strongest for the first 5 min (p<0.01). The following n-back task revealed a positive impact of prefrontal tDCS on error rate, accuracy and reaction time. This was accompanied by increased P2- and P3- event-related potentials (ERP) component-amplitudes for the 2-back condition at the electrode Fz. A source localization using sLORETA for the time window 250-450 ms showed enhanced activity in the left parahippocampal gyrus for the 2-back condition. These results suggest that anodal tDCS of the left DLPFC and/or cathodal tDCS of the contralateral supraorbital region may modulate regional electrical activity in the prefrontal and anterior cingulate cortex in addition to improving working memory performance.

Effects of alcohol consumption on iron metabolism.

BACKGROUND/OBJECTIVES: Patients with alcohol abuse frequently suffer from malnutrition which may result in insufficient iron distribution and iron overload or deficiency. Iron metabolism can be described by a combination of biochemical soluble transferrin receptor, ferritin, C-reactive protein (CRP), and hematological parameters. Here, vitamin B12 and folic acid state were assessed. Results on iron metabolism in patients with alcohol dependence in comparison with social drinkers are presented. MATERIALS/METHODS: Samples from 101 patients with dependent alcohol consumption were included. The control group comprised 115 social drinkers. Inclusion criteria for patients with chronic regular drinking/social drinkers were positive/negative score of the Alcohol Use Disorders Identification Test (AUDIT), and positive/negative score for alcohol abuse/dependence (DSM-IV criteria). RESULTS: Absolute values for ferritin and sTfR are increased in patients with alcohol dependence with current consumption (ALC) compared with social drinkers. No major differences are observed in the ratio of sTfR/log ferritin in comparison with social drinkers. Hemoglobin concentrations correlated between the two groups. Mean corpuscular volume (MCV) was significantly increased in the ALC collective compared to social drinkers. Eighty patients of the alcohol-dependent group had sufficient iron repletion, 11 had iron overload, 6 are suspicious for functional iron deficiency, and 4 are suspicious for reduced iron supply. No vitamin B12/folate deficiencies are observed in alcohol-dependent patients. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: No major abnormalities of iron metabolism are seen in patients with chronic alcohol ingestion besides the well-known macrocytic anemia. Iron overload is relatively frequent and observed in 9% of cases. No differences in vitamin B12 and folate levels were found between individuals with alcohol dependence and social drinkers.

Transcranial Direct Current Stimulation (tDCS) for major depression - Interim analysis of cloud supervised technical data from the DepressionDC trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) of prefrontal cortex regions has been reported to exert antidepressant effects, though large scale multicenter trials in major depressive disorder (MDD) supporting this notion are still lacking. Application of tDCS in multicenter settings, however, requires measurement, storage and evaluation of technical parameters of tDCS sessions not only for safety reasons but also for quality control. To address this issue, we conducted an interim analysis of supervised technical data across study centers in order to monitor technical quality of tDCS in an ongoing multicenter RCT in MDD (DepressionDC trial). METHODS: Technical data of 818 active tDCS sessions were recorded, stored in a data cloud, and analysed without violating study blinding. Impedance, voltage and current were monitored continuously with one data point recorded every second of stimulation. RESULTS: Variability of impedance was considerable (1,42 kΩ, to 8,23 kΩ), inter-individually and even more intra-individually, but did not significantly differ between the study centre in Munich and all other sites. CONCLUSION: Measurement, centralized data storage via data cloud and remote supervision of technical parameters of tDCS are feasible and proposed for future RCTs on therapeutic tDCS in multiple settings.

Level and diurnal variations of hormones of interest to the cardiovascular system in patients with heart transplants.

The lack of a nocturnal decrease in blood pressure in cyclosporine-treated cardiac transplant recipients may indicate abnormalities in the mechanism(s) responsible for circadian variability in other physiologic parameters such as in circulating hormones. This possibility was addressed through repeated determinations of circulating catecholamines, neuropeptide Y, pancreatic polypeptide, calcitonin gene-related peptide, plasma renin activity, aldosterone, atrial natriuretic factor and cortisol. The results from 10 patients with heart transplants were compared with those of 12 age-matched, healthy control subjects. Both groups were studied during 24-hour supine rest. There was no difference between patients and control subjects in mean levels of catecholamines, neuropeptide Y, pancreatic polypeptide and aldosterone. Patients had higher levels (+/- SD) of plasma renin activity (6.4 +/- 1.3 vs 2.6 +/- 0.4 ng/ml/hour, p less than 0.001), calcitonin gene-related peptide (47.7 +/- 9.9 vs 33.3 +/- 5.7 pmol/liter, p less than 0.01) and atrial natriuretic factor (93.0 +/- 56.7 vs 20.7 +/- 8.9 pg/ml, p less than 0.001) than control subjects, respectively. Cortisol was not detected in patients. Abnormal diurnal profiles in patients were found for calcitonin gene-related peptide, aldosterone and atrial natriuretic factor, and for pancreatic polypeptide, together with decreased levels, in patients with greater than 6 months follow-up. Except for hormones reflecting sympathetic nervous activity, all hormonal systems studied showed abnormalities in level or circadian rhythmicity, or both. The pancreatic polypeptide results suggest that parasympathetic neuropathy could develop in cyclosporine-treated heart transplant recipients.

A case-referent study on acute myeloid leukemia, background radiation and exposure to solvents and other agents.

The effect of potential risk factors for acute myeloid leukemia was evaluated in a case-referent study encompassing 42 cases and 244 referents, all deceased. Information on exposure was obtained with questionnaires mailed to the next of kin. Particularly the effect of background radiation was evaluated, as assessed with a gamma radiation index weighing the time spent outdoors and indoors and considering the building material (stone, wood, etc.) in the homes and the workplaces of the subjects. Especially between the ages of 20 and 49 a, to some extent also between 50 and 69 a but not above 70, there seemed to be an effect from background radiation and a trend suggesting an exposure-effect relationship. There was also about a sixfold increase in the rate ratio with regard to solvent exposure, which also seemed to modify the effect of background radiation. Other exposures were associated with relatively modest increases in the rate ratios and/or very small numbers of exposed individuals. It would be worthwhile to undertake further cancer epidemiologic studies of background radiation in which effective study designs are applied and a variety of potential confounders and modifiers of effect are identified and accounted for.

Relationship between treatment outcome and subtype of alcoholism in men.

The subdivision of alcoholism into type I and type II, as suggested by Cloninger et al., was applied to two groups of men alcoholics: 30 in treatment for alcoholism ("active" alcoholics) and 39 ex-alcoholics. Despite the fact that the duration of alcohol misuse did not differ between the groups, there were significantly more type II alcoholics among the ex-alcoholics and more type I alcoholics among the active alcoholics. The results seem to indicate a better prognosis in type II alcoholism. The type I and type II alcoholics differed also, as in previous studies, in their frequencies of drug misuse and criminality.

Prevention of catheter-related infections by a new, catheter-restricted antibiotic filling technique.

Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this study was to develop a technique preventing bacterial colonization of intravascular catheters. In 27 dogs a total of 70 catheters were implanted. On an average catheters were used for 207 days. Three protocols were compared: (1) flushing the catheters with a heparinized solution; (2) filling only the catheter lumen with alpha-chymotrypsin solution (225 units/ml); (3) filling only the catheter lumen with a solution containing a mixture of the aminoglycoside antibiotic gentamicin (20 mg/ml) and chymotrypsin (225 units/ml). Catheter fillings were always withdrawn before catheter use. Catheter exit sites were all treated with povidone iodine ointment once a day. Body temperatures and weights were recorded, bacteriological and electron microscopical examinations of catheters performed. Without gentamicin filling all catheters were colonized after a few weeks. The dogs showed clinical signs of chronic bacteraemia. Gentamicin filling eradicated colonization. No further bacteraemia was observed. We conclude that filling only the catheter lumen with a concentrated solution of chymotrypsin and gentamicin, combined with measures to prevent infections via the subcutaneous catheter tunnel, is an effective and safe technique to prevent catheter-related infections.

Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study.

BACKGROUND: Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been proposed as therapeutic intervention in major depression. According to clinical needs, this study addresses the question whether tDCS is effective in treatment resistant major depressive episodes. METHODS: Twenty-two patients with a major depressive episode were randomly assigned to a cross-over protocol comparing tDCS and placebo stimulation add-on to a stable antidepressant medication. The parameters of active tDCS were: 1 or 2 mA for 20 minutes/day, anode over the left dorsolateral prefrontal cortex, cathode over the contralateral supraorbital region. Active and placebo tDCS was applied for 2 weeks using indistinguishable DC stimulators. Patients, raters, and operators were blinded to treatment conditions. RESULTS: There was no significant difference in depression scores after 2 weeks of real compared with 2 weeks of sham tDCS. Scores on the Hamilton Depression Rating Scale were reduced from baseline by 14.7% for active tDCS and 10% for placebo tDCS. In contrast, subjective mood ratings showed an increase in positive emotions after real tDCS compared with sham tDCS. CONCLUSIONS: Anodal tDCS, applied for 2 weeks, was not superior to placebo treatment in patients with treatment resistant depression. However, secondary outcome measures are pointing to a positive effect of tDCS on emotions. Therefore, modified and improved tDCS protocols should be carried out in controlled pilot trials to develop tDCS towards an efficacious antidepressant intervention in therapy-resistant depression.