Non-Invasive Brain Stimulation in Conversion (Functional) Weakness and Paralysis: A Systematic Review and Future Perspectives

Conversion (functional) limb weakness or paralysis (FW) can be a debilitating condition, and often causes significant distress or impairment in social, occupational, or other important areas of functioning. Most treatment concepts are multi-disciplinary, containing a behavioral approach combined with a motor learning program. Non-invasive brain stimulation (NIBS) methods, such as electroconvulsive therapy (ECT), and transcranial magnetic stimulation (TMS) have been used in the past few decades to treat FW. In order to identify all published studies that used NIBS methods such as ECT, TMS and transcranial direct current stimulation (tDCS) for treating FW patients a systematic review of the literature was conducted in PubMed and Web of Science. In a second step, narratives were used to retrospectively determine nominal CGI-I (Clinical Global Impression scale–Improvement) scores to describe approximate changes of FW symptoms. We identified two articles (case reports) with ECT used for treatment of FW, five with TMS with a total of 86 patients, and none with tDCS. In 75 out of 86 patients treated with repetitive (r)TMS a nominal CGI-I score could be estimated, showing a satisfactory short-term improvement. Fifty-four out of seventy-five identified patients (72%) had a CGI-I score of 1 (very much improved), 13 (17%) a score of 2 (much improved), 5 (7%) a score of 3 (minimally improved), and 3 (5%) remained unchanged (CGI-I = 4). In no case did patients worsen after rTMS treatment, and no severe adverse effects were reported. At follow-up, symptom improvement was not quantifiable in terms of CGI-I for the majority of the cases. Patients treated with ECT showed a satisfactory short-term response (CGI-I = 2), but deterioration of FW symptoms at follow-up. Despite the predominantly positive results presented in the identified studies and satisfactory levels of efficacy measured with retrospectively calculated nominal CGI-I scores, any assumption of a beneficial effect of NIBS in FW has to be seen with caution, as only few articles could be retrieved and their quality was mostly poor. This article elucidates how NIBS might help in FW and gives recommendations for future study designs using NIBS in this condition

Takotsubo Cardiomyopathy With Inconspicuous Initial Electrocardiogram: A Potentially Serious Cardiac Pathology Related to Emotional Stress

Introduction: Takotsubo cardiomyopathy (TCM) is frequently associated with emotional or physical stress. Thus, patients with TCM might present primarily at a psychiatric clinic. Appropriate diagnosis and therapy may thus be delayed.Case report: A 43-year-old female patient presented as an emergency to the psychiatric outpatient clinic after experiencing severe work-related bullying. On admission, she complained of acute left thoracic chest pain as well as depressed mood, low energy, anhedonia, generalized anxiety, and sleep difficulties, present for several weeks. The initial electrocardiogram (ECG) was unremarkable; serum troponin levels, however, were markedly elevated. The patient was transferred to the department of cardiology. Via cardiac catheterization and MRI, an acute coronary syndrome was excluded and apical ballooning and left ventricular dysfunction, compatible with TCM, was found.Conclusion: Patients with acute psychopathology, recent emotional or physical stress, and acute cardiothoracic symptoms should receive immediate cardiological investigations. As the ECG may be normal in patients with TCM, concurrent measurement of the troponin serum level is recommended. Psychiatrists should consider TCM in patients who report recent stressful events accompanied by cardiothoracic symptoms

Sham or real—Post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial

Selecting a suitable sham condition within the frame of repetitive transcranial magnetic stimulation (rTMS) treatment trials is a central issue. On the one hand, the ideal sham condition should not have a real stimulation effect; on the other hand, it should not be recognized as sham by patients, particularly when considering that real stimulation conditions come along with rTMS specific side effects. Within the course of a multi-centre trial assessing the antidepressant effects of rTMS, patients were randomized to sham or real stimulation, in both cases using a standard stimulation coil. In one centre, patients (n = 33) were asked about their impression whether they received the sham or the real treatment, and if they would recommend the treatment to others. 29 patients returned the questionnaires and were included into the analysis. From 15 subjects with real stimulation, 11 suggested to have obtained real, and 4 to have obtained sham. From 14 sham stimulated subjects, 9 suggested to have obtained the real condition and 5 to have been sham stimulated. This difference was not significant (p = 0.60, chi square test). In addition, the major part of patients in both stimulation conditions would recommend rTMS to others. In both conditions, real and sham, the majority of subjects believed to have obtained the real condition. This implies suitability of the sham condition used since subjects appeared not to be able to identify the condition. The results imply the feasibility of a valid sham condition with a “real” coil

Prediction and prevention of suicide in patients with unipolar depression and anxiety

Epidemiological data suggest that between 59 and 87% of suicide victims suffered from major depression while up to 15% of these patients will eventually commit suicide. Male gender, previous suicide attempt(s), comorbid mental disorders, adverse life-situations, acute psycho-social stressors etc. also constitute robust risk factors. Anxiety and minor depression present with a low to moderate increase in suicide risk but anxiety-depression comorbidity increases this risk dramatically Contrary to the traditional psychoanalytic approach which considers suicide as a retrospective murder or an aggression turned in-wards, more recent studies suggest that the motivations to commit suicide may vary and are often too obscure. Neurobiological data suggest that low brain serotonin activity might play a key role along with the tryptophan hydroxylase gene. Social factors include social support networks, religion etc. It is proven that most suicide victims had asked for professional help just before committing suicide, however they were either not diagnosed (particularly males) or the treatment they received was inappropriate or inadequate. The conclusion is that promoting suicide prevention requires the improving of training and skills of both psychiatrists and many non-psychiatrists and especially GPs in recognizing and treating depression and anxiety. A shift of focus of attention is required in primary care to detect potentially suicidal patients presenting with psychological problems. The proper use of antidepressants, after a careful diagnostic evaluation, is important and recent studies suggest that successful acute and long-term antidepressant pharmacotherapy reduces suicide morbidity and mortality

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation