[Electroconvulsive therapy in people with intellectual disability]. / Elektrokonvulsionstherapie bei Menschen mit Intelligenzminderung.

Electroconvulsive therapy (ECT) is a highly effective treatment option for severe mental illness. Although people with intellectual disability (ID) have similar prevalence rates of mental disorders in comparison to the general population their access to ECT remains challenging. A systematic literature review was carried out on treatment with ECT in patients with ID and a case report on a patient with ID who underwent ECT is presented, to highlight a typical clinical routine. A total of 100 articles with 208 different case reports were retrieved. In summary, the results underline the effectiveness of ECT in people with ID, with side effects comparable to those in the general population. The ECT is effective in the treatment of severe affective and psychotic disorders and particularly in people with catatonia. The use of ECT can improve the patient's mental health and quality of life and is often a life-saving treatment option. The prophylaxis of relapses should be included as early as possible in the planning process. Providing an easy access to ECT treatment for people with ID is corroborated by its effectiveness and is in line with the right to equal treatment in accordance with article 25 of the United Nations Convention on the Rights of Persons with Disabilities.

The neuroleptic malignant syndrome-a systematic case series analysis focusing on therapy regimes and outcome.

INTRODUCTION: Neuroleptic malignant syndrome (NMS) is a rare, potentially life-threatening antipsychotic-associated disorder that requires an efficient and timely therapy. The aim of the study was to compare the effectiveness of different NMS therapies and to analyze its outcome depending on NMS severity. METHOD: Systematic search for NMS cases in biomedical databases. The focus of the analysis was on therapy with dantrolene, bromocriptine, and electroconvulsive therapy (ECT) when each was compared with symptomatic therapy. Primary outcomes were the survival rate and the duration of treatment. RESULT: 405 case reports were included. Overall, no statistically significant differences regarding mortality rate or duration of treatment were found between dantrolene, bromocriptine, or ECT compared to supportive care. A subgroup analysis regarding NMS severity showed that the mortality under specific NMS pharmacotherapy (dantrolene, bromocriptine) and under ECT was significantly lower than under purely symptomatic therapy in severe NMS (P = 0.018). The difference was not significant in mild and moderate cases. DISCUSSION: An overall superiority of the specific NMS therapy (dantrolene, bromocriptine, and ECT) was not found in this study. When regarding severity classification, specific therapies were superior but only in severe cases, and ECT showed the lowest mortality rate. In previous case series, an effect on survival or the duration of the disease could only be observed in part for specific therapies, but the evidence available is inconsistent. The results of this study support our hypothesis that NMS treatment with dantrolene, bromocriptine, and ECT is advantageous over purely symptomatic therapy in severe NMS cases.

[Antipsychotic-induced motor symptoms in schizophrenic psychoses-Part 2 : Catatonic symptoms and neuroleptic malignant syndrome]. / Antipsychotikaassoziierte motorische Symptome bei schizophrenen Psychosen ­ Teil 2 : Katatone Symptome und malignes neuroleptisches Syndrom.

In rare cases, pharmacotherapy in schizophrenic psychoses can be associated with life-threatening antipsychotic-induced movement disorders. The two most severe complications are antipsychotic-associated catatonic symptoms (ACS) and neuroleptic malignant syndrome (NMS). Although both constellations necessitate rapid medical care, the diagnosis is still a clinical challenge. Although there is no established treatment of ACS (here designated as a specific subtype of catatonic symptoms), an attempt should be made with benzodiazepines and memantine can also be helpful. In severe drug-refractory cases electroconvulsive therapy (ECT) can be indicated. The NMS represents a life-threatening constellation that frequently requires intensive care unit treatment. The medicinal treatment with benzodiazepines, bromocriptine, amantadine, dantrolene and/or ECT is also advocated. Finally, this review article also summarizes the currently available literature for treatment of genuine catatonic symptoms. In conclusion, the abovementioned clinical syndromes must be rapidly recognized and treated. Early recognition and treatment of these movement disorders can under certain circumstances be lifesaving and favorably influence the later clinical outcome.

Remifentanil as an adjunct to anaesthesia for electroconvulsive therapy fails to confer long-term benefits.

BACKGROUND: Adding the µ-opioid receptor agonist remifentanil to agents used to induce general anaesthesia in electroconvulsive therapy (ECT) can reduce the required doses of induction agents and their unfavourable effects on seizure threshold and quality. However, whether remifentanil has favourable long-term treatment effects in terms of response and remission rates, speed of response and remission, and side-effects has not been studied. METHODS: This retrospective, register-based cohort study involved patients with major depression consecutively treated at two units at different hospitals in Norway with the same ECT procedure. Both units used thiopental for ECT anaesthesia, but only one unit added remifentanil (R+; n=47; 541 sessions), whereas the other did not (R-; n=119; 1166 sessions). A Cox proportional hazards model for interval-censored data was conducted to examine the effects of remifentanil on the time to response and remission from depressive symptoms, whilst adjusting for age, sex, and baseline depression score. RESULTS: Both R+ and R- patients showed substantial reductions of depressive symptoms, with no difference in the response (76% in both groups) or remission (63% vs 65%) rate. However, R+ patients responded (hazard ratio=0.59; 95% confidence interval: 0.4-0.8) and remitted (hazard ratio=0.72; 95% confidence interval: 0.5-1.0) more slowly, and reported more often side-effects of nausea (30% vs 8%; P<0.001), dizziness (22% vs 8%; P=0.027), and headache (48% vs 23%; P=0.004). CONCLUSIONS: The use of adjunctive remifentanil was associated with more short-term side-effects and no favourable long-term clinical outcomes. The practice of routinely adding remifentanil to barbiturate anaesthesia should therefore be reconsidered.

Improvement in verbal memory performance in depressed in-patients after treatment with electroconvulsive therapy.

OBJECTIVE: Electroconvulsive therapy (ECT) is a highly effective and well-tolerated therapy for severe and treatment-resistant depression. Cognitive side-effects are still feared by some patients and clinicians. Importantly, cognitive impairments are among the most disabling symptoms of depression itself. METHODS: Patients suffering from a severe episode of depression were treated with either ECT or treatment as usual (TAU) in an in-patient setting. Matched healthy participants served as controls (HC). Verbal memory was tested with the California Verbal Learning Test (CVLT) before the specific treatment started (ECT = 15, TAU = 16, HC = 31) and 2 months after the last ECT session or 2 months after discharge respectively. RESULTS: Before the specific treatment started, depressed patients performed substantially worse compared with HC in total, short- and long-delay recall in the CVLT, while the ECT group showed the worst performance. More severely depressed patients showed worse performances in these measures. Intriguingly, verbal memory showed a significant improvement in ECT-treated patients, but not in the other groups. No differences between the groups were found at follow-up. CONCLUSION: Contrary to the widely feared assumption that ECT has long-term impact on memory functions, we found evidence that ECT is superior to TAU in improving verbal memory in depressed patients.

A New Type of ECT Stimuli: Burst Stimulus ECT.

OBJECTIVES: Pulse width in electroconvulsive therapy has significant influence on effectiveness and side effects. While shorter pulses are beneficial for cognitive performance, there is still a debate about a negative impact on ECT efficacy at least for ultra-brief pulse durations. METHODS: We report a first patient treated with burst stimulus ECT, i. e., with 4 consecutive 250-µs pulses, separated by another 250 µs. Within the same patient we compared 6 classical vs. 6 burst stimulus ECT sessions. RESULTS: In all cases a typical tonic-clonic seizure was observed. Seizure parameters like concordance, coherence and mid-ictal amplitude increased numerically, but not significantly with burst ECT. The time needed to show a reorientation was significantly shortened with burst stimuli (30 min vs. 14 min, p=0.007). CONCLUSIONS: In conclusion we present the first case of ECT in a single patient comparing "classical" single stimulus pulses vs. burst stimulus ECT. The new burst stimulus was better tolerated regarding reorientation time after the treatment, while parameters of seizure quality remained basically unchanged. Whether burst stimulus ECT has the potential to improve ECT quality by reducing side effects without losing efficacy has to be investigated in clinical trials.

[Ketamine as anesthetic agent in electroconvulsion therapy]. / Ketamin als Anästhetikum bei der Elektrokrampftherapie.

BACKGROUND: Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment for severe psychiatric disorders. Ketamine is known as a core medication in anesthesiology and has recently gained interest in ECT practice as there are three potential advantages: (1) ketamine has no anticonvulsive actions, (2) according to recent studies ketamine could possess a unique intrinsic antidepressive potential and (3) ketamine may exhibit neuroprotective properties, which again might reduce the risk of cognitive side effects associated with ECT. OBJECTIVES: The use of ketamine in psychiatric patients has been controversially discussed due to its dose-dependent psychotropic and psychotomimetic effects. This study was carried out to test if the occurrence of side effects is comparable and if seizure quality is better with ketamine when compared to thiopental. MATERIAL AND METHODS: This retrospective study analyzed a total of 199 patients who received ketamine anesthesia for a total of 2178 ECT sessions. This cohort was compared to patients who were treated with thiopental for 1004 ECT sessions. RESULTS AND DISCUSSION: A repeated measurement multiple logistic regression analysis revealed significant advantages in the ketamine group for seizure concordance and postictal suppression (both are surrogates for central inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and a higher maximum postictal heart frequency. Clinically relevant psychiatric side effects were rare in both groups. No psychiatric side effects occurred in the subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S-ketamine used increased in the first years but stabilized at 63 mg per patient in 2014. From these experiences it can be concluded that S-ketamine can be recommended at least as a safe alternative to barbiturates.

Signal-to-noise ratio of a mouse brain (13) C CryoProbe™ system in comparison with room temperature coils: spectroscopic phantom and in vivo results.

MRI and MRS in small rodents demand very high sensitivity. Cryogenic transmit/receive radiofrequency probes (CryoProbes) designed for (1) H MRI of mouse brain provide an attractive option for increasing the performance of small-animal MR systems. As the Larmor frequency of (13) C nuclei is four times lower than that for (1) H nuclei, an even larger sensitivity improvement is expected for (13) C applications. The aim of this work was to evaluate the performance of a prototype (13) C CryoProbe™ for mouse brain MRS. To investigate the possible gain of the (13) C CryoProbe™, we acquired localized single-voxel (13) C spectra and chemical shift images of a dimethyl sulfoxide phantom with the CryoProbe™, as well as with two room temperature resonators. The cryogenically cooled resonator achieved approximately four-fold higher signal-to-noise ratio in phantom tests when compared with the best-performing room temperature coil. In addition, we present localized (13) C spectra of mouse brain obtained with the CryoProbe™, as well as with one of the room temperature coils, demonstrating the performance in vivo. In summary, the cryogenic cooling technique significantly enhances the (13) C signal sensitivity at 9.4 T and enables the investigation of metabolism within mouse brain.

Bispectral index monitoring and seizure quality optimization in electroconvulsive therapy.

In ECT, the relative timing of seizure induction and anesthesia may critically impact on seizure quality when anesthetic agents with anticonvulsive properties such as barbiturates or propofol are used. Measuring the depth of anesthesia by bispectral index (BIS) monitoring and thereby identifying the optimal moment for seizure induction might enhance seizure quality.Seizures from 869 individual ECT -sessions with thiopental anesthetic from 118 patients were examined in this retrospective study. The associations of the BIS value at the moment of seizure induction with 7 established seizure parameters and with a novel model of seizure quality were tested by regression analyses.BIS value at induction correlated positively with seizure duration, central inhibition, coherence and maximal heart rate, but not with midictal amplitude. Higher seizure quality was related with a higher BIS value at the moment of seizure induction.The BIS value at seizure induction serves as an independent predictor of seizure quality, influencing most other established markers. BIS monitoring appears as a simple tool to identify the optimal moment for seizure induction.

Venlafaxin-associated post-ictal asystole during electroconvulsive therapy.

While post-stimulus asystoles occur quite often during electroconvulsive therapy (ECT) post-ictal or post-seizure sinus bradycardias or even asystoles are rare events. We report the case of an 82-year-old female patient with a current major depressive episode, who developed the rare event of a post-ictal asystole of 6 s and 4 ventricular escape beats during ECT. In the past this patient with a bipolar disorder and mild Alzheimer's disease had already been frequently treated with ECT with good success and no adverse events. Relevant comedication was venlafaxin, quetiapine, donepezil and clonidine, anesthesia was performed with ketamine and succinylcholine. Concurrent medication was completely unchanged compared to previous ECT sessions with the exception of venlafaxine, presumably at high serum levels. In summary, in line with some already existing reports, we expect the noradrenergic action of venlafaxin to have contributed substantially to the post-ictal asystole and want to indicate that the combination of ECT and venlafaxin might be harmful--especially in the elderly population.

Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats.

INTRODUCTION: The neurotrophin brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are a central part of the molecular concepts on neuroplastic changes associated with stress, anxiety and depression. An increasing number of studies uses serum BDNF levels as a potential indicator for central nervous system alterations. METHODS: To analyze the relationship between brain tissue and serum BDNF and NGF levels, we used electroconvulsive shocks (ECS), an animal model of electroconvulsive therapy, and studied the temporal profile of neurotrophin expression in the hippocampus, prefrontal cortex and serum. 88 male Sprague-Dawley rats received single or serial ECS treatments and were killed between 3 hours and 14 days after the last treatment. RESULTS: We found a 2.8-fold rise for BDNF (1.3-fold for NGF) in the prefrontal cortex, and a 2.2-fold rise (1.2-fold for NGF) in the hippocampus after 5 ECS sessions. The temporal expression profile and correlation analyses between tissue and serum BDNF indicate that BDNF crosses the blood-brain barrier. No such correlation was found for NGF. DISCUSSION: The time course of central and peripheral BDNF changes may significantly differ. However, we demonstrate substantial evidence that it can be justified to measure serum BDNF levels with a time delay to monitor brain tissue neurotrophin alterations.

The affinity of antipsychotic drugs to dopamine and serotonin 5-HT2 receptors determines their effects on prefrontal-striatal functional connectivity.

One of the major challenges of cross-species translation in psychiatry is the identification of quantifiable brain phenotypes linked to drug efficacy and/or side effects. A measure that has received increasing interest is the effect of antipsychotic drugs on resting-state functional connectivity (FC) in magnetic resonance imaging. However, quantitative comparisons of antipsychotic drug-induced alterations of FC patterns are missing. Consideration of receptor binding affinities provides a means for the effects of antipsychotic drugs on extended brain networks to be related directly to their molecular mechanism of action. Therefore, we examined the relationship between the affinities of three second-generation antipsychotics (amisulpride, risperidone and olanzapine) to dopamine and serotonin receptors and FC patterns related to the prefrontal cortex (PFC) and striatum in Sprague-Dawley rats. FC of the relevant regions was quantified by correlation coefficients and local network properties. Each drug group (32 animals per group) was subdivided into three dose groups and a vehicle control group. A linear relationship was discovered for the mid-dose of antipsychotic compounds, with stronger affinity to serotonin 5-HT2A, 5-HT2C and 5-HT1A receptors and decreased affinity to D3 receptors associated with increased prefrontal-striatal FC (p = 0.0004, r²â€¯= 0.46; p = 0.004, r²â€¯= 0.33; p = 0.002, r²â€¯= 0.37; p = 0.02, r²â€¯= 0.22, respectively). Interestingly, no correlation was observed for the low and high dose groups, and for D2 receptors. Our results indicate that drug-induced FC patterns may be linked to antipsychotic mechanism of action on the molecular level and suggest the technique's value for drug development, especially if our results are extended to a larger number of antipsychotics.

Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study.

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors.

Brain network reorganization differs in response to stress in rats genetically predisposed to depression and stress-resilient rats.

Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the specificity of the involved brain circuits. The rat strain bred for negative cognitive state (NC) represents a genetic animal model of TRD with high face, construct and predictive validity. Vice versa, the positive cognitive state (PC) strain represents a stress-resilient phenotype. Although NC rats show depressive-like behavior, some symptoms such as anhedonia require an external trigger, i.e. a stressful event, which is similar to humans when stressful event induces a depressive episode in genetically predisposed individuals (gene-environment interaction). We aimed to distinguish neurobiological predisposition from the depressogenic pathology at the level of brain-network reorganization. For this purpose, resting-state functional magnetic resonance imaging time series were acquired at 9.4 Tesla scanner in NC (N=11) and PC (N=7) rats before and after stressful event. We used a graph theory analytical approach to calculate the brain-network global and local properties. There was no difference in the global characteristics between the strains. At the local level, the response in the risk strain was characterized with an increased internodal role and reduced local clustering and efficiency of the anterior cingulate cortex (ACC) and prelimbic cortex compared to the stress-resilient strain. We suggest that the increased internodal role of these prefrontal regions could be due to the enhancement of some of their long-range connections, given their connectivity with the amygdala and other default-mode-like network hubs, which could create a bias to attend to negative information characteristic for depression.

Species-conserved reconfigurations of brain network topology induced by ketamine.

Species-conserved (intermediate) phenotypes that can be quantified and compared across species offer important advantages for translational research and drug discovery. Here, we investigate the utility of network science methods to assess the pharmacological alterations of the large-scale architecture of brain networks in rats and humans. In a double-blind, placebo-controlled, cross-over study in humans and a placebo-controlled two-group study in rats, we demonstrate that the application of ketamine leads to a topological reconfiguration of large-scale brain networks towards less-integrated and more-segregated information processing in both the species. As these alterations are opposed to those commonly observed in patients suffering from depression, they might indicate systems-level correlates of the antidepressant effect of ketamine.

Reduced connectivity and inter-hemispheric symmetry of the sensory system in a rat model of vulnerability to developing depression.

Defining the markers corresponding to a high risk of developing depression in humans would have major clinical significance; however, few studies have been conducted since they are not only complex but also require homogeneous groups. This study compared congenital learned helpless (cLH) rats, selectively bred for high stress sensitivity and learned helplessness (LH) behavior, to congenital non-learned helpless (cNLH) rats that were bred for resistance to uncontrollable stress. Naïve cLH rats show some depression-like behavior but full LH behavior need additional stress, making this model ideal for studying vulnerability to depression. Resting-state functional connectivity obtained from seed correlation analysis was calculated for multiple regions that were selected by anatomy AND by a data-driven approach, independently. Significance was determined by t-statistic AND by permutation analysis, independently. A significant reduction in functional connectivity was observed by both analyses in the cLH rats in the sensory, motor, cingulate, infralimbic, accumbens and the raphe nucleus. These reductions corresponded primarily to reduced inter-hemispheric connectivity. The main reduction however was in the sensory system. It is argued that reduced connectivity and inter-hemispheric connectivity of the sensory system reflects an internal convergence state which may precede other depressive symptomatology and therefore could be used as markers for vulnerability to the development of depression.

Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients.

Brain function and laterality in schizophrenia were investigated by means of a simple motor task with a self-generated left-hand sequential finger opposition (SFO) using a whole-brain high-speed (100 ms per slice) functional imaging technique. Neuroleptic-naïve, acutely ill schizophrenic patients were compared to schizophrenic patients under stable neuroleptic medication and matched controls. The goal was to evaluate both the motor function in first-episode patients and possible effects of different neuroleptic treatments on functional MRI results. Forty patients satisfying ICD 10 criteria (F20.x) for schizophrenia and sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examinations on a conventional 1.5 T MR unit. The primary sensorimotor cortex and the high-order supplementary motor area (SMA) were evaluated. There was a close similarity in the activation of the primary and high-order (SMA) sensorimotor areas between first-episode schizophrenic patients and controls. In contrast, a significant reduction in the overall blood oxygen level dependent (BOLD) response was seen in sensorimotor cortices (contra- and ipsilateral) in schizophrenic patients under stable medication with typical neuroleptics. This effect was not present in patients treated with atypical antipsychotics. Both antipsychotic treatments, however, led to a significant reduction in activation of the SMA region compared to controls and neuroleptic-naïve subjects. Thus, the present study provides no evidence for the localized involvement of the primary motor cortex or the SMA as a relatively stable vulnerability marker in schizophrenia. There is, however, strong evidence that neuroleptics themselves influence fMRI activation patterns and that there are major differences between typical neuroleptics and atypical antipsychotics.

Evaluation of a triple-lumen central venous heparin-coated catheter versus a catheter coated with chlorhexidine and silver sulfadiazine in critically ill patients.

OBJECTIVE: To compare the incidence of catheter colonization and catheter-related bloodstream infections between heparin-coated catheters and those coated with a synergistic combination of chlorhexidine and silver sulfadiazine. DESIGN: Randomized, controlled clinical trial. SETTING: A 20-bed medical-surgical intensive care unit. PATIENTS: A total of 180 patients requiring the insertion of a trilumen central venous catheter. INTERVENTIONS. Patients were randomized to receive either a trilumen heparin or chlorhexidine and silver sulfadiazine-coated catheter. MEASUREMENTS: Catheter colonization was defined by a semiquantitative catheter tip culture yielding 15 or more colony-forming units or quantitative culture of 1,000 or more colony-forming units/ml. Catheter-related bloodstream infection as the isolation of the same microorganism from a peripheral blood culture and catheter tip. RESULTS: A total of 260 catheters were cultured. Out of 132 heparin-coated catheters, 29 were colonized and out of 128 chlorhexidine and silver sulfadiazine-coated catheters, 13 were colonized ( p=0.03), relative risk RR=2.16 (1.18-3.97). This represents an incidence of 23.5 and 11.5 episodes of catheter colonization per 1,000 catheter-days, respectively ( p=0.0059), RR=2.04 (1.05-3.84). Microorganisms isolated in catheter colonization from heparin-coated catheters were gram-positive cocci 23, gram-negative bacilli 7, and Candida spp 4. In chlorhexidine and silver sulfadiazine-coated catheters were gram-positive cocci 6 and gram-negative bacilli 11 ( p=0.009). The incidence of catheter-related bloodstream infections per 1,000 catheter-days was 3.24 in heparin-coated catheters and 2.6 in chlorhexidine and silver sulfadiazine-coated catheters ( p=0.79), RR=1.22 (0.27-5.43). CONCLUSIONS: In critically ill patients the use of trilumen central venous catheters coated with chlorhexidine and silver sulfadiazine reduced the risk of catheter colonization due to prevention of gram-positive cocci and Candida spp.