Electroconvulsive Therapy in Children and Adolescents in Germany-A Case Series From 3 University Hospitals.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established, safe, and efficacious treatment for severe psychiatric disorders. In children and adolescents, it is used much less frequently than in adults, likely because of a lack of knowledge. METHODS: We retrospectively analyzed all patients aged 12 to 17 years who completed a course of ECT at 3 psychiatric university hospitals in Germany between 2010 and 2020. Clinical Global Impression Severity (CGI-S) scores were assessed based on electronic medical records. Changes in CGI-S scores were assessed using a paired samples t test. Predictors for response and remission were assessed using binomial logistic regression. RESULTS: We included 32 patients. The CGI-S scores improved significantly from before to after ECT treatment (6.9 vs 3.9, t = 10.0, P < 0.01). A total of 40.6% of patients responded (CGI ≤ 3) and 21.9% remitted (CGI ≤ 2). The number of ineffective medication trials in the 6 months before ECT treatment was significantly associated with response (odds ratio, 0.54; P = 0.028) and remission (odds ratio, 0.31; P = 0.048). Five patients reported subjective cognitive adverse effects, 2 patients exhibited a prolonged seizure, 1 patient reported headaches, and 1 patient experienced a mild allergic reaction after anesthesia with etomidate. A total of 65.6% of patients experienced no adverse effects at all. CONCLUSIONS: This retrospective analysis found ECT to be effective and safe in children and adolescents irrespective of their main diagnosis. The reported data point to the importance of an early use of ECT for severe psychiatric diseases in child and adolescent psychiatry.

[Use of electroconvulsive therapy in adolescents - A retrospective survey on 12- to 17-year-old patients at three university hospitals in Germany]. / Elektrokonvulsionstherapie im Kindes- und Jugendalter.

Use of electroconvulsive therapy in adolescents - A retrospective survey on 12- to 17-year-old patients at three university hospitals in Germany Abstract. Abstract. Background: Electroconvulsive therapy (ECT) is a highly effective and well-researched therapy in adult psychiatry and has been successfully used especially as a treatment for severe depressive, catatonic, and psychotic disorders. Although severe disease progressions also occur in child and adolescent psychiatry, ECT is used much less frequently there. This may be because hardly any data have been collected on the use, effectiveness, and tolerability of ECT in child and adolescent psychiatric patients. This article outlines the application, effectiveness, and tolerability of ECT when applied to young adolescents in Germany. Methods: A retrospective survey on ECT in 29 patients under 18 years of age was conducted at three German university centers. All documented cases were recorded and evaluated for effectiveness and tolerability. In addition, a comprehensive PubMed-based database search was carried out. Results and conclusions: Internationally, there are no meta-analyses or randomized controlled studies and hardly any published cases on electroconvulsive therapy in German child and adolescent psychiatry. Our data on ECT show high efficacy in previously treatment-resistant and severely ill patients. Side effects occurred rarely. There was no evidence of differences between adults and adolescents in indication (depression, catatonia, schizophrenia), effectiveness, tolerability, and negative predictors of response to ECT. The results also suggest that the use of ECT in adolescents should be considered earlier in the treatment course.

[Electroconvulsive Therapy - A beneficial and well tolerated therapy in children and adolescents with schizophrenia]. / Elektrokonvulsionstherapie ­ bei Kindern und Jugendlichen mit Schizophrenie wirksam und gut verträglich.

We report four cases of 12- to 17-year-old patients with schizophrenia, two of them suffering from catatonia, which were treated by ECT. Under a combined treatment with either ziprasidone or clozapine, and electroconvulsive therapy (ECT), they improved markedly. Severity and course of acute schizophrenia were evaluated by the Brief Psychiatric rating Scale (BPRS), severity and course of catatonia were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This article underlines the benefit, the safety and the tolerability of ECT in younger patients with schizophrenic disorders.

[Electroconvulsive Therapy (ECT) of a 15-year-old female patient suffering from a severe delusional depression: a case report]. / Fallbericht einer 15-jährigen Patientin mit einer schweren wahnhaften Depression, behandelt mit Elektrokonvulsionstherapie.

Electroconvulsive Therapy (ECT) of a 15-year-old female patient suffering from a severe delusional depression: a case report Abstract. OBJECTIVE: Electroconvulsive Therapy (ECT) is a modern therapy of severe psychiatric disorders. However, ECT is rarely used in treating children and adolescents with psychiatric disorders. This case report refers about a 15-year-old female patient suffering from severe depressive episodes with psychotic symptoms treated with ECT. METHOD: After unsuccessful combined behavioral therapy and medication, the patient received a total of 11 ECT treatments with right unilateral electrode placement. The severity of depressive symptoms was assessed by self (BDI-II) and external (HDRS21) scores before, during and after treatment. RESULTS: A rapid decline of depressive symptoms was observed. CONCLUSION: ECT provides a safe and effective method for the treatment of severe depressive disorders in childhood and adolescence and should be included earlier than usual into the standard therapeutic concepts.

A de novo nonsense mutation in ZBTB18 plus a de novo 15q13.3 microdeletion in a 6-year-old female.

ZBTB18 has been proposed as candidate gene for microcephaly and abnormalities of the corpus callosum based on overlapping microdeletions of 1q43q44. More recently, de novo mutations of ZBTB18 have been identified in patients with syndromic and non-syndromic intellectual disability. Heterozygous microdeletions of 15q13.3 encompassing the candidate gene CHRNA7 are associated with developmental delay or intellectual disability with speech problems, hypotonia, and seizures. They are characterized by significant variability and reduced penetrance. We report on a patient with a de novo ZBTB18 nonsense mutation and a de novo 15q13.3 microdeletion, both in a heterozygous state, identified by next generation sequencing and array-CGH. The 6-year-old girl showed global developmental delay, absent speech, therapy-refractory seizures, ataxia, muscular hypotonia, and discrete facial dysmorphisms. Almost all of these features have been reported for both genetic aberrations, but the severity could hardly been explained by the microdeletion 15q13.3 alone. We assume an additive effect of haploinsufficiency of ZBTB18 and CHRNA7 in our patient. Assembling the features of our patient and the published patients, we noted that only one of them showed mild anomalies of the corpus callosum. Moreover, we hypothesize that nonsense mutations of ZBTB18 are associated with a more severe phenotype than missense mutations. This report indicates that haploinsufficiency of additional genes beside ZBTB18 causes the high frequency of corpus callosum anomalies in patients with microdeletions of 1q43q44 and underlines the importance of an NGS-based molecular diagnostic in complex phenotypes.

[Transcranial magnetic stimulation (TMS), inhibition processes and attention deficit/hyperactivity disorder (ADHD) - an overview]. / Transkranielle Magnetstimulation (TMS), Inhibitionsprozesse und Aufmerksamkeitsdefizit-/ Hyperaktivitätsstörung (ADHS).

Motor system excitability can be tested by transcranial magnetic stimulation CFMS). In this article, an overview of recent methodological developments and research findings related to attention deficit/hyperactivity disorder (ADHD) is provided. Different TMS parameters that reflect the function of interneurons in the motor cortex may represent neurophysiological markers of inhibition in ADHD, particularly the so-called intracortical inhibition. In children with a high level of hyperactivity and impulsivity, intracortical inhibition was comparably low at rest as shortly before the execution of a movement. TMS-evoked potentials can also be measured in the EEG so that investigating processes of excitability is not restricted to motor areas in future studies. The effects of methylphenidate on motor system excitability may be interpreted in the sense of a 'fine-tuning' with these mainly dopaminergic effects also depending on genetic parameters (DAT1 transporter). A differentiated view on the organization of motor control can be achieved by a combined analysis of TMS parameters and event-related potentials. Applying this bimodal approach, strong evidence for a deviant implementation of motor control in children with ADHD and probably compensatory mechanisms (with involvement of the prefrontal cortex) was obtained. These findings, which contribute to a better understanding of hyperactivity/impulsivity, inhibitory processes and motor control in ADHD as well as the mechanisms of medication, underline the relevance of TMS as a neurophysiological method in ADHD research.

Transcranial sonography of subcortical structures in tic/tourette disorder.

Functional neuroimaging studies demonstrate disinhibition of the cortico-striatal-thalamo-cortical circuit. However, structural imaging studies revealed conflicting results, some suggesting smaller volumes of the caudate nucleus (CN) in children with Gilles de la Tourette syndrome (TS). Here we wanted to find out whether transcranial sonography (TCS) detects alterations of raphe nuclei, substantia nigra, lenticular nucleus (LN), or CN in children with Tic disorder or TS (TIC/TS).The study included 25 treatment-naive children (age: 12.2 ± 2.5 years) with a DSM-V based diagnosis of Tic disorder or TS (10 subjects), without other psychiatric or neurologic diagnosis, and 25 healthy controls (age: 12.17 ± 2.57 years), matched for age and sex. Parental rating of behavioral, emotional abnormalities, somatic complaints and social competencies of the participants were assessed using the Child Behavior Check List (CBCL/4-18R). TCS of deep brain structures was conducted through the preauricular acoustic bone windows using a 2.5-MHz phased-array ultrasound system. Fisher's exact test and Mann-Whitney-U test were used for comparisons between TIC/TS patients and healthy volunteers. The number of participants with hyperechogenic area of left CN in the TIC/TS sample was increased, compared to the healthy control group. TIC/TS patients with hyperechogenic CN showed an increased occurrence of thought- and obsessive-compulsive problems. This TCS study revealed pathologic structural changes in CN, its higher occurrence in TIC/TS compared to healthy controls and the relation to comorbidity of thought problems. Further research should focus on the molecular cause of these alterations, probably the disturbed iron metabolism.

A case of catatonia in a 14-year-old girl with schizophrenia treated with electroconvulsive therapy.

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

Intra- and inter-cortical motor excitability in Alzheimer's disease.

Transcranial magnetic stimulation (TMS) provides evidence for facilitatory and inhibitory motor dysfunctions in Alzheimer's disease (AD). The corpus callosum (CC) is affected in AD already at early stages consistent with the hypothesis that AD patients exhibit alterations in transcallosally mediated motor inhibition (ipsilateral silent period, iSP). Therefore, here we aimed at investigating the integrity not only of intra-, but also of inter-hemispheric mechanisms of cortical motor excitability in AD. We determined the iSP, the resting motor threshold (RMT), and the amplitude of motor evoked potentials (MEP) in 19 AD patients and 19 healthy controls using single-pulse TMS. Furthermore, we used paired-pulse TMS to study the intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF). All subjects underwent comprehensive neuropsychologic, clinical, and laboratory testing, and neuroimaging to exclude significant co-morbidity. In AD patients, the RMT was significantly reduced (Oneway-ANOVA). An analysis of covariance (ANCOVA) revealed a strong group specific interaction of the inhibitory interstimulus intervals (p = 0.005) with a reduced ICI in AD. Furthermore, we found a significantly prolonged iSP-latency (p = 0.003) in AD compared to controls, whereas the iSP-duration was not different. The iSP-latency correlated significantly with the ICI (ANCOVA) (p = 0.02). The ICF did not differ significantly between groups. Our data suggest comprehensive but still subclinical dysfunctions of motor cortical inhibition in mild to moderate clinical stages of AD with strong interactions of intra- and inter-hemispheric inhibitory phenomena. Future studies are needed to show the potential prognostic relevance of these findings for the further course of the disease.

Brain Arousal as Measured by EEG-Assessment Differs Between Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Depression.

Objective: Disturbed regulation of vigilance in the wake state seems to play a key role in the development of mental disorders. It is assumed that hyperactivity in adult ADHD is an attempt to increase a general low vigilance level via external stimulation in order to avoid drowsiness. For depression, the avoidance of stimulation is interpreted as a reaction to a tonic increased vigilance state. Although ADHD is assumed to start during childhood, this vigilance model has been barely tested with children diagnosed for ADHD so far. Methods: Resting-state EEG (8 min) measures from two groups of children diagnosed with either ADHD [N = 76 (16 female, 60 male), age: (mean/SD) 118/33 months] or depression [N = 94 (73 female, 21 male), age: 184/23 months] were analyzed. Using the VIGALL toolbox, EEG patterns of vigilance level, and regulation were derived and compared between both groups. In correlation analysis, the relations between vigilance measures, attentional test performance (alertness and inhibition), and mental health symptoms were analyzed. Results: Children with ADHD differed from children with most prominent depressive symptoms in brain arousal regulation and level, but EEG vigilance was not related to behavior problems and not related to the attentional test performance. Brain arousal was dependent on the age of the participant in the whole sample; younger children showed lower vigilance stages than teenagers; this effect was not present when analyzed separately for each diagnostic group. EEG assessment time and received medication had no effect on the EEG vigilance. Discussion: Although based on a small sample, this explorative research revealed that EEG vigilance level is different between children with ADHD and with depression. Moreover, even the standard procedure of the clinical routine EEG (resting state) can be used to differentiate brain arousal states between participants with ADHD and depression. Because routine EEG is not specialized to vigilance assessment, it may not be sufficiently sensitive to find vigilance-symptomatology associations. Further research should address developmental changes in EEG measurements in children and use bigger samples of participants within the same age range.

Modulation of motorcortical excitability by methylphenidate in adult voluntary test persons performing a go/nogo task.

This study investigated the interaction between motorcortical excitability (short interval cortical inhibition, intracortical facilitation and long interval cortical inhibition), different requirement conditions [choice reaction test (CRT), attention/go/nogo], and their pharmacological modulation by methylphenidate (MPH) in normal healthy adults (n = 31) using a transcranial magnetic stimulation paradigm. MPH was administered in a dosage of 1 mg/kg body weight, maximum 60 mg. Additionally, serum level and clearance of MPH were controlled. The statistical analysis of variance revealed a significant three-way interaction of 2 (MPH) x 3 (CRT) x 6 (ISI) predicting motor evoked potential amplitudes (P = 0.032, MPH none and full dose, n = 31). In order to compare effects of dosage an additional between-subjects factor (half vs. full MPH dose) was introduced. None of the interactions involving this between-subject factor reached statistical significance. Exploring interactions with MPH only, a 3 (MPH none, half and full dose) x 3 (CRT) x 6 (ISI) analysis of variance revealed significant two-way interactions for MPH x ISI (P = 0.040) and condition x ISI (P < 0.001, n = 18). Effects observed for MPH were strongest on facilitatory processes, weaker for intracortical inhibition. In sum, MPH seems to interact via striato-thalamo-cortical pathways with original motorcortical processes (ISI), to a lesser extent with task-dependent or behavioral parameters (CRT).

Effects of methylphenidate on motor system excitability in a response inhibition task.

BACKGROUND: Motor system excitability is based on a complex interaction of excitatory and inhibitory processes, which in turn are modulated by internal (e.g., volitional inhibition) and external (e.g., drugs) factors. A well proven tool to investigate motor system excitability in vivo is the transcranial magnetic stimulation (TMS). In this study, we used TMS to investigate the effects of methylphenidate (MPH) on the temporal dynamics of motor system excitability during a go/nogo task. METHODS: Using a double-blind, placebo-controlled, crossover design, 14 healthy adults (8 male, 6 female; aged 20-40 yrs) performed a spatial go/nogo task (S1-S2 paradigm) either under dl-methylphenidate (MPH, 20 mg) or placebo. TMS single and double-pulses (interstimulus interval: 3 ms) were delivered either at 120, 230 or 350 ms after the S2 stimulus (control, go and nogo trials). RESULTS: At the performance level, faster reaction times and a trend towards less impulsivity errors under MPH vs. placebo were observed.In nogo trials, i.e., when a prepared response had to be inhibited, motor evoked potentials (MEPs) had a smaller amplitude at an interval of 230 ms compared to 120 and 350 ms. The short-interval intracortical inhibition (SICI) increased over time.Under MPH, SICI in nogo trials was larger compared to placebo. With the interval between S2 and the TMS-pulse increasing, MEP amplitudes increased under MPH in nogo trials but an early inhibitory effect (at 120 ms) could also be observed. CONCLUSION: Our results show a distinct pattern of excitatory and inhibitory phenomena in a go/nogo task. MPH appears to significantly alter the dynamics of motor system excitability. Our findings suggest that a single dose of 20 mg MPH provides some fine-tuning of the motor system in healthy adults.

[Alternative agents used in ADHD]. / Substanzgebundene Alternativen in der Therapie von ADHS.

Attention-deficit/hyperactivity disorder (ADHD) is, with a prevalence of 2% to 6%, one of the most common neurobehavioral disorder affecting children and adolescents, persisting into adulthood. Comorbidity and psychosocial circumstances enter into the choice of intervention strategies. Several agents have been demonstrated effective in treating individuals with ADHD. Direct or indirect attenuation of dopamine and norepinephrine neurotransmission appears closely related to both the stimulant and nonstimulant medications efficacious in ADHD. However, important differences concerning efficacy and side effects exist both between and with the specific classes of agents like neuroleptics, antidepressants, antiepileptics, alpha-agonists, beta-blockers, buspiron, l-dopa, melatonin, pycnogenol, zinc, magnesium, polyunsaturated fatty acids, and homeopathy. Elucidating the various mechanisms of action of ADHD medications may lead to better choices in matching potential responses to the characteristics of individuals. We review the purported mechanism of action and available evidence for selected complementary and alternative medicine therapies for ADHD in childhood and adolescence.

Methylphenidate promotes the interaction between motor cortex facilitation and attention in healthy adults: A combined study using event-related potentials and transcranial magnetic stimulation.

OBJECTIVE: This study investigated simultaneously the impact of methylphenidate (MPH) on the interaction of inhibitory and facilitative pathways in regions processing motor and cognitive functions. METHOD: Neural markers of attention and response control (event-related potentials) and motor cortical excitability (transcranial magnetic stimulation) and their pharmacological modulation by MPH were measured simultaneously in a sample of healthy adults (n = 31) performing a cued choice reaction test. RESULTS: Methylphenidate modulated attentional gating and response preparation processes (increased contingent negative variation) and response inhibition (increased nogo P3). N1, cue- and go-P3 were not affected by MPH. Motor cortex facilitation, measured with long-interval cortical facilitation, was increased under MPH in the nogo condition and was positively correlated with the P3 amplitude. CONCLUSION: Methylphenidate seems particularly to enhance response preparation processes. The MPH-induced increased motor cortex facilitation during inhibitory task demands was accompanied by increased terminal response inhibition control, probably as a compensatory process.

Restoration of disturbed intracortical motor inhibition and facilitation in attention deficit hyperactivity disorder children by methylphenidate.

BACKGROUND: Previous investigations using transcranial magnetic stimulation (TMS) have shown that neural inhibitory motor circuits are disturbed in ADHD children. We sought to investigate the influence of methylphenidate (MPH) on inhibitory and facilitatory motor circuits of ADHD children with TMS paired pulse protocols using surplus long interval inter-stimulus intervals (ISI) not investigated so far. METHODS: Motorcortical modulation was tested with TMS paired pulse protocols employing ISI of 3, 13, 50, 100, 200, and 300 msec in 18 ADHD children before and on treatment with MPH. Clinical improvement by MPH was measured by the Conners score. RESULTS: Analysis of variance (ANOVA) revealed a significant three-way interaction "Group x Amplitude x ISI," p = .001. Subsequent two-factorial ANOVAs and t-tests showed group specific differences of motor evoked potential (MEP) amplitudes for inhibitory ISIs of 3 and 100 msec, and for facilitatory ISIs of 13 and 50 msec. Compared to controls, an adjustment of these parameters by MPH could be shown. On MPH, a significant bivariate correlation was found between the Conners score reduction and averaged MEP amplitude changes only for inhibitory ISIs (3 and 100 msec). CONCLUSIONS: In ADHD children, MPH modulates disturbed facilitatory and inhibitory motor circuits, which for the latter is associated with clinical improvement.

The Treatment of Illnesses Arising in Pregnancy.

BACKGROUND: The treatment of pregnant women who have illnesses unrelated to pregnancy can cause uncertainty among physicians. METHODS: We searched the PubMed database and specialty guidelines from Germany and abroad (the guidelines of the German Society for Gynecology and Obstetrics, the American Congress of Obstetri cians and Gynecologists, and the Royal College of Obstetricians and Gynaecologists) over the period 2007-2016 for information on standards for the diagnosis and treatment of five illnesses that can arise in pregnancy: bronchial asthma, migraine, hypothyroidism, hyperthyroidism, and varicose veins. RESULTS: Any diagnostic tests that are carried out in pregnant women should be simple and goal-directed. The choice of drugs that can be used is limited. For many drugs, no embryotoxic or teratogenic effect is suspected, but the level of evidence is low. CONCLUSION: When illnesses unrelated to pregnancy arise in pregnant women, attention must be paid to potential diver gences from the typical disease course and to pos sible drug side effects on the fetus in order to prevent serious complications for both mother and child.

Objective measurement of tissue tension in myofascial trigger point areas before and during the administration of anesthesia with complete blocking of neuromuscular transmission.

OBJECTIVES: Myofascial trigger points (MTPs) are extremely frequent in the human musculoskeletal system. Despite this, little is known about their etiology. Increased muscular tension in the trigger point area could be a major factor for the development of MTPs. To investigate the impact of muscular tension in the taut band with an MTP and thereby, the spinal excitability of associated segmental neurons, we objectively measured the tissue tension in MTPs before and during the administration of anesthesia using a transducer. METHODS: Three target muscles (m. temporalis, upper part of m. trapezius, and m. extensor carpi radialis longus) with an MTP and 1 control muscle without an MTP were examined in 62 patients scheduled for an operation. RESULTS: We found significant 2-way interactions (ANOVA, P<0.05) between the analyzed regions of the target muscles dependent on the time of measurement, that is, before and during a complete blocking of neuromuscular transmission. These effects could be demonstrated for each target muscle separately. DISCUSSION: An increased muscle tension in MTPs, and not a primary local inflammation with enhanced viscoelasticity, was the main result of our investigation. We interpret this increased muscular tension in the taut band with an MTP as increased spinal segmental excitability. In line with this, we assume a predominant, but not unique, impact of increased spinal excitability resulting in an augmented tension of segmental-associated muscle fibers for the etiology of MTP. Consequently, postisometric relaxation might be a promising therapeutic option for MTPs.