Johannes Buchmann

Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD)

OBJECTIVE The aim of this study was to investigate mechanisms of motor-cortical excitability and inhibition which may contribute to motor hyperactivity in children with attention deficit hyperactivity disorder (ADHD). METHODS Using transcranial magnetic stimulation (TMS), involvement of the motor cortex and the corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched controls. Contralateral silent period (cSP) and transcallosally mediated ipsilateral silent period (iSP) were investigated. RESULTS Resting motor threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar in both groups whereas iSP-latencies were significantly longer (p<0.05) and their duration shorter (p<0.01) in the ADHD group. For the ADHD group iSP duration tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores did neither correlate with iSP-latencies and -duration nor with childrens age. CONCLUSIONS The shortened duration of iSP in ADHD children could be explained by an imbalance of inhibitory and excitatory drive on the neuronal network between cortex layer III-the projection site of transcallosal motor-cortical fibers-and layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the result of defective myelination of fast conducting transcallosal fibers in ADHD. iSP may be a useful supplementary diagnostic tool to discriminate between ADHD and normal children.

Demyelination and axonal degeneration in corpus callosum assessed by analysis of transcallosally mediated inhibition in multiple sclerosis

OBJECTIVE Following focal transcranial magnetic cortex stimulation (fTMS), inhibition of voluntary EMG activity in the ipsilateral first dorsal interosseus (FDI) muscle was studied, in order to assess the functional integrity of the corpus callosum in patients with multiple sclerosis (MS). METHODS AND RESULTS Thirty-four patients suffering from definite MS and 12 healthy, age-matched normal subjects were examined. In mid-sagittal slices, 29 patients showed lesions within the truncus corporis callosi in T2-weighted MRI. In 20 patients, all areas (anterior, middle and posterior parts), in one both the anterior and posterior part, in 3 exclusively the anterior, in 4 the middle and in one the posterior area were affected. In 5 patients, lesions of corpus callosum were lacking. In normal subjects, fTMS elicited a transient inhibition (TI) of preactivated (50% of maximal force) isometric voluntary ipsilateral FDI muscle activity. Mean onset latencies of TI were 35.5+/-5.4 ms in right and 36.1+/-4.2 ms in left FDI. Mean duration of TI amounted to 23.0+/-8.4 ms for right and 24.6+/-8.4 ms for left FDI. In the MS group, TI latencies were significantly increased in 23 and TI durations in 16 cases, whereas a lack of TI was found in 5 patients bilaterally and in 6 unilaterally. In patients, mean onset latencies of TI were 40.4+/-13.8 ms in right and 43.3+/-14.4 ms in left FDI, TI duration amounted to 30.5+/-17.4 ms for right and 31.0+/-25.2 ms for left FDI. Increase of onset latencies and durations of TI were positively correlated with the summed area of lesions of corpus callosum in representative mid-sagittal MRI slices. Significant correlations between TI onset latencies and duration on the one hand, and central motor conduction latencies along corticospinal tracts (CML) on the other hand, were not found. CONCLUSION The present investigation indicates that measurement of TI elicited by fTMS seems to be a sensitive method for an assessment of demyelination and axonal degeneration within corpus callosum in MS patients.

Modulation of transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD) by medication with methylphenidate (MPH)

Motor hyperactivity is one of the most outstanding symptoms of attention deficit hyperactivity disorder (ADHD) which might be caused by a disturbed inhibitory motor control. Using focal transcranial magnetic stimulation (TMS) we tested the cortico-callosal inhibition (duration and latency of the ipsilateral Silent Period, iSP) in 23 children with ADHD (mean age 11+/-2.6 years) before and on treatment with methylphenidate (MPH). iSP latency was age correlated, whereas iSP duration as well as Conners scores were age independent. Analyses of mean differences revealed a significant prolongation of iSP duration (p=0.001), shortening of iSP latency (p=0.027) and reduction of Conners score (p=0.001) under medication. Increase of iSP duration and reduction of Conners score under medication were significantly correlated (t=-9.87, p=0.016). Reduced iSP duration and prolonged iSP latency in ADHD children could be the result of a disturbed transcallosally mediated inhibition, most probable due to a combination of maturation deficits of callosal fiber tracts as well as neuronal synaptical transmission within the neuronal network between ipsilaterally stimulated cortex layer III--the origin of transcallosal motor-cortical fibers--and contralateral layer V, the origin of the pyramidal tract. MPH may indirectly improve the dysbalance between excitatory and inhibitory interneuronal activities of this neuronal network via dopaminergic modulatory effects of the striato-thalamo-cortical loop.

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

BackgroundMotor 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.MethodsUsing 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).ResultsAt 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.ConclusionOur 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.

Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenialike disorder.

BACKGROUND We report on a 42-year-old female patient who presented with a schizophreniform disorder and complete relief of symptoms after specific therapy. METHODS Cerebrospinal fluid and magnetic resonance imaging findings led to the diagnosis of Lyme disease. RESULTS To our knowledge this is the first reported case with an exclusive psychiatric manifestation of Lyme disease. CONCLUSIONS In case of first manifestation of psychotic disorder, although neurological symptoms are lacking, Lyme disease should be considered and be excluded by cerebrospinal fluid analysis.

Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate

Using transcranial magnetic stimulation (TMS) in children with ADHD, an impaired transcallosally mediated motor inhibition (ipsilateral silent period, iSP) was found, and its restoration was correlated with improvement of hyperactivity under medication with methylphenidate (MPH). Hyperactivity has been reported to decrease during transition into adulthood, although some motor dysfunction might persist. As one underlying neurophysiological process, a development-dependent normalization of motor cortical excitability might be postulated. In order to test this hypothesis, we measured the iSP in 21 adult ADHD patients and twenty-one sex- and age-matched healthy controls. In 16 of these patients, a second TMS was performed under treatment with MPH. Our results indicate a persistence of impaired transcallosally mediated motor cortical inhibition (shortened duration) in ADHD adults, which was correlated with clinical characteristics of hyperactivity and restlessness, and was restored by MPH. In contrast to ADHD in childhood, the iSP latency was not impaired, suggesting a partial development-dependent normalization of motor cortical excitability in ADHD adults. ISP duration appears to be a sensitive parameter for the assessment of disturbed intercortical inhibition in adults with ADHD.

Intelligence moderates impulsivity and attention in ADHD children: an ERP study using a go/nogo paradigm.

Abstract Objectives. If the cardinal symptoms of ADHD – hyperactivity, impulsivity and inattention – are combined with a learning disability (70 ≥ IQ < 85), the question arises whether a child shows hyperkinetic behaviour because of intellectual overload in a challenging situation, for example at school. Perhaps, this behaviour is not a primary attention deficit disorder but an impulse control disorder, determined by the primarily intelligence level. It raised the question whether attention deficit and impulse control regarded as behavioural inhibition deficit may depend on intelligence and therefore should be separated into distinct clinical entities. Methods. A total of 45 children (15 with ADHD, 15 with learning disabilities (LD), 15 with ADHD and learning disabilities) were compared in a matched-pair design with 42 control children using a go/no go paradigm (visual continuous performance test, CPT). The dependent variable was the target P3 amplitude, averaged from a 10–20 EEG measurements under distinct trigger conditions. For statistical analysis, a three-factor analysis of variance (MANOVA) with repeated measurements was used. In a subsequent regression analysis with residuals, the influence of intelligence (IQ) was calculated and a “parallel analysis of variance” was conducted. Results. No differences in the P3 amplitudes in the comparison ADHD-control group were found. Reduced P3 amplitudes as main effects in the LD group compared with controls were found and a significant group-dependent interaction on reduced P3 amplitudes comparing ADHD + LD versus control group. Using residuals (IQ), this interaction was not longer verifiable. Conclusion. Impulsivity and attention deficit as the cardinal symptoms of ADHD, regarded as behavioural inhibition deficit, are essentially moderated by the primary intelligence, rather than by an attention deficit. The lower the IQ, the more ADHD surfaces as a disturbed impulsivity and lesser as an attention deficit.

HKS/ADHS und rechtliche Aspekte

With a prevalence of 2-6%, hyperkinetic disorders (F 90, ICD-10) and disturbances of activity and attention (F 90.0, ADHD, ICD-10) are among the psychiatric disorders most commonly diagnosed in children, adolescents, and adults. Children and adolescents diagnosed with ADHD suffer from hyperactivity and deficits in attention and impulse control. Adults usually have problems focusing on one goal, maintaining their attention, modulating emotions effectively, structuring their tasks, and controlling impulses and in executive functions. Legal implications derive from core symptoms and from treatment with stimulants governed by legislation on narcotics. This paper discusses juridical aspects of ADHD in connection with the administration of medication at school, trips abroad within and outside the Schengen area, driving, competitive sports, military service, the increased risk of delinquency, the individual capacity to incur criminal responsibility, developmental criteria for the ability to act responsibly, and modalities for withdrawal treatment or treatment during detention.

Möglichkeiten und Grenzen der Behandlung aggressiven Verhaltens bei Menschen mit geistiger Behinderung mit Risperidon

ZusammenfassungSituationsübergreifendes auto- und fremdaggressives Verhalten stellt trotz klarer Indikation für eine psychopharmakologische Intervention eine nach wie vor therapeutische Herausforderung dar. Neben der Beteiligung des dopaminergen und serotonergen Systems bei der Pathogenese des selbstverletzenden Verhaltens (SVV) wird auch das endogene Opioid-System in einen kausalen Zusammenhang gebracht. Dennoch ist sowohl die Effizienz klassischer Neuroleptika als auch die von Opiatantagonisten fraglich. In offenen und kontrollierten Studien reduzierte sich unter dem Serotonin-2A-Dopamin-D2-Antagonisten Risperidon auch längerfristig effektiv das SVV. Wir berichten über eine Untersuchung, in der 20 erwachsenen geistig behinderten Menschen mit vorrangig selbst- und fremdaggressivem Verhalten über einen Zeitraum von 35 Monaten Risperidon gegeben wurde. 17 Patienten zeigten nicht nur eine signifikante Reduktion des SVV, sondern auch insgesamt eine signifikante Verhaltensverbesserung. Die Evaluierung erfolgte in der Einrichtung durch Protokollierung mit dem DAS (“disability assessment schedule”).SummaryDespite definite indication for psychopharmacologic intervention, severe and persistent symptoms of aggressive and self-injurious behaviour still remain a therapeutic challenge. As recent research has demonstrated, not only the dopaminergic and serotonergic but also the endogenous opiate system plays a role in the pathogenesis of self-injurious behaviour. Nevertheless, the efficacy of classical neuroleptics as well as opiate antagonists is questioned. In open and controlled studies, the administration of the atypical neuroleptic risperidone (a serotonin 2A-dopamine D2 antagonist) was associated with a long-term effect in reducing self-injuries. In our clinical trial, 20 mentally retarded adults presenting with severe self-injurious and aggressive behaviour were administered risperidone over a follow-up period of 35 months. Clinical efficacy was measured with the Disability Assessment Schedule (DAS), conducted in a home for people with mental retardation. In 17 patients, a significant reduction in self-injurious behaviour is shown. Besides, there was a significant overall clinical improvement in behaviour.

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.