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Phenotype-Specific Diagnosis of Functional (Psychogenic) Movement Disorders
Published diagnostic criteria for functional (psychogenic) movement disorders (FMDs) include psychiatric symptoms and some historical variables to affect the threshold between categories of diagnostic certainty. Clinically
probable
and
possible
categories, however, do not suffice to rule in FMD or rule out complex organic movement disorders and therefore are of little practical help. In contrast, a handful of
unequivocal and reliably incongruent or inconsistent
clinical features in each functional movement phenotype, when present, allow a
clinically definite
diagnosis of FMD, regardless of any psychiatric symptom. We suggest that the use of phenotype-specific clinically definite FMD diagnostic criteria will increase inter-rater reliability and minimize false-positive diagnostic errors. This process involves the ascertainment of core (mandatory) examination features instead of supportive but insufficiently sensitive historical, psychiatric, and inconsistent examination features.
Journal Article
Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free L-arginine in humans
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis, whereas l-arginine (Arg) and l-homoarginine (hArg) serve as substrates for NO synthesis. ADMA and other methylated arginines are generally believed to exclusively derive from guanidine (N (G))-methylated arginine residues in proteins by protein arginine methyltransferases (PRMTs) that use S-adenosylmethionine (SAM) as the methyl donor. l-Lysine is known for decades as a precursor for hArg, but only recent studies indicate that arginine:glycine amidinotransferase (AGAT) is responsible for the synthesis of hArg. AGAT catalyzes the formation of guanidinoacetate (GAA) that is methylated to creatine by guanidinoacetate methyltransferase (GAMT) which also uses SAM. The aim of the present study was to learn more about the mechanisms of ADMA and hArg formation in humans. Especially, we hypothesized that ADMA is produced by N (G)-methylation of free Arg in addition to the known PRMTs-involving mechanism. In knockout mouse models of AGAT- and GAMT-deficiency, we investigated the contribution of these enzymes to hArg synthesis. Arg infusion (0.5 g/kg, 30 min) in children (n = 11) and ingestion of high-fat protein meals by overweight men (n = 10) were used to study acute effects on ADMA and hArg synthesis. Daily Arg ingestion (10 g) or placebo for 3 or 6 months by patients suffering from peripheral arterial occlusive disease (PAOD, n = 20) or coronary artery disease (CAD, n = 30) was used to study chronic effects of Arg on ADMA synthesis. Mass spectrometric methods were used to measure all biochemical parameters in plasma and urine samples. In mice, AGAT but not GAMT was found to contribute to plasma hArg, while ADMA synthesis was independent of AGAT and GAMT. Arg infusion acutely increased plasma Arg, hArg and ADMA concentrations, but decreased the plasma hArg/ADMA ratio. High-fat protein meals acutely increased plasma Arg, hArg, ADMA concentrations, as well as the plasma hArg/ADMA ratio. In the PAOD and CAD studies, plasma Arg concentration increased in the verum compared to the placebo groups. Plasma ADMA concentration increased only in the PAOD patients who received Arg. Our study suggests that in humans a minor fraction of free Arg is rapidly metabolized to ADMA and hArg. In mice, GAMT and N (G)-methyltransferases contribute to ADMA and hArg synthesis from Arg, whereas AGAT is involved in the synthesis of hArg but not of ADMA. The underlying biochemical mechanisms remain still elusive.
Journal Article
EMDR : the breakthrough therapy for overcoming anxiety, stress, and trauma
\"When EMDR was first published in 1997, it was hailed as the most important method to emerge in psychotherapy in decades. In the twenty years since, Eye Movement Desensitization and Reprocessing (EMDR) therapy has successfully treated psychological problems for millions of sufferers worldwide. In this updated edition, Francine Shapiro offers a new introduction that presents the latest applications of this remarkable therapy, as well as new scientific data demonstrating its efficacy. Drawing on the experiences of thousands of clinicians as well as a vast research literature on depression, addiction, PTSD, and other disorders, she explains how life experiences are physically stored in our brains, making us feel and act in harmful ways, and how EMDR therapy can bring relief, often in a remarkably short period of time. Applicable to survivors of trauma as well as people suffering from phobias and other experience-based disorders, EMDR is essential reading for anyone who seeks to understand why we hurt, how we heal, and how we get better.\"--Publisher's description.
Book
Updates in Functional Movement Disorders: from Pathophysiology to Treatment Advances
Purpose of ReviewThis review discusses advances in functional movement disorders (FMD) over the past 3 years, with a focus on risk factors, diagnosis, pathophysiology, neuroimaging studies, and treatment.Recent FindingsThe past decade has brought a revived interest in functional movement disorders, with a growing number of studies exploring pathophysiological mechanisms. Here, we review recent studies demonstrating changes in attention, emotional and sensorimotor function in FMD. Through international collaborative efforts, progress has been made in defining biomarkers and outcome measures, an important prerequisite towards standardization of diagnosis and reporting of outcomes in clinical trials. Of particular interest are neuroimaging studies demonstrating functional and structural changes in motor and emotional brain circuits, deepening our understanding of FMD as a neurocircuit disorder and potentially paving the way towards new treatments. Currently available treatment modalities have shown successful outcomes via outpatient, inpatient, and virtual delivery.SummaryThe last 3 years have seen tremendous efforts to better understand, diagnose, and treat FMD. The disease model has been broadened to include a biopsychosocial formulation, and insights on the pathophysiology on FMD are informing treatment efforts. Several international multidisciplinary research collaborations are underway to define biomarkers and best outcome measures, highlighting the path towards improved standardization of future treatment trials. Additionally, the rise of telemedicine during the COVID-19 pandemic has reduced geographic barriers and paved the way for virtual therapy sessions and self-guided programs.
Journal Article
A randomized cross-over study protocol to evaluate long-term gait training with a pediatric robotic exoskeleton outside the clinical setting in children with movement disorders
Individuals with neuromuscular disorders display a combination of motor control deficits and lower limb weakness contributing to knee extension deficiency characterized by exaggerated stance phase knee flexion. There is a lack of evidence for long-term improvement of knee extension deficiency with currently available clinical treatment programs. Our previous work testing a wearable robotic exoskeleton with precisely timed assistive torque applied at the knee showed immediate increases in knee extension during walking for children with cerebral palsy, which continued to improve over an acute practice period. When we applied interleaved assistance and resistance to knee extension, we observed improvements in knee extension and increased muscle activation indicating the potential for muscle strengthening when used over time. There is a need for additional, high-quality trials to assess the impact of dosage, intensity and volume of training necessary to see persistent improvement in lower limb function for these patient populations. This randomized crossover study (ClinicalTrials.gov: NCT05726591) was designed to determine whether 12 weeks of overground gait training with a robotic exoskeleton outside of the clinical setting, following an initial in clinic accommodation period, has a beneficial effect on walking ability, muscle activity and overall motor function. Participants will be randomized to either complete the exoskeleton intervention or continue their standard therapy for 12 weeks first, followed by a crossover to the other study component. The primary outcome measure is change in peak knee extension angle during walking; secondary outcome measures include gait speed, strength, and validated clinical scales of motor function and mobility. Assessments will be completed before and after the intervention and at 6 weeks post-intervention, and safety and compliance will be monitored throughout. We hypothesize that the 12-week exoskeleton intervention outside the clinical setting will show greater improvements in study outcome measures than the standard therapy.
Journal Article
Multifunctional wearable devices for diagnosis and therapy of movement disorders
Wearable systems that monitor muscle activity, store data and deliver feedback therapy are the next frontier in personalized medicine and healthcare. However, technical challenges, such as the fabrication of high-performance, energy-efficient sensors and memory modules that are in intimate mechanical contact with soft tissues, in conjunction with controlled delivery of therapeutic agents, limit the wide-scale adoption of such systems. Here, we describe materials, mechanics and designs for multifunctional, wearable-on-the-skin systems that address these challenges via monolithic integration of nanomembranes fabricated with a top-down approach, nanoparticles assembled by bottom-up methods, and stretchable electronics on a tissue-like polymeric substrate. Representative examples of such systems include physiological sensors, non-volatile memory and drug-release actuators. Quantitative analyses of the electronics, mechanics, heat-transfer and drug-diffusion characteristics validate the operation of individual components, thereby enabling system-level multifunctionalities.
Integration of diverse nanostructures allows the fabrication of a wearable system capable of storing data, performing diagnostics and delivering drugs.
Journal Article