Botulinumtoxin bei nichtneurogenen Blasenfunktionsstörungen

Zusammenfassung: Die nichtneurogene überaktive Harnblase mit oder ohne Detrusorüberaktivität und/oder Inkontinenz ist ein belastendes Symptom für viele Menschen, das bis vor wenigen Jahren nur mit anticholinergen Medikamenten oder operativ behandelt werden konnte. Intradetrusorinjektionen mit BotulinumtoxinTypA stellen eine minimal-invasive Alternative für Patienten dar, die auf Anticholinergika nicht ansprechen oder diese nicht vertragen. Dieser Übersichtsartikel fasst die relevanten Arbeiten der letzten 6Jahre zu diesem Thema zusammen und gibt Auskunft über die Wirksamkeit, die Nebenwirkungen, die verwendeten Dosierungen und Injektionstechniken. Insgesamt zeigte sich eine gute initiale Wirksamkeit, die etwa ab dem 4. Tag nach Injektion beginnt und durchschnittlich bis zu 31Wochen anhalten kann. Es ist allerdings je nach Dosis mit einer Erhöhung der Restharnmengen zu rechnen, die auch die Anwendung von intermittierendem Selbstkatheterismus notwendig machen können. Die Anwendung von Botulinumtoxin in der Harnblase ist noch immer keine offiziell zugelassene Therapi

Sakrale Neuromodulation bei neurogenen Blasenfunktionsstörungen

Zusammenfassung: Die sakrale Neuromodulation (SNM) stellt bei therapierefraktären neurogenen Blasenfunktionsstörungen eine vielversprechende Therapieoption dar. Es bleibt allerdings zu zeigen, welche Typen der neurogenen Blasenfunktionsstörungen und welche zugrunde liegenden neurologischen Erkrankungen am besten auf die SNM ansprechen. Die SNM wurde ständig weiterentwickelt und ist heute ein minimal-invasives, in Lokalanästhesie durchführbares Therapieverfahren, das vor größeren rekonstruktiven Eingriffen zumindest erwogen werden sollte. Es wird eine Elektrodenimplantation ins Sakralforamen S3 oder S4 durchgeführt und in einer Testphase über Tage bis Wochen unter Führen eines Blasentagebuches geprüft, ob die SNM dem Patienten einen relevanten Nutzen bringt. Wenn sich eine positive Testphase zeigt, wird der Neuromodulator gluteal (oder seltener in die Bauchdecke) implantiert. Der Wirkmechanismus der SNM ist nicht gänzlich geklärt, doch Afferenzen dürften eine Schlüsselrolle spielen. So scheint die SNM via periphere Afferenzen eine Modulation von Rückenmarkreflexen und Gehirnzentren zu bewirken. Das implantierte Neuromodulationssystem führt zu keiner Einschränkung der Aktivitäten der Patienten. Allerdings gilt es zu beachten, dass bei Neuromodulatorträgern Hochfrequenzwärmetherapie und unipolare Elektrokauterisation kontraindiziert sind, dass bei einer extrakorporellen Stoßwellenlithotripsie der Brennpunkt nicht in unmittelbarer Nähe des Neuromodulators oder der Elektrode liegen darf, dass Ultrasonographie und Strahlentherapie im Bereich der Implantatkomponenten vermieden werden sollten, dass bei Schwangerschaft der Neuromodulator auszuschalten ist und dass MR-Untersuchungen nur bei zwingender Indikation und bei ausgeschaltetem Neuromodulator durchgeführt werden solle

The facilitatory effect of duloxetine combined with pelvic floor muscle training on the excitability of urethral sphincter motor neurons

INTRODUCTION AND HYPOTHESIS: Aim of this study was to investigate the excitability of sphincter motor neurons under the influence of pelvic floor muscle training (PFMT) and duloxetine. Due to their mechanisms of action, there might be a synergistic effect of duloxetine and PFMT in regard to the facilitation of spinal reflexes controlling urethral sphincter contractions and hence continence. METHODS: In ten healthy female subjects, clitoral electric stimulation (CES) and transcranial magnetic stimulation (TMS) were used to determine individual motor thresholds for external urethral sphincter (EUS) contractions before and after PFMT, duloxetine, and PFMT + duloxetine. RESULTS: PFMT and duloxetine alone significantly decreased the motor thresholds for EUS contractions during CES and TMS. However, the combined treatment reduced the motor threshold for EUS contractions significantly stronger compared to PFMT or duloxetine alone. CONCLUSIONS: The results are suggestive for a synergistic facilitatory effect of PFMT and duloxetine on sphincter motor neuron activation

Cortical substrate of bladder control in SCI and the effect of peripheral pudendal stimulation

We investigate (i) the central representation of lower urinary tract (LUT) control and (ii–iii) the acute and 23 short-term central neuromodulatory effect of peripheral pudendal nerve stimulation in incomplete spinal 24 cord injured (SCI) patients using functional magnetic resonance imaging (fMRI). The urinary bladder of eight 25 SCI patients has been passively filled and emptied using a catheter, to identify the neural substrate of bladder 26 control (i), and with simultaneous peripheral pudendal nerve stimulation to investigate its acute central 27 neuromodulatory effect (ii). To identify the potential effects of pudendal nerve stimulation treatment (iii), 28 six patients underwent a 2-week training using pudendal nerve stimulation followed by another fMRI 29 session of bladder filling. The pre- and post-training fMRI results have been compared and correlated with 30 the patient's pre- and post-training urological status. Our results suggest that the central representation of 31 bladder filling sensation is preserved in the subacute stage of incomplete SCI. However, compared to earlier 32 data from healthy subjects, it shows decreased neural response in right prefrontal areas and increased in left 33 prefrontal regions, indicating diminished inhibitory micturition control as well as, compensatory or de- 34 compensatory reorganization of bladder control. We also provide evidence for a neuromodulatory effect of 35 acute pudendal nerve stimulation, which was most prominent in the right posterior insula, a brain region 36 implicated in homeostatic interoception in human. Pudendal stimulation training also induced significant 37 neuromodulation, predominantly signal increases, in the normal cortical network of bladder control. 38 Correlations with the patient's urological status indicate that this neuromodulatory effect may reflect the 39 clinical improvement following training

Patient-Reported Side Effects of Intradetrusor Botulinum Toxin Type A for Idiopathic Overactive Bladder Syndrome

Objective: The aim of the study was a prospective assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder (OAB). Patients and Methods: Botulinum toxin A injection was performed in 56 patients with idiopathic OAB. Patients were followed up for 6 months concerning side effects and patients' satisfaction. Results: Different types of side effects were assessed such as dry mouth (19.6%), arm weakness (8.9%), eyelid weakness (8.9%), leg weakness (7.1%), torso weakness (5.4%), impaired vision (5.4%) and dysphagia (5.4%). In all cases, symptoms were mild and transient. Urological complications such as gross hematuria (17.9%), acute urinary retention (8.9%) and acute urinary tract infection (7.1%) were noticed. In all cases, acute urinary retention was transient and treated with temporary intermittent self-catheterization. There was no statistically significant correlation between dosage and observed side effects. Patients' satisfaction rate was high (71.4%). Conclusion: Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects. In general, side effects were transient, mild and did not require special treatment. Copyright (C) 2010 S. Karger AG, Base

A systematic review and activation likelihood estimation meta-Analysis of the central innervation of the lower urinary tract: Pelvic floor motor control and micturition

Purpose Functional neuroimaging is a powerful and versatile tool to investigate central lower urinary tract (LUT) control. Despite the increasing body of literature there is a lack of comprehensive overviews on LUT control. Thus, we aimed to execute a coordinate based meta-Analysis of all PET and fMRI evidence on descending central LUT control, i.e. pelvic floor muscle contraction (PFMC) and micturition. Materials and methods A systematic literature search of all relevant libraries was performed in August 2020. Coordinates of activity were extracted from eligible studies to perform an activation likelihood estimation (ALE) using a threshold of uncorrected p 0.001. Results 20 of 6858 identified studies, published between 1997 and 2020, were included. Twelve studies investigated PFMC (1xPET, 11xfMRI) and eight micturition (3xPET, 5xfMRI). The PFMC ALE analysis (n = 181, 133 foci) showed clusters in the primary motor cortex, supplementary motor cortex, cingulate gyrus, frontal gyrus, thalamus, supramarginal gyrus, and cerebellum. The micturition ALE analysis (n = 107, 98 foci) showed active clusters in the dorsal pons, including the pontine micturition center, the periaqueductal gray, cingulate gyrus, frontal gyrus, insula and ventral pons. Overlap of PFMC and micturition was found in the cingulate gyrus and thalamus. Conclusions For the first time the involved core brain areas of LUT motor control were determined using ALE. Furthermore, the involved brain areas for PFMC and micturition are partially distinct. Further neuroimaging studies are required to extend this ALE analysis and determine the differences between a healthy and a dysfunctional LUT. This requires standardization of protocols and task-execution

Transcranial sonography for diagnosis of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>In idiopathic Parkinson's disease (IPD) transcranial sonography (TCS) represents an alternative diagnostic method to verify clinical diagnosis. Although the phenomenon of an increased echogenicity of the Substantia nigra (SN) is well known this method is still not widly used in the diagnostic workup. Until now reliability of this method is still a matter of debate, partly because data only existed from a few laboratories using the same ultrasound machine. Therefore our study was conducted to test the reliability of this method by using a different ultrasound device and examining a large population of control and IPD subjects by two examiners to calculate interobserver reliability.</p> <p>Method</p> <p>In this study echogenicity of SN was examined in 199 IPD patients and 201 control subjects. All individuals underwent a neurological assessment including Perdue pegboard test and Webster gait test. Using a Sonos 5500 ultrasound device area of SN was measured, echogenicity of raphe, red nuclei, thalamus, caudate and lenticular nuclei, width of third and lateral ventricle were documented.</p> <p>Results</p> <p>We found a highly characteristic enlargement of the SN echogenic signal in IPD. The cut-off value for the SN area was established using a ROC curve with a sensitivity of 95% corresponding to an area of SN of 0.2 cm²and was found to be equivalent to the cut-off values of other studies using different ultrasound devices.</p> <p>Conclusions</p> <p>Our study shows that TCS is a reliable and highly sensitive tool for differentiation of IPD patients from individuals without CNS disorders.</p

GenSeed-HMM: A tool for progressive assembly using profile HMMs as seeds and its application in Alpavirinae viral discovery from metagenomic data

This work reports the development of GenSeed-HMM, a program that implements seed-driven progressive assembly, an approach to reconstruct specific sequences from unassembled data, starting from short nucleotide or protein seed sequences or profile Hidden Markov Models (HMM). The program can use any one of a number of sequence assemblers. Assembly is performed in multiple steps and relatively few reads are used in each cycle, consequently the program demands low computational resources. As a proof-of-concept and to demonstrate the power of HMM-driven progressive assemblies, GenSeed-HMM was applied to metagenomic datasets in the search for diverse ssDNA bacteriophages from the recently described Alpavirinae subfamily. Profile HMMs were built using Alpavirinae-specific regions from multiple sequence alignments using either the viral protein 1 (VP1) (major capsid protein) or VP4 (genome replication initiation protein). These profile HMMs were used by GenSeed-HMM (running Newbler assembler) as seeds to reconstruct viral genomes from sequencing datasets of human fecal samples. All contigs obtained were annotated and taxonomically classified using similarity searches and phylogenetic analyses. The most specific profile HMM seed enabled the reconstruction of 45 partial or complete Alpavirinae genomic sequences. A comparison with conventional (global) assembly of the same original dataset, using Newbler in a standalone execution, revealed that GenSeed-HMM outperformed global genomic assembly in several metrics employed. This approach is capable of detecting organisms that have not been used in the construction of the profile HMM, which opens up the possibility of diagnosing novel viruses, without previous specific information, constituting a de novo diagnosis. Additional applications include, but are not limited to, the specific assembly of extrachromosomal elements such as plastid and mitochondrial genomes from metagenomic data. Profile HMM seeds can also be used to reconstruct specific protein coding genes for gene diversity studies, and to determine all possible gene variants present in a metagenomic sample. Such surveys could be useful to detect the emergence of drug-resistance variants in sensitive environments such as hospitals and animal production facilities, where antibiotics are regularly used. Finally, GenSeed-HMM can be used as an adjunct for gap closure on assembly finishing projects, by using multiple contig ends as anchored seeds

Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

Phylodynamics and movement of Phycodnaviruses among aquatic environments

Phycodnaviruses have a significant role in modulating the dynamics of phytoplankton, thereby influencing community structure and succession, nutrient cycles and potentially atmospheric composition because phytoplankton fix about half the carbon dioxide (CO2) on the planet, and some algae release dimethylsulphoniopropionate when lysed by viruses. Despite their ecological importance and widespread distribution, relatively little is known about the evolutionary history, phylogenetic relationships and phylodynamics of the Phycodnaviruses from freshwater environments. Herein we provide novel data on Phycodnaviruses from the largest river system on earth—the Amazon Basin—that were compared with samples from different aquatic systems from several places around the world. Based on phylogenetic inference using DNA polymerase (pol) sequences we show the presence of distinct populations of Phycodnaviridae. Preliminary coarse-grained phylodynamics and phylogeographic inferences revealed a complex dynamics characterized by long-term fluctuations in viral population sizes, with a remarkable worldwide reduction of the effective population around 400 thousand years before the present (KYBP), followed by a recovery near to the present time. Moreover, we present evidence for significant viral gene flow between freshwater environments, but crucially almost none between freshwater and marine environments