Axel Schramm

Ultrasound and electrophysiologic findings in patients with Guillain–Barré syndrome at disease onset and over a period of six months

OBJECTIVE To investigate cross-sectional areas (CSAs) of several peripheral nerves including the vagus nerve and the diameter of spinal nerves as measured by nerve ultrasound (NUS) and nerve conduction studies (NCS) in Guillain-Barré syndrome (GBS) patients over at least six months compared to healthy controls. METHODS NUS and/or NCS of several nerves, the vagus nerve, and the 5th/6th cervical spinal nerves were performed in patients with GBS at days 2-3 after symptom onset, at days 10-14 after immunoglobulin therapy and after six months compared to healthy controls. RESULTS 27 GBS-patients and 31 controls were included. Using NUS significant enlargement was found in all measured nerves (P<0.001), except the sural nerve (P=0.086) compared to the controls at onset. The vagus (median 3.0 mm(2) vs. 2.0 mm(2), P<0.0001) and the cervical spinal nerves were significantly enlarged (median 3.5/4.0 mm vs. 2.6/3.2 mm, p<0.0001), the vagus most obviously in patients with autonomic dysregulation (AD, 4.0 mm(2)). Six months later, NCS showed persisting pathology in CMAP-amplitudes with amelioration of F-wave pathology. NUS showed restitution in the spinal nerves (median 2.6/3.2 mm) and the vagus (median 2.0 mm(2)) in all patients excluding the vagus in those with persistent AD (median 4.0 mm(2)). The peripheral nerves did not change significantly (P>0.05). CONCLUSION Ultrasonographic detection of cervical spinal nerve enlargement supports the diagnosis of GBS in the early phase. Its regression may be a good parameter for the clinical restitution over time. Vagus enlargement may be a risk marker for development of AD. SIGNIFICANCE Ultrasound is a reliable diagnostic follow-up tool in early GBS.

Vagus nerve somatosensory evoked potentials in Parkinson’s disease

Recent studies have emphasized that the pathology of Parkinson’s disease (PD) extends beyond the nigrostriatal system [1, 2]. According to the work of Braak [3], it may start in deep brain stem nuclei including the glossopharyngeal/ vagus nerve complex. A method of vagus nerve somatosensory evoked potentials (VN-SEP) for the assessment of vagus nerve function has recently been developed by Fallgatter et al. [4]. In this pilot study, we tested the hypothesis that VN-SEP may be affected in PD patients. In a prospective observational study approved by the local ethics committee and performed in accordance with the 1964 Declaration of Helsinki, 21 patients [7 females, age 66.7 ± 10.0 years (mean ± SD), range 45–79 years, mean disease duration 6.5 ± 4.1 years] with a clinical diagnosis of PD according to the British brain bank criteria [5] and 21 healthy ageand sex-matched controls (age 70.0 ± 10.2 years, range 49–81 years) were recruited after giving informed consent. All patients were on antiparkinsonian medication and had a disease stage of 2.2 ± 0.7 on the Hoehn and Yahr scale [6]. None of the participants showed signs of cognitive impairment in clinical evaluation. Stimulation was done according to published procedures [4, 7] on the inner side of the tragus (electrical square impulses of 0.1-ms duration, interstimulus interval 2 s, stimulus intensity 8 mA). Evoked potentials were recorded bipolarily from the electrode positions C3–F3, C4–F4, Fz– F3, Fz–F4 (scalp electrodes, impedances\2 kX, band-pass 0.1–1 kHz, analysis time 10 ms, averaging of 100 artifactfree epochs). Statistical analyses were performed by means of univariate ANOVAs for peak latencies (P1, N1, P2) and peak-to-peak amplitudes (P1-N1, N1-P2) separately. ANOVA for the VN-SEP latencies (Table 1) showed significant main effects for the within-subject factors ‘‘recording site’’ (CF vs. FzF, F1 = 4.484, p = 0,035) and ‘‘potential component’’ (P1, N1, P2, F1,2 = 198.925, p \ 0.001) and for the between-subject factor ‘‘diagnosis’’ (patients vs. controls, F1 = 10.544, p = 0.001). No significant interactions for any of the other variables nor significant main effects, for any of the amplitude variables occurred (not shown). Post-hoc t-tests indicated longer latencies in the PD group compared to controls. The available evidence suggests that VN-SEP represents far field potentials of brainstem activity from vagus nuclei that can be elicited upon electrical stimulation of its T. Polak (&) F. Metzger A. C. Ehlis J. B. Langer A. J. Fallgatter Department of Psychiatry, Psychosomatics and Psychotherapy, University Clinic Wuerzburg, Fuechsleinstr. 15, 97080 Wuerzburg, Germany e-mail: Polak_T@klinik.uni-wuerzburg.de

Relevance of sonography for botulinum toxin treatment of cervical dystonia: an expert statement

Botulinum neurotoxin A (BoNT A) is the first-line treatment for cervical dystonia. However, although BoNT A has a favorable safety profile and is effective in the majority of patients, in some cases the treatment outcome is disappointing or side effects occur when higher doses are used. It is likely that in such cases either the target muscles were not injected accurately or unintended weakness of non-target muscles occurred. It has been demonstrated in clinical trials for spastic movement disorders that sonography-guided BoNT A injections could improve treatment outcome. As the published evidence for a benefit of sonography-guided BoNT injection in patients with cervical dystonia is scarce, it is the aim of this review to discuss the relevance of sonography in this indication and provide a statement from clinical experts for its use. The clear advantage of sonography-guided injections is non-invasive, real-time visualization of the targeted muscle, thus improving the precision of injections and potentially the treatment outcomes as well as avoiding adverse effects. Other imaging techniques are of limited value due to high costs, radiation exposure or non-availability in clinical routine. In the hands of a trained injector, sonography is a quick and non-invasive imaging technique. Novel treatment concepts of cervical dystonia considering the differential contributions of distinct cranial and cervical muscles can reliably be implemented only by use of imaging-guided injection protocols.

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research.

Botulinum-Neurotoxin in der Behandlung der Spastizität im Erwachsenenalter

Spasticity is one of the major causes of functional impairment in adults with lesions of the central nervous system. For instance, approximately 30% of post-stroke patients suffer from different degrees of spasticity with possible consecutive impairments. Numerous studies or meta-analyses showed that local injections of botulinum toxin in spastic muscles lead to dose-dependent reduction in muscle tone and improvement of passive movements (e. g. facilitated care), especially following repeated injections.However, country-specific regulations and patient-remote administration in German health care often do not allow adequate provision of this therapy. Thus, the present consensus statement based on the EBM analyses of the published international literature tries to highlight recent advances and the standard in the field of local spasticity treatment, aiming to facilitate communication between the decision makers and German reimbursement institutions in health care. Prior to initiation of BoNT-A injections, patient-oriented goals should be identified in a multiprofessional context to assure realistic goals for this specific treatment and patient expectations. In Germany for the treatment of focal spasticity following stroke three products have been approved: Botox® (Pharm Allergan, Ettlingen), Dysport® (Ipsen Pharma, Ettlingen) and Xeomin® (Merz Pharma, Frankfurt/Main). For all preparations safety has been repeatedly shown. Functional improvements have also been illustrated for selected patients concerning hand/arm function and gait. The dose per muscle and the selection of muscles to be injected have to be individualized according to the patients symptoms and should be accompanied by modern neurorehabilitative therapies such as redression or repetitive activation of the injected and antagonistic muscles.

Combined accelerometer and EMG analysis to differentiate essential tremor from Parkinson's disease

In this study, we intended to differentiate patients with essential tremor (ET) from tremor dominant Parkinson disease (PD). Accelerometer and electromyographic signals of hand movement from standardized upper extremity movement tests (resting, holding, carrying weight) were extracted from 13 PD and 11 ET patients. The signals were filtered to remove noise and non-tremor high frequency components. A set of statistical features was then extracted from the discrete wavelet transformation of the signals. Principal component analysis was utilized to reduce dimensionality of the feature space. Classification was performed using support vector machines. We evaluated the proposed method using leave one out cross validation and we report overall accuracy of the classification. With this method, it was possible to discriminate 12/13 PD patients from 8/11 patients with ET with an overall accuracy of 83%. In order to individualize this finding for clinical application we generated a posterior probability for the test result of each patient and compared the misclassified patients, or low probability scores to available clinical follow up information for individual cases. This non-standardized post hoc analysis revealed that not only the technical accuracy but also the clinical accuracy limited the overall classification rate. We show that, in addition to the successful isolation of diagnostic features, longitudinal and larger sized validation is needed in order to prove clinical applicability.

Detection radius of EMG for fasciculations: Empiric study combining ultrasonography and electromyography

OBJECTIVE The aims of this study were to investigate the detection radius and sensitivity of EMG for fasciculations. METHODS Muscle ultrasonography was performed simultaneously to EMG recordings in patients with fasciculations in the context of amyotrophic lateral sclerosis. Ultrasonography and EMG parameters were analyzed for selected fasciculations. RESULTS A total of 381 fasciculations were detected by ultrasonography in 18 muscles of 10 patients. Out of these, 125 (33%) were EMG-negative. In contrast, none of the fasciculations detected by EMG were ultrasonography-negative. EMG detection probability decreased significantly with increasing distance from the center of the fasciculation. EMG detection rate was 98% when the EMG needle was located within the fasciculation and 50% at 7.75 mm distance from the fasciculation center. In addition, EMG detection depended significantly on cross-sectional area of the fasciculation and presence of neurogenic changes. CONCLUSIONS For detecting the same fasciculations, EMG is less sensitive than ultrasonography. EMG detection probability decreases sharply at a distance comparable to motor unit size. SIGNIFICANCE These results extend previous knowledge about superior sensitivity of ultrasonography for fasciculations. Moreover, our novel bimodal detection method provides first in vivo data about the EMG detection radius for fasciculations in a clinical setting.

Towards a multi-sensor system for the diagnosis of neurological disorders

The occurrence of fasciculations is an indication for several neurological disorders. However, due to the low amplitude and irregular occurrence, these involuntary muscle movements are hard to quantify. Currently used techniques have to be applied manually from a trained specialist and lack the possibility of a remote measurement of fasciculations. Therefore, we introduce a new approach which is able to remotely measure fasciculations with high temporal resolution. Moreover, we compare the sensitivity of our technique with established methods and give an outlook how our technology can be expanded to a multi-sensor system for the automated diagnosis of neurological disorders.

P 157 Detection radius of EMG for fasciculations: combined ultrasonographic-electromyographic analysis

Background Fasciculations are caused by spontaneous discharges of single motor units. In electromyography (EMG), they are characterized by single motor unit action potentials. Muscle ultrasonography is increasingly applied as a non-invasive screening tool for the examination of fasciculations. In the context of motor neuron disease, the sensitivity of muscle ultrasonography to detect fasciculations was superior to EMG. Limited detection radius of concentric needle EMG may explain this discrepancy, but a direct EMG-ultrasonography-correlation of single fasciculations has not been reported so far. In the current study, we aimed to define an “EMG detection radius” of fasciculations by simultaneous recording of EMG and muscle ultrasonography. Methods Parallel to concentric needle EMG, we recorded in-plane high-resolution videos of muscle ultrasonography showing the needle tip within the transverse section of the muscle. A total of 200 fasciculations were acquired during 50 recordings of 10 patients with motor neuron disease. Amplitude and duration of EMG fasciculation potentials were subsequently correlated to the corresponding ultrasonographic muscle displacement and the distance from the EMG needle tip. Results The onset of ultrasonographic muscle displacement was concurrent to its EMG fasciculation potential whereas the plateau phase and the backward movement occurred when the EMG had already returned to baseline. About 40% of fasciculations observed on ultrasonography were not detected in EMG and this included fasciculations located close to the needle tip. The amplitude of EMG-positive fasciculations was negatively correlated to their distance from the needle tip. However, the correlation differed significantly between different patients and between different muscles. Discussion Analysis of fasciculations on simultaneous EMG and ultrasonography recordings improves the understanding of the “EMG-detection radius” of fasciculations. A relevant portion of ultrasonographic fasciculations was not detected on EMG which may in part explain the superior sensitivity of ultrasonography. Different localization of neuromuscular endplates and of myofibrils along the longitudinal axis of the analyzed muscles might explain the occurrence of “EMG-negative” fasciculations. Alternatively, muscle remodeling or changes of axon terminals due to neurodegeneration may alter the sensitivity of EMG. Further studies are needed to classify fasciculations of other entities with this method.

Botulinum-Neurotoxin in der Behandlung der Spastizität im Erwachsenenalter@@@Botulinum toxin in the treatment of adult spasticity: Ein interdisziplinärer deutscher 10-Punkte-Konsensus 2010@@@An interdisciplinary german 10-point consensus 2010

Spasticity is one of the major causes of functional impairment in adults with lesions of the central nervous system. For instance, approximately 30% of post-stroke patients suffer from different degrees of spasticity with possible consecutive impairments. Numerous studies or meta-analyses showed that local injections of botulinum toxin in spastic muscles lead to dose-dependent reduction in muscle tone and improvement of passive movements (e. g. facilitated care), especially following repeated injections.However, country-specific regulations and patient-remote administration in German health care often do not allow adequate provision of this therapy. Thus, the present consensus statement based on the EBM analyses of the published international literature tries to highlight recent advances and the standard in the field of local spasticity treatment, aiming to facilitate communication between the decision makers and German reimbursement institutions in health care. Prior to initiation of BoNT-A injections, patient-oriented goals should be identified in a multiprofessional context to assure realistic goals for this specific treatment and patient expectations. In Germany for the treatment of focal spasticity following stroke three products have been approved: Botox® (Pharm Allergan, Ettlingen), Dysport® (Ipsen Pharma, Ettlingen) and Xeomin® (Merz Pharma, Frankfurt/Main). For all preparations safety has been repeatedly shown. Functional improvements have also been illustrated for selected patients concerning hand/arm function and gait. The dose per muscle and the selection of muscles to be injected have to be individualized according to the patients symptoms and should be accompanied by modern neurorehabilitative therapies such as redression or repetitive activation of the injected and antagonistic muscles.