[Treatment goals in patients with post-stroke upper limb spasticity following injection of botulinum toxin A : Results of the German-Austrian subgroup of the ULIS-II study]. / Therapieziele bei Patienten mit Armspastik nach Schlaganfall nach Injektion mit Botulinumtoxin A : Ergebnisse der deutsch-österreichischen Subgruppe der ULIS-II-Studie.

BACKGROUND: The ULIS-II was an international cohort study (NCT01020500) evaluating current treatment of upper limb spasticity in post-stroke adult patients with botulinum toxin A (BoNT-A) in real-life practice. OBJECTIVE: Post hoc analysis to compare current management of post-stroke adult patients regarding goal setting and attainment with BoNT-A in Germany (D) and Austria (A) with the full cohort of ULIS-II. MATERIAL AND METHODS: The ULIS-II was a global, open-label, prospective, multicenter observational study with 2 visits conducted in 84 centers worldwide. A total of 468 patients aged ≥18 years with post-stroke upper limb spasticity were included. The primary outcome measure was the responder rate defined as achievement of a goal attainment scale (GAS) score of 0, 1 or 2 after 1 cycle of BoNT-A. RESULTS: A total of 57 patients from D/A were included in the efficacy analysis. The number of patients in D/A and the full cohort achieving the primary (78.9% vs. 79.6%) and secondary treatment goal (76.8% vs. 75.6%), respectively, was comparable. Deviating from the full cohort, the most common primary treatment goal in D/A was related to impairment (33.3%). Compared to baseline there was a marked reduction in concomitant therapies at the follow-up visit after 3-5 months in the D/A group: patients receiving oral anti-spastic medication 61.4% vs. 40.4%, positioning 50.9% vs. 36.8% and splinting 43.9% vs. 31.6%. Injection control techniques were less frequently used in the D/A group compared to the global study cohort (electrical stimulation: 26.3% vs. 45.8% and electromyography: 12.3% vs. 29.2%). No adverse events were documented in the D/A cohort. CONCLUSION: A single injection of BoNT-A in adult patients with post-stroke spasticity of the arm led to a high response rate of approximately 80% in both cohorts. The BoNT-A injections in post-stroke adult patients contributed to an improvement in the daily life of patients and their carers beyond simple reduction of muscle tone or spasticity.

[Prophylaxis of recurring low-flow priapism : Experimental botulinum neurotoxin injection into the ischiocavernosus muscle]. / Prophylaxe des rezidivierenden Low-flow-Priapismus : Experimentelle Botulinumneurotoxin-Injektionen in die Mm. ischiocavernosi.

The treatment of recurring low-flow priapism with the usual medications is still unsatisfactory. The case of an otherwise healthy young man experiencing low-flow priapism at the age of 31 is presented. A reason for his condition could not be identified. Over the course of several months, he required emergency urological treatment more than ten times. Treatment with cyproterone acetate (Androcur® 50 mg/day) stopped the spontaneous erections, but resulted in erectile impotence, reduced motivation, decreased interest in sex, weight gain of 10 kg, breast enlargement combined with touch sensitivity on both sides, and hair loss on both legs. In addition, the patient complained about painful cramps in his pelvic muscles. After appropriate explanations he agreed to try botulinum neurotoxin injections into both ischiocavernosus muscles. The objective was to reduce muscle tone in order to improve venous drainage of blood from the penis. The latest relapse of priapism occurred more than 6 months ago.

An open-label cohort study of the improvement of quality of life and pain in de novo cervical dystonia patients after injections with 500 U botulinum toxin A (Dysport).

OBJECTIVES: It remains to be determined whether the benefits of botulinum toxin type A (BoNT-A) on cervical dystonia (CD) motor symptoms extend to improvements in patient's quality of life (QoL). This analysis of a large, multicentre study was conducted with the aim of investigating changes in QoL and functioning among de novo patients receiving 500 U BoNT-A (abobotulinumtoxinA; Dysport) for the treatment of the two most frequent forms of CD, predominantly torticollis and laterocollis. DESIGN: A prospective, open-label study of Dysport (500 U; Ipsen Biopharm Ltd) administered according to a defined intramuscular injection algorithm. SETTING: German and Austrian outpatient clinics. PARTICIPANTS: 516 male and female patients (aged ≥18 years) with de novo CD. The majority of patients had torticollis (78.1%). 35 patients had concomitant depression (MedDRA-defined). MAIN OUTCOME MEASURES: Change from baseline to weeks 4 and 12 in Craniocervical Dystonia Questionnaire (CDQ-24) total and subscale scores, patient diary items ('day-to-day capacities and activities', 'pain' and 'duration of pain') and global assessment of pain. RESULTS: Significant improvements were observed in CDQ-24 total and subscale scores at week 4 and were sustained up to week 12 (p<0.001). Changes in CDQ-24 scores did not significantly differ between the torticollis and laterocollis groups or between patients with or without depression. There were also significant reductions in patient diary item scores for activities of daily living, pain and pain duration at weeks 4 and 12 (p<0.001). Pain relief (less or no pain) was reported by 66% and 74.1% of patients at weeks 4 and 12, respectively. Changes in pain parameters demonstrated a positive relationship with change in Tsui score. CONCLUSIONS: After standardised open-label treatment with Dysport 500 U, improvements in QoL and pain intensity up to 12 weeks in patients with CD were observed.

[Cervical dystonia: clinical-radiological correlations and recommendations for the correction of botulinum therapy].

Seventy-eight patients with confirmed primary cervical dystonia CD were studied. All patients underwent CT of the soft tissues of the neck using slices at cervical vertebrae and MRI images of the cervical spine and of soft tissues. MRI images of 50 patients who did not have CD were used for comparison. This was followed by measuring the largest diameter along with the description of the shape of all observable muscles including the small muscles of the occipital area. In lateral flexion and rotation, 19% of patients showed disorders of muscles acting on head joints (laterocaput/torticaput). Muscles that act on the cervical spine were affected (laterocollis/torticollis) in 20% of patients. Both types of the disorder, but with various degrees of the caput- and collis- involvement, were presented in 61% of patients. Consequently, the ratio for these forms was approximately estimated as 1:1:3. The following conclusions have been made: In lateral flexion, clinical differentiation between laterocollis and laterocaput is possible. Lateral shift is always a result of laterocollis on one side and laterocaput on the opposite side. In rotation, clinical differentiation between torticollis and torticaput is not always possible. CT slices at levels C1 and C2 are advisable in these cases. Comparing the positions of vertebrae on both levels will provide a safe differentiation between torticollis and torticaput. Analysis of forward flexion (differentiation between antecollis and antecaput) can be accomplished by lateral observation of the angles between the cervical spine and the thoracic spine, respectively, and between the cervical spine and the base of skull. The same applies to the analysis of backward flexion (differentiation between retrocollis and retrocaput). Sagittal shift forwards usually does not require further diagnosis: it is almost always caused by bilateral dystonic activities of the Mm. sternocleidomastoidei.

Ultrasound-guided cannulation of the great saphenous vein at the ankle in infants.

BACKGROUND: The establishment of peripheral venous access in infants is the most common invasive technique in paediatric anaesthesia. Venous puncture can be challenging due to the small size of vessels in this patient population. The present study was designed to investigate the practicability of ultrasound-guided vascular access to the great saphenous vein (GSV) at the level of the medial malleolus in infants ≤ 12 months. METHODS: Ninety consecutive infants ≤ 12 months undergoing elective surgery were included in this prospective study and divided into two age groups (0-6 and 7-12 months). After anaesthesia induction with sevoflurane, an ultrasound investigation of both GSVs at the level of the medial malleoli was performed. Subsequently, venous access in one GSV was established under direct ultrasound control. Anatomical ultrasound data and success rates of venous accesses were analysed. RESULTS: While not deeper relative to the skin, the GSV was significantly larger in older infants. The success rate in infants ≤ 6 months was 96%, whereas in older infants, the success rate was 100%. The overall success rate in all infants was 98%. CONCLUSIONS: Ultrasound facilitates venous puncture of the GSV in the vast majority of infants ≤ 12 months. Direct visualization via ultrasound is a promising technique for the establishment of venous access in the GSV at the level of the medial malleolus in infants.

[The phenomenology of cervical dystonia]. / Zur Phänomenologie der zervikalen Dystonien.

BACKGROUND: Cervical dystonia is the most common form of focal dystonia. Most cases of cervical dystonia are idiopathic and generally it is a life-long disorder. In recent years, Botulinum toxin type A (BtA) has become the first line therapy. However, some patients are resistant to it. This problem leads to the study of the clinical forms of cervical dystonias with the help of CT and MRI. PATIENTS AND METHODS: 78 patients with diagnosed primary cervical dystonia were examined. All underwent CT of the soft tissues of the neck with the aid of slices at the level of cervical vertebra 3 and 7. The cervical spine and the soft tissues of the neck were examined using magnetic resonance tomography in T 1 and T 2 with a slice thickness of 2 mm and in T 1 tilted towards the deep neck muscles. For comparison the MRT image data of 50 patients who had no cervical dystonia was analysed. The largest diameters were measured and the shape of all muscles captured in the neck region was described, including the small neck muscles. RESULTS: It was shown that in lateral flexion and in rotation, in 1 / 5 of patients the disorder affected only muscles which work on atlanto-occipital joints (latero- or torticaput), and in a further 1 / 5 it affected only muscles which work on the cervical spine (latero- or torticollis). 3 / 5 showed both disorders, but with a different degree of caput and collis involvement. Thus a ration of 1:1:3 was obtained in relation to this. CONCLUSIONS: 1. In lateral tilt, differentiation between laterocollis and laterocaput is clinically possible. 2. Lateral shift always occurs when laterocollis is present on one side and laterocaput on the other. 3. In rotation, clinical differentiation between torticollis and torticaput is not always possible. In this case CT sections at levels C 3 and C 7 are recommended. By comparing the vertebral position at the two levels it is possible to differentiate reliably between torticollis and torticaput. 4. Anteflexion--differentiation between anterocollis and anterocaput--is analysed by lateral inspection of the angle between the cervical spine and the thoracic spine or between the cervical spine and the base of the skull. The same applies for the analysis of retroflexion, the differentiation between retrocollis and retrocaput. 5. A posteroanterior sagittal shift requires no further diagnosis: it is often caused by bilateral dystonic activity of the sternocleidomastoid muscles.

[Treatment of lingual dystonia with botulinum toxin injections. First report]. / Behandlung lingualer Dystonie mit Botulinum-Toxin-Injektionen. Erste Fallberichte.

This is the first report about successful botulinum toxin therapy of the intrinsic muscles of the tongue in two patient with lingual dystonias. In these patients botulinum toxin was injected direct into the tongue.

[Botulinum toxin treatment : therapy success in cases of depression and ongoing pension applications]. / Botulinum-Toxin-Behandlung : Einfluss von Depression und laufendem Rentenverfahren auf den Therapieerfolg.

INTRODUCTION: A discrepancy is often observed between the presence of botulinum toxin antibodies (Btx-Ab) and successful therapy. We studied whether depression and an ongoing pension application explain this contradiction. METHOD: Sixty-five patients treated with Btx were questioned for subjective therapy failure (TF). The extensor digitorum brevis test (EDB test) indicated the presence of Btx-Ab. The Beck Depression Inventory and an exploration investigated for a depressive disturbance as well as an ongoing application for pension. We correlated the EDB test and the TF with a depressive disturbance and the wish for a pension. RESULTS: Forty-three patients had TF, from which 22 Btx-Ab were positive. A depressive disturbance was found in 25 patients, and an ongoing application for pension in 21. The EDB test and TF did not however correlate TF with a depressive disturbance (P=0.003) and a pension desire (P=0.021). The TF mostly appeared at the beginning of treatment. DISCUSSION: A depressive disturbance and an ongoing application for a pension influence the therapeutic success more strongly initially than the development of Btx-Ab. CONCLUSION: Besides Btx-Ab a depressive disturbance and an ongoing application for pension influences the therapeutic success.

[Proof of botulinum toxin antibodies with the Extensor Digitorum Brevis Test]. / Nachweis von Botulinum-Toxin-Antikörper. Korrelation des Extensor-digitorum-brevis-Test mit dem Mouse Diaphragma Bioassay.

INTRODUCTION: Some patients treated with botulinum toxin (btx) develop neutralizing btx antibodies (btx-ab). The expensive Mouse Diaphragm Bioassay (MDB) is considered as the gold standard by many authors. We wanted to examine whether the Extensor Digitorum Brevis Test (EDB test) is a reliable method to test for btx-ab. METHOD: We performed an electroneurography of the m. extensor digitorum brevis on both feet of 23 patients with known MDB. Afterwards the right feet were injected with 25 U of btx, and 21-28 days later the electroneurography was performed on both sides again. Finally we correlated the measured values (muscular wave latency, amplitude, area, and duration) intraindividually and with the MDB results. RESULTS: The parameters area and amplitude correlated highly significantly with the MDB (P<0.001 for both tests). Decreasing the amplitude to at least 65% of its initial value indicated the presence of btx-ab. In that way 22 of 23 EDB classifications were identical to those of the MDB, yielding a sensitivity of 92.86% and a specificity of 100%. CONCLUSION: The EDB test is a reliable technique for detecting btx-ab with high sensitivity and specificity. The EDB test can replace the MDB.

[Effect of botulinum toxin a and B on vegetative cardiac innervation]. / Die Wirkung von Botulinumtoxin A und B auf die vegetative kardiale Innervation.

The objective of this study was to examine whether vegetative cardiac innervation is affected by local application of botulinum toxin A and B. For that purpose, heart rate variability (HRV) was measured in 29 patients treated with botulinum toxin A and 26 patients treated with botulinum toxin B both prior to and three weeks following injection. Among the 14 parameters studied, 9 and 10 had significantly changed in terms of decreased HRV following treatment with botulinum toxin A and B, respectively. Obviously, either type of botulinum toxin exerts a systemic effect, although a clear-cut difference between the two preparations was undetectable. By and large, the changes observed tend to be low compared to, for instance, cardiac effects known to occur with tricyclic agents. However, the results might be of relevance for the use of botulinum toxins in patients with a history of cardiac disease since a reduction in HRV correlates with an increased incidence of cardiovascular events. Therefore, an ECG study is advised prior to onset of therapy with botulinum toxin. In addition, nonjudicious use of botulinum toxin outside a defined range of medical indications should be reassessed.

A double-blind randomised placebo-controlled evaluation of three doses of botulinum toxin type A (Dysport) in the treatment of spastic equinovarus deformity after stroke.

BACKGROUND/OBJECTIVES: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport) in post-stroke calf spasticity. METHODS: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. RESULTS: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002-0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators' and patients' assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. CONCLUSION: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed.

Botulinum toxin for treatment of spasticity in adults.

Although a few hundred papers have been published on the treatment of adult spasticity with botulinum toxin, the number of randomized placebo-controlled double-blind studies, by comparison, is relatively small. Criteria of highest evidence classes are met by the following observations: 1) Botulinum toxin improves motor functions (ability to walk and stand in the presence of spastic equinus deformity and knee flexor spasticity, upper-extremity movements). 2) Botulinum toxin makes attendance of spastic adults easier (personal hygiene in patients presenting with severe adductor spasticity; self-care and dressing in the presence of arm spasticity). 3) Early initiation of treatment with botulinum toxin yields better results than delayed institution (hemispasticity).

[Camptocormia--segmental dystonia. Proposal of a new definition for an old disease]. / Kamptokormia--eine segmentale Dystonie. Vorschlag einer neuen Definition für eine alte Krankheit.

Camptocormia is defined as a forced posture with a forward-bent trunk which appears during standing and sitting. It was first described in 1818 by Brodie. In the last 100 years, numerous cases were observed. A psychogenic origin was presumed in most cases. We describe four patients with typical symptoms of camptocormia who present with the clinical and electromyographical criteria of a segmental dystonia. A new classification of camptocormia is proposed including (1) the primary form, a segmental dystonia of the abdominal wall muscles and (2) secondary forms. Among other conditions (psychogenic disorder, neurosis, myopathy, myositis, Parkinson's disease, multiple-system atrophy, thoracolumbar kyphosis, paraneoplastic syndrome), camptocormia is to be considered in essential tremor. A combination of dystonia of the abdominal wall muscles and essential tremor seems possible.

IgA cross-reactivity between a nuclear autoantigen and wheat proteins suggests molecular mimicry as a possible pathomechanism in celiac disease.

Celiac disease patients display IgA antibody reactivity to wheat as well as to human proteins. We used serum IgA from celiac patients and, for control purposes, from patients with Crohn's disease, ulcerative colitis and from healthy individuals to identify celiac disease-specific IgA autoantigens in nitrocellulose-blotted extracts from various human cell types (epithelial, endothelial, intestinal cells, fibroblasts). The pattern, recognition intensity and time course of IgA autoreactivity was monitored using serial serum samples obtained from celiac children before and under gluten-free diet. By immunoblot inhibition and subcellular (cytosolic, nuclear) cell fractionation we identified a 55 kDa nuclear autoantigen expressed in intestinal, endothelial cells and in fibroblasts which was recognized by IgA antibodies of approximately half of the celiac disease patients and cross-reacted with wheat proteins. IgA reactivity to the 55 kDa autoantigen disappeared during gluten-free diet and was inhibited after pre-absorption of sera with wheat proteins but not with tissue transglutaminase, previously reported as the unique celiac disease-specific autoantigen. In conclusion, we defined a novel 55 kDa celiac disease-specific nuclear IgA autoantigen which shares epitopes with wheat proteins and which is different from tissue transglutaminase and calreticulin. Although the newly defined autoantigen was recognized much less frequently than tissue transglutaminase, our data suggest molecular mimicry between wheat and human proteins as a possible pathomechanism for the induction and/or maintenance of mucosal tissue damage in celiac disease.

Digital selenium radiography: anti-scatter grid for chest radiography in a clinical study.

The purpose of this study was to evaluate the diagnostic performance of an additional stationary anti-scatter grid in digital selenium radiography (DSR) compared with images acquired with only an air gap. Chest radiographs were obtained with DSR in 100 patients with and without an anti-scatter grid. Four observers scored 12 anatomical landmarks, catheters and wire cerclages for their visualization in both subsets of images. Statistical analysis was performed using a paired t-test. Anatomical landmarks, catheters and wire cerclages were statistically better visualized in regions of high attenuation when the images were performed with an anti-scatter grid. No statistically significant difference was noted for peripheral regions, nor for sex and weight of the patient between the two modalities. Therefore, an anti-scatter grid is not recommended for chest radiography as it increases the radiation exposure of patients without having a significant impact on visualization for all regions of the chest.

Screening by anti-endomysium antibody for celiac disease in diabetic children and adolescents in Austria.

BACKGROUND: Unrecognized celiac disease (CD) may be found in a substantial proportion of patients with type I diabetes mellitus. METHODS: A cohort of 403 Austrian children and adolescents with type I diabetes mellitus (210 males and 193 females; age range, 1-22 years) was screened for celiac disease using the IgA anti-endomysium antibody test (EMA) and the immunoglobulin (Ig)G anti-gliadin (AGA-IgG) and IgA anti-gliadin (AGA-IgA) antibody test. RESULTS: Twelve patients' sera (2.98%) yielded positive EMA results and two patients' sera (0.49%) with IgA deficiency had high AGA-IgG values. All but one of these patients underwent intestinal biopsy. Six (1.49%) had clear histologic evidence of CD (flat mucosa), whereas three (0.74%) showed minor histologic changes (increase in intraepithelial lymphocytes) and four (0.99%), including the EMA-negative patients with IgA deficiency, had a normal mucosa. When the cases with silent and potential CD were combined, the overall prevalence in the current cohort was 2.98%. There was no difference in the hemoglobin (Hb)A1c level between antibody-positive and -negative patients, and subsequent gluten-free diet did not change this metabolic parameter. CONCLUSION: The prevalence of clinically unrecognized CD, found by EMA screening, is much higher in Austrian children with diabetes than in a comparable population without diabetes. The prevalence of CD in diabetic children in Austria is distinctly lower, however, than in several other countries.