The effect on blink frequency of a selective blue-filtering photochromic lens in patients with benign essential blepharospasm.

Objective: The aim of this clinical study was to assess the impact of a non-invasive selective blue-filtering photochromic lens coating Crizal Prevencia on the treatment and response of benign essential blepharospasm (BEB). Patients and methods: Twenty-four patients were recruited in the outpatient clinic of the Medical University of Vienna in a randomized, double-blind, cross-over study design. Blink frequencies were assessed in patients with BEB before and 14 days after intervention with either a filtering ophthalmic lens or a placebo lens, respectively. Outcome parameters include sub-group analysis of a blink frequency under six different conditions: three photopic conditions, one resting condition, one reading condition, and one video game condition. Results: From 24 recruited patients, 15 patients were available for final analysis. Comparing the optical blue filtering lens to placebo, showed a reduced blink frequency in specific subtests, but not compared to baseline. Discussion: In conclusion, optical filtering glasses might have a beneficial effect on BEB and provide a non-invasive therapeutic add-on option, in addition to botulinum neurotoxin therapy, for patients with BEB and should necessarily be further investigated in a multicenter setting, resulting in larger sample sizes to gain valid information about the effect of photochromic blue filter glasses in BEB.Clinical trial registration: https://drks.de/search/en/trial/DRKS00032135, DRKS00032135.

Cognitive Performance After Facial Botulinum Toxin Treatment in a Cohort of Neurologic Patients: An Exploratory Study.

OBJECTIVE: To investigate higher cognitive functions after mimicry changes after facial botulinum toxin (BTX) injections, we tested verbal and nonverbal reasoning in patients with blepharospasm or hemifacial spasm before and after their long-term botulinum toxin treatment. DESIGN: Explorative, nonrandomized, clinical trial. SETTING: Patients receiving ambulatory care and control participants from the general community. PARTICIPANTS: Volunteer sample (N=84) of patients (n=21) with blepharospasm or hemifacial spasm who received facial BTX injections. Control participants included patients (n=30) with cervical dystonia who received cervical BTX injections and individuals without neurological disorders (n=33). INTERVENTIONS: The 2 groups receiving injections were tested before and 3 weeks after their treatment. The group without neurological disorders received no injections. MAIN OUTCOME MEASURES: Verbal and nonverbal reasoning scores. RESULTS: The key unexpected finding was that patients who received facial BTX injections perform significantly worse in nonverbal reasoning tasks, when compared with those who did not receive injections (P=.022). There was no significant difference in the baseline reasoning scores and at follow-up for verbal reasoning between the 3 groups. There was no correlation between toxin dose and reasoning scores (verbal: P=.132; nonverbal: P=.294). CONCLUSIONS: Because of potential confounders, the results do not yet allow any conclusion on causality. Further research is needed to confirm our findings.

Microvascular rarefaction in patients with cerebrovascular events.

Capillary density rarefaction and endothelial dysfunction contribute to chronic hypoperfusion and cerebral small vessel disease. Previous animal experiments revealed spatiotemporal microvascular remodeling directing post-stroke brain reorganization. We hypothesized that microcirculatory changes during acute cerebrovascular events could be reflected systemically and visualized sublingually. In a prospective observational trial in vivo sublingual sidestream darkfield videomicroscopy was performed in twenty-one patients with either acute stroke (n = 13 ischemic, n = 1 ischemic with hemorrhagic transformation and n = 2 hemorrhagic stroke) or transitory ischemic attacks (n = 5) within 24 h after hospital admission and compared to an age- and sex-matched control group. Repetitive measurements were performed on the third day and after one week. Functional and perfused total capillary density was rarefied in the overall patient group (3060 vs 3717 µm/mm2, p = 0.001 and 5263 vs 6550 µm/mm2, p = 0.002, respectively) and in patients with ischemic strokes (2897 vs. 3717 µm/mm2, p < 0.001 and 5263 vs. 6550 µm/mm2, p = 0.006, respectively) when compared to healthy controls. The perfused boundary region (PBR), which was measured as an inverse indicator of glycocalyx thickness, was markedly related to red blood cell (RBC) filling percentage (regarded as an estimate of microvessel perfusion) in the overall patient group (r = -0.843, p < 0.001), in patients with ischemic strokes (r = -0.82, p = 0.001) as well as in healthy volunteers (r = -0.845, p < 0.001). In addition, there were significant associations between platelet count or platelet aggregation values (as measured by whole blood impedance aggregometry) and microvascular parameters in the overall patient collective, as well as in patients with ischemic strokes. In conclusion, cerebrovascular events are associated with altered systemic microvascular perfusion.

Estimation of patent foramen ovale size using transcranial Doppler ultrasound in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO)is associated with cryptogenic stroke, especially in young adults. Transcranial Doppler (TCD) ultrasound is used as a screening tool before transesophageal echocardiography (TEE). However, the use of Valsalva maneuver (VM) to identify a right-to-left-shunt underlies interindividual variability. Here, we aimed to assess whether a pressure-controlled standardization of VM is useful to estimate PFO size. METHODS: We included patients aged 18-80 years with a PFO according to TEE. Subjects underwent TCD with microembolic signals (MES) counted under four pressure conditions (i.e., at rest, 15 mbar, 40 mbar, and maximum expiratory pressure). Findings were correlated with TEE-based PFO size. The predictive value of TCD at rest and VM-based TCD for PFO size estimation was assessed by stepwise multivariate linear regression models and multiple cross-tab-analyses. RESULTS: We screened 203 subjects after a cerebrovascular event, of which 78 (48 males [61.5%], median age 55 years [22-80]) with PFO were included. We found an association between MES count and expiratory pressure (p < .001). Predefined MES count categories at TCD pressure conditions correlated significantly with PFO size measured by TEE. We propose a PFO size estimation model based on TCD at rest and under VM, which classified PFO size correctly in 64.1% with the highest accuracy for small PFOs. CONCLUSION: Our data provide evidence that TCD with step-wise barometric standardization allows an estimation of PFO size with good accuracy. Though TCD will not replace TEE in future, this might be of clinical value in circumstances where TEE cannot be easily performed.

Denervation Dynamics After Intramuscular BNT Injection in Patients With Focal Spasticity Monitored by MRI and Dynamometry-a Blinded Randomized Controlled Pilot Study.

Introduction: Botulinumtoxin associated muscle denervation (BNTMD) can be detected by magnet resonance imaging (MRI), MRI may provide further insights into the exact timeline of BNTMD and the potential impact and timing of physical exercise. We aimed to assess the time interval until detection of BNTMD by MRI and whether immediate physical exercise after intramuscular BNT injection has a measurable effect on clinical parameters and the intramuscular denervation dynamics illustrated by MRI. Materials and Methods: Eleven age-matched patients were randomized to an "exercise" or "no-exercise" group. Eighty mouse-units of incobotulinumtoxin were injected into the spastic biceps muscle. MRI of the injected region, hand-held dynamometry of elbow flexor strength and clinical rating scales (mAS, CGI-I) were conducted in predefined intervals. Results: We could not detect BNTMD within 24 h but 7 days after injection independent of group allocation (exercise n = 6, no-exercise n = 5). Denervation signs were more diffuse and spread into adjacent muscles in patients having received exercise. We could not detect differences concerning clinical measures between the two groups. Conclusions: Physical exercise might influence BNTMD dynamics and promote propagation of T2-MR muscle denervation signs from the injected site into adjacent muscles. Trial registration: clinicaltrialsregister.eu, Identifier 2017-003117-25.

Pulse-synchronous torsional nystagmus.

Purely torsional spontaneous nystagmus almost always has a central vestibular cause. We describe a man with spontaneous pulse-synchronous torsional nystagmus in which the clockwise component corresponded to his pulse upswing, in keeping with a peripheral vestibular cause; following imaging we diagnosed left-sided superior canal dehiscence syndrome. Identifying pulse synchronicity of spontaneous nystagmus may help to distinguish central from peripheral vestibular torsional nystagmus, and is readily confirmed at the bedside using Frenzel's glasses and a pulse oximeter.

[Treatment satisfaction in patients with cervical dystonia : Subgroup analysis of INTEREST-IN-CD-2]. / Behandlungszufriedenheit bei Patienten mit zervikaler Dystonie : Subgruppenanalyse von INTEREST-IN-CD-2.

BACKGROUND: Even though treatment guidelines recommend botulinum neurotoxin A (BoNT-A) as first line treatment for primary cervical dystonia (CD), there are only limited data on how BoNT-A-injections are administered in routine clinical practice. OBJECTIVE: This subgroup analysis evaluated patient satisfaction and symptom control under consideration of BoNT­A treatment modalities in German and Austrian CD patients (DE/AT, n = 79) compared to the full international cohort (n = 995). MATERIAL AND METHODS: The INTEREST-IN-CD2 was a prospective, multicenter, longitudinal observational study. Course of treatment in adult primary CD patients under BoNT­A treatment was assessed over a time period of 3 years. Primary outcome measure was the long-term satisfaction of patients with treatment, measured as maximum satisfaction between two consecutive injections as well as satisfaction at the time of reinjection. RESULTS: Treatment satisfaction at the maximum effect was stable and comparably good in both populations during the study (82.3-92.7% and 85.0-89.9%). Satisfaction decreased with decreasing BoNT­A effect at the end of the treatment interval: it was comparable at the start of the study in both groups (54.2% vs. 51.4%), decreased numerically in the DE/AT group to 32.7% but remained stable in the total population. Analysis of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scores did not reveal any substantial differences between the DE/AT subgroup and total cohort. CONCLUSION: Overall, the study confirmed good clinical symptom control by BoNT­A. The numerical differences in the current satisfaction seen in the comparison of DE/AT to the total cohort are possibly due to different proportions of BoNT­A naïve patients in both groups, as they expressed different levels of satisfaction than previously treated patients.

Slowed vertical saccades as a hallmark of hereditary spastic paraplegia type 7.

Anecdotal oculomotor disturbances have been described in spastic paraplegia type 7 (SPG7). We investigated oculomotor and vestibular dysfunction in five patients with genetically verified SPG7. All five patients exhibited significantly slower velocities of vertical saccades compared to controls, but significantly faster than in progressive supranuclear palsy, with upward saccades being particularly affected. Horizontal saccades, cerebellar oculomotor markers, and vestibuloocular reflex seem to be variably affected. Thus, albeit subclinical in some cases, slowing of the vertical saccades may belong to the phenotype of SPG7 and may serve as a valuable biomarker for differentiation from spastic ataxias and atypical parkinsonism.

Correction to: Non-vitamin K antagonist oral anticoagulants in patients with an increased risk of bleeding.

Correction to: Wien Klin Wochenschr 2018 https://doi.org/10.1007/s00508-018-1381-5 Unfortunately, the original version of this article contained two mistakes.The text passage "It should be mentioned here that in the case of apixaban, dose adjustment is not based on GFR. A lower dosage of apixaban ….

Non-vitamin K antagonist oral anticoagulants in patients with an increased risk of bleeding.

The non-vitamin K antagonist oral anticoagulants (NOACs) have considerably changed clinical practice and are increasingly being used as an alternative to vitamin K antagonists (VKAs) for 3 main reasons: 1) an improved benefit-risk ratio (in particular lower rates of intracranial bleeding), 2) a more predictable effect without the need for routine monitoring, and 3) fewer food and drug interactions compared with VKAs. Currently, there are four NOACs available: the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, and the thrombin inhibitor dabigatran. This consensus paper reviews the properties and usage of NOACs in a number of high-risk patient populations, such as patients with chronic kidney disease, patients ≥80 years of age and others and provides guidance for the use of NOACs in patients at risk of bleeding.

Congenital fiber-type disproportion in an ambulatory rehabilitation setting : A case report.

Congenital fiber-type disproportion is a rare condition, histologically characterized by a relative type 1 fiber hypotrophy. The main clinical feature is mild-to-severe muscle weakness. In this report, we present the case of a 21-year-old patient with congenital fiber-type disproportion in an outpatient rehabilitative setting to evaluate the feasibility and results of an assessment battery, including bioimpedance analysis (BIA), dynamometry, 3D gait analysis, 6­min walk test (6MWT), and the timed up and go test (TUG). The patient had a notable decrease in all functional scores. BIA: lean body mass, 38.4 kg (50.2 ± 5.3), body fat, 1.6% (12.4 ± 4.4); hand dynamometry: 18.5 kg left/20.0 kg right (44.8 ± 6.6); walking speed, 58 cm/s (122.7 ± 11.1), step length, 43.0 cm (61.6 ± 3.5); 6MWT: 478.5 m (638 ± 44); TUG: 9.4 s (8.1 ± 1.0). No adverse events were reported. The tests used were easily applicable in clinical routine and well tolerated by our patient.

MR neurography of ulnar nerve entrapment at the cubital tunnel: a diffusion tensor imaging study.

OBJECTIVES: MR neurography, diffusion tensor imaging (DTI) and tractography at 3 Tesla were evaluated for the assessment of patients with ulnar neuropathy at the elbow (UNE). METHODS: Axial T2-weighted and single-shot DTI sequences (16 gradient encoding directions) were acquired, covering the cubital tunnel of 46 patients with clinically and electrodiagnostically confirmed UNE and 20 healthy controls. Cross-sectional area (CSA) was measured at the retrocondylar sulcus and FA and ADC values on each section along the ulnar nerve. Three-dimensional nerve tractography and T2-weighted neurography results were independently assessed by two raters. RESULTS: Patients showed a significant reduction of ulnar nerve FA values at the retrocondylar sulcus (p = 0.002) and the deep flexor fascia (p = 0.005). At tractography, a complete or partial discontinuity of the ulnar nerve was found in 26/40 (65%) of patients. Assessment of T2 neurography was most sensitive in detecting UNE (sensitivity, 91%; specificity, 79%), followed by tractography (88%/69%). CSA and FA measurements were less effective in detecting UNE. CONCLUSION: T2-weighted neurography remains the most sensitive MR technique in the imaging evaluation of clinically manifest UNE. DTI-based neurography at 3 Tesla supports the MR imaging assessment of UNE patients by adding quantitative and 3D imaging data. KEY POINTS: • DTI and tractography support conventional MR neurography in the detection of UNE • Regionally reduced FA values and discontinuous tractography patterns indicate UNE • T2-weighted MR neurography remains the imaging gold standard in cases of UNE • DTI-based ulnar nerve tractography offers additional topographic information in 3D.

Early treatment with IgM-enriched intravenous immunoglobulin does not mitigate critical illness polyneuropathy and/or myopathy in patients with multiple organ failure and SIRS/sepsis: a prospective, randomized, placebo-controlled, double-blinded trial.

INTRODUCTION: Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting. METHODS: In this prospective, randomized, double-blinded and placebo-controlled trial, 38 critically ill patients with multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs of CIPNM were included. Patients were randomly assigned to be treated either with IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by the CIPNM severity sum score based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM). RESULTS: A total of 38 critically ill patients were included and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19). Baseline characteristics were similar between the two groups. CIPNM could not be improved by IVIG treatment, represented by similar CIPNM severity sum scores on day 14 (IVIG vs. placebo: 4.8 ± 2.0 vs. 4.5 ± 1.8; P = 0.70). CIPNM severity sum score significantly increased from baseline to day 14 (3.5 ± 1.6 vs. 4.6 ± 1.9; P = 0.002). After an interim analysis the study was terminated early due to futility in reaching the primary endpoint. CONCLUSIONS: Early treatment with IVIG did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01867645.

Antipsychotics for acute and chronic pain in adults.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 4, 2008. The role of antipsychotics as adjuvant analgesics is a subject of longstanding controversy. Neuroleptanalgesia (that is a state of quiescence, altered awareness, and analgesia produced by a combination of taking an opioid analgesic and an antipsychotic), an established term for the management of acute pain, was shown to negatively influence disease course and total mortality in unstable angina patients. Nevertheless, antipsychotics are used to treat chronic pain (for example chronic headache, fibromyalgia and diabetic neuropathia). With atypical antipsychotics, a new class of antipsychotics, both fewer extrapyramidal side effects and additional benefits may be available. OBJECTIVES: To assess the analgesic efficacy and adverse effects of antipsychotics in acute or chronic pain in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, and EMBASE in October 2011 and January 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults prescribed any dose of an oral antipsychotic for acute or chronic pain, where subjective pain assessment was described as either the primary or a secondary outcome, were included in this review. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent review authors, and results were compared for differences. Discrepancies were resolved by discussion. All trials were quality scored according to the methods set out in section six of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: A total of 770 participants were involved in the 11 included studies. Data from five included randomised double-blind studies showed beneficial effects of antipsychotics in the treatment of acute and chronic pain. Quantitative analysis of these studies showed a significant reduction of mean pain intensity after administration of the antipsychotic compared to placebo or another active compound, weighted mean difference (WMD) -1.78 (95% CI -2.71 to -0.85) for the continuous data; and relative risk (RR) 0.43 (95% CI 0.25 to 0.73), number needed to treat to benefit (NNT) 2.6 for the dichotomous data. Nevertheless, the test for heterogeneity was significant for both the continuous data (P = 0.0007) and the dichotomous data (P = 0.04). Obviously this makes the calculated NNT less reliable and caution is warranted when interpreting these results.The most frequently reported adverse effects were extrapyramidal (that is involuntary movements, parkinsonism and akathisia) and sedating effects. AUTHORS' CONCLUSIONS: The recent search found five new studies which were all excluded, so the review remains the same as previously.Antipsychotics might be used as an add-on therapy in the treatment of painful conditions. Nevertheless, extrapyramidal and sedating side effects have to be considered before using antipsychotics for treating painful conditions.Results for antipsychotics in the treatment of different painful conditions are mixed and most sample sizes in the reviewed RCTs are small. Further studies on atypical antipsychotics in larger double-blind placebo-controlled studies that include standardised pain assessment and documentation are warranted.

The pattern and time course of somatosensory changes in the human UVB sunburn model reveal the presence of peripheral and central sensitization.

The ultraviolet B (UVB) sunburn model was characterized with a comprehensive battery of quantitative sensory testing (QST). Primary hyperalgesia in UVB-irradiated skin and secondary hyperalgesia in adjacent nonirradiated skin were studied in 22 healthy subjects 24h after irradiation with UVB at 3-fold minimal erythema dose of a skin area 5 cm in diameter at the thigh and compared to mirror-image contralateral control areas. The time course of hyperalgesia over 96 h was studied in a subgroup of 12 subjects. Within the sunburn area, cold hyperesthesia (P=.01), profound generalized hyperalgesia to heat (P<.001), cold (P<.05), pinprick and pressure (P<.001), and mild dynamic mechanical allodynia (P<.001) were present. The finding of cold hyperalgesia and cold hyperesthesia is new in this model. The sunburn was surrounded by large areas of pinprick hyperalgesia (mean±SEM, 218±32 cm(2)) and a small rim of dynamic mechanical allodynia but no other sensory changes. Although of smaller magnitude, secondary hyperalgesia and dynamic mechanical allodynia adjacent to the UVB-irradiated area were statistically highly significant. Primary and secondary hyperalgesia developed in parallel within hours, peaked after 24-32 h, and lasted for more than 96 h. These data reveal that the UVB sunburn model activates a broad spectrum of peripheral and central sensitization mechanisms and hence is a useful human surrogate model to be used as a screening tool for target engagement in phases 1 and 2a of drug development.

Central origin of pinprick hyperalgesia adjacent to an UV-B induced inflammatory skin pain model in healthy volunteers.

Background and purpose The UV-B model is an established pain model of different types of hyperalgesia in animal and human pain research. Beside the skin region of the sunburn in human volunteers pinprick hyperalgesia has been described in a large zone of non-inflamed skin adjacent to the sunburn. However, there are opposing results on the existence of pinprick hyperalgesia and most notably a controversial discussion is still on-going whether this mechanical hyperalgesia in the undamaged tissue adjacent to and at some distance from the site of inflammation is of peripheral or central origin. We therefore addressed this in our study by hypothesising that pinprick hyperalgesia around a circular spot of UV-B inflamed skin is not reduced by a superficial local anaesthetic block and therefore underlies centrally mediated mechanisms. Methods This exploratory study was conducted in a prospective, controlled, randomised, single-blinded fashion in relation to the study hypothesis in 12 healthy volunteers. Before circular irradiation with UV-B light (3-times the individual minimal erythema dose at both thighs), a strip of continuous intradermal local anaesthetic block with lidocaine 2% was established via two single plasmaphoresis hollow fibres. These were positioned perpendicular to one thigh overlapping on the midline of the leg at the distal part of the planned irradiation site, and compared with the contralateral control side without anaesthetic block. The local anaesthetic block was established and then maintained via a syringe pump. The area of pinprick hyperalgesia was measured by pricking on a large skin surface including 360° around the circular irradiation site. This was done with a slightly painful pin (256 mN) until 8h after irradiation. Primary outcome was the area of pinprick hyperalgesia in the skin adjacent to the sunburn at 8h. Results Large areas of mechanical hyperalgesia to pinprick surrounding the adjacent skin of the sunburn developed on both sides after 8h without any significant difference between the side of the anaesthetic strip showing an area of 72.6±39.7 cm2 (mean±SD) and the control side (59.1±20.1 cm2); p = 0.24. Moreover, mechanical hyperalgesia to various pin stimuli of different strength was unchanged by the anaesthetic block. Conclusion This trial provides evidence that the development of mechanical hyperalgesia surrounding an experimental sunburn was not influenced by continuous peripheral afferent blockade with local anaesthetic at 8h after UV-B irradiation. Our data support the hypothesis that in the UV-B model peripheral nociceptive afferent input of inflamed skin may enhance central hypersensitivity of mechanosensitive nociceptors in a larger receptive field far beyond the inflamed skin. Furthermore, these findings are in line with other pain models demonstrating comparable central hypersensitivity around the site of injury. Implications As for other pain models this finding provides further evidence that the UV-B model offers secondary mechanical hyperalgesia in addition to its known primary hyperalgesia. Consequently, this is a further validation for the utilisation of the UV-B model in human pain research.

The First Case(s) of Botulism in Vienna in 21 Years: A Case Report.

UNLABELLED: We describe two linked cases of botulinum toxin intoxication to provide the clinician with a better idea about how botulism cases may present since early diagnosis and treatment are crucial in botulism. Botulinum toxin is the strongest neurotoxin known. METHODS: We review the available literature, the compiled clinical data, and observations. RESULTS: After a slow onset of clinical signs a married couple living in Vienna presented with dysphagia, difficulties in accommodation, inability to sweat, urinary and stool retention, dizziness, and nausea. They suffered intoxication with botulinum toxin type B. Botulism is a rarely occurring disease in Austria. In the last 21 years there were only twelve reported cases. CONCLUSION: Both patients went to a general practitioner as well as several specialists before they were sent to and correctly diagnosed at our outpatient department. To avoid long delays between intoxication and diagnosis we think it is crucial to advert to the complex symptoms a nonsevere intoxication with botulinum toxin can produce, especially since intoxications have become rare occurrences in the industrialized societies due to the high quality of industrial food production.