Guideline on the use of onabotulinumtoxinA in chronic migraine: a consensus statement from the European Headache Federation

OnabotulinumtoxinA is being increasingly used in the management of chronic migraine (CM). Treatment with onabotulinumtoxinA poses challenges compared with traditional therapy with orally administered preventatives. The European Headache Federation identified an expert group that was asked to develop the present guideline to provide recommendations for the use of onabotulinumtoxinA in CM. The expert group recommend onabotulinumtoxinA as an effective and well-tolerated treatment of CM. Patients should preferably have tried two to three other migraine prophylactics before start of onabotulinumtoxinA. Patients with medication overuse should be withdrawn from the overused medication before initiation of onabotulinumtoxinA if feasible, if not onabotulinumtoxinA can be initiated from the start or before withdrawal. OnabotulinumtoxinA should be administered according to the PREEMPT injection protocol, i.e. injecting 155 U–195 U to 31–39 sites every 12-weeks. We recommend that patients are defined as non-responders, if they have less than 30% reduction in headache days per month during treatment with onabotulinumtoxinA. However other factors such as headache intensity, disability and patient preferences should also be considered when evaluating response. Treatment should be stopped, if the patient does not respond to the first two to three treatment cycles. Response to continued treatment with onabotulinumtoxinA should be evaluated by comparing the 4 weeks before with the 4 weeks after each treatment cycle. It is recommended that treatment is stopped in patients with a reduction to less than 10 headache days per month for 3 months and that patients are re-evaluated 4–5 months after stopping onabotulinumtoxinA to make sure that the patient has not returned to CM. Questions regarding efficacy and tolerability of onabotulinumtoxinA could be answered on the basis of scientific evidence. The other recommendations were mainly based on expert opinion. Future research on the treatment of CM with onabotulinumtoxinA may further improve the management of this highly disabling disorder.     

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity

Background

Maldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation.

Methods

This retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as >?20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO₂). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively.

Results

A total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8?years [interquartile range (IQR) 16.5–30.6]) and the median time between CMR and CPET was 2.8?months [IQR 0–13.8]. Fifty-three patients (36%) had MPBF (95% CI 29–45%). The mean % predicted VO₂ was 63?±?16%. Patients with MPBF had lower mean % predicted VO₂ compared to patients without MPBF (60?±?14% versus 65?±?16%, p?=?0.04). On multivariable analysis, a lower % predicted VO₂ was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6–7.4, p?<?0.001).

Conclusion

In patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

     

Prenatal diagnosis of mediastinal neurenteric cyst: a case report and review of the literature

Neurenteric cyst is a very rare developmental anomaly. Prenatal diagnosis of mediastinal neurenteric cysts has been reported rarely. We present a case of neurenteric cyst associated with vertebral anomalies diagnosed by prenatal ultrasonography at 31 weeks of gestation, which was treated successfully in the early neonatal period. In addition, we searched the English literature for all cases of mediastinal neurenteric cyst diagnosed in the prenatal period reported to date. We found that only 17 cases were reported previously. We reviewed the reports of these 17 patients along with our case, and we investigated the prenatal and postnatal diagnosis and treatment approaches and the factors influencing the prognosis. Fetuses with mediastinal neurenteric cysts should be monitored regularly by ultrasonography. Fetuses with no signs of hydrops are more likely to survive with proper neonatal center transfer, regular follow-up, and appropriate postnatal approach. Fetuses with hydrops findings have a high risk of fetal and neonatal death.     

Quantitative assessment of thyroid gland elasticity with shear-wave elastography in pediatric patients with Hashimoto’s thyroiditis

Objective

Hashimoto’s thyroiditis is the most common autoimmune thyroid disorder in the pediatric age range. Measurement of thyroid gland size is an essential component in evaluation and follow-up of thyroid pathologies. Along with size, tissue elasticity is becoming a more commonly used parameter in evaluation of parenchyma in inflammatory diseases. The aim of the current study was to assess thyroid parenchyma elasticity by shear-wave elastography in pediatric patients with Hashimoto’s thyroiditis; and compare the elasticity values to a normal control group.

Materials and methods

In this study; thyroid glands of 59 patients with a diagnosis of Hashimoto’s thyroiditis based on ultrasonographic and biochemical features, and 26 healthy volunteers without autoimmune thyroid disease and thyroid function disorders, were evaluated with shear-wave elastography. Patients with Hashimoto thyroiditis were further subdivided into three categories based on gray-scale ultrasonography findings as focal thyroiditis (grade 1), diffuse thyroiditis (grade 2), and fibrotic thyroid gland (grade 3).

Results

Patients with Hashimoto’s thyroiditis (n = 59) had significantly higher elasticity values (14. 9 kPa; IQR 12.9–17.8 kPa) than control subjects (10.6 kPa; IQR 9.0–11.3 kPa) (p < 0.001). Of the 59 patients with Hashimoto’s thyroiditis, 23 patients had focal thyroiditis involving less than 50% of the gland categorized as grade 1, 24 patients had diffuse involvement of the thyroid gland categorized as grade 2, and 12 patients had marked hyperechoic septations and pseudonodular appearance categorized as grade 3 on gray-scale ultrasound. Based on elastography, grade 3 patients had significantly higher elasticity values (19.7 kPa; IQR 17.8–21.5 kPa) than patients with grade 2 (15.5 kPa; IQR 14.5–17.8 kPa) and grade 1 thyroiditis (12.8 kPa; IQR 11.9–13.1 kPa) (p < 0.05). Patients with grade 2 thyroiditis had significantly higher elasticity values than those with grade 1 thyroiditis (p < 0.05).

Conclusion

Gray-scale ultrasound findings of heterogeneous echotexture and hypoechoic echogenicity reflect a longer duration of inflammation and may not be found in the initial stages of thyroiditis. Our results indicate that shear-wave elastography could be used to evaluate the degree of fibrosis in Hashimoto’s thyroiditis.

     

Liver abscess due to <Emphasis Type="Italic">Fusobacterium</Emphasis> species detected on ultrasonography: a case report

An oral infection harboring Fusobacterium species can gain entrance to the liver via hematogenous spread in the form of septic embolus, and can thereby cause abscesses. Such spread, described as Lemierre syndrome, is life threatening. We present such a case history of a man in his mid-40s, who presented with infection and Fusobacterium liver abscess with an acute fulminant disease course. The initial diagnosis was arrived at by ultrasound imaging and blood investigations. He was treated with antibiotics, ultrasound-guided liver abscess drainage, and extraction of the infected molar tooth. He was discharged 6 weeks after admission. To date, there have been no reports describing the ultrasound images of a Fusobacterium liver abscess in detail. Hence, we herein present the ultrasound images of a Fusobacterium liver abscess.     

Velocity–pressure loops for continuous assessment of ventricular afterload: influence of pressure measurement site

VPloop, the graphical representation of pressure versus velocity, and its characteristic angles, GALA and β, can be used to monitor cardiac afterload during anesthesia. Ideally VPloop should be measured from pressure and velocity obtained at the same arterial location but standard of care usually provide either radial or femoral pressure waveforms. The purpose of this study was to look at the influence of arterial sites and the use of a transfer function (TF) on VPloop and its related angles. Invasive pressure signals were recorded in 25 patients undergoing neuroradiology intervention under general anesthesia with transesophageal flow velocity monitoring. Pressures were recorded in the descending thoracic aorta, abdominal aorta, femoral and radial arteries. We compared GALA and β from VPloops generated from each location and in high and low risk patients. GALA was similar in the central locations (55°[49–63], 52°[47–61] and 54°[45–62] from descending thoracic to femoral artery, median[interquartile], p?=?0.10), while there was a difference in β angle (16°[4–27] to 8°[3–15], p?<?0.0001). GALA and β obtained from radial waveforms were different (39°[31–47] compared to 46°[36–54] and 6°[2–14] compared to 16°[4–27] for GALA and β angles respectively, p?<?0.001) which was corrected by the use of a TF (45°[32–55] and 17°[5–28], p?=?ns). GALA and β are underestimated when measured with a radial catheter. Using pressure waveforms from femoral locations alters VPloops, GALA and β in a smaller extend. The use of a TF on radial pressure allows to correctly plot VPloops and their characteristic angles for routine clinical use.     

ADARRI: a novel method to detect spurious R-peaks in the electrocardiogram for heart rate variability analysis in the intensive care unit

We developed a simple and fully automated method for detecting artifacts in the R-R interval (RRI) time series of the ECG that is tailored to the intensive care unit (ICU) setting. From ECG recordings of 50 adult ICU-subjects we selected 60 epochs with valid R-peak detections and 60 epochs containing artifacts leading to missed or false positive R-peak detections. Next, we calculated the absolute value of the difference between two adjacent RRIs (adRRI), and obtained the empirical probability distributions of adRRI values for valid R-peaks and artifacts. From these, we calculated an optimal threshold for separating adRRI values arising from artifact versus non-artefactual data. We compared the performance of our method with the methods of Berntson and Clifford on the same data. We identified 257,458 R-peak detections, of which 235,644 (91.5%) were true detections and 21,814 (8.5%) arose from artifacts. Our method showed superior performance for detecting artifacts with sensitivity 100%, specificity 99%, precision 99%, positive likelihood ratio of 100 and negative likelihood ratio <0.001 compared to Berntson’s and Clifford’s method with a sensitivity, specificity, precision and positive and negative likelihood ratio of 99%, 78%, 82%, 4.5, 0.013 for Berntson’s method and 55%, 98%, 96%, 27.5, 0.460 for Clifford’s method, respectively. A novel algorithm using a patient-independent threshold derived from the distribution of adRRI values in ICU ECG data identifies artifacts accurately, and outperforms two other methods in common use. Furthermore, the threshold was calculated based on real data from critically ill patients and the algorithm is easy to implement.     

Lung real time three-dimensional imaging in critically ill ventilated patients: a global diagnosis concordance study

Lung ultrasound (LUS) increases clinical diagnosis performance in intensive care unit (ICU). Real-time three-dimensional (3-D) imaging was compared with two-dimensional (2-D) LUS by assessing the global diagnosis concordance. In this single center, prospective, observational, pilot study, one trained operator performed a 3-D LUS immediately after a 2-D LUS in eight areas of interest on the same areas in 16 ventilated critically ill patients. All cine loops were recorded on a computer without visible link between 2-D and 3-D exams. Two experts blindly reviewed cine loops. Four main diagnoses were proposed: normal lung, consolidation, pleural effusion and interstitial syndrome. Fleiss κ and Cohen’s κ values were calculated. In 252 LUS cine loops, the concordance between 2-D and 3-D exams was 83.3% (105/126), 77.6% (99/126) and 80.2% (101/126) for the trained operator and the experts respectively. The Cohen’s κ coefficient value was 0.69 [95% Confidence Interval (CI) 0.58–0.80] for expert 1 meaning a substantial agreement. The inter-rater reliability was very good (Fleiss’ κ value?=?0.94 [95% CI 0.87–1.0]) for 3-D exams. The Cohen’s κ was excellent for pleural effusion (κ=?0.93 [95% CI 0.76–1.0]), substantial for normal lung diagnosis (κ?=?0.68 [95% CI 0.51–0.86]) and interstitial syndrome (κ?=?0.62 [95% CI 0.45–0.80]) and fair for consolidation diagnoses (κ?=?0.47 [95% CI 0.30–0.64]). In ICU ventilated patients, there was a substantial concordance between 2-D and 3-D LUS with a good inter-rater reliability. However, the diagnosis concordance for lung consolidation is poor.     

Performance of a second generation pulmonary capnotracking system for continuous monitoring of cardiac output

Technologies for minimally-invasive cardiac output measurement in patients during surgery remain little used in routine practice. We tested a redeveloped system based on CO₂ elimination (VCO₂) by the lungs for use in ventilated patients, which can be seamlessly integrated into a modern anesthesia/monitoring platform, and provides automated, continuous breath-by-breath cardiac output monitoring. A prototype measurement system was constructed to measure VCO₂ and end-tidal CO₂ concentration with each breath. A baseline measurement of non-shunt cardiac output was made during a brief oscillating change in ventilator rate, according to the differential CO₂ Fick approach and repeated at 5–10 min intervals. Continuous breath-by-breath monitoring of cardiac output was performed between these intervals from measurement of VCO₂, using a derivation of the Fick equation applied to pulmonary CO₂ elimination and cardiac output displayed in real time. Measurements were compared with simultaneous measurements by thermodilution in 50 patients undergoing cardiac surgery or liver transplantation. Overall mean bias [sd] for agreement in cardiac output measurement was ??0.3 [1.1] L/min, percentage error?±?38.7%, intraclass correlation coefficient?=?0.91. Concordance in measurement of changes of at least 15% in cardiac output was 81.4%, with a mean angular bias of ??1.7°, and radial limits of agreement of ±?76.2° on polar plot analysis. The accuracy and precision compared favourably to other clinical techniques. The method is relatively seamless and automated and has potential for continuous, cardiac output monitoring in ventilated patients during anesthesia and critical care.