An evaluation of kurtosis beamforming in magnetoencephalography to localize the epileptogenic zone in drug resistant epilepsy patients

Objective

Kurtosis beamforming is a useful technique for analysing magnetoencephalograpy (MEG) data containing epileptic spikes. However, the implementation varies and few studies measure concordance with subsequently resected areas. We evaluated kurtosis beamforming as a means of localizing spikes in drug-resistant epilepsy patients.

Semaglutide,reduction in glycated haemoglobin and the risk of diabetic retinopathy

Aims

To evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme.

Materials and methods

The SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon‐like peptide‐1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2‐year, pre‐approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo. DR data from across the SUSTAIN trials were evaluated, and post hoc analyses of the SUSTAIN 6 data were conducted. These included subgroup analyses to identify at‐risk patients and a mediation analysis with initial change in glycated haemoglobin (HbA1c; percentage‐points at week 16) as a covariate, to examine the role of the magnitude of reduction in HbA1c as an intermediate factor affecting risk of DRC.

Results

There was no imbalance in DR adverse events across the SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c reduction during the first 16 weeks of treatment in patients who had pre‐existing DR and poor glycaemic control at baseline, and who were treated with insulin.

Conclusions

Early worsening of DR is a known phenomenon associated with the rapidity and magnitude of improvement in glycaemic control with insulin; the DRC findings in SUSTAIN 6 are consistent with this. Guidance regarding the early worsening of DR is recommended with insulin. Similar recommendations may be appropriate for semaglutide.     

Ten‐year trends in contact allergy to formaldehyde and formaldehyde‐releasers

Background

Preservatives such as formaldehyde and formaldehyde‐releasers are common causes of contact allergy.

Objectives

To examine trends in contact allergy to formaldehyde and formaldehyde‐releasers in patch tested patients in Denmark over a 10‐year period (2007‐2016), and to investigate relevant sources of formaldehyde among the patients.

Methods

A cross‐sectional registry study on patch test data from patients tested with formaldehyde and formaldehyde‐releasers (N = 8463) was performed. The presence of released formaldehyde in products from formaldehyde‐allergic patients was identified with chemical analyses (chromotropic acid or acetylacetone test).

Results

The prevalence of contact allergy to formaldehyde 1% was 1.5%, and ranged between 0.97% and 2.3%, with a decreasing trend in this 10‐year period. Contact allergy to formaldehyde 2% was found in 2.4%, and no significant trend was observed. Quaternium‐15 was the formaldehyde‐releaser most often positive (0.86%). Patients allergic to formaldehyde often had simultaneous positive patch test reactions to formaldehyde‐releasers (36%). Almost 63% of the patients with formaldehyde allergy used products that released formaldehyde; cosmetics were the most common sources.

Conclusions

Although contact allergy to formaldehyde 1% decreased in this 10‐year time period, contact allergies to formaldehyde and formaldehyde‐releasers overall remain frequent in patients. In most cases, formaldehyde‐allergic patients are exposed to ≥1 products containing formaldehyde. Improved regulation on permitted amounts of free formaldehyde in cosmetics is still warranted, including direct labelling of formaldehyde when it is present in small but relevant amounts.

     

Post-fracture Risk Assessment: Target the Centrally Sited Fractures First! A Substudy of NoFRACT

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1–SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm²), total hip (800 versus 876 mg/cm²), and lumbar spine (1024 versus 1062 mg/cm²); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2–SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1–SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

To describe the outcome of Dravet syndrome (DS) in adolescents and adults we conducted a longitudinal retrospective study of two independent cohorts of 34 adolescents (group 1) and 50 adults (group 2). In both cohorts, we collected information about genetic mutation, and semiology of seizures at onset and during disease course. At the last evaluation, we considered the following features: epilepsy (distinguishing myoclonic/complete and nonmyoclonic/incomplete phenotype), neurologic signs, intellectual disability (ID), and behavioral disorders. Moreover, in both cohorts, we performed a correlation analysis between early characteristics of the disease and the outcome of DS with regard to seizure persistence, ID, behavioral disorder, and neurologic impairment at last evaluation. Group 1 includes 22 adolescents with complete form of DS and 12 with incomplete form; group 2 includes 35 adults with complete form and 15 with incomplete form. The seizures persisted in 73.6% of adolescents and in 80% of adults, but epilepsy severity progressively decreased through age. Seizure persistence correlated with the complete phenotype and with the occurrence of reflex seizures. At last evaluation, ID was moderate or severe in 70.5% of adolescents and in 80% of adults. The most severe cognitive and motor impairment was observed in patients with persisting seizures. The severity of cognition, language, and neurologic impairment at last evaluation correlated statistically with the complete phenotype. The study confirms that the global outcome of DS is poor in most cases, albeit epilepsy severity decreases throughout adulthood. The improvement of epilepsy throughout ages is not associated with improvement in intellectual abilities and motor skills; this confirms that the unfavorable outcome is not a pure consequence of epilepsy.     

CDR2L Is the Major Yo Antibody Target in Paraneoplastic Cerebellar Degeneration

The pathogenesis of Yo‐mediated paraneoplastic cerebellar degeneration (PCD) is unclear. We applied cerebrospinal fluid and serum from PCD patients as well as CDR2 and CDR2L antibodies to neuronal tissue, cancer cell lines, and cells transfected with recombinant CDR2 and CDR2L to elucidate which is the major antigen of Yo antibodies. We found that Yo antibodies bound endogenous CDR2L, but not endogenous CDR2. However, Yo antibodies can bind the recombinant CDR2 protein used in routine clinical testing for these antibodies. Because Yo antibodies only bind endogenous CDR2L, we conclude that CDR2L is the major antigen of Yo antibodies in PCD. ANN NEUROL 2019;86:316–321     

Simultaneous detection of hepatocellular carcinoma and vessel thrombus by using SPIO-enhanced B-TFE with the T<Subscript>2</Subscript> preparation pulse technique

The purpose of this study was to compare between superparamagnetic iron oxide (SPIO)-enhanced three-dimensional balanced turbo field-echo (B-TFE) sequence with T₂ preparation pulse (T₂ prep) and T₂*-weighted imaging (T₂*WI) for the simultaneous detection of hepatocellular carcinoma (HCC) and vessel thrombus. For 1.5-T magnetic resonance imaging, SPIO was administered to 23 patients with a portal or venous tumor thrombus, and B-TFE with T₂ prep and T₂*WI were acquired. Regions of interest in the B-TFE and T₂*WI were selected for the tumor, liver, tumor thrombus, and vessels. The contrasts of the HCC in the liver and the tumor thrombus in the vessels were determined from clinical image. Contrast was calculated using the mean value of the signal intensity on the HCC to the liver and tumor thrombus to vessels. The mean contrasts between HCC and the liver with the use of B-TFE and T₂*WI were 0.61 ± 0.05 and 0.70 ± 0.04, respectively. The contrast of HCC to the liver was significantly higher in T₂*WI than in B-TFE (p < 0.05). The mean contrasts between the tumor thrombus and vessels with the use of B-TFE and T₂*WI were 0.28 ± 0.02 and 0.10 ± 0.02, respectively. The contrast of tumor thrombus in the vessels was higher in B-TFE than in T₂*WI (p < 0.01). Kupffer imaging can be used to assess liver function and acquire morphological images using three-dimensional B-TFE with T₂ prep. This technique would be helpful for simultaneous detection of HCC and tumor thrombus.