Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1

Aim Difficulties in neurocognition and social interaction are the most prominent causes of morbidity and long‐term disability in children with neurofibromatosis type 1 (NF1). Symptoms of attention‐deficit–hyperactivity disorder (ADHD) have also been extensively recognized in NF1. However, systematic evaluation of symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited. Method We present a retrospective, cross‐sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD. Results Sixty‐six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5y 4mo). Forty percent of our NF1 sample had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T ≥ 60), and 14% reached levels consistent with those seen in children with ASDs (T ≥ 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral disorders. There was a statistically significant relationship between symptoms of ADHD and ASD (χ²=9.11, df=1, p=0.003, φ=0.56). Particularly salient were the relationships between attention and hyperactivity deficits, with impairments in social awareness and social motivation. Interpretation We found that symptoms of ASD in our NF1 population were raised, consistent with previous reports. Further characterization of the specific ASD symptoms and their impact on daily function is fundamental to the development and implementation of effective interventions in this population, which will probably include a combination of medical and behavioral approaches.     

DIFFERENTIAL RECALL BIAS AND SPURIOUS ASSOCIATIONS IN CASE/CONTROL STUDIES

Consider a case/control study designed to investigate a possible association between exposure to a putative risk factor and development of a particular disease. Let E denote the information required to specify a subject's exposure to the risk factor. We examine the effect that errors in the recorded values of E (which we denote by E^*) have on inferences of an association between disease and the risk factor. We concentrate on situations where the errors in recorded exposure are such that exposure is underestimated for controls and overestimated for cases. This phenomenon is referred to as differential recall bias and may lead to spurious inferences of an association between exposure and disease. We describe how the standard inferential techniques used in the analysis of data from case/control studies may be adjusted to take account of specified mechanisms whereby E is distorted to produce E^*. Such adjustments may be used to determine the sensitivity of an analysis to the phenomenon of differential recall bias and to quantify the extent of such bias that would be required to overturn the conclusions of the analysis. There remains the matter of judging whether a given distortion mechanism is reasonable in a particular context. This emphasizes the need for investigators to take account of differential recall bias in validation studies of exposure assessment techniques. The methodology developed here is applied to a recent major study investigating the possible association between lung cancer and exposure to environmental tobacco smoke. The log-odds ratio of 0⋅23 based on recorded exposure differs significantly from 0 (p<0⋅02). However, the association is rendered non-significant by a very modest degree of differential recall bias. For example, if 3⋅8 per cent of exposed controls report no exposure, 3⋅8 per cent of unexposed cases report exposure, and all other subjects report exposure accurately, the log-odds ratio drops to 0⋅07 and the corresponding p-value increases to 0⋅49.     

Integration of Merged Delayed‐Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study

MDCT/MRI Fusion for the Guidance of VT Ablation . Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar‐related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D‐mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation. Methods: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D‐mapping systems and registered to high‐density endocardial and epicardial maps. Low‐voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall‐thinning (WT) at MDCT. Results: Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall‐thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). Conclusion: The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high‐spatial resolution to better define structure–function relationship in scar‐related VT. (J Cardiovasc Electrophysiol, Vol. 24, pp. 419‐426, April 2013)     

Intermittent Capture of the Left Bundle With Permanent His Bundle Pacing: Mechanistic Insights and Implications for an Emerging Field

We present a case of a patient with elevated His lead capture thresholds and intermittent recruitment of the left bundle. The patient underwent a noninvasive electrophysiology study and was determined to have a left bundle branch block due to postrepolarization refractoriness. The nature of bundle branch block can have important implications for optimal patient selection and device programming in the emerging field of His bundle pacing.     

Coeliac disease,epilepsy, and cerebral calcifications: association with TG6 autoantibodies

A 4‐year‐old boy presented with occipital seizures but normal initial neuroimaging and proved refractory to antiepileptic medications. On repeat neuroimaging after 1 year, he had developed bi‐occipital calcification and was then found to have positive coeliac serology. He was diagnosed with coeliac disease, epilepsy, and cerebral calcifications (CEC) and became seizure free after starting the gluten‐free diet. Positive antibody binding to neurons and glia was demonstrated on indirect immunofluorescence. High levels of immunoglobulin‐A directed against transglutaminase isoenzyme 6 (TG6) were found in the patient’s serum. The positive response to the diet, TG6 antibodies, and neuronal antibody binding suggest that CEC might be autoimmune in nature, as in other extra‐intestinal manifestations of gluten‐related diseases, such as gluten ataxia.     

Cutaneous Alternariosis in an Adolescent Patient

Abstract:  Cutaneous alternariosis is a rare infection typically observed only in immunocompromised adults, but we report here that the infection can occur in apparently healthy adolescents. We saw a clinically healthy adolescent boy who presented with cutaneous alternariosis 6 weeks after suffering a laceration to his right ankle. Treatment with itraconazole resulted in significant improvement after 1 month.