Identification and management of poor response to growth‐promoting therapy in children with short stature

Growth hormone (GH) is widely prescribed for children with short stature across a range of growth disorders. Recombinant human (rh) insulin‐like growth factor‐1 (rhIGF‐1) therapy is approved for severe primary IGF‐I deficiency – a state of severe GH resistance. Evidence is increasing for an unacceptably high rate of poor or unsatisfactory response to growth‐promoting therapy (i.e. not leading to significant catch up growth) in terms of change in height standard deviation score (SDS) and height velocity (HV) in many approved indications. Consequently, there is a need to define poor response and to prevent or correct it by optimizing treatment regimens within accepted guidelines. Recognition of a poor response is an indication for action by the treating physician, either to modify the therapy or to review the primary diagnosis leading either to discontinuation or change of therapy. This review discusses the optimal investigation of the child who is a candidate for GH or IGF‐1 therapy so that a diagnosis‐based choice of therapy and dosage can be made. The relevant parameters in the evaluation of growth response are described together with the definitions of poor response. Prevention of poor response is addressed by discussion of strategy for first‐year management with GH and IGF‐1. Adherence to therapy is reviewed as is the recommended action following the identification of the poorly responding patient. The awareness, recognition and management of poor response to growth‐promoting therapy will lead to better patient care, greater cost‐effectiveness and increased opportunities for clinical benefit.     

Should We Establish a New Protocol for the Treatment of Peripartum Myocardial Infarction?

Peripartum myocardial infarction is a rare event that is associated with high mortality rates. The differential diagnosis includes coronary artery dissection, coronary artery thrombosis, vascular spasm, and stenosis. Our evaluation of 2 cases over a 5-year time period has led to a hypothesis that peripartum myocardial infarction is an immune-mediated event secondary to coronary endothelial sensitization by fetal antigen. In our patients, we supplemented standard medical therapy with immunotherapy consisting of corticosteroids, plasmapheresis, and intravenous immunoglobulin. Herein, we present our most recent case-that of a 29-year-old black woman (gravida V, para IV), 2 weeks postpartum with no relevant medical history. She presented with a 1-week history of chest pain. Initial electrocardiographic and cardiac biomarkers were consistent with acute coronary syndrome. Echocardiography revealed reduced systolic function with inferior-wall hypokinesis. Angiography revealed diffuse disease with occlusion of the left anterior descending coronary artery not amenable to revascularization. We were successful in treating the myocardial infarction without the use of catheter-based interventions, by modifying the immunologic abnormalities. Two cases do not make a protocol. Yet we believe that this case and our earlier case lend credence to the hypothesis that peripartum myocardial infarction arises from sensitization by fetal antigens. This concept and the immune-modifying treatment protocol that we propose might also assist in understanding and treating other inflammatory-disease states such as peripartum cardiomyopathy and standard acute myocardial infarction. All of this warrants further investigation.     

WHITE MATTER INTEGRITY AND ITS RELATIONSHIP TO PTSD AND CHILDHOOD TRAUMA—A SYSTEMATIC REVIEW AND META‐ANALYSIS

Recent reviews and meta‐analyses reported structural gray matter changes in patients suffering from adult‐onset posttraumatic stress disorder (PTSD) and in subjects with and without PTSD who experienced childhood trauma. However, it remains unclear if such structural changes are also affecting the white matter. The aim of this systematic review is to provide a comprehensive overview of all empirical investigations measuring white matter integrity in populations affected by PTSD and/or childhood trauma. To this end, results from different methodological approaches were included. Twenty‐five articles are reviewed of which 10 pertained to pediatric PTSD and the effects of childhood trauma measured during childhood, seven to the effects of childhood trauma measured during adulthood, and eight to adult‐onset PTSD. Overall, reductions in white matter volume were reported more often than increases in these populations. However, the heterogeneity of the exact locations indicates only a weak overlap across published studies. In addition, a meta‐analysis was carried out on seven whole‐brain diffusion tensor imaging (DTI) studies in adults. Significant clusters of both increases and decreases were identified in various structures, most notably the cingulum and the superior longitudinal fasciculus. Future research directions are discussed.     

Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala

Major depression has been repeatedly associated with amygdala hyper‐responsiveness to negative (but not positive) facial expressions at early, automatic stages of emotion processing using subliminally presented stimuli. However, it is not clear whether this “limbic bias” is a correlate of depression or represents a vulnerability marker preceding the onset of the disease. Because childhood maltreatment is a potent risk factor for the development of major depression in later life, we explored whether childhood maltreatment is associated with amygdalar emotion processing bias in maltreated but healthy subjects. Amygdala responsiveness to subliminally presented sad and happy faces was measured by means of fMRI at 3 T in N = 150 healthy subjects carefully screened for psychiatric disorders. Childhood maltreatment was assessed by the 25‐item childhood trauma questionnaire (CTQ). A strong association of CTQ‐scores with amygdala responsiveness to sad, but not happy facial expressions emerged. This result was further qualified by an interaction of emotional valence and CTQ‐scores and was not confounded by trait anxiety, current depression level, age, gender, intelligence, education level, and more recent stressful life‐events. Childhood maltreatment is apparently associated with detectable changes in amygdala function during early stages of emotion processing which resemble findings described in major depression. Limbic hyper‐responsiveness to negative facial cues could be a consequence of the experience of maltreatment during childhood increasing the risk of depression in later life. Limitation: the present association of limbic bias and maltreatment was demonstrated in the absence of psychopathological abnormalities, thereby limiting strong conclusions. Hum Brain Mapp 34:2899–2909, 2013. © 2012 Wiley Periodicals, Inc.     

Delusional misidentification syndrome and other unusual delusions in advanced Parkinson's disease

BackgroundUnusual delusional syndromes are rare protean diseases with speculative etiopathogenic mechanisms.MethodsSeven consecutive patients with advanced PD were evaluated over a 15-year period at the Movement Disorders Unit in the Neurology Service, Hospital de Clínicas, Federal University of Paraná, and the Paraná State Parkinson's Patients Association.ResultsWe describe advanced Parkinson's disease patients presenting with unusual delusional syndromes, including cases of Ekbom, Othello, Capgras' and Diogenes syndromes, reduplicative paramnesia and mirrored-self misidentification.ConclusionThere are a few isolated reports of unusual neuropsychiatric disorders in patients with PD. We believe that these syndromes associated with advanced PD in elderly patients presenting with cognitive impairment and polypharmacy are probably often underestimated. Neurologists should be aware for these rare and treatable conditions.