ABSTRACT
A 7-Year-Old Boy with Fever and Dark UrineA 7-year-old boy with surgically repaired tetralogy of Fallot presented for evaluation of fever and dark urine. How do you approach the evaluation, and what is the diagnosis?
Subject(s)
Tetralogy of Fallot , Male , Humans , Child , Tetralogy of Fallot/diagnosis , FeverABSTRACT
Establishment of the corpus callosum involves coordination between callosal projection neurons and multiple midline structures, including the glial wedge (GW) rostrally and hippocampal commissure caudally. GW defects have been associated with agenesis of the corpus callosum (ACC). Here we show that conditional Lhx2 inactivation in cortical radial glia using Emx1-Cre or Nestin-Cre drivers results in ACC. The ACC phenotype was characterized by aberrant ventrally projecting callosal axons rather than Probst bundles, and was 100% penetrant on 2 different mouse strain backgrounds. Lhx2 inactivation in postmitotic cortical neurons using Nex-Cre mice did not result in ACC, suggesting that the mutant phenotype was not autonomous to the callosal projection neurons. Instead, ACC was associated with an absent hippocampal commissure and a markedly reduced to absent GW. Expression studies demonstrated strong Lhx2 expression in the normal GW and in its radial glial progenitors, with absence of Lhx2 resulting in normal Emx1 and Sox2 expression, but premature exit from the cell cycle based on EdU-Ki67 double labeling. These studies define essential roles for Lhx2 in GW, hippocampal commissure, and corpus callosum formation, and suggest that defects in radial GW progenitors can give rise to ACC.
Subject(s)
Agenesis of Corpus Callosum/genetics , Agenesis of Corpus Callosum/pathology , LIM-Homeodomain Proteins/genetics , Mutation/genetics , Neuroglia/pathology , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/pathology , Transcription Factors/genetics , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Disease Models, Animal , Female , Glial Fibrillary Acidic Protein/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Ki-67 Antigen/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neocortex/pathology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nestin/genetics , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Repressor Proteins/metabolism , T-Box Domain Proteins , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolismABSTRACT
When healthy subjects undergo brain imaging, incidental findings are not rare. The optimal response to such findings has been the focus of considerable discussion. The current report describes the operations and results of a system that provides a review of incidental findings by an appropriate medical professional. A web-based system was created whereby investigators performing brain MRI scans on healthy subjects could refer images with suspected concerns to a board certified radiologist who had a Certificate of Added Qualification in Neuroradiology. The specific details of this system are described. Among 27 scans suspected by an investigator of having a significant finding, all but one were referred by a researcher with a PhD. The most common concerns described by these investigators were for the possible presence of a cyst or of enlarged ventricles. The most common findings reported by the radiologist were Virchow-Robin spaces and cysts. Findings were generally of low clinical significance, with 1 major exception. Identifying the optimal response to incidental findings in neuroimaging research remains a challenge. The current report describes a system for providing expert assistance and so addresses these issues in the setting of suspected incidental findings. To our knowledge the current system is the first to provide a specific means for evaluation of incidental findings in neuroimaging research.