ABSTRACT
Our laboratory and others have reported the ability to detect individual Alzheimer's disease (AD) amyloid plaques in transgenic mouse brain in vivo by magnetic resonance imaging (MRI). Since amyloid plaques contain iron, most MRI studies attempting to detect plaques in AD transgenic mouse brain have employed techniques that exploit the paramagnetic effect of iron and have had mixed results. In the present study, using five-way anatomic spatial coregistration of MR images with three different histological techniques, properties of amyloid plaques in AD transgenic mouse brain were revealed that may explain their variable visibility in gradient- and spin-echo MR images. The results demonstrate differences in the visibility of plaques in the cortex and hippocampus, compared to plaques in the thalamus, by the different MRI sequences. All plaques were equally detectable by T(2)SE, while only thalamic plaques were reliably detectable by T(2)*GE pulse sequences. Histology revealed that cortical/hippocampal plaques have low levels of iron while thalamic plaques have very high levels. However, the paramagnetic effect of iron does not appear to be the sole factor leading to the rapid decay of transverse magnetization (short T(2)) in cortical/hippocampal plaques. Accordingly, MRI methods that rely less on iron magnetic susceptibility effect may be more successful for eventual human AD plaque MR imaging, particularly since human AD plaques more closely resemble the cortical and hippocampal plaques of AD transgenic mice than thalamic plaques.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/pathology , Plaque, Amyloid/pathology , Alzheimer Disease/metabolism , Amyloid Precursor Protein Secretases/genetics , Animals , Cerebral Cortex/anatomy & histology , Cerebral Cortex/pathology , Hippocampus/anatomy & histology , Hippocampus/pathology , Humans , Iron/metabolism , Magnetic Resonance Imaging/methods , Mice , Mice, Transgenic , Organ Specificity , Thalamus/anatomy & histology , Thalamus/pathologyABSTRACT
OBJECTIVE: To evaluate the prevalence of obstructive sleep apnea in a large population of children with achondroplasia and to evaluate the effectiveness of adenoidectomy and/or tonsillectomy as treatment. METHODS: Retrospective review of 95 children with achondroplasia. RESULTS: Thirty-six patients (38%) had clinical evidence of obstructive sleep apnea. Thirty-four patients underwent surgery, with more than 1 procedure required in 10 children (29%). Adenotonsillectomy was the initial procedure for 22 of 34 patients, and further therapy was required in only 18% of this group. Adenoidectomy was the initial procedure for 10 of 34, with 90% requiring further surgery for recurrent obstructive sleep apnea. Tonsillectomy alone was performed in 2 patients: 1 was effectively treated and 1 later required adenoidectomy. Endotracheal intubation was accomplished in all patients without complication; 53% required a smaller endotracheal tube than would be predicted by their age. Eight postoperative complications were recorded. CONCLUSIONS: Obstructive sleep apnea is very common in children with achondroplasia. Surgery is effective, but recurrent symptoms are common, particularly when the initial procedure is adenoidectomy. The complication rate is higher than that observed in a general pediatric population but is readily managed with standard therapy. Anesthesia can be given safely to these patients with special consideration for limited neck extension and appropriate endotracheal tube size.