Abstract Breakdown of neuro-glial N -acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused ...by mutations to the sole NAA catabolizing enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to define NAA function, with available evidence suggesting NAA serves as an acetyl donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic hallmark of Canavan disease, which contrasts with a broad spectrum of alternative neurodegenerative contexts in which levels of NAA are inversely proportional to pathological progression. Recently generated data in the nur7 mouse model of Canavan disease suggests loss of aspartoacylase function results in compromised energetic integrity prior to oligodendrocyte death, abnormalities in myelin content, spongiform degeneration, and motor deficit. The present study utilized a next-generation “oligotropic” adeno-associated virus vector (AAV-Olig001) to quantitatively assess the impact of aspartoacylase reconstitution on developmental myelination. AAV-Olig001-aspartoacylase promoted normalization of NAA, increased bioavailable acetyl-CoA, and restored energetic balance within a window of postnatal development preceding gross histopathology and deteriorating motor function. Long-term effects included increased oligodendrocyte numbers, a global increase in myelination, reversal of vacuolation, and rescue of motor function. Effects on brain energy observed following AAV-Olig001-aspartoacylase gene therapy are shown to be consistent with a metabolic profile observed in mild cases of Canavan disease, implicating NAA in the maintenance of energetic integrity during myelination via oligodendroglial aspartoacylase.
Imaging of Pediatric Hearing Loss Shekdar, Karuna V; Bilaniuk, Larissa T
Neuroimaging clinics of North America,
02/2019, Letnik:
29, Številka:
1
Journal Article
Recenzirano
Temporal bone high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging are valuable tools in the evaluation of pediatric hearing loss. Computed tomography is important in the ...evaluation of pediatric conductive hearing loss and is the imaging modality of choice for evaluation of osseous abnormalities. MR imaging is the modality of choice for evaluation of sensorineural hearing loss. A broad spectrum of imaging findings can be seen with hearing loss in children. HRCT and MR imaging provide complementary information and are often used in conjunction in the preoperative evaluation of pediatric candidates for cochlear implantation.
Metastatic involvement of brain is rare in neuroblastoma (NB). We retrospectively evaluated conventional and advanced imaging and clinical findings of seven patients with secondary intra-axial brain ...NB metastases.
Magnetic resonance imaging and computed tomography examinations of patients with metastatic brain NB were reviewed. Recent iodine-123 metaiodobenzylguanidine ((123)I-MIBG) scans were also reviewed. A medical record review was performed for relevant clinical, laboratory, histopathologic, and genetic data.
Mean age at the time of primary tumor diagnosis was 35 months, and all were considered high-risk NB at diagnosis. Mean time interval between diagnosis and brain involvement was 23.2 months. Extensive prior extra-central nervous system (CNS) disease was present in all patients, but concomitant extra-CNS disease at the time of brain involvement was absent in three (43%) patients. Various forms of disease, including intraparenchymal, intraventricular, and leptomeningeal lesions were detected. Most intraparenchymal lesions were supratentorial and hemorrhagic; however, hemorrhage was absent in multiple leptomeningeal nodules in one patient. Contrast enhancement of lesions was present on all contrast-enhanced studies. Restricted diffusion of lesions was present in two patients. Arterial spin labeling (ASL) perfusion in two patients also revealed increased cerebral blood flow. Recent (123)I-MIBG scans were available in four patients and showed lesions in two patients with larger metastases but failed to demonstrate lesions in another two patients with smaller lesions.
Brain metastases of NB are often supratentorial and hemorrhagic and demonstrate contrast enhancement. Diffusion-weighted imaging can show restricted diffusion. ASL images may reveal increased perfusion. MIBG scans may not show smaller brain metastases.
Cerebroretinal microangiopathy with calcification and cysts is a multisystem autosomal-recessive disorder in which there is an obliterative angiopathy of small vessels, primarily in the brain, ...retina, and gastrointestinal tract. We present the case of a 14-year-old boy with cerebroretinal microangiopathy with calcification and cysts illustrating the classic occlusive retinal telangiectasias. His condition was diagnosed using multiple imaging modalities, including upper gastrointestinal endoscopy of the upper gastrointestinal tract, magnetic resonance imaging, optical coherence tomography, and fluorescein angiography.
Objective The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin ...transfusion syndrome (TTTS). Study Design This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. Results There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) ( P = 1.0, odds ratio OR 1, 95% confidence interval CI 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) ( P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) ( P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) ( P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) ( P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality ( P = .055, OR 3.025/point) by logistic regression analysis. Conclusion The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.
In a 2-year-old girl with signs and symptoms of a posterior fossa tumor, the computed tomographic scan showed what appeared to be a brain stem glioma. However, magnetic resonance imaging (MRI) ...demonstrated the lesion to be extrinsic to the brain stem. Posterior fossa exploration disclosed a medulloblastoma filling the 4th ventricle. This discrepancy in imaging techniques points out the usefulness of MRI in the evaluation and treatment of posterior fossa lesions.
Thirty-two cases of proved pineal tumor were analyzed. Calcification was seen in 75%. The size, character, and position of the calcification were useful indicators of abnormality on plain-film ...evaluation. Fray's cranioangle method was more sensitive than Oon's method in determining abnormal position of the calcified pineal tumor on the lateral skull film. Most calcifications were displaced postero-inferiorly or inferiorly, which can be explained by obstructive hydrocephalus or direct tumor expansion.
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