Abstract Background Pediatric postoperative cerebellar mutism syndrome (CMS) is a rare but well-known complication of medulloblastoma (Mb) resection with devastating effects on expressive language, mobility, cognition, and emotional regulation that diminishes quality of life for many Mb survivors. The specific anatomical and neuronal basis of CMS remains obscure. We address this issue by identifying patterns of surgical damage and secondary axonal degeneration in Mb survivors with CMS. Methods Children with Mb deemed high risk for CMS based on intraventricular location of the tumor had T1 images analyzed for location(s) of surgical damage using a specially developed algorithm. We used three complementary methods of spatial analysis to identify surgical damage linked to CMS diagnosis. Magnetization transfer ratio (MTR) images were analyzed for evidence of demyelination in anatomic regions downstream of the cerebellum, indicating neuronal dysfunction. Results Spatial analyses highlighted damage to the fastigial nuclei and their associated cerebellar cortices as the strongest predictors of CMS. CMS-related MTR decrease was greatest in the ventral periaqueductal gray (PAG) area and highly consistent in the left red nucleus. Conclusion Our evidence points to disruption of output from the fastigial nuclei as a likely causal trigger for CMS. We propose that core CMS symptoms result from a disruption in the triggering of survival behaviors regulated by the PAG, including the gating of vocalization and volitional movement. The fastigial nuclei provide the densest output to the PAG from the cerebellum, thus sparing these structures may provide a greater likelihood of CMS prevention.
Advances in brain imaging have allowed for more sophisticated mapping of crucial neural structures. Functional MRI (fMRI) measures local changes in blood oxygenation associated with changes in neural activity and is useful in mapping cortical activation. Applications of this imaging modality have generally been restricted to cooperative patients; however, fMRI has proven successful in localizing the motor cortex for neurosurgical planning in uncooperative children under sedation. The authors demonstrate that the use of fMRI to localize the visual cortex in sedated children can be safely and effectively performed, allowing for more accurate presurgical planning to spare visual structures.Between 2007 and 2009, 11 children (age range 1-11 years) underwent fMRI for neurosurgical planning while under sedation. Blood oxygen level-dependent fMRI was performed to detect visual cortex activation during stimulation through closed eyelids. Visual stimulation was presented in block design with periods of flashing light alternated with darkness.Functional MRI was successful in identifying visual cortex in each of the 11 children tested. There were no complications with propofol sedation or the fMRI. All children suffered from epilepsy, 5 had brain tumors, and 1 had tuberous sclerosis. After fMRI was performed, 6 patients underwent surgery. Frameless stereotactic guidance was synchronized with fMRI data to design an approach to spare visual structures during resection. There were no cases where a false negative led to unexpected visual field deficits or other side effects of surgery. In 2 cases, the fMRI results demonstrated that the tracts were already disrupted: in one case from a prior tumor operation and in another from dysplasia.Functional MRI for evaluation of visual pathways can be safely and reproducibly performed in young or uncooperative children under light sedation. Identification of primary visual cortex aids in presurgical planning to avoid vision loss in appropriately selected patients.
Radiation necrosis, for which abnormal WM enhancement is a hallmark, is an uncommon complication of craniospinal irradiation in children with medulloblastoma. The magnetization transfer ratio measures macromolecular content, dominated by myelin in the WM. We investigated whether the pretreatment supratentorial (nonsurgical) WM magnetization transfer ratio could predict patients at risk for radiation necrosis after radiation therapy for medulloblastoma.
MATERIALS AND METHODS:
Ninety-five eligible patients with medulloblastoma (41% female; mean age, 11.0 [SD, 5.4] years) had baseline balanced steady-state free precession MR imaging before proton or photon radiation therapy. Associations among baseline supratentorial magnetization transfer ratio, radiation necrosis (spontaneously resolving/improving parenchymal enhancement within the radiation field)3, age, and the presence of visible brain metastases were explored by logistic regression and parametric/nonparametric techniques as appropriate.
RESULTS:
Twenty-three of 95 (24.2%) children (44% female; mean age, 10.7 [SD, 6.7] years) developed radiation necrosis after radiation therapy (19 infratentorial, 1 supratentorial, 3 both). The mean pretreatment supratentorial WM magnetization transfer ratio was significantly lower in these children (43.18 versus 43.50, P = .03). There was no association between the supratentorial WM magnetization transfer ratio and age, sex, risk/treatment stratum, or the presence of visible brain metastases.
CONCLUSIONS:
A lower baseline supratentorial WM magnetization transfer ratio may indicate underlying structural WM susceptibility to radiation necrosis and may identify children at risk for developing radiation necrosis after craniospinal irradiation for medulloblastoma.
This paper concerned nanocrystalline cellulose(NCC)’s isolation from microcrystalline cellulose(MCC) by sulfuric acid hydrolysis, meanwhile centrifuging, ultrasonic treatment and freeze-drying were carried out afterwards. It covered the effect of reaction conditions on the yield of NCC. It indicated that hydrolysis time was the factor that matters most and it was possible to obtain the largest yield with hydrolysis time being 108min, hydrolysis temperature being 43oC and sulfuric acid concentration being 33%. It also investigated the microcosmic morphology of NCC by Transmission Electronic Microscopy(TEM). MCC and NCC’s thermal properties were studied further.
Previous discovery that long-term administration of pentoxifylline (PTX) to mice chronically exposed to smoke led to the development of pulmonary fibrosis rather than emphysema initiated our curiosity on whether the Wnt/β-catenin pathway, a set of signaling proteins essential to organ development and lung morphogenesis in particular were activated in the pathogenesis of pulmonary fibrosis.Male BALB/c mice were randomized into four study groups: Group Sm, smoke exposure and taken regular forage; Group PTX, no smoke but taken PTX-rich forage; Group Sm + PTX, smoke exposure and taken PTX-rich forage; Group control: shamed smoke exposure and taken regular forage. Animals were sacrificed at day 120. Morphometry of the lung sections and the expressions of TGF-β(1), hydroxyproline, β-catenin, cyclin D1, T cell factor 1 (Tcf-1) and lymphoid enhancer factor 1 (Lef-1) mRNA, etc, in the lung homogenate or in situ were qualitatively or quantitatively analyzed.As expected, smoke exposure along with PTX administration for 120 days, lungs of the mice progressed to be a fibrosis-like phenotype, with elevated fibrosis score (3.9 ± 1.1 vs. 1.7 ± 0.6 in Group Sm, P < 0.05). TGF-β(1) (pg/g) (1452.4 ± 465.7 vs. 818.9 ± 202.8 in Group Sm, P < 0.05) and hydroxyproline (mg/g) (5.6 ± 0.6, vs. 2.4 ± 0.1 in Group Sm, P < 0.05) were also consistently increased. The upregulation of β-catenin measured either by counting the cell with positive staining in microscopic field (17.4 ± 7.9 vs. 9.9 ± 2.9 in Group Sm, P < 0.05) or by estimation of the proportion of blue-stained area by Masson's trichrome (11.8 ± 5.6 vs. 4.7 ± 2.4 in Group Sm) in Group SM + PTX was much more noticeable as than those in Group Sm. The expression of β-catenin measured by positive cell counts was correlated to TGF-β(1) concentration in lung tissue (r = 0.758, P < 0.001). PTX per se caused neither fibrosis nor emphysema though expression of β-catenin and downstream gene cyclin D(1) may also be altered by this medication.PTX mediated transformation of pulmonary emphysema into pulmonary fibrosis under chronic cigarette smoke exposure is associated with upregulation of β-catenin and elevation of TGF-β(1), implying that activation of Wnt/β-catenin signaling may be involved in the pathogenesis of pulmonary fibrosis.
Introduction: Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including ischemic lesions and neurocognitive dysfunction. Hydroxyurea has been utilized extensively for management of SCA, but its effects on brain function have not been established. Methods: We examined prospectively the effects of one year of treatment with hydroxyurea on brain function in a cohort of children with SCA (HbSS/HbSβ0-thalassemia) by baseline and exit evaluations, including comprehensive neurocognitive testing, transcranial Doppler ultrasound (TCD), and brain MRI [silent cerebral infarcts (SCI), gray matter cerebral blood flow (GM-CBF), and blood oxygen level dependent (BOLD) signal from visual stimulation]. Results: Nineteen patients with SCA, mean age 12.4 years (range 7.2-17.8), were evaluated. At baseline, subjects had these mean values: full scale IQ (FSIQ) 81.9, TCD velocity 133 cm/sec, GM-CBF 64.4 ml/100g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After one year of hydroxyurea, there were significant increases in FSIQ (+2.8, p=0.036) and reading comprehension (+4.8, p=0.016), a significant decrease in TCD velocity (-11.4 cm/sec, p=0.007), and no significant changes in GM-CBF, BOLD, or SCI frequency. Furthermore, FSIQ was associated with higher hemoglobin F (HbF) and lower GM-CBF, but not with hemoglobin level. Discussion: Significant improvement of neurocognition and decreased TCD velocity following one year of treatment support the use of hydroxyurea for improving neurocognitive outcomes in SCA. Understanding the mechanisms of benefit, as indicated by relationships of neurocognitive function with HbF, hemoglobin, and CBF, requires further evaluation.
Abstract INTRODUCTION Craniopharyngioma accounts for approximately 4% of childhood central nervous system tumors and has a 5-year overall survival rate exceeding 90%. Survivors of childhood craniopharyngioma may experience neurologic sequalae, including visual and fine motor deficits, and subclinical hearing loss associated with tumor and treatment. Contemporary treatment includes radical surgery or more limited surgery and proton radiotherapy (PRT). Here we report on a longitudinal fMRI study probing visual, auditory, and motor function in pediatric craniopharyngioma patients. METHOD: The study (NCT01419067) was IRB approved and informed consent was obtained for each patient. Functional MR images were acquired at 4 time points: after surgery and before PRT (TP1), and 18-months (TP2), 36-months (TP3), and 60-months (TP4) after PRT. Data from a sensory survey fMRI task (visual: flashing checkerboard; auditory: dissonant ascending/descending pure tones; and sensory/motor: button pushing when stimuli were on) for 67 patients were analyzed at the 4 time points. The median age was 11.7 years (range 8.3-20.2 years) and the female/male ratio was 37/30. RESULTS Significant brain activation was seen in visual cortices, auditory cortices, and supplementary motor area (SMA) and motor cortices for all 4 time points. Over the time, visual and motor cortices showed minimum changes in activation; however, there was a small increase in SMA. For the auditory cortices, the activation volume in Heschl’s gyri increased bilaterally, and the lateralization index decreased (TP1: 70%; TP2: 46%; TP3: 39%; and TP4: 26%) due to larger increases in the right Heschl’s gyrus. CONCLUSION Increasing activation in Heschl’s gyri, especially on the right side, after PRT suggests decreasing efficiency in distinguishing tones in these patients. These findings may be associated with late effects involving the specific gyri or neuropathways affected by surgery or irradiation.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(144 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(216 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(288 450 300)'/%3e%3c/svg%3e)