Childhood Obstructive Sleep Apnea Associates with Neuropsychological Deficits and Neuronal Brain Injury

BACKGROUND: Childhood obstructive sleep apnea (OSA) is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function. METHODS AND FINDINGS: We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6–16 y) group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared. Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency). Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001) and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03). CONCLUSIONS: Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential

Sequential diffusion-weighted magnetic resonance imaging study of lysophosphatidyl choline-induced experimental demyelinating lesion: an animal model of multiple sclerosis

Purpose: To differentiate the surrounding edema from the focal demyelinating lesion during the early phase of the lesion using an apparent diffusion coefficient (ADC), and to monitor the changes in ADCs during the complete progression of a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion, an animal model of multiple sclerosis (MS). Material and Methods: Eighteen rats divided into two groups-demyelinating lesion (group I, N = 12) and vehicle group (saline injected; group II, N = 6)-were studied. A 0.2-μl quantity of 1% LPC solution in isotonic saline was injected in the rat brain internal capsule (IC) area to create the demyelinating lesion. Six rats were used exclusively for histology. Diffusion-weighted (DW) images were acquired at different diffusion weightings on the 3rd, 5th, 10th, 15th, and 20th days after LPC injection. ADC was measured from three regions of interest (ROIs) within the IC: focal demyelinating lesion (area A), surrounding area of the lesion (area B), and contralateral IC area (area C). Results: Histology revealed demyelination of the IC area during the early phase of lesion progression up to day 10 and remyelination thereafter. Elevated ADCs were observed for the surrounding edematous area (area B), compared to the focal demyelinating lesion (area A) during the early phase of the demyelination process, while substantial reduction of ADCs was noticed during remyelination for both regions. Conclusion: Measurement of ADC showed clear differentiation of the surrounding edema from the LPC-induced focal demyelinating lesion in rats, especially during the early phase of the lesion progression

Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rats

Free radicals have been implicated in neuronal injury during ischemia reperfusion in stroke. Therefore, in the present study, melatonin, a potent antioxidant, was studied in male Wistar rats subjected to 2 h of transient middle cerebral artery occlusion. Melatonin (10, 20 and 40 mg/kg i.p.) was administered four times in an animal at the time of middle cerebral artery occlusion, 1 h after middle cerebral artery occlusion, at the time of reperfusion and 1 h after reperfusion. Two hours after reperfusion, rats were euthanized for estimation of oxidative stress markers (malondialdehyde and reduced glutathione). The doses of 20 and 40 mg/kg of melatonin significantly attenuated the raised level of malondialdehyde (287±28, 279±52 nmol/g wet tissue, respectively) as compared to the levels (420±61 nmol/g wet tissue) in vehicle-treated middle cerebral artery-occluded rats. There was an insignificant change in levels of reduced glutathione at these doses (95±42, 88.7±36 μg/g wet tissue, respectively) as compared to those in the vehicle-treated middle cerebral artery-occluded rats (108.21±21 μg/g wet tissue). However, there was an insignificant difference between 20 and 40 mg/kg treated rats. Therefore, the dose of 20 mg/kg i.p. was used to evaluate the neuroprotective effect by using diffusion-weighted imaging (30 min after reperfusion), assessing the neurological deficit (24 h after middle cerebral artery occlusion) and estimating oxidative stress markers (72 h after middle cerebral artery occlusion). In the 20 mg/kg melatonin-treated group, percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated (9.8±3.9) as compared to that in the vehicle-treated group (21.4±4.7). The neurological deficit was significantly improved in the melatonin group (1.8±0.06) as compared to that in the vehicle-treated (2.9±0.38) group. The level of malondialdehyde (321.4±31 nmol/g wet tissue) and reduced glutathione (142.6±13 μg/g wet tissue) in the melatonin-treated group was also significantly decreased as compared to the level of malondialdehyde (623±22 nmol/g wet tissue) and reduced glutathione (226.6±19 μg/wet tissue) in the vehicle-treated group. The present study indicates that melatonin has a neuroprotective action in focal ischemia, which may be attributed to its antioxidant property

Protective role of cyclosporine in experimental unilateral blunt testicular trauma: evaluation by <SUP>31</SUP>P MR spectroscopy

Magnetic resonance (MR) imaging is a useful tool to study the anatomy of the testis while <SUP>31</SUP>P magnetic resonance spectroscopy (MRS) provides a non-invasive alternative method to demonstrate the metabolic status of testes. This study was designed to test whether the protective role of cyclosporine in experimental unilateral blunt testicular trauma (UBTT) could be assessed by <SUP>31</SUP>P MRS. Male Wistar rats ( n=30) aged 20 days were randomised into group I (sham surgery), group II (UBTT) and group III (UBTT and cyclosporine for 7 days). Contralateral testicles of 5 rats from each group was evaluated by <SUP>31</SUP>P MRS at 30 and 60 days of age and phosphomonoesters (PM), phosphodiesters (PD), and adenosine triphosphate (ATP) levels were measured. At 60 days of age the PM/ATP ratio was 0.32±0.08 in group I whereas it was 0.68±0.31 in the group II ( p &lt; 0.05). Group III rats showed PM, PD and PM/ATP ratios similar to the controls. In conclusion, it is observed that UBTT causes contralateral testicular damage which could be prevented by short-term cyclosporine treatment and <SUP>31</SUP>P MRS is an excellent modality for such an evaluation

Evidence for Cortical Dysfunction and Widespread Manganese Accumulation in the Nonhuman Primate Brain following Chronic Manganese Exposure: A 1H-MRS and MRI Study

Exposure to high levels of manganese (Mn) is known to produce a complex neurological syndrome with psychiatric disturbances, cognitive impairment, and parkinsonian features. However, the neurobiological basis of chronic low-level Mn exposure is not well defined. We now provide evidence that exposure to levels of Mn that results in blood Mn concentrations in the upper range of environmental and occupational exposures and in certain medical conditions produces widespread Mn accumulation in the non-human primate brain as visualized by T1-weighted magnetic resonance imaging. Analysis of regional brain Mn distribution using a ‘‘pallidal index equivalent’ ’ indicates that this approach is not sensitive to changing levels of brain Mn measured in post-mortem tissue. Evaluation of longitudinal 1H-magnetic resonance spectroscopy data revealed a significant decrease (p 0.028) in the N-acetylaspartate (NAA)/creatine (Cr) ratio in the parietal cortex and a near significant decrease (p 0.055) in frontal white matter (WM) at the end of the Mn exposure period relative to baseline. Choline/Cr or myo-Inositol/Cr ratios did not change at any time during Mn exposure. This indicates that the changes in the NAA/Cr ratio in the parietal cortex are not due to changes in Cr but in NAA levels. In summary, these findings suggest that during chronic Mn exposure a significant amount of the metal accumulates not only in the basal ganglia but also in WM and in cortical structures where it is likely to produce toxic effects. This is supported by a significantly decreased, in the parietal cortex, NAA/Cr ratio suggestive of ongoing neuronal degeneration or dysfunction

Single Voxel Image from the Left Hippocampus in an 11-y-Old Normal Male Child

<p>Blue areas are outer volume suppression bands that improve the accuracy of the hippocampal signal by suppressing surrounding lipid signal. On the right is a spectroscopy signal from a 11 year old male child, the spectrum demonstrating peaks from NAA, Cho, and Cr.</p

Hippocampal Neuronal NAA/Cho Metabolites Are Decreased in Children with OSA aged 9–16 y

<p>The ratio of NAA to Cho is decreased in the hippocampus of OSA patients compared to normal children.</p