Sleep Disturbances in Alzheimer’s and Parkinson’s Diseases

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders and exact a burden on our society greater than cardiovascular disease and cancer combined. While cognitive and motor symptoms are used to define AD and PD, respectively, patients with both disorders exhibit sleep disturbances including insomnia, hypersomnia and excessive daytime napping. The molecular basis of perturbed sleep in AD and PD may involve damage to hypothalamic and brainstem nuclei that control sleep-wake cycles. Perturbations in neurotransmitter and hormone signaling (e.g., serotonin, norepinephrine and melatonin) and the neurotrophic factor BDNF likely contribute to the disease process. Abnormal accumulations of neurotoxic forms of amyloid β-peptide, tau and α-synuclein occur in brain regions involved in the regulation of sleep in AD and PD patients, and are sufficient to cause sleep disturbances in animal models of these neurodegenerative disorders. Disturbed regulation of sleep often occurs early in the course of AD and PD, and may contribute to the cognitive and motor symptoms. Treatments that target signaling pathways that control sleep have been shown to retard the disease process in animal models of AD and PD, suggesting a potential for such interventions in humans at risk for or in the early stages of these disorders.     

Cingulate gyrus morphology in children and adolescents with fetal alcohol spectrum disorders

Alcohol consumption during pregnancy can lead to a variety of cognitive and other birth defects, collectively termed fetal alcohol spectrum disorders (FASD), and including the Fetal Alcohol Syndrome (FAS). This study examined the impact of gestational alcohol exposure on the morphology of the cingulate gyrus, given this region's role in cognitive control, attention, and emotional regulation, all of which are affected in children with FASD. Thirty-one youth (ages 8–16) with histories of heavy prenatal alcohol exposure (n = 21) and demographically matched comparison subjects (n = 10) underwent structural magnetic resonance imaging. The cingulate gyrus was manually delineated, and parcellated volumes of grey and white matter were compared across groups. Alcohol-exposed individuals had significantly smaller raw cingulate grey matter, white matter, and tissue volumes compared with controls. After adjustment for respective cranial tissue constituents, only white matter volumes remained significantly reduced, and this held regardless of whether or not the child qualified for a diagnosis of FAS. A correlation between posterior cingulate grey matter volume and the WISC-III Freedom from Distractibility Index was also observed in alcohol-exposed children. These data suggest that cingulate white matter is compromised beyond global white matter hypoplasia in alcohol-exposed individuals, regardless of FAS diagnosis. The observed volumetric reductions in the cingulate gyrus may contribute to the disruptive and emotionally dysregulated behavioral profile commonly observed in this population.     

Anterior, Total, and Two-Stage Corpus Callosum Section: Differential and Incremental Seizure Responses

Summary: Published reports suggest that control of generalized seizures is improved by callosotomy but do not necessarily indicate that completion of failed anterior callosotomy is beneficial. We studied 42 patients after anterior callosotomy and 22 after total callosotomy, of whom 14 underwent a two-stage procedure. Cure or marked diminution of seizures was most dramatic for atonic and tonic-clonic seizures after anterior callosotomy (100 and 83%), and for tonic-clonic and tonic seizures after total callosotomy (68 and 57%). For the 14 patients who failed to improve after anterior section and then underwent total section, incremental responses were noted for all seizure types, with cure or marked diminution of partial seizures in 2 of 14 patients, of tonic-clonic seizures in 6 of 10, of tonic seizures in 2 of 4, of atonic seizures in 2 of 5, and of myoclonic seizures in 1 of 1. More than two seizure types, verbal IQ <80, and diffuse ictal EEG patterns were significantly more common in the anterior callosotomy failures. Total callosotomy can be of benefit when anterior callosotomy fails, especially for persistent tonic- clonic and tonic seizures, and will most often be necessary in patients with diffuse cerebral abnormalities.     

血浆置换显示干细胞移植后环孢素A引起的微血管病溶血性贫血和利福平的相应颜色反应

患者为1例39岁女性,患T/NK细胞淋巴瘤,在外周血异基因干细胞移植后15天,发生环孢素A(CSA)毒性相关的微血管病溶血性贫血(MAHA).因血清肌酐从移植前的0.4mg/dL,上升至移植后第9和15天的1.0和2.9 mg/dL.故停用CSA.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

Presenilins and APP in neuritic and synaptic plasticity: implications for the pathogenesis of Alzheimer's disease

A key neuropathological hallmark of Alzheimer’s disease (AD) is the loss of neocortical and hippocampal synapses, which is closely correlated with the degree of memory impairment. Mutations in the genes encoding the amyloid precursor protein (APP) and presenilins are responsible from some cases of early-onset autosomal-dominant AD. This article reviews the current understanding of how alterations in the cellular functions of APP and presenilins may result in the dysfunction and degeneration of synapses in AD. APP mutations result in increased production/aggregation of amyloid β-peptide (Aβ), which induces oxidative stress, resulting in the impairment of synaptic membrane ion, glutamate, and glucose transporters. APP mutations may also compromise the production and/or function of secreted forms of APP that are believed to play important roles in learning and memory processes. Presenilin (PS1) mutations result in a major defect in endoplasmic reticulum (ER) calcium regulation, which may perturb synaptic function in ways that lead to impaired synaptic plasticity and neuronal degeneration. Studies in transgenic mice that express APP and PS1 mutations have provided evidence that the mutations result in altered cellular calcium homeostasis and synaptic plasticity, and impaired learning and memory. This article provides a brief review of the pathophysiological interactions of APP and presenilins with synaptic proteins, and discusses how AD-linked mutations in APP and PS1 may disrupt synaptic processes that contribute to memory formation.