The challenges in scoring hypopneas in children: is pulse wave amplitude drop the answer?

BackgroundIdentifying electroencephalogram (EEG) cortical arousals are crucial in scoring hypopneas and respiratory efforts related arousals (RERAs) during a polysomnogram. As children have high arousal threshold, many of the flow limited breaths or hypopneas may not be associated with visual EEG arousals, hence this may lead to potential underestimation of the degree of sleep disordered breathing. Pulse wave amplitude (PWA) is a signal obtained from finger photoplethysmography which correlates directly to finger blood flow. The drop in PWA has been shown to be a sensitive marker for subcortical/autonomic and cortical arousals. Our aim was to use the drop in PWA as a surrogate for arousals to guide scoring of respiratory events in pediatric patients.MethodsTen polysomnograms for patients between the ages of 5–15 years who had obstructive apnea-hypopnea indices between 1 and 5 events/hour were identified. Patients with syndromes were excluded. A drop in PWA signal of at least 30% that lasted for 3 s was needed to identify subcortical/autonomic arousals. Arousals were rescored based on this criteria and subsequently respiratory events were rescored. Paired t-tests were employed to compare PSG indices scored with or without PWA incorporation.ResultsThe sample of 10 children included 2 females, and the average age was 9.8 ± 3.1 years. Overall, polysomnography revealed an average total sleep time of 464.1 ± 25 min, sleep efficiency of 92% +/−4.2, sleep latency of 19.6 ± 17.0 min, rapid eye movement (REM) latency 143 ± 66 min, N1 3.9% +/−2.0, N2 50.3% +/−12.0, N3 28.2% +/−9.1, REM 16.7% +/−4.0, and wakefulness after sleep onset (WASO) 18.1 ± 7.5 min. Including arousals from PWA changes, respiratory indices significantly increased including total AHI (2.3 ± 0.7 vs 5.7 ± 2.1, p < 0.001), obstructive AHI (1.45 ± 0.7 vs 4.8 ± 1.8, p < 0.001), and RDI (2.36 ± 0.7 vs 7.6 ± 2.0, p < 0.001). Likewise, total arousal index was significantly higher (8.7 ± 2.3 vs 29.4 ± 6.5, p < 0.001).ConclusionsThe drop in pulse wave amplitude signal is a useful marker to guide scoring arousals that are not otherwise easily identified in pediatric polysomnography and subsequently helped in scoring respiratory events that otherwise would not be scored. Further studies are needed to delineate if such methodology would affect clinical outcome.     

Spinal neuronal inhibition and EEG synchrony by electrical stimulation in subcortical forebrain regions of the cat

Summary In cats anaesthetized with sodium pentobarbital and 70% N₂O, single lumbar dorsal horn neurons were excited by controlled noxious radiant heating of glabrous hindpaw skin. The EEG was recorded from the pericruciate cortex and posterior lateral gyrus. Subcortical forebrain sites where electrical stimulation inhibited dorsal horn neuronal heat-evoked responses contralaterally were identified by mapping the caudate nucleus, internal capsule, septum, nucleus accumbens and basal forebrain regions. Inhibitory sites were mainly located in the ventral forebrain (ventral septum, diagonal band, basal forebrain). The caudate nucleus and internal capsule had a low incidence and effectiveness of inhibitory sites. In the basal forebrain, the incidence and effectiveness of inhibitory sites decreased from caudal to rostral regions. There was a rostral limit of inhibitory sites, both medially and laterally. The magnitude of inhibition increased with graded increases in brain stimulation intensity. The mean incremental increase in inhibition was greater for caudal than for rostral basal forebrain sites. Mean stimulus currents for threshold of inhibition and for inhibition to 50% of control heat responses were lower for caudal than for rostral sites. Responses of the dorsal horn neurons to increasing temperatures of noxious skin heating were monotonic linear functions over the temperature range studied (48–53° C). Stimulation in both rostral and caudal basal forebrain decreased the slope of this stimulus-response function, with a greater decrease for caudal sites. Cortical EEG synchronization was evoked by stimulation in the caudate nucleus and rostral basal forebrain. For both regions, most synchronogenic sites did not produce descending inhibition of dorsal horn neurons. The significance of these findings in relation to descending inhibition from other brain regions and stimulation-produced analgesia is discussed.     

Morphology and distribution of Alzheimer neuritic (senile) and amyloid plaques in striatum and diencephalon

Summary Mapping of striatal and diencephalic plaque distribution was conducted in 25 cases of dementia of the Alzheimer type. This analysis was carried out by fluorescence microscopy of paraffinembedded tissue sections treated with Thioflavine S as fluorochrome. Consistent differences in plaque morphology and density between nuclei and fiber tracts were observed. Striatal and pallidal distribution was uneven, with plaque aggregation near and within certain fiber tracts: capsules, medullary laminae, and radial fasciculi. Diencephalic plaques showed also preferred aggregation near and within fiber tracts and within the intralaminar nuclei.The different subcortical plaque morphologies observed according to the nuclear or fiber tract location of the amyloid plaque, indicates that the peripheral (halo) portion of the plaque is determined by the neuropil response to the primary event: the amyloid deposit.No correlation was observed between the distribution of plaques and any particular neurotransmitter system. In that respect, plaques were present within the nucleus basalis. Neurofibrillary tangle distribution was also seen to be dissociated from plaque distribution.     

皮层下动脉硬化性脑病的智能障碍分析

目的：探讨皮质下动脉硬化性脑病对智能活动的影响。方法：采用韦氏成人智力量表对３４例皮质下动脉硬化性脑病患者和４３例正常人进行比较分析。结果：病人各组分测验成绩明显低于对照组,且随ＣＴ显示白质损害程度的加重逐渐减少。智商比较病人各组与对照组差异有显著性（Ｐ＜０．０５～０．０１）。当合并脑萎缩时智能损害更为严重,而多发腔隙性脑梗塞对智能影响不大。结论：皮质下动脉硬化性脑病的智能障碍的病理生理基础为侧脑室周围及半卵园中心等白质损害,其损害范围和程度与智能障碍的程度呈正相关,脑萎缩的出现在其智能障碍发展过程中起一定作用。     

Selective drawing disorders after right subcortical stroke: a neuropsychological premorbid and follow-up case study

We report the case of a patient affected by a subcortical lesion of the right non-dominant hemisphere, and demonstrate that he had selective constructional disorders by comparing his post-stroke performances with those assessed 18 months before the stroke. A detailed analysis was made of the visuospatial, perceptual, representational and executive competences involved in drawing tasks at one, two and six months post-stroke. Neuropsychological follow-up revealed the progressive recovery of all visuospatial abilities. This study provides some interpretative elements for constructional disorders and, in particular, for the closing-in phenomenon observed only during the subacute phase.

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Sommario Descriviamo un paziente affetto da una lesione sottocorticale dell'emisfero destro. Le prestazioni del paziente dopo l'ictus cerebrale, confrontate con quelle osservate prima dell'evento patologico, hanno dimostrato la presenza di selettivi disturbi costruttivi. Abbiamo effettuato un approfondito esame delle prestazioni costruttive, con prove visuospaziali che esplorano i livelli percettivo, rappresentazionale ed esecutivo, esaminando il paziente fino a sei mesi dopo l'ictus. Il follow-up neuropsicologico ha dimostrato un progressivo recupero di tutte le competenze visuospaziali. Questo studio fornisce dunque alcuni elementi interpretativi per i disordini costruttivi ed, in particolare, per il fenomeno del closing-in osservato nelle prime fasi dello studio longitudinale.

     

Neuropsychiatric characteristics of PiB-negative subcortical vascular dementia versus behavioral variant frontotemporal dementia

BackgroundNeuropsychiatric symptoms of subcortical vascular dementia (SVaD) are mainly associated with damage to frontal-subcortical circuits and may be similar to symptoms of behavioral variant frontotemporal dementia (bvFTD). The aim of this study was to determine whether the neuropsychiatric manifestations of the Pittsburgh compound B (PiB)-negative SVaD and bvFTD groups differ.MethodsWe compared the Caregiver-Administered Neuropsychiatry Inventory (CGA-NPI) between 48 patients with PiB(−) SVaD and 31 patients with bvFTD. A stepwise logistic regression was applied to determine the best model to predict SVaD.ResultsThe SVaD group showed a higher frequency of depression, whereas the bvFTD group had a higher frequency of elation, aberrant motor behavior and appetite/eating disorders. Regarding NPI subscores, the bvFTD group had greater severity of elation, apathy, disinhibition, aberrant motor behavior and appetite/eating disorders, whereas SVaD did not have significantly higher subscores in any domains. The most predictive models that tend to find suggestions of SVaD, as opposed to bvFTD, are as follows: (1) the presence of depression and the absence of appetite/eating disorders, (2) higher NPI subscores of depression and lower NPI subscores of irritability and aberrant motor behavior.ConclusionApart from apathy, SVaD differed from bvFTD in that negative symptoms were more common in SVaD than bvFTD, whereas positive symptoms were predominant in bvFTD compared to SVaD.     

Effects of APOE ɛ4 on brain amyloid,lacunar infarcts,and white matter lesions: a study among patients with subcortical vascular cognitive impairment

The relationship between the apolipoprotein E ?4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer’s disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(−) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79–2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70–11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54–7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.     

Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

Background:

Little attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM.

Methods:

A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.

Results:

Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.

Conclusions:

These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.     

Genetics of subcortical vascular dementia

Subcortical vascular dementia or cerebral small vessel disease is a common cause of disability in the elderly. On magnetic resonance imaging the disease is manifested as white matter lesions, lacunes and microbleeds. Its etiology is complex, with age and hypertension as established risk factors. The heritability of white matter lesions is constantly high over different populations. Linkage studies identified several loci for these lesions however no genes responsible for the linkage signals had been identified so far. Results from genetic association studies using the candidate gene approach support the role of APOE, the renin–angiotensin system, as well as the Notch3 signaling pathway in the development of subcortical vascular dementia. The recent genomegenome wide association study on white matter lesions identified a novel locus on chromosome 17q25 harboring several genes such as TRIM65 and TRIM47 which pinpoints to possible novel mechanisms leading to these lesions.     

Abstracts from british neuropsychological society meeting 26-27 April 2000, London,UK

Accumulating evidence indicates action naming may rely more on frontal-subcortical circuits, and noun naming may rely more on temporal cortex. Therefore, noun versus action fluency might distinguish frontal and subcortical dementias from cortical dementias primarily affecting temporal and/or parietal cortex such as Alzheimer's disease (AD). We hypothesized patients with subcortical dementia, e.g., normal pressure hydrocephalus (NPH) and patients with dementias predominantly affecting frontal cortex, e.g., behavioral variant frontotemporal dementia (bv-FTD) and progressive nonfluent aphasia (PNFA) have more difficulty on action fluency versus noun fluency (e.g., animal naming). Patients with AD, who have temporo parietal cortical dysfunction, should have more difficulty on noun versus verb fluency. A total of 234 participants, including healthy controls (n = 20) and patients diagnosed with NPH (n =144), AD (n = 33), bv-FTD (n = 22) or PNFA (n =15) were administered animal fluency, action fluency, and letter fluency tasks, and the Mini-Mental State Examination (MMSE, to control for dementia severity). NPH and bv-FTD/PNFA patients had significantly higher MMSE scores and animal fluency than AD patients (after adjusting for age), but their action fluency tended to be lower than in AD. Only NPH and bvFTD/PNFA patients showed significantly lower action verb than animal fluency. Results provide novel evidence that action naming relies more on frontal-subcortical circuits while noun naming relies more on temporoparietal cortex, indicating action verb fluency may be more sensitive than noun fluency, particularly for detecting frontal-subcortical dysfunction.