Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Gender,intoxication and the developing brain: Problematisations of drinking among young adults in Australian alcohol policy

In this article, we draw on recent scholarly work in the poststructuralist analysis of policy to consider how policy itself functions as a key site in the constitution of alcohol ‘problems’, and the political implications of these problematisations. We do this by examining Australian alcohol policy as it relates to young adults (18–24 years old). Our critical analysis focuses on three national alcohol policies (1990, 2001 and 2006) and two Victorian state alcohol policies (2008 and 2013), which together span a 25-year period. We argue that Australian alcohol policies have conspicuously ignored young adult men, despite their ongoing over-representation in the statistical ‘evidence base’ on alcohol-related harm, while increasingly problematising alcohol consumption amongst other population subgroups. We also identify the development of a new problem representation in Australian alcohol policy, that of ‘intoxication’ as the leading cause of alcohol-related harm and rising hospital admissions, and argue that changes in the classification and diagnosis of intoxication may have contributed to its prioritisation and problematisation in alcohol policy at the expense of other forms of harm. Finally, we draw attention to how preliminary and inconclusive research on the purported association between binge drinking and brain development in those under 25 years old has been mobilised prematurely to support calls to increase the legal purchasing age from 18 to 21 years. Our critical analysis of the treatment of these three issues – gender, intoxication, and brain development – is intended to highlight the ways in which policy functions as a key site in the constitution of alcohol ‘problems’.     

Influence of COMT genotype and affective distractors on the processing of self-generated thought

The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val¹⁵⁸Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function.     

Neuroendocrine,epigenetic, and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.     

Self-Mutilation in Neurodegeneration with Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.     

Neural mechanisms regulating different forms of risk-related decision-making: Insights from animal models

Over the past 20 years there has been a growing interest in the neural underpinnings of cost/benefit decision-making. Recent studies with animal models have made considerable advances in our understanding of how different prefrontal, striatal, limbic and monoaminergic circuits interact to promote efficient risk/reward decision-making, and how dysfunction in these circuits underlies aberrant decision-making observed in numerous psychiatric disorders. This review will highlight recent findings from studies exploring these questions using a variety of behavioral assays, as well as molecular, pharmacological, neurophysiological, and translational approaches. We begin with a discussion of how neural systems related to decision subcomponents may interact to generate more complex decisions involving risk and uncertainty. This is followed by an overview of interactions between prefrontal-amygdala-dopamine and habenular circuits in regulating choice between certain and uncertain rewards and how different modes of dopamine transmission may contribute to these processes. These data will be compared with results from other studies investigating the contribution of some of these systems to guiding decision-making related to rewards vs. punishment. Lastly, we provide a brief summary of impairments in risk-related decision-making associated with psychiatric disorders, highlighting recent translational studies in laboratory animals.     

EEG power spectral density under Propofol and its association with burst suppression,a marker of cerebral fragility

ObjectiveUnder General Anesthesia (GA), age and Burst Suppression (BS) are associated with cognitive postoperative complications, yet how these parameters are related to per-operative EEG and hypnotic doses is unclear. In this prospective study, we address this question comparing age and BS occurrences with a new score (BP_TIVA) based on Propofol doses, EEG and alpha-band power spectral densities, evaluated for SEF₉₅ = 8–13 Hz.Methods59 patients (55 [34–67] yr, 67% female) undergoing neuroradiology or orthopedic surgery were included. Total IntraVenous Anesthesia was used for Propofol and analgesics infusion. Cerebral activity was monitored from a frontal electrodes montage EEG.ResultsBP_TIVA was inversely correlated with age (Pearson r = −0.78, p < 0.001), and was significantly lower (p < 0.001) when BS occurred during the GA first minutes (induction). Additionally, the age-free BP_TIVA score was better associated with BS at induction than age (AUC = 0.94 versus 0.82, p < 0.05).ConclusionWe designed BP_TIVA score based on hypnotics and EEG. It was correlated with age yet was better associated to BS occurring during GA induction, the latter being a cerebral fragility sign.SignificanceThis advocate for an approach based on evaluating the cerebral physiological age (« brain age ») to predict postoperative cognitive evolution.     

Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

Exclusion of Patients With Brain Metastases in Published Phase III Clinical Trials for Advanced Breast Cancer

Metastatic HER2-positive (HER2+) and triple-negative breast cancer (TNBC) confer a 30% or higher risk of developing brain metastases (BrM), but BrM is typically an exclusion criteria for clinical trials, which limits the generalizability of trial results to these patients. We therefore analysed trends in the enrollment of patients with BrM, as well as the use of outcomes specific to the central nervous system (CNS), in phase III clinical trials evaluating systemic therapy for patients with advanced HER2+ and/or TNBC. Notably, 10 of the 34 trials (29%, 95% confidence interval = 15.1%-47.5%) evaluated CNS-specific outcomes and trials that completely excluded patients with BrM were significantly less likely to meet their primary endpoint (n = 6/17, 35%) than those that permitted conditional enrollment (n = 13/15, 87%) (P = .005), suggesting that enrollment of patients with BrM is not detrimental to trial success.     

接受机械取栓治疗的急性脑梗死患者血栓特征研究进展

急性脑梗死是威胁我国人民健康的重大疾病,其致死率及致残率均较高,造成了沉重的社会负担。及时开通导致梗死的责任血管以恢复脑灌注是治疗该病的关键。机械取栓技术的应用使得患者的血栓组织能够被获取并得到研究。本文介绍了近年来通过机械取栓术获取的血栓的相关研究发现,以纤维蛋白为主的血栓是造成取栓困难的重要组织学原因,影像学方法可以在术前评估血栓特征。这些发现提示临床工作者可以积极开发新型血栓取出装置用于处理难治性血栓,并有必要探索精确便捷的血栓特征影像学评价方法,从而提高机械取栓疗效。