Is the blood–CSF barrier altered in disease?

OBJECTIVE: To illustrate the influence of cerebrospinal fluid (CSF) flow on lumbar CSF protein concentration and to test for an altered blood-CSF barrier permeability as additional influence. PATIENTS AND METHODS: Consecutively hospitalized patients with normotensive hydrocephalus (n = 21) underwent lumbar puncture with CSF being sampled in sequential portions. CSF/blood quotients of albumin (QAlb) and of immunoglobulin G (QIgG) were compared intra-individually and with calculated values from a reference patient sample. RESULTS AND CONCLUSIONS: QAlb and QIgG of intra-individual sequential portions correlated highly with each other (median r = 0.95), suggesting lumbar CSF flow as the main thecal determinant of lumbar QAlb and QIgG variation. In addition, QIgG, relative to QAlb, was significantly lower in study patients compared with a reference patient sample (P = 0.002), implying an alteration of the blood-CSF barrier permeability as a minor determinant of QAlb and QIgG variation in study patients.     

Where is the brain in all of this?

Clinical Autonomic Research -     

Where is the “where” in the brain? A meta‐analysis of neuroimaging studies on spatial cognition

Spatial representations are processed in the service of several different cognitive functions. The present study capitalizes on the Activation Likelihood Estimation (ALE) method of meta‐analysis to identify: (a) the shared neural activations among spatial functions to reveal the “core” network of spatial processing; (b) the specific neural activations associated with each of these functions. Following PRISMA guidelines, a total of 133 fMRI and PET studies were included in the meta‐analysis. The overall analysis showed that the core network of spatial processing comprises regions that are symmetrically distributed on both hemispheres and that include dorsal frontoparietal regions, presupplementary motor area, anterior insula, and frontal operculum. The specific analyses revealed the brain regions that are selectively recruited for each spatial function, such as the right temporoparietal junction for shift of spatial attention, the right parahippocampal gyrus, and the retrosplenial cortex for navigation and spatial long‐term memory. The findings are integrated within a systematic review of the neuroimaging literature and a new neurocognitive model of spatial cognition is proposed.     

Where in the brain is morality? Everywhere and maybe nowhere

The neuroscience of morality has focused on how morality works and where it is in the brain. In tackling these questions, researchers have taken both domain-specific and domain-general approaches-searching for neural substrates and systems dedicated to moral cognition versus characterizing the contributions of domain-general processes. Where in the brain is morality? On one hand, morality is made up of complex cognitive processes, deployed across many domains and housed all over the brain. On the other hand, no neural substrate or system that uniquely supports moral cognition has been found. In this review, we will discuss early assumptions of domain-specificity in moral neuroscience as well as subsequent investigations of domain-general contributions, taking emotion and social cognition (i.e., theory of mind) as case studies. Finally, we will consider possible cognitive accounts of a domain-specific morality: Does uniquely moral cognition exist?     

vCJD – predicting the future?

The recent emergence of variant Creutzfeldt-Jakob disease (vCJD) in the UK, and demonstration that vCJD is caused by the same prion strain that causes bovine spongiform encephalopathy, have led to concerns about the possibility of a human epidemic. Although only 79 cases of vCJD have occurred to date, it is likely that hundreds of thousands of infected cattle entered the human food chain in the late 1980s and early 1990s, and the average incubation period of vCJD is unknown. Mathematical models have not yet been able to give useful predictions of future numbers of cases, and in the absence of a blood test for vCJD, current attempts to reduce uncertainties about future numbers of cases are based on the accumulation of PrPSc in lymphoreticular tissues. Extensive lymphoreticular PrPSc accumulation has been seen in all cases of symptomatic vCJD so far examined, and in one case 8 months prior to the onset of symptoms. Animal models of prion disease suggest that lymphoreticular involvement occurs early in the incubation period and reliably predicts future neurological disease. Based on these data, large scale anonymous studies looking for PrP accumulation in surgically removed tonsillectomy and appendicectomy specimens are underway. Examination of the first 3000 specimens has not revealed any positive samples, but at the moment the significance of negative findings is uncertain. It is anticipated that by the time these studies are complete more data will be available on how early PrP can be demonstrated in lymphoreticular tissue in vCJD, which together with the results from examination of further samples, will allow some comment as to the likelihood of a large human vCJD epidemic.     

What is the brain?

From a structural perspective, there are ten basic parts of the vertebrate CNS that are almost universally agreed upon. These parts have been grouped in at least five different ways corresponding to five different theories about its basic plan or architecture. Two classical models that remain popular today are derived from (1) comparative anatomy and the body's segmental organization, and (2) comparative embryology and the neural tube's transverse and longitudinal organization. A new approach is concerned with deciphering the genetic program that assembles the nervous system during embryogenesis; how it will correspond to the other models remains to be determined. The simplest current model to explain the organization of the mammalian nervous system involves a segmental trunk that mediates reflex sensory-motor functions, and suprasegmental cerebral hemispheres and cerebellum.     

The story of O – is oxytocin the mediator of the placebo response?

Abstract  While the placebo responses in various medical conditions have been shown to follow a few basic principles such as expectancies, reward learning and Pavlovian conditioning, the underlying neurobiology and the mediating hormonal and/or neuromodulating processing have remained obscure. We here report the collected evidence that oxytocin (OXT), a 389-amino acid polypeptide located on chromosome 3p25 that is released in the brain (hypothalamus) and in peripheral tissue, is the central mediator of the placebo response: we hypothesize that exogenous OXT via an OXT agonist will enhance the placebo response, while exogenous OXT blockade by an antagonist will reduce the placebo response in placebo analgesia and other placebo models. It is furthermore proposed that the placebo response in trials may be predicted by circulating plasma OXT levels, the OXT receptor density in the brain and/or the presence of one or more of the single nucleotide polymorphisms of the OXT promoter gene.     

Congenital perisylvian dysfunction – is it a spectrum?

Aim  This study examines the overlap between children with bulbar cerebral palsy (Worster–Drought syndrome [WDS]) and perisylvian polymicrogyria.
Method  A total of 121 children (81 males, 40 females; mean age 5y 5mo, SD 3y 6mo; age range 1mo–15y 4mo) were studied using retrospective clinical data and magnetic resonance imaging. In all, 70 children had WDS with normal perisylvian imaging, 31 had congenital bilateral perisylvian polymicrogyria (CBPP), and 20 had congenital unilateral perisylvian polymicrogyria (CUPP).
Results  All groups shared aetiological markers (male sex, congenital contractures, low familial incidence, excess antenatal events). There was a common phenotype of pseudobulbar palsy with mild limb pyramidal signs in all children with WDS, 90% of those with CBPP, and one-third of those with CUPP, often also associated with learning disability * , epilepsy, and behavioural difficulties. A further 15% of children with CUPP acquired this phenotype through an epileptic encephalopathy. Pseudobulbar palsy rather than polymicrogyria was more predictive of additional impairments other than epilepsy.
Interpretation  We propose that congenital perisylvian dysfunction is a spectrum encompassing the WDS phenotype and perisylvian polymicrogyria imaging abnormalities. As with other prenatal brain abnormalities, there is not necessarily concordance between imaging and clinical findings, although the phenotype is often more severe to manifest imaging abnormality. Clinical phenotype is the best indicator of prognosis. Epileptic encephalopathy can cause an acquired form of perisylvian dysfunction where there is.     

Time is brain: is MRI the clock?

PURPOSE OF REVIEW: MRI is increasingly used as the primary imaging modality in acute stroke, since it allows treatment based on individual pathophysiology rather than strict time windows. RECENT FINDINGS: PET studies have confirmed that regions with disturbed diffusion frequently indicate irreversible tissue damage, although they may in part be viable. The mismatch between a larger perfusion deficit and a smaller diffusion abnormality contains both critically hypoperfused regions as well as oligemic regions. Although mismatch is thus not perfect, recent prospective trials have convincingly shown that mismatch patients treated with revascularization therapies benefit from reperfusion, while patients without mismatch do not. This is particularly important for patients presenting beyond the first three hours. In addition, several studies have investigated MRI as a tool to assess the risk of thrombolytic treatment. Parameters reflecting severe ischemia, blood-brain barrier damage and preexisting small-vessel disease emerge as risk factors for intracerebral hemorrhage, while microbleeds are not clearly associated with an increased risk. SUMMARY: Based on data from prospective trials, the mismatch concept is an acceptable method to identify patients who benefit from recanalization therapies. The concept, however, still needs to be further improved and standard definitions are required before widespread use can be recommended.     

Gut–brain axis and the spread of α‐synuclein pathology: Vagal highway or dead end?

Spread of α‐synuclein pathology from the peripheral to central nervous system may be an important etiological factor in Parkinson's disease, although there are some unanswered questions about its correlation with neuronal loss. Experimental evidence has highlighted the gastrointestinal tract as a potential starting point for aggregated α‐synuclein, with the vagus nerve acting as a “highway” by which pathology may be transmitted to the lower brain stem. This review begins by highlighting the key studies demonstrating that α‐synuclein pathology has the ability to spread from certain sites in the gastrointestinal tract to the brain (and vice versa). We go on to assess the recent epidemiological studies that have shown that vagotomy and appendectomy may have the potential to reduce the risk of developing Parkinson's disease. Finally, we discuss the factors in the gastrointestinal tract (such as dysbiosis of the gut microbiota, infection, and inflammation) that may trigger α‐synuclein aggregation in the first place, as well as other potential mechanisms underlying the distribution of α‐synuclein pathology in the brain. © 2019 International Parkinson and Movement Disorder Society