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Nature Reviews. Disease Primers May 2021Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic... (Review)
Review
Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic neurodegenerative disease that causes an amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants. AD is a common cause of cognitive impairment acquired in midlife and late-life but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. This Primer conceives of AD biology as the brain disorder that results from a complex interplay of loss of synaptic homeostasis and dysfunction in the highly interrelated endosomal/lysosomal clearance pathways in which the precursors, aggregated species and post-translationally modified products of Aβ and tau play important roles. Therapeutic endeavours are still struggling to find targets within this framework that substantially change the clinical course in persons with AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Cognitive Dysfunction; Humans; Neurodegenerative Diseases; Neurofibrillary Tangles
PubMed: 33986301
DOI: 10.1038/s41572-021-00269-y -
Fluids and Barriers of the CNS Nov 2020The blood-brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain's metabolic activity as well as... (Review)
Review
The blood-brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain's metabolic activity as well as neuronal function. Thus, the functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenvironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain-blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical aspects that correlate between BBB disruption and different neurological and pathological conditions. Finally, we discussed several biomarkers that can help to assess the BBB permeability and integrity in-vitro or in-vivo and briefly explain their advantages and disadvantages.
Topics: Biological Transport; Biomarkers; Blood-Brain Barrier; Brain Diseases; Humans
PubMed: 33208141
DOI: 10.1186/s12987-020-00230-3 -
Psychological Medicine Nov 2020Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis.
METHODS
A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition.
RESULTS
We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains.
CONCLUSIONS
Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).
Topics: Attention; Brain Diseases; Cognition; Humans; Memory, Short-Term; Randomized Controlled Trials as Topic; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 33070785
DOI: 10.1017/S0033291720003670 -
Seminars in Pediatric Neurology Dec 2019This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika... (Review)
Review
This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika virus infection and perinatally acquired infections (enterovirus, parechovirus, rotavirus, parvovirus). Congenital infections are due to pathogens that can cross the placenta and are more likely to injure the brain when the infection occurs early in pregnancy. There are many similarities, with regards to brain lesions, for congenital Zika syndrome and congenital cytomegalovirus infection. Perinatally acquired viral infections tend to injure the white matter, with cystic evolution being more likely in the (late) preterm infant compared to the full-term infant. Congenital and perinatally acquired viral infections can be associated with adverse neurological outcomes. Prevention is important, especially as therapeutic options are limited. In this review both congenital as well as perinatally acquired viral infections will be discussed with a focus on neuro-imaging findings.
Topics: Brain; Brain Diseases; Humans; Infant, Newborn; Infections
PubMed: 31813517
DOI: 10.1016/j.spen.2019.08.005 -
Developmental Medicine and Child... Nov 2020In this paper we reframe febrile seizures, which are viewed as a symptom of an underlying brain disorder. The general observation is that a small cohort of children will... (Review)
Review
In this paper we reframe febrile seizures, which are viewed as a symptom of an underlying brain disorder. The general observation is that a small cohort of children will develop febrile seizures (2-5% in the West), while the greater majority will not. This suggests that the brain that generates a seizure, in an often-mild febrile context, differs in some ways from the brain that does not. While the underlying brain disorder appears to have no significant adverse implication in the majority of children with febrile seizures, serious long-term outcomes (cognitive and neuropsychiatric) have been recently reported, including sudden death. These adverse events likely reflect the underlying intrinsic brain pathology, as yet undefined, of which febrile seizures are purely a manifestation and not the primary cause. A complex interaction between brain-genetics-epigenetics-early environment is likely at play. In view of this emerging data, it is time to review whether febrile seizures are a single entity, with a new and multidimensional approach needed to help with predicting outcome. WHAT THIS PAPER ADDS: A febrile seizure is due to a brain's aberrant response to high temperature. Problems in a small group of children are now being identified later in life. There is no clear correlation between duration or other characteristics of febrile seizures and subsequent mesial temporal sclerosis.
Topics: Brain Diseases; Child, Preschool; Cognitive Dysfunction; Epilepsy; Humans; Infant; Mental Disorders; Seizures, Febrile
PubMed: 32748466
DOI: 10.1111/dmcn.14642 -
Science Advances Sep 2022Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In... (Review)
Review
Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with the etiology and progression of neurodegeneration and other neurological pathologies. Hence, brain lipids are emerging as important potential targets for the early diagnosis and prognosis of neurological diseases. This review aims to highlight the significance and usefulness of lipidomics in diagnosing and treating brain diseases. We explored lipid alterations associated with brain diseases, paying attention to organ-specific characteristics and the functions of brain lipids. As the recent advances in brain lipidomics would have been impossible without advances in analytical techniques, we provide up-to-date information on mass spectrometric approaches and integrative analysis with other omic approaches. Last, we present the potential applications of lipidomics combined with artificial intelligence techniques and interdisciplinary collaborative research for treating brain diseases with clinical heterogeneities.
Topics: Artificial Intelligence; Brain; Brain Diseases; Humans; Lipid Metabolism; Lipidomics; Lipids
PubMed: 36112688
DOI: 10.1126/sciadv.adc9317 -
Nature Reviews. Neurology Mar 2019The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can... (Review)
Review
The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional circuitry. The development of DBS has opened new opportunities to access and interrogate malfunctioning brain circuits and to test the therapeutic potential of regulating the output of these circuits in a broad range of disorders. Despite the success and rapid adoption of DBS, crucial questions remain, including which brain areas should be targeted and in which patients. This Review considers how DBS has facilitated advances in our understanding of how circuit malfunction can lead to brain disorders and outlines the key unmet challenges and future directions in the DBS field. Determining the next steps in DBS science will help to define the future role of this technology in the development of novel therapeutics for the most challenging disorders affecting the human brain.
Topics: Brain Diseases; Deep Brain Stimulation; Humans; Mental Disorders
PubMed: 30683913
DOI: 10.1038/s41582-018-0128-2 -
Translational Psychiatry Apr 2022There is emerging evidence that diet has a major modulatory influence on brain-gut-microbiome (BGM) interactions with important implications for brain health, and for... (Review)
Review
There is emerging evidence that diet has a major modulatory influence on brain-gut-microbiome (BGM) interactions with important implications for brain health, and for several brain disorders. The BGM system is made up of neuroendocrine, neural, and immune communication channels which establish a network of bidirectional interactions between the brain, the gut and its microbiome. Diet not only plays a crucial role in shaping the gut microbiome, but it can modulate structure and function of the brain through these communication channels. In this review, we summarize the evidence available from preclinical and clinical studies on the influence of dietary habits and interventions on a selected group of psychiatric and neurologic disorders including depression, cognitive decline, Parkinson's disease, autism spectrum disorder and epilepsy. We will particularly address the role of diet-induced microbiome changes which have been implicated in these effects, and some of which are shared between different brain disorders. While the majority of these findings have been demonstrated in preclinical and in cross-sectional, epidemiological studies, to date there is insufficient evidence from mechanistic human studies to make conclusions about causality between a specific diet and microbially mediated brain function. Many of the dietary benefits on microbiome and brain health have been attributed to anti-inflammatory effects mediated by the microbial metabolites of dietary fiber and polyphenols. The new attention given to dietary factors in brain disorders has the potential to improve treatment outcomes with currently available pharmacological and non-pharmacological therapies.
Topics: Autism Spectrum Disorder; Brain; Brain Diseases; Cross-Sectional Studies; Diet; Epilepsy; Gastrointestinal Microbiome; Humans; Mental Disorders
PubMed: 35443740
DOI: 10.1038/s41398-022-01922-0 -
Alzheimer's & Dementia : the Journal of... Aug 2017A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.
INTRODUCTION
A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.
METHODS
Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA.
RESULTS
A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum.
DISCUSSION
There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.
Topics: Brain; Brain Diseases; Humans
PubMed: 28259709
DOI: 10.1016/j.jalz.2017.01.014 -
Neurology Mar 2016To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously... (Review)
Review
OBJECTIVE
To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients.
METHODS
We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients.
RESULTS
We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features.
CONCLUSION
De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy.
Topics: Adolescent; Adult; Brain Diseases; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Male; Middle Aged; Munc18 Proteins; Mutation; Neurodevelopmental Disorders; Young Adult
PubMed: 26865513
DOI: 10.1212/WNL.0000000000002457