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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 -
Current Neurology and Neuroscience... Jul 2022Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin... (Review)
Review
PURPOSE OF REVIEW
Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin encephalopathy and progress to kernicterus spectrum disorder, a chronic condition characterized by hearing loss, extrapyramidal dysfunction, ophthalmoplegia, and enamel hypoplasia. Epidemiological data show that the implementation of universal pre-discharge bilirubin screening programs has reduced the rates of hyperbilirubinemia-associated complications. However, acute bilirubin encephalopathy and kernicterus spectrum disorder are still particularly common in low- and middle-income countries.
RECENT FINDINGS
The understanding of the genetic and biochemical processes that increase the susceptibility of defined anatomical areas of the central nervous system to the deleterious effects of bilirubin may facilitate the development of effective treatments for acute bilirubin encephalopathy and kernicterus spectrum disorder. Scoring systems are available for the diagnosis and severity grading of these conditions. The treatment of hyperbilirubinemia in newborns relies on the use of phototherapy and exchange transfusion. However, novel therapeutic options including deep brain stimulation, brain-computer interface, and stem cell transplantation may alleviate the heavy disease burden associated with kernicterus spectrum disorder. Despite improved screening and treatment options, the prevalence of acute bilirubin encephalopathy and kernicterus spectrum disorder remains elevated in low- and middle-income countries. The continued presence and associated long-term disability of these conditions warrant further research to improve their prevention and management.
Topics: Bilirubin; Brain Diseases; Humans; Infant, Newborn; Kernicterus; Phototherapy
PubMed: 35588044
DOI: 10.1007/s11910-022-01204-8 -
The American Journal of Medicine Oct 2019Encephalopathy refers to dysfunction of the level or contents of consciousness due to brain dysfunction and can result from global brain insults or focal lesions. The... (Review)
Review
Encephalopathy refers to dysfunction of the level or contents of consciousness due to brain dysfunction and can result from global brain insults or focal lesions. The underlying causes of encephalopathy include both primary neurologic and systemic conditions. This article discusses the differential diagnosis of encephalopathy, with a focus on primary neurologic causes. A practical schema for organizing the differential diagnosis is to group etiologies by their pace of onset and evolution (eg, sudden, acute, subacute, chronic).
Topics: Brain Diseases; Cognition; Consciousness; Diagnosis, Differential; Humans
PubMed: 31330129
DOI: 10.1016/j.amjmed.2019.07.001 -
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 -
Brain & Development Jan 2021The cardinal symptom of acute encephalopathy is impairment of consciousness of acute onset during the course of an infectious disease, with duration and severity meeting... (Review)
Review
The cardinal symptom of acute encephalopathy is impairment of consciousness of acute onset during the course of an infectious disease, with duration and severity meeting defined criteria. Acute encephalopathy consists of multiple syndromes such as acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion and clinically mild encephalitis/encephalopathy with reversible splenial lesion. Among these syndromes, there are both similarities and differences. In 2016, the Japanese Society of Child Neurology published 'Guidelines for the Diagnosis and Treatment of Acute Encephalopathy in Childhood', which made recommendations and comments on the general aspects of acute encephalopathy in the first half, and on individual syndromes in the latter half. Since the guidelines were written in Japanese, this review article describes extracts from the recommendations and comments in English, in order to introduce the essence of the guidelines to international clinicians and researchers.
Topics: Acute Disease; Brain Diseases; Child; Child, Preschool; Encephalitis; Female; Humans; Japan; Male; Seizures; Syndrome
PubMed: 32829972
DOI: 10.1016/j.braindev.2020.08.001 -
Brain : a Journal of Neurology Feb 2021Developmental encephalopathies, including intellectual disability and autistic spectrum disorder, are frequently associated with infant epilepsy. Epileptic... (Review)
Review
Developmental encephalopathies, including intellectual disability and autistic spectrum disorder, are frequently associated with infant epilepsy. Epileptic encephalopathy is used to describe an assumed causal relationship between epilepsy and developmental delay. Developmental encephalopathies pathogenesis more independent from epilepsy is supported by the identification of several gene variants associated with both developmental encephalopathies and epilepsy, the possibility for gene-associated developmental encephalopathies without epilepsy, and the continued development of developmental encephalopathies even when seizures are controlled. Hence, 'developmental and epileptic encephalopathy' may be a more appropriate term than epileptic encephalopathy. This update considers the best studied 'developmental and epileptic encephalopathy' gene variants for illustrative support for 'developmental and epileptic encephalopathy' over epileptic encephalopathy. Moreover, the interaction between epilepsy and developmental encephalopathies is considered with respect to influence on treatment decisions. Continued research in genetic testing will increase access to clinical tests, earlier diagnosis, better application of current treatments, and potentially provide new molecular-investigated treatments.
Topics: Animals; Brain; Brain Diseases; Developmental Disabilities; Epilepsy; Humans; Neurons
PubMed: 33279965
DOI: 10.1093/brain/awaa371 -
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 -
Best Practice & Research. Clinical... Dec 2019The versatile clinical manifestations of the Hashimoto's chronic autoimmune thyroiditis often include psycho-neurological disorders. Although hypothyroidism disturbs... (Review)
Review
The versatile clinical manifestations of the Hashimoto's chronic autoimmune thyroiditis often include psycho-neurological disorders. Although hypothyroidism disturbs significantly the ontogenesis and functions of central nervous system, causing in severe cases of myxedema profound impairment of cognitive abilities and even psychosis, the behavioral, motor and other psychoneurological disorders accompany euthyroid and slightly hypothyroid cases and periods of Hashimoto's disease as well, thus constituting the picture of so called "Hashimoto's encephalopathy". The entity, although discussed and explored for more than 50 years since its initial descriptions, remains an enigma of thyroidology and psychiatry, because its etiology and pathogenesis are obscure. The paper describes the development of current views on the role of thyroid in ontogeny and functions of brain, as well as classical and newest ideas on the etiology and pathogenesis of Hashimot's encephalopathy. The synopsis of the world case reports and research literature on this disorder is added with authors' own results obtained by study of 17 cases of Hashimoto's thyroiditis with schizophrenia-like clinical manifestations. The relation of the disease to adjuvant-like etiological factors is discussed. Three major mechanistic concepts of Hashimoto's encephalopathy are detailed, namely cerebral vasculitis theory, hormone dysregulation theory and concept, explaining the disease via direct action of the autoantibodies against various thyroid (thyroperoxidase, thyroglobulin, and TSH-receptor) and several extrathyroid antigens (alpha-enolase and other enzymes, gangliosides and MOG-protein, onconeuronal antigens) - all of them expressed in the brain. The article demonstrates that all above mentioned concepts intermingle and prone to unification, suggesting the unified scheme of pathogenesis for the Hashimoto's encephalopathy. The clinical manifestations, criteria, forms, course, treatment and prognosis of Hashimoto's encephalopathy and its comorbidity to other diseases - are also discussed in brief. The relation between Hashimoto's encephalopathy and non-vasculitis autoimmune encephalomyelitides of paraneoplastic and non-paraneoplastic origin is emphasized [1 figure, bibliography - 200 references].
Topics: Brain; Brain Diseases; Encephalitis; Hashimoto Disease; Humans; Hypothyroidism; Thyroid Gland
PubMed: 31801687
DOI: 10.1016/j.beem.2019.101364