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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 -
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 -
Acta Neuropathologica Jan 2014Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and... (Review)
Review
Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions.
Topics: Alcohol-Induced Disorders, Nervous System; Alcoholism; Brain; Brain Diseases; Ethanol; Humans
PubMed: 24370929
DOI: 10.1007/s00401-013-1233-3 -
Acta Neurobiologiae Experimentalis 2007Dopaminergic neurons of the midbrain are the main source of dopamine (DA) in the brain. DA has been shown to be involved in the control of movements, the signaling of... (Review)
Review
Dopaminergic neurons of the midbrain are the main source of dopamine (DA) in the brain. DA has been shown to be involved in the control of movements, the signaling of error in prediction of reward, motivation, and cognition. Cerebral DA depletion is the hallmark of Parkinson's disease (PD). Other pathological states have also been associated with DA dysfunction, such as schizophrenia, autism, and attention deficit hyperactivity disorder in children, as well as drug abuse. DA is closely associated with reward-seeking behaviors, such as approach, consumption, and addiction. Recent researches suggest that the firing of DA neurons is a motivational substance as a consequence of reward-anticipation. This hypothesis is based on the evidence that, when a reward is greater than expected, the firing of certain DA neurons increases, which consequently increases desire or motivation towards the reward.
Topics: Animals; Behavior; Brain Diseases; Dopamine; Humans; Learning; Mesencephalon; Motivation; Reward
PubMed: 18320725
DOI: 10.55782/ane-2007-1664 -
Nutrients Aug 2020Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for... (Review)
Review
Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for brain and eye development. Additionally, DHA plays a significant role in mental health throughout early childhood and even into adulthood. In the brain, DHA is important for cellular membrane fluidity, function and neurotransmitter release. Evidence indicates that a low intake of marine omega-3s increases the risk for numerous mental health issues, including Attention Deficit Hyperactivity Disorder (ADHD), autism, bipolar disorder, depression and suicidal ideation. Studies giving supplemental marine omega-3s have shown promise for improving numerous mental health conditions. This paper will review the evidence surrounding marine omega-3s and mental health conditions.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Brain; Brain Diseases; Child; Dietary Supplements; Docosahexaenoic Acids; Humans; Mental Disorders; Mood Disorders; Neurodevelopmental Disorders; Seafood
PubMed: 32759851
DOI: 10.3390/nu12082333 -
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 -
International Journal of Molecular... Nov 2020Polycystic ovary syndrome (PCOS) is an endocrine condition associated with reproductive and psychiatric disorders, and with obesity. Eating disorders, such as bulimia... (Review)
Review
Polycystic ovary syndrome (PCOS) is an endocrine condition associated with reproductive and psychiatric disorders, and with obesity. Eating disorders, such as bulimia and recurrent dieting, are also linked to PCOS. They can lead to the epigenetic dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis, thereby impacting on ovarian folliculogenesis. We postulate that PCOS is induced by psychological distress and episodes of overeating and/or dieting during puberty and adolescence, when body dissatisfaction and emotional distress are often present. We propose that upregulated activation of the central HPG axis during this period can be epigenetically altered by psychological stressors and by bulimia/recurrent dieting, which are common during adolescence and which can lead to PCOS. This hypothesis is based on events that occur during a largely neglected stage of female reproductive development. To date, most research into the origins of PCOS has focused on the prenatal induction of this disorder, particularly in utero androgenization and the role of anti-Müllerian hormone. Establishing causality in our peripubertal model requires prospective cohort studies from infancy. Mechanistic studies should consider the role of the gut microbiota in addition to the epigenetic regulation of (neuro) hormones. Finally, clinicians should consider the importance of underlying chronic psychological distress and eating disorders in PCOS.
Topics: Adolescent; Adolescent Behavior; Age of Onset; Brain Diseases; Child; Feeding and Eating Disorders; Female; Humans; Polycystic Ovary Syndrome; Psychology, Adolescent; Puberty; Risk Factors
PubMed: 33153014
DOI: 10.3390/ijms21218211 -
Journal of Inherited Metabolic Disease May 2023Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13),...
Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, that is, age 6 years. However, impact of dietary relaxation on long-term outcomes is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations (Boy et al., J Inherit Metab Dis, 2017;40(1):75-101; Kolker et al., J Inherit Metab Dis 2011;34(3):677-694; Kolker et al., J Inherit Metab Dis, 2007;30(1):5-22) and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes.
Topics: Humans; Glutaryl-CoA Dehydrogenase; Lysine; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Glutarates
PubMed: 36221165
DOI: 10.1002/jimd.12566 -
Revue Neurologique Dec 2019Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which... (Review)
Review
Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown.
Topics: Africa South of the Sahara; Africa, Eastern; Brain Diseases; Dwarfism, Pituitary; Electroencephalography; Humans; Nodding Syndrome; Phenotype; Syndrome
PubMed: 31753452
DOI: 10.1016/j.neurol.2019.09.005 -
Alcohol Research & Health : the Journal... 2003Hepatic encephalopathy (HE) is a brain disorder caused by chronic liver failure, particularly in alcoholics with cirrhosis, which results in cognitive, psychiatric, and... (Review)
Review
Hepatic encephalopathy (HE) is a brain disorder caused by chronic liver failure, particularly in alcoholics with cirrhosis, which results in cognitive, psychiatric, and motor impairments. In these patients, the number of functional liver cells is reduced, and some blood is diverted around the liver before toxins are removed. As a result, toxins such as ammonia and manganese can accumulate in the blood and enter the brain, where they can damage nerve cells and supporting cells called astrocytes. Positron emission tomography analyses have determined that ammonia levels are elevated in the brains of HE patients; ammonia accumulation can alter the expression of various important brain genes. Magnetic resonance images show that manganese is deposited in a brain area called the globus pallidus; manganese deposits may be responsible for structural changes in the astrocytes that are characteristic of HE. Treatment of patients with HE involves measures to lower ammonia levels in the blood, medications to counteract ammonia's effects on brain cell function, devices to compensate for liver dysfunction, and liver transplantation.
Topics: Brain; Hepatic Encephalopathy; Humans; Liver Diseases, Alcoholic
PubMed: 15535452
DOI: No ID Found