-
Arquivos de Neuro-psiquiatria Jan 2015
Topics: Facies; Hirschsprung Disease; Humans; Intellectual Disability; Microcephaly
PubMed: 25608118
DOI: 10.1590/0004-282X20140224 -
Revista de Saude Publica 2022To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with...
OBJECTIVE
To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining.
METHODS
In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly measured. A linear regression was used to determine the association of head circumference with brain volume and clinical variables. Microcephaly was defined as head circumference that were two standard deviations below the mean of significant clinical variables. We further applied an association rule mining to find rules associating microcephaly with several sociodemographic and clinical variables.
RESULTS
In our sample of 2,508 adults, the mean head circumference was 55.3 ± 2.7cm. Head circumference was related to height, cerebral volume, and sex (p < 0.001 for all). Microcephaly was present in 4.7% of the sample (n = 119). Out of 34,355 association rules, we found significant relationships between microcephaly and a clinical dementia rating (CDR) > 0.5 with an informant questionnaire on cognitive decline in the elderly (IQCODE) ≥ 3.4 (confidence: 100% and lift: 5.6), between microcephaly and a CDR > 0.5 with age over 70 years (confidence: 42% and lift: 2.4), and microcephaly and males (confidence: 68.1% and lift: 1.3).
CONCLUSION
Head circumference was related to cerebral volume. Due to its low cost and easy use, head circumference can be used as a screening test for microcephaly, adjusting it for gender and height. Microcephaly was associated with dementia at old age.
Topics: Adult; Aged; Brain; Brazil; Cephalometry; Head; Humans; Male; Microcephaly
PubMed: 35649085
DOI: 10.11606/s1518-8787.2022056004175 -
Cells Jul 2022How the brain develops and achieves its final size is a fascinating issue that questions cortical evolution across species and man's place in the animal kingdom.... (Review)
Review
How the brain develops and achieves its final size is a fascinating issue that questions cortical evolution across species and man's place in the animal kingdom. Although animal models have so far been highly valuable in understanding the key steps of cortical development, many human specificities call for appropriate models. In particular, microcephaly, a neurodevelopmental disorder that is characterized by a smaller head circumference has been challenging to model in mice, which often do not fully recapitulate the human phenotype. The relatively recent development of brain organoid technology from induced pluripotent stem cells (iPSCs) now makes it possible to model human microcephaly, both due to genetic and environmental origins, and to generate developing cortical tissue from the patients themselves. These 3D tissues rely on iPSCs differentiation into cortical progenitors that self-organize into neuroepithelial rosettes mimicking the earliest stages of human neurogenesis in vitro. Over the last ten years, numerous protocols have been developed to control the identity of the induced brain areas, the reproducibility of the experiments and the longevity of the cultures, allowing analysis of the later stages. In this review, we describe the different approaches that instruct human iPSCs to form cortical organoids, summarize the different microcephalic conditions that have so far been modeled by organoids, and discuss the relevance of this model to decipher the cellular and molecular mechanisms of primary and secondary microcephalies.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Mice; Microcephaly; Neurogenesis; Organoids; Reproducibility of Results
PubMed: 35883578
DOI: 10.3390/cells11142135 -
Seminars in Pediatric Neurology Sep 2009Genetic microcephaly and lissencephaly are 2 of the most common brain malformations. Each of them is a heterogeneous group of disorders caused by mutations of many... (Review)
Review
Genetic microcephaly and lissencephaly are 2 of the most common brain malformations. Each of them is a heterogeneous group of disorders caused by mutations of many different genes. They are a significant cause of neurological morbidity in children worldwide, responsible for many cases of mental retardation, cerebral palsy, and epilepsy. Recent advances in molecular genetics have led to the identification of several genes causing these disorders, and thus accurate molecular diagnosis and improved genetic counseling has become available for many patients and their families. More recently identified genes include STIL, causing primary autosomal recessive microcephaly (microcephaly vera), and TUBA1A, causing lissencephaly. Numerous other disease genes are likely still to be identified. Functional studies of genes that cause microcephaly and lissencephaly have provided valuable insight into the molecular mechanisms of human brain development.
Topics: Animals; Humans; Lissencephaly; Magnetic Resonance Imaging; Microcephaly
PubMed: 19778709
DOI: 10.1016/j.spen.2009.07.001 -
Jornal de Pediatria 2016This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. (Review)
Review
OBJECTIVE
This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases.
SOURCES
Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word "Zika virus" in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC - United States).
SUMMARY OF FINDINGS
Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature.
CONCLUSION
The development of diagnostic techniques that confirm a cause-effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation.
Topics: Aedes; Animals; Brazil; Disease Outbreaks; Female; Humans; Infant, Newborn; Insect Vectors; Microcephaly; Pregnancy; Pregnancy Complications, Infectious; Zika Virus; Zika Virus Infection
PubMed: 27049675
DOI: 10.1016/j.jped.2016.02.009 -
International Journal of Environmental... Oct 2016Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden... (Review)
Review
Zika virus (ZIKV) is a flavivirus related to the Dengue, yellow fever and West Nile viruses. Since the explosive outbreaks of ZIKV in Latin America in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. The severity of this condition raises grave concerns, and extensive studies on the possible link between ZIKV infection and microcephaly have been conducted. There is substantial evidence suggesting that there is a causal link between ZIKV and microcephaly, however, future studies are warranted to solidify this association. To summarize the most recent evidence on this issue and provide perspectives for future studies, we reviewed the literature to identify existing evidence of the causal link between ZIKV infection and microcephaly within research related to the epidemics, laboratory diagnosis, and possible mechanisms.
Topics: Disease Outbreaks; Female; Fetus; Humans; Infant; Latin America; Microcephaly; Pregnancy; Zika Virus; Zika Virus Infection
PubMed: 27775637
DOI: 10.3390/ijerph13101031 -
Microbes and Infection Dec 2018Zika virus (ZIKV) greatly impacted the international scientific and public health communities in the last two years due to its association with microcephaly and other... (Review)
Review
Zika virus (ZIKV) greatly impacted the international scientific and public health communities in the last two years due to its association with microcephaly and other neonatal alterations. This review will discuss lessons learned from viral pathogenesis, epidemiology and clinical findings observed during the ZIKV outbreak occurred between 2014 and 2016 in Brazil.
Topics: Brazil; Disease Outbreaks; Female; Humans; Microcephaly; Placenta; Pregnancy; Viral Tropism; Zika Virus; Zika Virus Infection
PubMed: 29501560
DOI: 10.1016/j.micinf.2018.02.008 -
Brain : a Journal of Neurology Aug 2023Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes...
Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyses sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of loss-of-function SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival. All individuals surviving beyond infancy developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly, making diabetes one of the most frequent age-dependent non-cerebral abnormalities. We studied the function of SMPD4 at the cellular and organ levels. Knock-down of SMPD4 in human neural stem cells causes reduced proliferation rates and prolonged mitosis. Moreover, SMPD4 depletion results in abnormal nuclear envelope breakdown and reassembly during mitosis and decreased post-mitotic NPC insertion. Fibroblasts from affected individuals show deficient SMPD4-specific neutral sphingomyelinase activity, without changing (sub)cellular lipidome fractions, which suggests a local function of SMPD4 on the nuclear envelope. In embryonic mouse brain, knockdown of Smpd4 impairs cortical progenitor proliferation and induces premature differentiation by altering the balance between neurogenic and proliferative progenitor cell divisions. We hypothesize that, in individuals with SMPD4-related disease, nuclear envelope bending, which is needed to insert NPCs in the nuclear envelope, is impaired in the absence of SMPD4 and interferes with cerebral corticogenesis and survival of pancreatic beta cells.
Topics: Humans; Animals; Mice; Nuclear Envelope; Microcephaly; Sphingomyelin Phosphodiesterase; Nuclear Pore; Mitosis; Diabetes Mellitus
PubMed: 36732302
DOI: 10.1093/brain/awad033 -
Dialogues in Clinical Neuroscience Dec 2018Expansion of the human brain, and specifically the neocortex, is among the most remarkable evolutionary processes that correlates with cognitive, emotional, and social... (Review)
Review
Expansion of the human brain, and specifically the neocortex, is among the most remarkable evolutionary processes that correlates with cognitive, emotional, and social abilities. Cortical expansion is determined through a tightly orchestrated process of neural stem cell proliferation, migration, and ongoing organization, synaptogenesis, and apoptosis. Perturbations of each of these intricate steps can lead to abnormalities of brain size in humans, whether small (microcephaly) or large (megalencephaly). Abnormalities of brain growth can be clinically isolated or occur as part of complex syndromes associated with other neurodevelopmental problems (eg, epilepsy, autism, intellectual disability), brain malformations, and body growth abnormalities. Thorough review of the genetic literature reveals that human microcephaly and megalencephaly are caused by mutations of a rapidly growing number of genes linked within critical cellular pathways that impact early brain development, with important pathomechanistic links to cancer, body growth, and epilepsy. Given the rapid rate of causal gene identification for microcephaly and megalencephaly understanding the roles and interplay of these important signaling pathways is crucial to further unravel the mechanisms underlying brain growth disorders and, more fundamentally, normal brain growth and development in humans. In this review, we will (a) overview the definitions of microcephaly and megalencephaly, highlighting their classifications in clinical practice; (b) overview the most common genes and pathways underlying microcephaly and megalencephaly based on the fundamental cellular processes that are perturbed during cortical development; and (c) outline general clinical molecular diagnostic workflows for children and adults presenting with microcephaly and megalencephaly.
Topics: Autistic Disorder; Brain; Humans; Megalencephaly; Microcephaly; Mutation; Organ Size
PubMed: 30936767
DOI: 10.31887/DCNS.2018.20.4/gmirzaa -
Journal of Tropical Pediatrics Feb 2016
Topics: Arthralgia; Exanthema; Female; Fever; Humans; Infant, Newborn; Microcephaly; Micronesia; Pregnancy; Pregnancy Complications, Infectious; South America; Zika Virus; Zika Virus Infection
PubMed: 26895850
DOI: 10.1093/tropej/fmw006