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Dialogues in Clinical Neuroscience 2024Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a multifaceted etiology. This case report explores the ischemic cryptogenic vascular... (Review)
Review
INTRODUCTION
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a multifaceted etiology. This case report explores the ischemic cryptogenic vascular dissection as a potential underlying cause of ASD.
METHODS
A 9-year-old child presented with symptoms of ASD, including social interaction difficulties, repetitive behaviors, and cognitive challenges. Despite conventional ASD treatments, significant improvement was only observed after addressing an underlying ischemic cryptogenic vascular dissection identified through DCE-CT.
RESULTS
Following a reconstructive treatment approach to the vascular dissection, the patient showed marked improvement in cognitive functions, social abilities, and a reduction in ASD-related symptoms whether during the perioperative period or during approximately 5-month follow-up.
CONCLUSION
This case suggests that ischemic cryptogenic vascular dissection may contribute to the symptoms of ASD. Identifying and treating underlying vascular anomalies may offer a new avenue for mitigating ASD symptoms, emphasizing the need for comprehensive diagnostic estimations in ASD management.
Topics: Humans; Autism Spectrum Disorder; Child; Male; Microcephaly
PubMed: 38829782
DOI: 10.1080/19585969.2024.2359918 -
Revista Da Associacao Medica Brasileira... Jul 2018the present study analysed the association between Zika-virus and microcephaly during the gestational period of women in Brazil.
AIM
the present study analysed the association between Zika-virus and microcephaly during the gestational period of women in Brazil.
METHODOLOGY
Systematic reviews of intervention research, current publications of clinical investigations were used systematic search strategies in three electronic databases PubMed, SciELO and Google academic. The following keywords were used: Microcephaly, gestation, Zika-virus to perform the search, and 1020 articles were obtained after exclusion, 45 were left and 35 were eligible. The collection period was from 2004 to 2017.
RESULTS
Epidemiological data suggest a temporal association between the quantitative increase and the Zika-virus epidemic, especially in Northeast Brazil. It is not consensual to measure the cephalic perimeter curve to be considered.
CONCLUSION
Given this, the application of techniques to accurately diagnose the relationship between causes and effects in the pathogenesis of Zika virus infection in the central nervous system should be prioritized.
Topics: Brazil; Disease Outbreaks; Female; Humans; Microcephaly; Pregnancy; Pregnancy Complications, Infectious; Zika Virus; Zika Virus Infection
PubMed: 30365666
DOI: 10.1590/1806-9282.64.07.635 -
Cells Feb 2023Congenital microcephaly (CM) exhibits broad clinical and genetic heterogeneity and is thus categorized into several subtypes. However, the recent bloom of disease-gene... (Review)
Review
Congenital microcephaly (CM) exhibits broad clinical and genetic heterogeneity and is thus categorized into several subtypes. However, the recent bloom of disease-gene discoveries has revealed more overlaps than differences in the underlying genetic architecture for these clinical sub-categories, complicating the differential diagnosis. Moreover, the mechanism of the paradigm shift from a brain-restricted to a multi-organ phenotype is only vaguely understood. This review article highlights the critical factors considered while defining CM subtypes. It also presents possible arguments on long-standing questions of the brain-specific nature of CM caused by a dysfunction of the ubiquitously expressed proteins. We argue that brain-specific splicing events and organ-restricted protein expression may contribute in part to disparate clinical manifestations. We also highlight the role of genetic modifiers and de novo variants in the multi-organ phenotype of CM and emphasize their consideration in molecular characterization. This review thus attempts to expand our understanding of the phenotypic and etiological variability in CM and invites the development of more comprehensive guidelines.
Topics: Humans; Microcephaly; Brain; Phenotype; Genetic Heterogeneity
PubMed: 36831309
DOI: 10.3390/cells12040642 -
Cadernos de Saude Publica Oct 2018In August 2015, pediatric neurologists at public hospitals in Recife, Pernambuco State, Brazil, observed an increase in the number of disproportional microcephaly cases...
In August 2015, pediatric neurologists at public hospitals in Recife, Pernambuco State, Brazil, observed an increase in the number of disproportional microcephaly cases associated with other congenital anomalies. The fact caused social commotion and mobilization of the academic community and led the Brazilian Ministry of Health to declare a national public health emergency, followed by the declaration of a Public Health Emergency of International Concern by the World Health Organization. The hypothesis for the phenomenon was congenital Zika virus (ZIKV) infection, based on spatial-temporal correlation and the clinical-epidemiological characteristics of the two epidemics. Further evidence accumulated, and within the scope of epidemiologial reasoning fulfilled criteria that gave support to the hypothesis. The plausibility of the hypothesis is based on the neurotropism of ZIKV, demonstrated in animals, affecting neural progenitors in the developing brain, and in humans, due to neurological complications in adults following infection. Isolation of viral RNA and antigens in the amniotic fluid of infected mothers and in brains of newborns and fetuses with microcephaly further demonstrated the consistency of the hypothesis. The criterion of temporality was met by identifying adverse pregnancy outcomes in a cohort of mothers with a history of rash and positive ZIKV serology. Finally, the first case-control study demonstrated a strong association between microcephaly and congenital ZIKV infection. The knowledge built with the epidemiological paradigm was supported by the scientific community, thereby establishing the consensus for a causal relationship between ZIKV and the microcephaly epidemic.
Topics: Brazil; Evidence-Based Medicine; Female; Health Knowledge, Attitudes, Practice; Humans; Microcephaly; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Prevalence; Risk Factors; Zika Virus Infection
PubMed: 30328996
DOI: 10.1590/0102-311X00069018 -
Annals of Global Health Aug 2019Brazil presented an alarming number of newborns with microcephaly in the years 2015 and 2016. The investigation of the cases raised the suspicion of the association of...
BACKGROUND
Brazil presented an alarming number of newborns with microcephaly in the years 2015 and 2016. The investigation of the cases raised the suspicion of the association of these cases with maternal infections by the zika virus. Also, in 2015, there was an epidemic of zika virus infection in Brazil, reinforcing this hypothesis.
OBJECTIVE
The objective of this study was to identify factors associated with the diagnosis of microcephaly in newborns, including zika virus infection.
METHODS
We conducted a case-control study. The cases were defined as children who received clinical and imaging diagnosis of microcephaly, born after October 2015 in Ceará, Brazil, which recorded the highest number of microcephaly cases in Brazil during the outbreak. The cases were identified in medical records of public and private maternity hospitals and in child development stimulation clinics tracked until June 2017. Epidemiological, clinical, and socioeconomic variables were collected, visiting their homes and confirming data from their medical records. Controls were children without microcephaly identified in the vicinity of the residence of each case. Logistic regression models were used to control confounding.
FINDINGS
We evaluated 58 cases and 116 controls. The odds of having a baby with microcephaly was 14 times higher among mothers who had zika virus infection (p < 0.001), after multivariate analysis. Arboviruses infections symptoms, as fever (p = 0.220), skin change (p < 0.001), and joint pain (p = 0.002) also demonstrated an association with microcephaly.
CONCLUSIONS
Maternal infection zika virus was associated with a diagnosis of microcephaly. Our study contributes to the investigation of the epidemiological factors associated with the diagnosis of microcephaly.
Topics: Arthralgia; Brazil; Case-Control Studies; Exanthema; Female; Fever; Humans; Infant; Male; Microcephaly; Zika Virus Infection
PubMed: 31468955
DOI: 10.5334/aogh.2394 -
Investigative Ophthalmology & Visual... Nov 2020The purpose of this study was to analyze the natural history and phenotypic overlap of patients with microcephaly and a chorioretinopathy or familial exudative...
PURPOSE
The purpose of this study was to analyze the natural history and phenotypic overlap of patients with microcephaly and a chorioretinopathy or familial exudative vitreoretinopathy (FEVR) ocular phenotype caused by mutations in KIF11, TUBGCP4, or TUBGCP6.
METHODS
Patients diagnosed with congenital microcephaly and chorioretinopathy or FEVR were included. Molecular investigations consisted of targeted genetic sequencing. Data from medical records, ophthalmologic examination and imaging, electroretinography, and visual fields were analyzed for systemic and ophthalmic features and evidence of posterior segment disease progression.
RESULTS
Twelve patients from 9 families were included and had a median of 8 years of follow-up. Nine patients had KIF11 variants, two had heterozygous TUBGCP6 variants, and one had heterozygous variants in TUBGCP4. All patients had reduced visual function and multiple individuals and families showed features of both chorioretinopathy and FEVR. Progression of posterior segment disease was highly variable, with some degree of increased atrophy of the macula or peripheral retina or increased vitreoretinal traction observed in 9 of 12 patients.
CONCLUSIONS
Microcephaly due to mutations in KIF11, TUBGCP4, or TUBGCP6 can be associated with retinal disease on a spectrum from chorioretinal atrophy to FEVR-like posterior segment changes. Visually significant disease progression can occur and patients should be monitored closely by a team experienced in ophthalmic genetics.
Topics: Adolescent; Child; Child, Preschool; DNA Mutational Analysis; Electroretinography; Familial Exudative Vitreoretinopathies; Female; Follow-Up Studies; Genetic Association Studies; Humans; Infant; Infant, Newborn; Kinesins; Male; Microcephaly; Microtubule-Associated Proteins; Mutation; Retinal Diseases; Vision Disorders; Visual Acuity; Visual Field Tests; Visual Fields
PubMed: 33137195
DOI: 10.1167/iovs.61.13.2 -
Journal of Human Genetics Mar 2022Neutral sphingomyelinases have an important role in generation of ceramide and phosphorylcholine from sphingomyelins which then act as secondary messengers in various...
Neutral sphingomyelinases have an important role in generation of ceramide and phosphorylcholine from sphingomyelins which then act as secondary messengers in various signaling pathways of the cellular machinery. They function ubiquitously with a predominant role in the central nervous system. Neutral sphingomyelinase type 3, encoded by SMPD4 gene has recently been reported to cause a severe autosomal recessive neurodevelopmental disorder with congenital arthrogryposis and microcephaly. We report a 22-month-old girl having characteristic features of neurodevelopmental delay, prenatal onset growth failure, arthrogryposis, microcephaly and brain anomalies including severe hypomyelination, simplified gyral pattern and hypoplasia of corpus callosum and brain stem. In addition, she was noted to have nystagmus and visual impairment secondary to macular dystrophy and retinal pigment epithelial stippling at posterior pole. Copy number variant analysis from trio whole exome sequencing (ES) enabled identification of a homozygous 11 kb deletion encompassing exons 18-20 of SMPD 4 gene, confirming the diagnosis of SMPD4-related disorder in her.
Topics: Arthrogryposis; Brain; Female; Humans; Infant; Microcephaly; Nervous System Malformations; Neurodevelopmental Disorders; Pregnancy
PubMed: 34621002
DOI: 10.1038/s10038-021-00981-3 -
Orphanet Journal of Rare Diseases Jun 2011Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of... (Review)
Review
Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder.
Topics: Gene Expression Regulation; Humans; Microcephaly; Mutation; Pakistan; Rare Diseases
PubMed: 21668957
DOI: 10.1186/1750-1172-6-39 -
JAMA Pediatrics Dec 2020Congenital cytomegalovirus (cCMV) has received far less clinical and public health attention as a teratogenic infection than the Zika virus epidemic. However, cCMV may...
IMPORTANCE
Congenital cytomegalovirus (cCMV) has received far less clinical and public health attention as a teratogenic infection than the Zika virus epidemic. However, cCMV may be responsible for a large fraction of microcephaly cases in the United States.
OBJECTIVE
To evaluate the association between cCMV and the prevalence at birth of microcephaly in the United States.
DESIGN, SETTING, AND PARTICIPANTS
This population-based cohort study included pregnant women and their newborns identified in 2 insurance claims databases from the United States: Medicaid Analytic eXtract (January 1, 2000, to December 31, 2013) and IBM Research MarketScan, a database for employer-sponsored private health insurance (January 1, 2011, to September 30, 2015). All pregnancies that resulted in live births in women with full health benefits were included. Analysis began June 2016 and ended May 2020.
EXPOSURES
Congenital cytomegalovirus infection documented in inpatient or outpatient newborn claims records.
MAIN OUTCOMES AND MEASURES
The primary outcome was microcephaly at birth documented in inpatient or outpatient newborn and/or maternal claims records. Cases with chromosomal abnormalities or neural tube defects were excluded. The association between cCMV and microcephaly was estimated in the pooled cohort using prevalence ratios (PRs) and 95% CIs.
RESULTS
In the pooled cohort of 2 338 580 pregnancies (2 075 410 pregnancies [88.7%] were among women younger than 35 years), 336 infants (0.014%) had a cCMV diagnosis. The prevalence of microcephaly among newborns with and without a cCMV diagnosis was 655 and 2.8 per 10 000 live births, respectively (PR, 232; 95% CI, 154-350). After restricting to CMV-tested newborns (572 [0.024%]) to correct for preferential testing of infants with microcephaly, the PR was 15 (95% CI, 5.2-41). However, this PR is biased if other cCMV-related outcomes (eg, hearing loss) trigger testing because cCMV prevalence in tested infants, with ([46%]) or without microcephaly (22 of 559 [3.9%]), would overestimate that in the source population. Therefore, the prevalence of cCMV in overall infants with microcephaly (22 of 669 [3.2%]) was compared with that from an external unbiased sample of US infants screened at birth (449 of 100 332 [0.45%]) to estimate a PR of 7.4 (95% CI, 4.8-11.5) as a conservative lower bound.
CONCLUSIONS AND RELEVANCE
Congenital cytomegalovirus infection increases the prevalence of microcephaly at birth by at least 7-fold. Prevention of CMV infection during pregnancy might substantially reduce the number of newborns with microcephaly and other cCMV-related outcomes in the United States.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Microcephaly; Neonatal Screening; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Risk Factors; United States
PubMed: 32926077
DOI: 10.1001/jamapediatrics.2020.3009 -
Magnetic Resonance Imaging Feb 2021G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and...
G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and GIT1 knockout (KO) mice exhibit learning and memory deficits. We noted that male and female GIT1-KO mice exhibit neuroimaging phenotypes including microcephaly, and altered cortical layering, with a decrease in neuron density in cortical layer V. Micro-CT and magnetic resonance microscopy (MRM) were used to identify morphometric phenotypes for the skulls and throughout the GIT1-KO brains. High field MRM of actively-stained mouse brains from GIT1-KO and wild type (WT) controls (n = 6 per group) allowed segmenting 37 regions, based on co-registration to the Waxholm Space atlas. Overall brain size in GIT1-KO mice was ~32% smaller compared to WT controls. After correcting for brain size, several regions were significantly different in GIT1-KO mice relative to WT, including the gray matter of the ventral thalamic nuclei and the rest of the thalamus, the inferior colliculus, and pontine nuclei. GIT1-KO mice had reduced volume of white matter tracts, most notably in the anterior commissure (~26% smaller), but also in the cerebral peduncle, fornix, and spinal trigeminal tract. On the other hand, the basal ganglia appeared enlarged in GIT1-KO mice, including the globus pallidus, caudate putamen, and particularly the accumbens - supporting a possible vulnerability to addiction. Volume based morphometry based on high-resolution MRM (21.5 μm isotropic voxels) was effective in detecting overall, and local differences in brain volumes in GIT1-KO mice, including in white matter tracts. The reduced relative volume of specific brain regions suggests a critical, but not uniform, role for GIT1 in brain development, conducive to brain microcephaly, and aberrant connectivity.
Topics: Animals; Brain; Cell Cycle Proteins; Female; GTPase-Activating Proteins; Gene Knockout Techniques; Male; Mice; Microcephaly; Neuroimaging; Neurons; X-Ray Microtomography
PubMed: 33010377
DOI: 10.1016/j.mri.2020.09.023