Cortical Overgrowth in Fetuses With Isolated Ventriculomegaly

Abstract

Mild cerebral ventricular enlargement is associated with schizophrenia, autism, epilepsy, and attention-deficit/hyperactivity disorder. Fetal ventriculomegaly is the most common central nervous system (CNS) abnormality affecting 1% of fetuses and is associated with cognitive, language, and behavioral impairments in childhood. Neurodevelopmental outcome is partially predictable by the 2-dimensional size of the ventricles in the absence of other abnormalities. We hypothesized that isolated fetal ventriculomegaly is a marker of altered brain development characterized by relative overgrowth and aimed to quantify brain growth using volumetric magnetic resonance imaging (MRI) in fetuses with isolated ventriculomegaly. Fetal brain MRI (1.5 T) was performed in 60 normal fetuses and 65 with isolated ventriculomegaly, across a gestational age range of 22-38 weeks. Volumetric analysis of the ventricles and supratentorial brain structures was performed on 3-dimensional reconstructed datasets. Fetuses with isolated ventriculomegaly had increased brain parenchyma volumes when compared with the control cohort (9.6%, P < 0.0001) with enlargement restricted to the cortical gray matter (17.2%, P = 0.002). The extracerebral cerebrospinal fluid and third and fourth ventricles were also enlarged. White matter, basal ganglia, and thalamic volumes were not significantly different between cohorts. The presence of relative cortical overgrowth in fetuses with ventriculomegaly may represent the neurobiological substrate for cognitive, language, and behavioral deficits in these children.

Normative biometry of the fetal brain using magnetic resonance imaging

“…The extra-cerebral CSF linear measurement showed an increase from 22 to 30 weeks when it reached a peak and decreased from 30 to 38 weeks. Interestingly, this is a similar evolution pattern of the 2D and 3D measurements of the CSP (Kyriakopoulou et al 2014). The 2D extra-cerebral CSF measurement will be predominantly affected by the development of the temporal lobes, while the 3D extra-cerebral CSF measurement will be affected by the development of all brain lobes.…”

“…This variability may be attributed to differences in the anatomical definition of the structure and inclusion of the third ventricle or the cavum septum pellucidum. We have previously shown in a sub-group ( n  = 60) of this cohort that the volumes of the CSP, third and fourth ventricles, change significantly with GA (Kyriakopoulou et al 2014). Extra-cerebral CSF volume increased at a relative growth rate of 9.6% per week from 22 to 38 weeks.…”

“…Similar to the evolution pattern of the extra-cerebral CSF volume, the 2D and 3D measures of the CSP also peak at 30 weeks (Kyriakopoulou et al 2014), while amniotic fluid volume follows a similar bell-shaped trajectory peaking at around 30–32 weeks (Brace and Wolf 1989). In addition, our data on intracranial parameters indicate an increase in volume range in the supratentorial brain tissue, cerebellum, total lateral ventricles, and cortex around that time.…”

Developmental neurotoxicity of inhaled ambient ultrafine particle air pollution: Parallels with neuropathological and behavioral features of autism and other neurodevelopmental disorders

“…VM associated with such deficits persists after birth [189] and is more prevalent in males [190]. Prenatal VM is predictive of time to first-episode psychosis, and schizophrenia diagnosis [179,190-193]. …”

Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice

“…It has been associated with multiple developmental CNS disorders, including autism and schizophrenia (Barttfeld et al 2011; Bigler 1987; Fannon et al 2000; Movsas et al 2013; Sanfilipo et al 2000; Schulz et al 1983; Wright et al 2000), idiopathic mental retardation, periventricular leukomalacia (Volpe 2001, 2003, 2005), fragile X syndrome, and attention deficit disorder and, in the absence of other CNS abnormalities, to developmental delays (Gilmore et al 2001, 2008). Its consequences can include progressive hydrocephalus, gray matter migration abnormalities, loss of parenchymal brain tissue, agenesis of the corpus callosum, and delayed or abnormal maturation of white matter, that is, reduced MBP (myelin basic protein) expression, diminished total axon volume, trisomies, and microcephaly (Bigler 1987; Gilmore et al 1998, 2001, 2008; Griffiths et al 2010; Kuban et al 1999; Kyriakopoulou et al 2014, Manfredi et al 2010). Ventriculomegaly is associated with such deficits, persists after birth (Gilmore et al 2001), and is more prevalent in males (Gilmore et al 1998).…”