Pachygyria (from the Greek meaning "thick" or "fat" gyri) is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, the onset and severity depending on the severity of the cortical malformation. Infantile spasms are common in affected children, as is intractable epilepsy.
Presentation
The term 'pachygyria' does not directly relate to a specific malformation but rather is used to generally describe physical characteristics of the brain in association with several neuronal migration disorders; most commonly disorders relating to varied degrees of lissencephaly. Lissencephaly is present in 1 of 85,470 births and the life span of those affected is short as only a few survive past the age of 20. Pachygyria is a condition identified by a type of cortical genetic malformation. Clinicians will subjectively determine the malformation based on the degree of malposition and the extent of thickened abnormal grey differentiation present.
Connections to epilepsy, lissencephaly, and subcortical band heterotopia
Various degrees of intensity and locations of epilepsy are associated with malformations of cortical development. Researchers suggest that approximately 40% of children diagnosed with drug-resistant epilepsy have some degree of cortical malformation.
Lissencephaly (to which pachygyria is most closely linked) is associated with severe mental retardation, epilepsy, and motor disability. Two characteristics of lissencephaly include its absence of convolutions (agyria) and decreased presence of convolutions (pachygyria). The types of seizures associated with lissencephaly include: persisting spasms focal seizures tonic seizures atypical seizures atonic seizures
Other possible symptoms of lissencephaly include telecanthus, estropia, hypertelorism, varying levels of mental retardation, cerebellar hypoplasia, corpus callosum aplasia, and decreased muscle tone and tendon reflexes. Over 90% of children affected with lissencephaly have seizures.
Patients with subcortical band heterotopia (another disorder associated with pachygyria) typically have milder symptoms and their cognitive function is closely linked to the thickness of the subcortical band and the degree of pachygyria present.
Causes
Pachygyria is caused by a breakdown in the fetal neuronal migration process due to genetic or possibly environmental influences. The affected cerebral cortex will typically have only four developed layers instead of the normal six. One of the best known and most common types of neuronal migration disorders is lissencephaly, a diffuse cortical malformation relating directly to agyria and pachygyria. Incomplete neuronal migration during the early fetal brain development is the precursor to lissencephaly. Should neurons follow an abnormal migration during development possible cortical malformations include classical lissencephaly (as stated above) and subcortical band heterotopia with an agyria-pachygyria band spectrum.
Normal neuronal migration
Normal neuronal migration involves the development of six cortical layers, each one performing distinct functions.
Normal cerebral development occurs in three dynamic and overlapping stages: first stage: stem cells proliferate and differentiate into neurons or glial cells within the forebrain and the ventricular and subventricular zones lining the cerebral cavity; in humans this stage lasts from gestational weeks 5–6 to 16–20; second stage: migration away from the origin in a radial fashion along the glial fibers from the periventricular region of the ganglionic eminences towards the pial surface; the generations settle into a pattern within the cortical plate during this stage; in humans this stage lasts from gestational weeks 6–7 to 20–24; third stage: apoptosis and synaptogenesis within the six cortical layers to develop correct cortical organization; in humans this stage lasts from gestational week 16 until long after birth.
Most types of incomplete neuronal migration to the cortex occur during the third and fourth gestational months. The abnormal migration of the neurons causes them to not reach their proper final destinations, which results in failure of the sulci and gyri to form.
The stage of cortical development at which migration is arrested is directly related to the level of structural malposition.
One of the most critical stages in brain development is when the post-mitotic neurons migrate from the ventricular zone to form the cortical plate. Migration arrested toward the latter part of development usually restricts the abnormal cell position to the cortex level.