Pachygygyria: what it is and health effects of this malformation

Pachygygyria is a type of brain malformation of the lissencephaly type. Let us see what it looks like.

The brain is the result of many thousands of years of evolution of our species. It is one of the most complex natural phenomena of which we are aware, and the essence of what makes us human. Although it is no stranger to the umbrella of scientific knowledge, new questions about how it works are raised every day.

Its appearance is also very striking. On the part visible to the outside, it is composed of a group of convolutions (protuberances with similar shapes and locations for almost all people) and sulci (fissures or gaps located between the gyri), which serve for the correct location of anatomical sections.

The adoption of its particular shape occurs throughout the gestation process, and is linked to the way in which genes act on our prenatal development. Genetic alterations, or maternal exposure to certain pathogens and toxins, can compromise such a delicate Biological balance.

One such clinical circumstance will be discussed in particular in this article, pachygyriawhich implies a situation of great severity and risk for the continuity of life. Its most essential characteristics, its causes and its frequent symptoms will be discussed here.

What is pachygyria?

Pachygyria is a congenital and serious malformation, which affects the organization of the neurons and the structure of the brain.. It is characterized by the presence of scarcely pronounced cerebral gyri, as well as by the thinning of the cortex, which alters the global structure of the organ (scarce apparent elevations in its surface, being the circumvolutions thicker and wider than those observed in the population average). This neuropathology, which has multiple consequences for the sufferer, would be included in the nosological category of cortical dysgenesis.

Specifically, pachygyria belongs to the family of the lissencephaliasbetween agyria (total absence of convolutions) and subcortical band heterotopia (presence of a "layer" of gray matter in the area located between the walls of the lateral ventricles and the cortex itself), according to Dobyns' classification. Such structural involvement is usually posteriorly predominant, although occasionally it also spreads to the front of the brain and compromises a wide range of cognitive functions.

In fact, it is a severe health condition, with very high mortality rates in the early years (it affects 1/90,000 people (it affects 1/90,000 people in its severe forms, although there is no information on mild forms). It is also associated with the presence of physical and mental symptoms of enormous significance, which compromise daily autonomy and/or pose a real danger to survival. The most notable are muscular hypotonia, ataxia or epileptiform seizures (resistant to medical treatment and of very early onset), as well as severe intellectual disability and general developmental delay.

Diagnosis is usually carried out by two very different, but also complementary, strategies: clinical examination for signs/symptoms, and the use of structural neuroimaging techniques such as magnetic resonance imaging (MRI)..

The latter procedure is very useful, since it allows obtaining detailed images of the sulci/cracks and convolutions, which greatly facilitates the clinical certification of this pathology (especially if one takes into consideration that many of its symptoms can be confused with other more common problems). The absence of dysmorphias (facial alterations typical of chromosomal anomalies) could hinder its early detection.

What are the symptoms of pachygyria?

Pachygygyria has three basic symptoms: seizures, severe developmental disturbance and intellectual disability. This triad can be easily detected as early as the fourth/fifth month of life, and usually warrants consultation with the pediatrician. Although the overall prognosis is obscure (as these symptoms are resistant to pharmacological intervention or directly untreatable), early attention can minimize or prevent the occurrence of more serious complications (such as infectious processes, which are common in these patients).

Epileptic seizures

Pachygyria is one of the diseases with epileptiform seizures in children, which can be life-threatening. Its onset is early, as a high percentage of a high percentage of subjects experience them within the time frame between the fourth and seventh month after birth. (exceptionally after 18 months of age). It usually consists of abrupt onset seizures, both in flexion (abdominal twisting in which the body adopts a posture similar to that of a "closed knife") and in extension (arms and legs stretched out in the form of a "cross"). Until the expansion of functional neuroimaging technologies, these epilepsies were considered cryptogenic (of unknown origin).

Developmental delay

Delay in motor development, as well as in the use of language, is a common feature in people diagnosed with pachygyria. It is very frequent that the basic verbal catalog is not acquired to construct communicative acts fully, or that laxity in the arms and legs is evidenced.

Many of these infants are unable to maintain an upright, standing position without the support/assistance of others. A significant percentage also show a sign that will predict the problems mentioned above: microcephaly, that is, a reduction in the expected growth of head circumference.or, in other words, a reduction in the expected growth of the cranial perimeter.

3. Intellectual disability

People with pachygyria have a severe intellectual disability, with alterations in almost all cognitive functions and the potential to develop autonomy. and the potential to develop a full personal autonomy.

Such difficulty would respond to the abnormal migration of neurons (which will be detailed later) and becomes more evident when the child must deal with all the demands of school or other contexts that require social and/or motor skills. The identification of such a situation is key, because it will depend on it that an appropriate program of curricular adaptation and therapeutic pedagogy can be deployed.

What are the causes of pachygyria?

Pachygyria is caused by an abnormal migration of neurons during gestation.. This process takes place between the seventh and twentieth week, and is essential for the system to acquire a correct functionality from birth onwards.

It is a peculiar "journey" that nerve cells undertake to relocate in order to enable the characteristic cognition of the human being, and which requires their wandering from the ventricles to the external cerebral cortex (traveling enormous distances in proportion to their size). This phenomenon does not occur continuously, but rather in intermittent "spurts".

Although the general purpose is to form six differentiated layers of tissue, ready to host the unfathomable complexity of the mind.in order to accommodate the unfathomable complexity of the mind, in this case only four would be formed (and subject to many structural problems). This laminar disposition motivates the agenesis of the convolutions and/or the sulci, being a result of the deficient organization of the brain. The observation of this abnormality, thanks to optical or electron microscopes, evidences an anatomopathology that we proceed to point out (for each of its four layers).

The first layer (molecular or plexiform), which is the outermost layer of our cerebral cortex, would not show any aberrations whatsoever.. The neurons in this region would have a shape and location identical to those of an unproblematic brain. However, in the second one some important differences already appear: the number of cells is clearly lower and they are disorganized, coexisting with neurons of layers II, V and VI of the normal brain. This quantitative/qualitative alteration has an impact on the general appearance of the organ (as it forms the true cortex of the organ).

The third layer is also very different from that of the six-layered cortex. Here the neurons are poorly organized and are distributed as broad columns, resulting in a tissue of low density or thickness. There is also some evidence of lamellar necrosisresponsible for hindering proper cell migration. Finally, the fourth layer would also have a thin appearance, but built with white matter invaded by a myriad of heterotopic neurons (located in spaces other than those they should occupy).

In addition to deficiencies in neuronal migration, which is the etiological basis common to all lissencephalies, multiple environmental and genetic risk factors are known. In the following lines we proceed to describe them in detail.

1. Exposure to substances and/or viral infections

Pachygyria usually appears in the fourth month of gestation, after the neural migration stage. Although it is a problem that tends to occur sporadically (perhaps influenced by genetic factors), it is known that exposure to certain chemicals is known to be closely related to the likelihood of developing it..

The most common are ethanol (ethyl alcohol), methylmercury (resulting from the activity of industries that use acetaldehyde; such as paper, plastics, paints, rubber or leather) and retinoic acid (a metabolite of vitamin A); but radiation exposure could also play a key role.

Cytomegalovirus infections (throughout pregnancy) have been linked to both pachygyria and other severe alterations in neuronal migration. When an individual comes into contact with this particular pathogen they usually retain it for life, but acute episodes during gestation can be very dangerous. The problem is that it tends not to be too invasive (asymptomatic) in those who are healthy, so it is advisable that diagnostic tests be carried out if it is believed to have been in contact with an acutely infected person.

2. Genetic alterations

A succession of alterations in the genome have been described that are associated with an increased risk of pachygyria. The most common is the one involving chromosomes 17 and Xwhich are the most frequently detected when a cause is found at this level (which is not always possible). In other cases, a mutation in the reelin gene (essential for neural migration) has been found on chromosome 7.

Finally, it is also known that the absence of the LIS1 gene severely damages the structure of neurons and their cortical arrangement, so it has been postulated as a suspect in the etiopathogenesis of pachygyria.