Pachygyria: What It Is, And Health Effects Of This Malformation
The brain is the result of many thousands of years of evolution of our species. It is one of the most complex natural phenomena that we are aware of, and the essence of what makes us human. Although it is no stranger to the umbrella of scientific knowledge, new questions about its functioning arise every day.
Its appearance is also very striking. In 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 grooves (fissures or gaps that are located between the turns), which serve for correct location of anatomical sections.
The adoption of its particular form 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 very delicate biological balance.
In this article, one of these clinical circumstances will be addressed in particular, the pachygyria, which implies a situation of great severity and risk for the continuity of life. Here its most essential characteristics, its causes and its frequent symptoms will be discussed.
Pachygyria is a serious congenital malformation that affects the organization of neurons and the structure of the brain It is characterized by the presence of barely pronounced cerebral gyri, as well as by the thinning of the cortex, which alters the overall structure of the organ (few apparent elevations on its surface, the gyri being thicker and wider than those observed in the population average). This neuropathology, which has multiple consequences for those who suffer from it, would be included in the nosological category of cortical dysgenesis.
Specifically, pachygyria belongs to the lissencephaly family, between agyria (total absence of gyri) 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 the Dobyns classification. Such structural involvement is usually predominantly posterior, although occasionally it also disperses to the front part 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 first years (it affects 1/90,000 people in its severe forms, although there is no information about it in its mild forms). It is also associated with the presence of physical and mental symptoms of enormous importance, which compromise daily autonomy and/or pose a real danger to survival. The most notable are muscle hypotonia, ataxia or epileptiform seizures (resistant to medical treatment and of very early onset), as well as severe intellectual disability and general developmental delay.
The diagnosis is usually carried out through two very different, although also complementary, strategies: clinical examination of the signs/symptoms and the use of structural neuroimaging techniques such as magnetic resonance imaging
This last procedure is very useful, since it allows obtaining images with great detail of the sulci/fissures and convolutions, which greatly facilitates the clinical certification of this pathology (especially if one takes into consideration that many of its symptoms can be be confused with other more common problems). The absence of dysmorphisms (facial alterations typical of chromosomal abnormalities) could hinder early detection.
What are the symptoms of pachygyria?
Pachygyria has three basic symptoms: seizures, severe developmental disturbance, and intellectual disability. This triad can be easily detected from the fourth/fifth month of life, and usually warrants consultation with the pediatrician. Although the general prognosis is dark (since these are symptoms resistant to pharmacological intervention or directly untreatable), early care can minimize or avoid the appearance of more serious complications (such as infectious processes, which are common in these patients. ).
1. Epileptic seizures
Pachygyria is one of the diseases that cause childhood epileptiform seizures, which can pose a serious risk to life. Its establishment is early, since A high percentage of subjects experience them within the time frame between the fourth and seventh month after birth (exceptionally after 18 months). 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 shape of a “cross”). Until the expansion of functional neuroimaging technologies, these epilepsies were considered cryptogenic (of unknown origin).
2. 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 common that the basic verbal catalog is not acquired to fully construct communicative acts, or that laxity is evident in the arms and legs.
Many of these infants are unable to maintain an upright, standing position without the support/help of third parties. A significant percentage also shows a sign that will predict the problems mentioned: microcephaly or what is the same, a reduction in the expected growth of the cranial perimeter.
People with pachygyria have a severe intellectual disability, practically all cognitive functions being altered and the potential to develop full personal autonomy.
Such difficulty would respond to the abnormal migration of neurons (which will be detailed below) and becomes more evident when the boy/girl 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 whether an adequate program of curricular adaptation and therapeutic pedagogy can be deployed.
What are the causes of pachygyria?
The pachygyria It is caused by abnormal migration of neurons during pregnancy This process extends between the seventh and twentieth week, and is essential for the system to acquire correct functionality from birth.
It is a peculiar “journey” that nerve cells undertake to relocate in a way that enables the cognition characteristic of the human being, and that requires their wandering from the ventricles to the external cerebral cortex (traversing enormous distances in proportion to their size). . This phenomenon does not happen continuously, but rather occurs as intermittent “streaks.”
Yes ok The general purpose is to form six differentiated layers of tissue, prepared to host the unfathomable complexity of the mind, in this case only four would be formed (and also subject to many structural problems). This laminar arrangement motivates the agenesis of the gyri and/or sulci, being a result of the deficient organization of the brain. The observation of this abnormality, thanks to optical or electron microscopes, shows 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 aberrations of any kind The neurons in this region would be identical in shape and location to those in a normal brain. However, in the second, some important differences already emerge: the number of cells is clearly lower and they appear disorganized, coexisting with neurons from layers II, V and VI of the normal brain. This quantitative/qualitative alteration impacts the general appearance of the organ (since it forms the true cortex of the organ).
The third layer is also very different from that of the six-sheet cortex. Here the neurons are poorly organized and distributed as broad columns, giving rise to a tissue of low density or thickness. There is also some evidence of lamellar necrosis, responsible for hindering proper migration of cells. Finally, the fourth layer would also appear thin, 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 common etiological basis for all lissencephalies, multiple environmental and genetic risk factors are known. In the next lines we proceed to describe them in detail.
1. Exposure to substances and/or viral infections
Pachygyria usually appears in the fourth month of pregnancy, 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 closely related to the probability of suffering from it
The most common are ethanol (ethyl alcohol), methylmercury (which results from the activity of the industry that uses 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 related to both pachygyria and other serious alterations in neuronal migration. When an individual comes into contact with this specific pathogen, they usually retain it for life, but acute episodes during pregnancy can be very dangerous. The problem is that it tends to not be too invasive (asymptomatic) in those who are healthy, so it is recommended that diagnostic tests be carried out in case you believe you have been in contact with an infected person in the acute phase.
2. Genetic alterations
A succession of alterations in the genome have been described that are related to an increased risk of pachygyria. The most common is the one that involves chromosomes 17 and, which are the most frequently detected when a cause is identified at this level (which is not always possible). In other cases, a mutation has been found in the reelin gene (essential for neural migration) 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, which is why it has been postulated as a suspect in the etiopathogenesis of pachygyria.
