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 not strange to the umbrella of scientific knowledge, every day new questions are raised about its operation.
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 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.
This article will address in particular one of these clinical circumstances, pachygyria, which involves 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.
What is pachygyria?
Pachygyria is a serious and congenital malformation that affects the organization of neurons and the structure of the brain. It is characterized by the presence of scarcely pronounced cerebral gyrations, as well as by the thinning of the cortex, which alters the overall structure of the organ (few apparent elevations in its surface, being the convolutions thicker and more extensive than those observed in the population average). This neuropathology, which has multiple consequences for those who suffer it, would be included in the nosological category of cortical dysgenesis.
Specifically, pachygyria belongs to the family of lissencephaly, between agiria (total absence of convolutions) and heterotopia in the subcortical band (presence of a "layer" of gray matter in the area located between the walls of the lateral ventricles and the bark itself), according to the Dobyns classification. Such structural involvement is usually predominantly posterior, although occasionally it also disperses towards the front of the brain and involves 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, despite the fact that there is no information on this in the mild ones). It is also associated with the presence of enormously significant physical and mental symptoms, 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 very early onset), as well as severe intellectual disability and general developmental delay.
Diagnosis is usually carried out using two very different, but also complementary, strategies: the clinical examination of signs / symptoms and the use of structural neuroimaging techniques such as MRI.
This last procedure is very useful, since it allows images to be obtained in great detail on the grooves / fissures and convolutions, which greatly facilitates the clinical certification of this pathology (especially if it is taken into account that many of its symptoms can confused with other more common problems). The absence of dysmorphias (facial changes typical of chromosomal abnormalities) could hinder its early detection.
What are the symptoms of pachygyria?
Pachygyria has three elemental symptoms: seizures, severe developmental disturbance, and intellectual disability. This triad can be easily detected from the fourth / fifth month of life, and usually requires consultation with the pediatrician. Although the general prognosis is dark (since these are symptoms resistant to pharmacological intervention or directly intractable), early attention 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 occur with childhood epileptiform crises, which can pose a serious risk to life. Its establishment is early, since a high percentage of subjects experience them within the time range that mediates between the fourth and the seventh month after birth (exceptionally after 18 months). It usually consists of abrupt seizures, both in flexion (abdominal torsion in which the body adopts a posture similar to that of a "closed razor") 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. Delayed development
Delayed motor development, as well as language use, is a common trait in people diagnosed with pachygyria. It is very often that the basic verbal catalog is not acquired to fully build communicative acts, or that laxity in the arms and legs is evident.
Many of these infants fail to maintain the upright, standing position without the support / help of third parties. A significant percentage also shows a sign that will predict the problems cited: microcephaly, or what is equal, a reduction in the expected growth of the cranial perimeter.
3. Intellectual disability
People with pachygyria have a severe intellectual disability, practically all cognitive functions and the potential to develop full personal autonomy are altered.
Such difficulty would respond to the abnormal migration of neurons (which will be detailed below) 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. Identifying 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?
Pachygyria is caused by abnormal migration of neurons during pregnancy. This process runs from the seventh to the 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 characteristic human cognition, and that requires their ambulation from the ventricles to the external cerebral cortex (traveling enormous distances in proportion to their size) . Such a phenomenon does not occur continuously, but occurs as intermittent "streaks".
Although the general purpose is to form six distinct layers of tissue, prepared to host the unfathomable complexity of the mind, in this case only four would form (and also subject to many structural problems). This laminar disposition motivates the agenesis of the convolutions and / or the grooves, being a result of the deficient organization of the brain. The observation of this abnormality, thanks to the optical or electronic 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 aberrations of any kind. The neurons in this region would be identical in shape and location to those of a smooth brain. However, in the second, some important differences have already emerged: the number of cells is clearly lower and they appear disorganized, living 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-leaf cortex. Here the neurons are poorly organized and are distributed as wide columns, giving rise to a tissue of low density or thickness. There is also some indication of laminar necrosis, responsible for hindering an appropriate migration of the cells. To finish, the fourth layer would also look thin, but built with white matter invaded by a myriad of heterotopic neurons (located in different spaces than they should occupy).
In addition to deficiencies in the migration of neurons, which is the common etiological basis for all lissencephaly, 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 gestation, after the stage of neural migration. Although it is a problem that tends to appear 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 vitamin A metabolite); but also radiation exposure could play a key role.
Cytomegalovirus infections (throughout pregnancy) have been associated with both pachygyria and other serious disturbances of neuronal migration. When an individual comes into contact with this particular pathogen, he or she usually retains it for life, but acute episodes during pregnancy can be very dangerous. The problem is that it tends not to be too invasive (asymptomatic) in those who are healthy, so it is recommended that diagnostic tests be carried out in case 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 related to an increased risk of pachygyria. The most common is that involving chromosomes 17 and X, which are the most frequently detected when filing a cause 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 disposition, which is why it has been postulated as a suspect in the pathogenesis of pachygyria.
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