CORTICAL DYSPLASIA: CAUSES, SYMPTOMS AND TREATMENT - NEUROPSYCHOLOGY - 2025

The dysplasia cortical consists of a set of developmental malformations of the brain cortex, which is associated with increasingly refractory epilepsy type (one that is resistant to treatment).

Despite its complex structural abnormalities, this condition is difficult to see reflected on brain scans. This is because its manifestations can be very subtle, becoming pigeonholed as a normal brain image.

Image source: radiologyassistant.nl

Cortical dysplasia is a very peculiar congenital (present at birth) pathology that is associated with problems in the birth and migration of neurons. It is characterized by epileptic seizures that continue despite pharmacological treatments, and distinctive radiological images and histological features. The good news is that this condition can be improved by surgical intervention.

History

The concept of focal cortical dysplasia emerged in 1971 by Taylor et al. When they examined brain parts from patients who had had drug-resistant epilepsy.

They observed damage to the cytoarchitecture of the cortex such as: dysmorphic cells (which have altered cytoskeleton), balloon or balloon cells (they stand out for having a very thick membrane, being abnormally large and poorly defined borders) and dislamination (disorganized cell layers).

Currently it is known that this is only one type of cortical dysplasia, the best known and most frequent, called DCF type II or type Taylor. Although as we will see, there are more types with other different alterations.

Characteristics of cortical dysplasia

Cortical dysplasia is part of the well-known “malformations of cortical development” (MDC), a varied group of pathologies that stands out mainly for an altered development of the structure of the cerebral cortex.

The brain begins to develop before birth, in the intrauterine period, and goes through various phases that may overlap each other. The main stages of the development of the cerebral cortex are cell proliferation and differentiation, migration and organization of cells in their corresponding areas, and myelination.

Lesions in cortical development

Obviously, if there is any type of alteration in these processes, cortical development will be impaired and it will be reflected in various cognitive and behavioral deficits.

Specifically, cortical dysplasias occur due to lesions that occur during the period of proliferation or neurogenesis (growth of new neurons), or during the stage of cortical organization (neurons are placed in layers in the appropriate places).

In this way, neurons and glial cells in certain regions of the cerebral cortex are altered; what manifests itself as specific neurological deficits, epileptic seizures, delayed psychomotor development, etc.

In short, the typical lesions of this condition range from small, practically invisible alterations to serious alterations in the cortical organization with the appearance of abnormal cells, gliosis or ectopic neurons (it means that they are placed in the wrong places).

Thus, a group of large and bizarre neurons and grotesque cells are observed that occupy deep areas of the cerebral cortex and the white matter. However, the various advances in neuroimaging techniques make it possible to better detect these abnormalities of cortical dysplasia.

Symptoms

At this point we will ask ourselves: what do these brain alterations cause in the person? Next, I will try to answer the question by listing the most common symptoms:

Refractory epilepsy in 76% of patients

In the literature, cortical dysplasia appears continuously linked to epilepsy, assuming the cause of it. Epilepsy can be of any type, but is usually associated with drug-resistant (refractory) epilepsy.

For this reason, these patients have frequent seizures that begin at any age from the intrauterine stage and last throughout their lives; although they are more common in childhood.

Depending on where the brain abnormalities are located and the patient's age, the seizures can be: simple partial (they only affect a minimal part of the brain), complex partial (they involve both hemispheres of the brain and cause loss of consciousness) or generalized (seizures produced by altered electrical activity of virtually the entire brain)

Focal neurological deficits

They suppose problems in some specific part of our functioning due to cerebral causes.

They can be very varied such as: the sensitivity of one side of the face, the movement of a limb, the vision of one eye, difficulties in expressing speech, problems with emotional control, etc.

Intellectual problems

It can even sometimes be associated with a below-average level of intelligence, trouble concentrating, and difficulty learning new things.

Delay in cognitive and psychomotor development

The best way to know how a young child is developing is to observe his motor skills.

If their ability to move or acquire certain developmental challenges such as standing upright, starting to walk, being able to reach for a spoon, etc. They arrive very late or present difficulties without any known physical problems and with adequate stimulation, it is possible that there are neurological causes. This is what can happen to babies with cortical dysplasia.

Regarding the appearance of the brain, in some cases the abnormalities are difficult to observe because they are at the cellular level, microscopic. While in other cases it can be seen through brain scans. Some examples are:

Lissencephaly

The brain appears smooth, that is, it does not present the convolutions that are normally seen.

Polymicrogyria

It is characterized by more folds in the cerebral cortex than normal, but with shallow grooves.

Paquigiria

Fewer convolutions than usual, very flattened and thick.

Double cortex syndrome

It is a serious condition in which neurons pile up on each other due to migration problems, forming two cerebral cortices.

Causes

When the baby is in the womb is when the nervous system begins to develop. At first, brain cells are born and are grouped together.

Each one carries specific instructions on which part of the brain it has to travel to to get where it is. Little by little, conductive pathways emerge, such as roads, through which these cells move until they form 6 different layers of the cerebral cortex.

But this whole process is very complex and many factors intervene in it, when any of these processes is impaired, cortical dysplasia can arise.

It is known that, for this condition to occur, both genetic factors and environmental or acquired factors must be present. It can occur for reasons such as genetic abnormalities, prenatal infections, ischemia (problems with the blood supply to the brain), or exposure to toxic elements.

Genetic factors

They are not fully explored, and although more research is lacking, it is known that genetics have something to do with it as there are cases of families with cortical dysplasia and that it is not due to a single genetic mutation.

There are authors who have found that the TSC1 and TSC2 genes may be related to this condition since they seem to be responsible for the “balloon” cells that we mentioned earlier.

There are also alterations in the signaling pathways of the Wnt and Notch proteins. These are responsible for proper neuronal migration, something that is impaired in cortical dysplasia.

Thus, any genetic mutation that affects the regulation of these pathways could be associated with this pathology.

External factors

Radiation and methylazoxymethanol have been shown to cause DNA damage eventually leading to cortical dysplasia.

Types of cortical dysplasia

Cortical dysplasia can encompass any part of the brain, it can vary in extent and location; and it can even be focal, or multifocal (occupies several different areas of the brain).

When it encompasses an entire hemisphere or a large part of both hemispheres, it is known as Giant Cortical Dysplasia (GCD). Although the term focal cortical dysplasia, cortical dysgenesis or something more general, neuronal migration disturbances is commonly used.

Numerous classifications have been proposed due to the heterogeneous and complex structural alterations that this condition can cause. Cortical dysplasia is generally divided into:

Mild malformation of cortical development (MLDC):

It refers to a group of poorly defined microscopic histological alterations of lesions that are not visible by brain scans such as Magnetic Resonance. It can appear under the name of “microdysgenesis” and they are the mildest. Inside there are two subtypes:

- MLDC Type I: there are ectopic neurons (it means that they are located in or near layer I of the cortex, when they should not be there).

- MLDC Type II: it is characterized by microscopic heterotopias outside layer I, which refers to the fact that there are groups of neurons that have not finished migrating to their correct place and have been anchored where they should not.

Type I focal cortical dysplasia

It is also a very mild form, manifesting itself with epilepsy, alterations in learning and cognition. It usually begins to be seen in adults.

However, you may have no symptoms; in fact, there is a study that indicates that this type of dysplasia can be found in 1.7% of healthy individuals.

They are not usually seen with an MRI, or the alterations are very mild. They are usually found in the temporal area of ​​the brain, and are classified into two subgroups:

- DCF Type IA: alterations in the architecture in isolation.

- DCF Type IB: the architecture is also damaged, but there are also giant cells. Dysmorphic cells (with malformations in the cytoskeleton) are not observed here

Cortical Dysplasia Type II or Taylor:

In this case, the symptoms appear at a younger age, about childhood, and present more frequency of epileptic seizures and seizures than type I. In addition, it is the type that is most related to treatment-resistant epilepsy.

It is associated with an increase in abnormal cells, very large, with altered cytoskeleton (dysmorphic), and affecting the electrical signals of the brain.

They are also located in the wrong places, altering the usual architecture of the cerebral cortex. This occurs because they arise from an alteration in the process of cellular differentiation of neurons and glial cells, as well as their migration.

Within this category we can define two subcategories according to the existence or not of balloon cells or “balloon cells”.

Interestingly, where these types of cells are found is less associated with epilepsy than other nearby disturbed areas.

This type is best seen through brain scans, therefore its abnormalities can be more accurately corrected surgically.

These alterations are frequently located in non-temporal brain areas.

Dual pathology

Very associated with epilepsy, it is the presence of two pathologies at the same time: hippocampal sclerosis (alterations in the hippocampus and other associated brain areas) and focal cortical dysplasia that occupies temporal areas.

Treatment

There is no specific treatment for cortical dysplasia, rather interventions are focused on treating the most disabling symptoms, which are usually seizures. For this, antiepileptic and anticonvulsant drugs are used first and the progress of the affected person is observed.

On the other hand, there are cases in which epilepsy continues despite medication. This becomes very annoying, since up to 30 epileptic seizures a day can occur. In these cases it is recommended to resort to neurosurgery, which is giving very good results to alleviate this condition.

The brain is surgically intervened to remove or disconnect abnormal cells from other healthy areas of the brain. It can include the removal of an entire hemisphere (hemispherectomy), a small part of it, or multiple tiny areas.

Physical therapy is also often chosen, which can be very helpful for babies and children who have muscle weakness.

Regarding developmental delays, it is advisable to inform school workers so that they can adapt the school program to the needs of the child. Correct stimulation and care can greatly help these children to lead a satisfactory life.

References

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