CENTRAL NERVOUS SYSTEM DISEASES: CAUSES AND TYPES - NEUROPSYCHOLOGY

The diseases of the central nervous system can be divided two types: defects and alterations. The prenatal and postnatal development of our nervous system (NS) follows a very complex process based on numerous neurochemical events, genetically programmed and really susceptible to external factors, such as environmental influence.

When a congenital malformation occurs, the normal and efficient development of the cascade of developmental events is interrupted and diseases of the nervous system can appear. Therefore, structures and / or functions will begin to develop in an abnormal way, having serious consequences for the individual, both physically and cognitively.

The World Health Organization (WHO) estimates that approximately 276,000 newborns die during the first four weeks of life as a result of suffering from some type of congenital disease. Standing out for its great impact both at the level of those affected, their families, health systems and society, cardiac malformations, neural tube defects and Down syndrome.

Congenital anomalies that involve alterations of the central nervous system can be considered one of the main causes of fetal morbidity and mortality (Piro, Alongi et al., 2013). They can represent approximately 40% of infant deaths during the first year of life.

In addition, these types of abnormalities are an important cause of impaired functionality in the child population, leading to a wide variety of neurological disorders (Herman-Sucharska et al, 2009).

The frequency of suffering from this type of anomaly is estimated approximately between 2% and 3% (Herman-Sucharska et al, 2009). While within this range, between 0.8% and 1.3% of live-born children suffer from it (Jiménez-León et al., 2013).

Congenital malformations of the nervous system comprise a very heterogeneous group of anomalies, which can appear in isolation or as part of a larger genetic syndrome (Piro, Alongi et al., 2013). Approximately 30% of cases are related to genetic disorders (Herman-Sucharska et al, 2009).

Causes

Dividing the development of the embryo into different periods, the causes that would affect the formation of the nervous system are the following:

First trimester of gestation: abnormalities in the formation of the neural tube.
Second trimester of gestation: abnormalities in neuronal proliferation and migration.
Third trimester of gestation: abnormalities in neural organization and myelination.
Skin: cranial dermal sinus and vascular malformations (chrysoid aneurysm, Sinus pericranii).
Skull: craniostenosis, craniofacial anomalies and cranial bone defects.
Brain: dysraphias (encephalocele), hydrocephalus (aqueduct of Sylvio stenosis, Dandy-Walker syndrome), congenital cysts and phakomatosis).
Spinal: esponlidolisis, dysraphia cord (spina bifida asymptomatic, symptomatic spine, meningocele, myelocele bifida, myelomeningocele).

Thus, depending on the time of occurrence, duration, and intensity of the harmful exposure, different morphological and functional lesions will occur (Herman-Sucharska et al, 2009).

Types of central nervous system diseases

Central nervous system diseases can be divided into two types (Piro, Alongi et al., 2013):

Malformations

The malformations give rise to abnormalities of brain development. They can be the cause of genetic defects such as chromosomal abnormalities or imbalances of the factors that control genetic expression, and they can occur both at the time of fertilization and in later embryonic stages. In addition, it may recur.

Interruptions

A disruption of the normal development of the nervous system occurs as a consequence of multiple environmental factors, such as prenatal exposure to chemicals, radiation, infections or hypoxia.

In general, they are not recurrent once exposure to harmful agents is avoided. However, the timing of exposure is essential, as the earlier the exposure, the more serious consequences.

The most critical moment is the period from the third to the eighth week of gestation, where most of the organs and brain structures develop (Piro, Alongi et al., 2013). For example:

Cytomegalovirus infection before the middle of the gestation period can lead to the development of microcephaly or polymicrogyria.
Cytomegalovirus infection during the third trimester of gestation can cause encephalitis, the cause of other diseases such as deafness.

Alterations in neural tube formation

The fusion of this structure usually takes place around days 18 and 26 and the caudal area of the neural tube will give rise to the spine; the rostral part will form the brain and the cavity will constitute the ventricular system. (Jiménez-León et al., 2013).

Alterations in the formation of the neural tube occur as a consequence of a defect in its closure. When there is a general failure of the closure of the neural tube, anencephaly occurs. On the other hand, when a defective closure of the posterior area occurs, it will lead to affectations such as encephalocele and spina bifida occulta.

Spina bifida and anencephaly are the two most common neural tube malformations, affecting 1-2 out of every 1,000 live births (Jiménez-León et al., 2013).

Anencephaly

Anencephaly is a lethal disorder incompatible with life. It is characterized by an abnormality in the evolution of the cerebral hemispheres (partial or complete absence, together with partial or complete absence of the bones of the skull and scalp). (Herman-Sucharska et al, 2009).

Some neonates can survive a few days or weeks and show some sucking, gagging, or spasm reflexes. (Jiménez-León et al., 2013).

We can distinguish two types of anencephaly based on their severity:

Total anencephaly: it occurs as a consequence of damage to the neural plate or lack of induction of the neural tube between the second and third week of gestation. It presents with the absence of the three cerebral vesicles, absence of the hindbrain and without the development of both the roof of the skull and the optic vesicles (Herman-Sucharska et al, 2009).
Partial anencephaly: there is a partial development of the optic vesicles and the hindbrain (Herman-Sucharska et al, 2009).

Encephalocele

In encephalocele there is a defect in the mesoderm tissue with a herniation of different brain structures and their covers (Jiménez-León et al., 2013).

Within this type of alterations we can distinguish: bifid skull, encephalomeningocele (protrusion of the meningeal layers), anterior encephaloceles (ethmoities, sphenoid, nasoethmoidal and frontonasal), posterior encephaloceles (Arnol-Chiari malformation and abnormalities of the opccipito-cervical junction), optical abnormalities, endocrine abnormalities, and cerebrospinal fluid fistulas.

In general, these are alterations in which a diverticulum of the brain tissue and the meninges protrudes through defects in the cranial vault, that is, a defect of the brain in which the lining and the protective fluid remain outside, forming a protuberance both in the occipital region and in the frontal and syncipital region (Roselli et al., 2010)

Spina bifida

Normally, the term spina bifida is used to characterize a variety of abnormalities defined by a defect in the closure of the vertebral arches, affecting both superficial tissues and structures of the spinal canal (Triapu-Ustarroz et al., 2001).

Spina bifida occulta is generally asymptomatic. The case of open spina bifida is characterized by a defective closure of the skin and leads to the appearance of myelomeningocele.

In this case, the spinal line of the spine and the spinal canal do not close properly. Consequently, the medulla and meninges can protrude to the outside.

Furthermore, spina bifida is frequently related to hydrocephalus , which is characterized by an accumulation of cerebrospinal fluid (CSF) producing an abnormal enlargement of the ventricles and compression of brain tissues (Triapu Ustarroz et al., 2001).

On the other hand, when the most anterior area of the neural tube and associated structures develop abnormally, alterations will occur in the divisions of the cerebral vesicles and in the cranio-facial midline (Jiménez-León et al., 2013).

One of the most serious manifestations is holoprosencephaly, in which there is an abnormality in the hemispheric division of the prosoencephalon, as a significant cortical disorganization.

Alterations in cortical development

Current classifications of cortical developmental disorders include abnormalities related to cell proliferation, neuronal migration, and cortical organization.

Cell proliferation disturbances

For the proper functioning of our nervous system it is necessary that our structures reach an optimal number of neuronal cells, and that in turn they go through a process of cell differentiation that precisely determines each of their functions.

When defects in cell proliferation and differentiation occur, alterations such as microcephaly, macrocephaly and hemimegalencephaly may occur (Jiménez-León et al., 2013).

Microcephaly: in this type of alterations there is an evident cranial and cerebral disproportion due to a neuronal loss (Jiménez-León et al., 2013). The head circumference is approximately more than two standard deviations below the mean for her age and gender. (Piro, Alongi et al., 2013).
Macrocephaly megalencephaly: there is a larger brain size due to abnormal cell proliferation (Jiménez-León et al., 2013). The head circumference has a circumference greater than two standard deviations above the mean. When macrocephaly without hydrocephalus or dilation of the subarachnoid space is called megalencephaly (Herman-Sucharska et al, 2009).
Hemimegalencephaly: there is an enlargement of one of the cerebral or cerebellar hemispheres (Herman-Sucharska et al, 2009).

Migration alterations

It is necessary for neurons to initiate a migration process, that is, to move towards their final locations in order to reach cortical areas and begin their functional activity (Piro, Alongi et al., 2013).

When an alteration of this displacement occurs, alterations take place; lissencephaly may appear in its most severe form, and in milder forms, abnormal lamination of the neocortex or microdysgenesis appears (Jiménez-León et al., 2013).

Lissencephaly: this is an alteration in which the cortical surface is smooth and without grooves. It also presents a less serious variant, in which the cortex is thickened and with few furrows.

Alterations in cortical organization

The abnormalities of the cortical organization will refer to alterations in the organization of the different layers of the cortex and may be both microscopic and macroscopic.

They are usually unilateral in nature and are associated with other abnormalities in the nervous system such as hydrocephalus, holoprosencephaly or agenesis of the corpus callosum. Depending on the alteration that occurs, they may present asymptomatic or with mental retardation, ataxia or ataxic cerebral palsy (Jiménez-León et al., 2013).

Among the alterations of the cortical organization, polymicrogyria is an alteration that affects the organization of the deep layers of the cortex, and that gives rise to the appearance of a large number of small convolutions (Kline-Fath & Clavo García, 2011).

Diagnosis

The early detection of this type of alterations is essential for its subsequent approach. The WHO recommends care in both preconception and postconceptive periods with reproductive health practices or genetic tests for the general detection of congenital diseases.

Thus, the WHO indicates different interventions that can be carried out in three periods:

Before conception: in this period the tests are used to identify the risk of suffering from certain types of alterations and of transmitting them congenitally to their offspring. Family history and detection of carrier status are used.
During pregnancy: the most appropriate care should be determined based on the risk factors detected (early or advanced age of the mother, consumption of alcohol, tobacco or psychoactive substances). In addition, the use of ultrasound or amniocentesis can help detect defects related to chromosomal abnormalities and the nervous system.
Neonatal period: in this stage, physical examination and tests to detect hematological, metabolic, hormonal, cardiac and nervous system alterations are essential for the early establishment of treatments.

In congenital diseases of the nervous system, ultrasound examination during the gestation period is the most important method for detecting prenatal malformations. Its importance lies in its safe and non-invasive nature (Herman-Sucharska et al, 2009).

Magnetic resonance

On the other hand, different studies and attempts have been made to apply magnetic resonance imaging (MRI) for the detection of fetal malformations. Although it is non-invasive, the possible negative influence of exposure to the magnetic field on embryonic development is studied (Herman-Sucharska et al, 2009).

Despite this, it is an important complementary method for the detection of malformations when there is an obvious suspicion, being the optimal moment for its performance between weeks 20 and 30 of gestation (Piro, Alongi et al., 2013).

α-fetoprotein

In the case of the detection of alterations in the closure of the neural tube, this can be carried out through the measurement of the levels of α-fetoprotein, both in the maternal serum and in the amniotic fluid through the amniocentesis technique within the first 18 weeks of pregnancy.

If a result with high levels is obtained, a high-resolution ultrasound should be performed to detect possible defects early before week 20 (Jiménez-León et al., 2013).

Early detection of complex malformations and early diagnosis will be key to proper prenatal control of this type of abnormality.

Treatment

Many types of congenital malformations of the nervous system are amenable to surgical correction, ranging from in utero interventions for hydrocephalus and myelomeningocele to neonatal interventions. However, in other cases its surgical correction is delicate and controversial (Jiménez-León et al., 2013).

Depending on the functional consequences, in addition to a surgical or pharmacological approach, a multidisciplinary intervention with physiotherapeutic, orthopedic, urological and psychotherapeutic care will also be required (Jiménez-León et al., 2013).

In any case, the therapeutic approach will depend on the moment of detection, the severity of the anomaly and its functional impact.

References

Herman-Shucharska, I., Bekiesinska-Figatowska, M., & Urbanik, A. (2009). Fetal central nervous system malformations on MR images. Brain & Development (31), 185-199.
Jiménez-León, J., Betancourt-Fursow, Y., & Jiménez-Betancourt, C. (2013). Central nervous system malformations: neurosurgical correlation. Rev Neurol (57), S37-S45.
Olufemi Adeleye, A., & Dairo, MD (2010). Central nervous system congenital malformations in a daveloping country: issues and challenges against

their prevention. Childs Nerv Syst (26), 919-929.
Piro, E., Alongi, A., Domianello, D., Sanfilipo, C., Serra, G., Pepitone, L.,… Corsello, G. (2013). Malformations of central nervous system: Genral

issues. Mediterranean Medicine Act (29).
Polished, P. (sf). Congenital malformations. Obtained from www.neurorgs.com-RGS Neurosurgery Unit.
Roselli, Monica; Hooch, Esmeralda; Alfredo, Ardila;. (2010). Neuropsychology of Child Development. Mexico: The Modern Manual.
Tirapu-Ustarroz, J., Landa-González, N., & Pelegrín-Valero, C. (2001). Neuropsychological deficits in hydrocephalus related to spina bifida. Rev Neurol, 32 (5), 489-497.

CENTRAL NERVOUS SYSTEM DISEASES: CAUSES AND TYPES - NEUROPSYCHOLOGY - 2025