Diseases of the Central Nervous System can be divided into 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 developmental cascade of events is disrupted and diseases of the nervous system can occur. Therefore, structures and/or functions will begin to develop abnormally, 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 some type of congenital disease. Highlighting its great impact, both at the level of those affected and their families, health systems and society, cardiac malformations, neural tube defects and Down syndrome.
Congenital anomalies involving 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 may account for approximately 40% of infant deaths during the first year of life.
Furthermore, these types of anomalies constitute an important cause of impairment of 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 to be approximately 2% to 3% (Herman-Sucharska et al, 2009). While within this range, between 0.8% and 1.3% of children born alive 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 form part of an important genetic syndrome (Piro, Alongi et al., 2013). Approximately 30% of cases are related to genetic diseases (Herman-Sucharska et al, 2009).
Causes
By dividing the development of the embryo into different periods, the causes that would affect the formation of the nervous system are as follows:
- First trimester of pregnancy : abnormalities in the formation of the neural tube.
- Second trimester of pregnancy : anomalies in neuronal proliferation and migration.
- Third trimester of pregnancy : 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 : dysrafia (encephalocele), hydrocephalus (stenosis of the aqueduct of Sylvio, Dandy-Walker syndrome), congenital cysts and phakomatosis).
- Spinal : sponlidolysis, spinal dysraphy (asymptomatic spina bifida, symptomatic spina bifida, meningocele, myelocele, myelomeningocele).
Thus, depending on the time of occurrence, duration and intensity of harmful exposure, different morphological and functional lesions will occur (Herman-Sucharska et al, 2009).
Types of diseases of the central nervous system
Diseases of the central nervous system can be divided into two types (Piro, Alongi et al., 2013):
malformations
Malformations lead to brain development abnormalities. They can be the cause of genetic defects, such as chromosomal abnormalities or imbalances in the factors that control gene expression, and can occur both at the time of fertilization and in later embryonic stages. Also, you may have recurrence.
Interruptions
There is a disruption in the normal development of the nervous system as a result of multiple environmental factors such as prenatal exposure to chemicals, radiation, infections or hypoxia.
In general, they do not recur when 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, when most of the brain’s organs and structures develop (Piro, Alongi et al., 2013). For example:
- Cytomegalovirus infection before mid-gestation can lead to the development of microcephaly or polymicrogyria.
- Cytomegalovirus infection during the third trimester of pregnancy can cause encephalitis, the cause of other conditions such as deafness.
Changes in neural tube formation
Fusion of this structure usually occurs on days 18 and 26 and the caudal area of the neural tube will give rise to the vertebral column; The rostral part will form the brain and the cavity will constitute the ventricular system. (Jiménez-León et al., 2013).
Changes in neural tube formation occur as a result of a defect in its closure. When there is a generalized failure of neural tube closure, anencephaly occurs. On the other hand, when defective closure of the posterior area occurs, it leads to effects such as encephalocele and occult spina bifida.
Spina bifida and anencephaly are the two most common malformations of the neural tube and affect 1-2 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 may survive a few days or weeks and show some sucking reflexes, moro, or spasms. (Jiménez-León et al., 2013).
We can distinguish two types of anencephaly based on their severity:
- Total anencephaly : occurs as a result of damage to the neural plate or absence of neural tube induction between the second and third weeks of gestation. It presents with the absence of the three cerebral vesicles, absence of the posterior brain and without the development of the skull roof and optic vesicles (Herman-Sucharska et al, 2009).
- Partial anencephaly : there is partial development of the optic vesicles and hindbrain (Herman-Sucharska et al, 2009).
encephalocele
In encephalocele, there is a mesoderm tissue defect with a herniation of different brain structures and their coverings (Jiménez-León et al., 2013).
Within this type of alteration we can distinguish: bifid skull, encephalomeningocele (protrusion of the meningeal layers), anterior encephaloceles (ethmo-ages, sphenoidal, nasoethmoidal and frontonasal), posterior encephaloceles (Arnol-Chiari malformation and abnormalities of the occipito-cervical junction), optical abnormalities, endocrine disorders, and cerebrospinal fluid fistulas.
These are usually changes in which a diverticulum of brain tissue and meninges protrudes through defects in the cranial vault, i.e., a defect in the brain in which the lining and protective fluid are left out, forming a bulge in the occipital region. and in the frontal and sincipital region (Roselli et al., 2010)
Spina bifida
Usually, 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 the superficial tissues and the structures of the spinal canal (Triapu-Ustarroz et al., 2001).
Occult spina bifida is usually 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 and spinal canal do not close properly. Consequently, the medulla and meninges may bulge out.
Furthermore, spina bifida is often related to hydrocephalus , characterized by an accumulation of cerebrospinal fluid (CSF), causing an abnormal increase in ventricular size 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, there will be changes in the divisions of the cerebral vesicles and in the craniofacial 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, with an important cortical disorganization.
Changes in cortical development
Current classifications of disorders of cortical development include abnormalities related to cell proliferation, neuronal migration, and cortical organization.
Changes in cell proliferation
For the proper functioning of the nervous system, it is necessary that our structures reach an ideal number of neuronal cells and that, in turn, you are going through a process of cell differentiation that precisely determines each of its 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 alteration there is 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 age and sex. (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 is a circumference greater than two standard deviations above the mean. When macrocephaly without hydrocephalus or dilatation of the subarachnoid space is called megalencephaly (Herman-Sucharska et al, 2009).
- Hemimegalencephaly: one of the cerebral or cerebellar hemispheres is pleasant (Herman-Sucharska et al, 2009).
migration changes
It is necessary for neurons to start a migration process, that is, for them to move towards their definitive locations to reach cortical areas and start their functional activity (Piro, Alongi et al., 2013).
When this offset changes, changes occur; In its most severe form, lissencephaly may appear, and in milder forms, abnormal lamination of the neocortex or microdysgenesis occurs (Jiménez-León et al., 2013).
- Lissencephaly: if a change in the smooth cortical surface shown without grooves. It also has a less severe variant, in which the bark is thicker and has fewer grooves.
Changes in cortical organization
Cortical organization abnormalities refer to changes in the organization of the different layers of the cortex and can be microscopic and macroscopic.
They are usually of the unilateral type 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 can occur asymptomatically or with mental retardation, ataxia or ataxic cerebral palsy (Jiménez-León et al., 2013).
Within the alterations of cortical organization, polymicrogyria is an alteration that affects the organization of the deep layers of the cortex and leads to the appearance of a large number of small convolutions (Kline-Fath & Clavo García , 2011).
Diagnosis
Early detection of this type of alteration is essential for its subsequent approach. WHO recommends attention in the preconceptual and postconceptual periods with reproductive health practices or genetic testing for the general detection of congenital disorders.
Thus, the WHO points out different interventions that can be carried out in three periods:
- Before conception : during this period, tests are used to identify the risk of suffering certain types of alterations and transmitting them congenitally to their offspring. Family history and carrier status detection are used.
- During pregnancy : the most appropriate care must be determined based on the risk factors detected (early or advanced age of the mother, consumption of alcohol, tobacco or psychoactive substance). In addition, the use of ultrasound or amniocentesis can help detect defects related to chromosomal and nervous system abnormalities.
- Neonatal period : physical examination and tests to detect hematological, metabolic, hormonal, cardiac and nervous alterations are essential in this phase for the early establishment of treatments.
In congenital diseases of the nervous system, ultrasound examination during the gestational 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).
MRI
On the other hand, different studies and attempts have been made to apply magnetic resonance imaging (MRI) to detect fetal malformations. Although not 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 detecting malformations when there is an obvious suspicion, with the ideal time to perform it between the 20th and 30th weeks of pregnancy (Piro, Alongi et al., 2013).
α-fetoprotein
In the case of detecting changes in neural tube closure, this can be done by measuring α-fetoprotein levels, both in maternal serum and in amniotic fluid, using the amniocentesis technique during the first 18 weeks of pregnancy
If a result is obtained with high levels, a high-resolution ultrasound should be performed to detect possible defects before the twentieth week (Jiménez-León et al., 2013).
Early detection of complex malformations and early diagnosis will be essential for adequate prenatal control of these types of alterations.
Treatment
Many of the types of congenital malformations of the nervous system are susceptible to surgical correction, from interventions in the uterus in the case of 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 time of detection, the severity of the anomaly and its functional impact.
