Central Nervous System Diseases

The Diseases of the nervous system central Two subtypes can be divided: malformations and alterations.

Prenatal and postnatal development of our nervous system (SN) follows a very complex process based on numerous neurochemical events, genetically programmed and actually 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 may appear. 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 suffering from some form of congenital disease. Stressing its great impact both at the level of those affected, their families, health systems and society, heart malformations, neural tube and the Down's Syndrome .

Congenital anomalies involving central nervous system disturbances can be considered a major cause 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.

In addition, these types of anomalies are a major cause of impairment of the functionality in the child population, resulting in a wide variety of neurological disorders (Herman-Sucharska et al, 2009).

The frequency of this type of anomalies is estimated to be between 2% and 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 NS include a very heterogeneous group of anomalies, which may occur in isolation or as part of a major genetic syndrome (Piro, Alongi et al., 2013). Approximately 30% of cases are related to genetic disorders (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 may be the cause of genetic defects such as chromosomal abnormalities or imbalances of the factors controlling gene expression, and may occur both at the time of fertilization and in later embryonic stages. In addition, recurrence may occur.
• Interruptions: There is disruption of 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 are not of a recurrent type once exposure to harmful agents is avoided. However, timing of exposure is essential, since the earlier the exposure, the more serious the consequences will be.

However, the time of exposure to the anomalous process or external harmful agent is essential, since the earlier the exposure, the more serious the consequences. The most critical moment is the period from the third to the eighth week of gestation, where most organs and structures of the brain develop (Piro, Alongi et al., 2013). For example:

• The Cytomegalovirus infection Before half the time of gestation can lead to the development of Microcephaly or Polymicrogyria .
• Cytomegalovirus infection during the third trimester of gestation can lead to encephalitis, a cause of other diseases such as deafness.

Dividing the development of the embryo in different periods, the causes that would affect the formation of the SN are the following:

• First trimester of gestation : Abnormalities in neural tube formation.
• Second trimester of gestation : Anomalies in proliferation and neuronal migration.
• Third trimester of gestation : Abnormalities in neural organization and in myelination.

In addition, congenital abnormalities can appear either at the cranial, encephalic or spinal level.

• Skin : Cranial Dermal sinus and vascular malformations (Chrysoid aneurysm, Sinus pericranii).
• Skull : Craniosthenosis, craniofacial anomalies and cranial bone defects.
• Brain : Dysraphias (Encephalocele), Hydrocephalus (Sylvian Aqueduct Stenosis, Dandy-Walker Syndrome), congenital cyst and facomatosis).
• Spinals : Spondylolysis, Spinal Dysphraia (asymptomatic spina bifida, symptomatic spina bifida, dermal sinus, anchored marrow, sacral lipoma, etc.- open spina bifida -Meningocele, myelocele, myelomeningocele-).

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

Alterations of 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 neural tube formation occur as a consequence of a defect in its closure. When a generalized neural tube closure failure occurs, Anencephaly . On the other hand, when a defective closure of the back area occurs, it will Encefelocele and spina bifida oculta.

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

Anencephaly

The Anencephaly Is a lethal alteration incompatible with life. It is characterized by an abnormality in the evolution of the cerebral hemispheres (partial or complete absence, along with partial or complete absence of the bones of the skull and the scalp (Herman-Sucharska et al, 2009). Weeks and show some sucking reflexes, Moro or spasms (Jiménez-León et al., 2013).

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

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

Encephalocele

At Encephalocele There is a tissue defect in the Mesoderm 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 (ethmoid, sphenoidal, nasoetmoid and frontonasal), posterior encephaloceles (Arnol-Chiari malformation and opccipito-cervical junction abnormalities ), Optic abnormalities, endocrine abnormalities and cerebrospinal fluid fistulas.

In general, these are alterations in which a diverticulum of the brain tissue and the meninges protrude through defects in the cranial vault, that is to say, a defect of the brain in which the coating and the protective liquid are left, forming a Protrusion in both the occipital region and the frontal and sincipital region (Roselli et al., 2010)

Spina bifida

Typically, 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).

The hidden spina bifida is usually asymptomatic. The case of open spina bifida is characterized by defective closure of the skin and leads to the appearance of Myelomeningocele . In this case, the spinal line of the spine and the duct Do not close correctly. Consequently, the medulla and the meninges can protrude outside.

In addition, spina bifida is frequently related to Hydrocephalus , Which is characterized by an accumulation of cerebrospinal fluid (CSF) producing an abnormal increase in the size of the ventricles and compression of the brain tissues (Triapu Ustarroz et al., 2001).

On the other hand, when the anterior neural tube and associated structures develop abnormally, there will be alterations in the divisions of the cerebral vesicles and in the cranial-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 prosoencéfalo, as an important cortical disorganization.

Alterations of cortical development

Current classifications of alterations in cortical development include abnormalities related to cell proliferation, neuronal migration, and cortical organization.

Alterations of cell proliferation

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 you are going through a process of cellular differentiation that precisely determines each of its functions.

When defects in cell proliferation and differentiation occur, alterations such as microcephaly, Macrocephaly And hemimegalencephaly (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 cranial perimeter presents approximately more than two typical deviations below the average for its 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 cranial perimeter has 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: There is an enlargement of one of the cerebellar or cerebral hemispheres (Herman-Sucharska et al, 2009).

Migration alterations

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

When there is an alteration of this displacement, alterations take place, in their most severe form, the Lisencephaly And in milder forms, abnormal lamination of neocortex or microdisgenesis appears (Jiménez-León et al., 2013).

• Lisencephalia: S E is an alteration in which the cortical surface is smooth and without furrows. In addition it presents / displays a variant, less serious, in which the crust is thickened and with shortage of furrows.

Alterations of cortical organization

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

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

Diagnosis

Early detection of this type of alterations is essential for its subsequent approach. The WHO recommends attention in both preconception and postconceptional periods with reproductive health practices or genetic testing for the general detection of congenital diseases. Thus, the WHO points out different interventions that can be performed in three periods:

• Before conception : In this period the tests are used to identify the risk of suffering certain types of alterations and congenitally transmit their offspring. Family history and detection of carrier status are used.
• During gestation : The most appropriate care must be determined based on the risk factors detected (early or advanced age of lamadre, consumption of alcohol, tobacco or psychoactive substance). In addition, the use of Ultrasound Or amniocentesis can help detect defects related to chromosomal and SN abnormalities.
• Neonatal period : Physical examination and tests to detect hematological, metabolic, hormonal, cardiac, and NS changes are essential at this stage for the early establishment of treatments.

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

On the other hand, different studies and attempts have been made to apply magnetic resonance (MRI) for the detection of fetal malformations. Although it is noninvasive, the possible negative influence of magnetic field exposure 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 time for its realization between weeks 20 and 30 of gestation (Piro, Alongi et al., 2013).

In the case of detection of alterations in neural tube closure, this can be done by measuring the levels of Α-fetoprotein , Both the maternal serum and the amniotic fluid through the amniocentesis technique within the First 18 weeks of pregnancy. If a high-level result is obtained, a high-resolution ultrasound scan should be performed to detect possible defects early by week 20 (Jiménez-León et al., 2013).

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

Treatment of diseases of the nervous system

Many of the types of congenital malformations of NS are susceptible to surgical correction, both from interventions In utero In the case of hydrocephalus and myelomeningocele, or through 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 both the time of detection, the severity of the anomaly and the functional impact of it.

Prevention

Due to the enormous impact of congenital diseases of the nervous system, it is considered the prevention of these anomalies as an essential point within the health system. Numerous investigations have shown how different alterations respond effectively to primary and secondary prevention measures.

For example, maternal supplementation with folic acid Before conception substantially reduces abnormalities resulting from defects in neural tube closure by 50-70% (Olufemi and Dairo, 2010). Thus, prevention programs in many countries include the prescription of multivitamins with folic acid, since an intake of 400 μg / day before conception occurs and during the first 12 weeks of pregnancy prevents much of these defects (Jiménez- Leon et al., 2013).

On the other hand, the use of prenatal images such as ultrasound allows the early detection of abnormalities allowing a more effective intervention.

In addition, avoid exposure to harmful external agents such as valproic acid , Exposure to radiation, intake of folate antagonists (trimethoprim, carbamazepine, phenytoin and phenobarbital), malnutrition or Alcohol consumption Jiménez-León et al., 2013), will significantly reduce the probability of occurrences of alterations related to the development of the nervous system.

In general, WHO (2015) in relation to the general prevention of congenital anomalies, offers a series of guidelines that refer to primary prevention:

• Dietary regulation of women of childbearing age, guaranteed sufficient intake of vitamins and minerals, especially folic acid, either through a supplement orally or with foods such as corn or wheat flour.
• Restrict the consumption of harmful substances such as alcohol.
• Control of diseases such as diabetes .
• Avoid exposure to harmful environmental agents such as heavy metals and pesticides during gestation.
• Exposure to justified drugs and radiation, based on a detailed analysis of benefits and risks.
• Improve vaccination coverage. Administration of vaccination against rubella in girls and even one month before pregnancy in non-vaccinated adult women who have not previously had this disease.
• Promotion of early detection.

conclusion

Congenital diseases of the NS can have important functional consequences for the individuals who suffer from them. Although many Can correct through pediatric surgery, early detection is critical. This type of disease can have a genetic or environmental origin, and this second factor is a key point for its prevention.

References

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