Schizencephaly of the brain

The formation of abnormal clefts in the thickness of the cerebral hemispheres - schizencephaly of the brain (from the Greek schizo - split, split and enkephalos - the brain) - is one of the congenital cerebral defects. [1]

Epidemiology

Clinical statistics estimate the incidence of schizencephaly in one case per 65-70 thousand births. The estimated prevalence is 1.48 per 100,000 births. An open type of anomaly is detected 2.5 times more often. Closed schizencephaly is bilateral in 40-43% of cases, and open - in almost 80%.

In almost all patients with unilateral open cleft of the cerebral hemisphere, the head is asymmetric; with bilateral schizencephaly, asymmetry is noted in approximately 60% of cases.

According to some reports, most often this defect is found in childhood, on average, at the age of 5-6 years.

Causes of the schizencephaly

Although the exact etiology of schizencephaly, as one of the  malformations of the brain , is unknown, its connection with a number of factors, both non-genetic and genetic, is obvious. The main reasons for which there may be schizencephaly of the brain in a newborn are associated with violations of its prenatal formation - the migration of neuroblasts during embryogenesis and early morphogenesis.

Schizencephaly can be caused by intrauterine damage to the fetus by cytomegalovirus (type 5 herpes virus), which is asymptomatically present in the mother and, reactivating in the body of the unborn child, can affect the brain, as well as the spinal cord, eyes, lungs and gastrointestinal tract. Read more -  Cytomegalovirus during pregnancy

Deviations in brain development can be triggered by hypoxia -  oxygen starvation of the fetus  or intracranial hemorrhage - antenatal stroke, which, as studies have shown, is most often caused by mutations in the COL4A1 gene on chromosome 13, which encodes type IV collagen - the main protein in the basement membranes of body tissues, including, endothelium of blood vessels. Mutations found in this gene cause pathology of small cerebral vessels and stroke in the fetus. In addition, disruption of the type IV collagen network during fetal development negatively affects cell migration, proliferation, and differentiation. [2]

Schizencephaly has also been associated with mutations: germline in the homeobox gene EMX2 (on chromosome 10),  [3]which regulates morphogenesis and is expressed in dividing neuroblasts of the developing cerebral cortex; the SIX3 gene (on chromosome 2) encoding the protein transcription factor SIX3, which plays an important role in the development of the forebrain (prosencephalon) of the embryo; the SHH gene (on chromosome 7),  [4]which encodes the ligand of the protein signaling pathway involved in the morphogenesis of the cerebral hemispheres.

Risk factors

In addition to sporadic gene mutations or the possible inheritance of a defective gene, experts consider teratogenic effects of alcohol and drugs, as well as antiepileptic drugs (anticonvulsants) used during pregnancy, some anticoagulants, and drugs of retinoic acid (synthetic vitamin A) to be risk factors for schizencephaly. [5], [6]

In addition to cytomegalovirus, the threat of development of congenital brain defects is HSV 1 - herpes simplex virus type 1, herpes virus type 3 - Varicella zoster virus (varicella zoster virus) and a virus of the genus Rubivirus (causing measles rubella). Read more in the publication -  Viral infections as a cause of embryo- and fetopathy

Pathogenesis

Prenatal formation of the brain and its cortex from the neuroectoderm of the prechordal region begins at the fifth or sixth week of gestation. And it is during this period - as a result of abnormal proliferation and migration of neuroblast cells along the neural tube - that a cleft occurs in the medulla, which further leads to a violation of its development. And the pathogenesis of which lies in cortical dysplasia and destructive changes in the  cerebral hemispheres . [7], [8]

This genetically determined cortical malformation can affect one or both hemispheres of the brain, and its essence is the formation of a cleft that connects the inner soft shell (pia mater) of the cerebral hemisphere with one or both lateral ventricles of the brain (ventriculi laterales), which are lined with ependyma, consisting of neuroglial cells, similar to the epithelial cells of the mucous membranes. The lining of the cleft is gray matter, but its heterotopia occurs: due to the delay in the migration of neurons to the cerebral cortex, they are located incorrectly - in the form of a continuous layer (columns) of gray matter, which is adjacent directly to the junction of pia mater and ependyma. [9], [10]

Most clefts are located in the posterior frontal or parietal lobes, but may occur in the occipital and temporal lobes.

Schizencephaly can be of two types - open and closed. When open, the CSF-filled cleft runs through the hemispheres from the ependyma in the center to the pia mater without a connecting band of gray matter.

Closed schizencephaly is gray matter-covered bands (called "lips" by imaging specialists) that touch and grow together. In the first case, the cerebrospinal fluid between the cavity of the ventricle and the subarachnoid space circulates freely, in the second case, the cleft prevents its circulation.

Often there is a lack of part of the hemispheres with their replacement with cerebrospinal fluid. Often there is  microcephaly , the absence of a transparent septum (septum pellucidum) in the brain and hypoplasia of the optic nerve (septo-optic dysplasia), as well as aplasia of the corpus callosum (corpus callosum).

Symptoms of the schizencephaly

The clinical symptoms of schizencephaly vary depending on which part of the brain is affected, whether the anomaly is open, closed, unilateral, or bilateral. And their severity is determined by the degree of splitting and the presence of other cerebral anomalies.

The closed type of defect may be asymptomatic or be detected in adults of average intelligence when presenting for epileptic seizures and minor neurological problems (limitation of movement).

The first signs of open schizencephaly, which has a more severe course with a bilateral nature, are manifested by convulsions, muscle weakness and motor disorders. There are severe cognitive impairments (with lack of speech). Patients may have paresis and paralysis of varying degrees (upper and lower extremities) with impaired motor functions (up to the inability to walk).

Bilateral schizencephaly of the brain in a newborn leads to a delay in the development of both physical and mental. With bilateral cleft in infants, spastic diplegia and tetraplegia (paralysis of all limbs) are noted, with unilateral - spastic hemiplegia (unilateral paralysis).

Complications and consequences

In schizencephaly, consequences and complications include:

• epilepsy, often refractory (resistant to drugs), which manifests itself in children under three years of age;
• muscle hypotension, partial or complete paralysis;
• accumulation of cerebrospinal fluid in the brain -  hydrocephalus  with increased intracranial pressure.

Diagnostics of the schizencephaly

Instrumental diagnostics can detect schizencephaly of the brain, and this is MRI -  magnetic resonance imaging (MRI) of the brain , which makes it possible to obtain images in different planes, visualize the size of the defect, determine its exact localization and predict neurological outcome. [11], [12]

The presence of a cleft can be determined by  ultrasound of the fetus  at 20-22 weeks of gestation, but this congenital malformation is considered a neonatal diagnosis.

Differential diagnosis

On the basis of tomographic visualization of cerebral structures, differential diagnosis with focal cortical dysplasia and other  brain dysgenesis is carried out .

Treatment of the schizencephaly

In all cases of the presence of abnormal clefts in the thickness of the cerebral hemispheres, the treatment is symptomatic, aimed at stopping seizures, increasing muscle tone and developing motor skills.

For convulsions  , antiepileptic drugs are used .

Physiotherapy is being done. For example, in Europe, the technique of dynamic neuromuscular treatment by Vaclav Vojta (a Czech pediatric neurologist who has worked in Germany for more than 35 years) is used. This method is based on the principles of reflex locomotion and, as studies have shown, promotes cortical and subcortical activation of the brain and central nervous system.

Ergotherapy is aimed at the development of fine motor skills, occupational therapy is aimed at the development of elementary skills, speech therapy is aimed at the development of speech.

If this defect is complicated by hydrocephalus, surgical treatment consists of placing a ventricular-peritoneal shunt to drain cerebrospinal fluid.

Prevention

Preventive measures include proper obstetric management of pregnancy and timely  prenatal diagnosis of congenital diseases , as well as access to genetic counseling (when planning a pregnancy).

Forecast

For patients with schizencephaly, the prognosis may vary depending on the size of the clefts and the degree of neurological impairment.