Polymicrogyria of the brain

A congenital defect - the formation of many abnormally small convolutions with a general change in the cellular structure of the cerebral cortex - is defined as polymicrogyria of the brain (from Latin gyrus - gyrus). [1]

Epidemiology

According to statistics, among all types  of brain dysgenesis,  congenital anomalies of its cortex are observed in about a third of cases, but there are no data on the prevalence of isolated polymicrogyria.

Causes of the polymicrogyria

So far, the specific causes of polymicrogyria are being clarified, but the essence of its etiology - like all  malformations of the brain  - lies in the deviations of its embryonic development.[2]

In this case, the process of gyrification of the fetal brain is disrupted - the formation of characteristic folds of the cerebral cortex, which begins approximately from the middle of pregnancy. Convolutions form from the tops of these folds, and furrows form from the depressions between them. In conditions of limited space of the cranium, the formation of convolutions and furrows provides an increase in the area of the cerebral cortex.[3]

Violations of intrauterine development of the cerebral cortex in most cases are due to chromosomal abnormalities and gene mutations. This may be a mutation in one gene or a deletion of several neighboring ones.[4]

Polymicrogyria is isolated, but it can also occur with other brain anomalies - genetically determined syndromes, in particular, with DiGeorge syndrome (chromosome 22q11.2 deletion syndrome); [5]Adams-Oliver, Zellweger, Walker-Warburg syndromes; Aicardi syndrome (with agenesis of the corpus callosum of the brain), Smith-Kingsmore syndrome (with macrocephaly), Goldberg-Sprintzen syndrome (with microcephaly and facial dysmorphism), etc.[6], [7]

Risk factors

Risk factors for polymicrogyria include:

• hereditary genetic defects;
• spontaneous genetic mutations in the embryo;
• negative impact on the fetus of toxins or infections, in the first place, defeat by  cytomegalovirus during pregnancy ;
• cerebral ischemia due to insufficiency of perfusion of the placenta and  oxygen starvation of the fetus ;
• subdural hemorrhage of the fetus of various origins.[8]

Pathogenesis

Despite the fact that the physiological mechanism underlying gyrification remains unclear today (there are several versions of it), the pathogenesis of polymicrogyria is associated with impaired neurogenesis of brain structures, including migration, division, and proliferation of embryonic neural crest cells, neuroblasts. And also with the above-mentioned violation of the gyrification of the fetal brain.

These disorders result in defects in the connective tissue  membranes of the brain  - soft (pia mater) and arachnoid (arachnoidea mater), including changes in the thickness of the layers and their number, fusion of the molecular layers of adjacent gyri, increased vascularization of the membranes with impaired cerebral perfusion (and possible focal hemorrhages in the soft cortex, edema of the underlying white matter and atrophy of part of the cortex).[9]

In the histogenesis of the cerebral cortex, the basement membrane of its pia mater plays an important role. Studies have shown that polymicrogyria and other cortical defects can be associated with unstable growth of this membrane with defects in its protein and glycoprotein components (type IV collagen, fibronectin, laminins, etc.), which leads to a pathological change in the cellular structure of the cortex.

Among the genes whose changes were detected in polymicrogyria, for example, the GPR56 (or ADGRG1) gene on chromosome 16q21 is noted, which encodes the membrane G-protein of cell adhesion receptors - intercellular contacts that regulate the process of embryo morphogenesis and determine one or another form of the resulting tissue. Mutations in this gene are associated with the development of bilateral fronto-parietal polymicrogyria.[10]

Symptoms of the polymicrogyria

If polymicrogyria in a child affects one side of the brain, it is called unilateral (unilateral), and if the cortex of both hemispheres is affected, the defect, respectively, is bilateral or bilateral. Cortical malformation in the form of polymicrogyria affects mainly the dorsolateral cortex.

The first signs and the clinical picture that develops over time depend entirely on which specific areas of the brain are affected by the anomaly.

Unilateral focal polymicrogyria affects relatively small areas of the brain and most often spreads to the frontal or fronto-parietal cortex, as well as the perisylvian cortex - near the sylvian (lateral) sulcus. Manifested  by convulsive seizures , other neurological symptoms may be absent.

Manifestations of bilateral forms of polymicrogyria: recurrent seizures of epilepsy, developmental delay, muscle weakness, strabismus (strabismus), problems with swallowing (dysphagia) and speech (dysarthria).

So, in addition to frequent convulsions, bilateral frontal (frontal) polymicrogyria is manifested by a delay in the general and mental development of the child, spastic tetraplegia (flaccid paralysis of the lower and upper extremities), ataxia (disorder in coordination of movements), dysbasia (gait disturbance) and often ataxia (complete inability to stand ) and abasia (inability to walk).

Frontoparietal polymicrogyria or bilateral frontoparietal polymicrogyria is characterized by such symptoms as: developmental delay, cognitive impairment (moderate or severe), convulsions, lack of conjugation of gaze and strabismus, ataxia, muscle hypertonicity.[11]

If there is bilateral perisylvian polymicrogyria, then among the symptoms (manifested at birth, in infancy, or closer to two or three years of age), the most common are: convulsions and spasticity of the limbs, dysphagia and salivation, partial bilateral paralysis of the muscles of the face, tongue, jaw and larynx, and also developmental delay - general and cognitive.

The most severe form, affecting the entire brain, is bilateral generalized polymicrogyria. This condition causes severe cognitive retardation, movement problems, and seizures, persistent tonic-clonic epileptic seizures that are difficult or impossible to control with medication.[12]

Complications and consequences

The consequences of polymicrogyria include:

• myoclonic encephalopathy in the form of severe seizures of generalized epilepsy -  West syndrome ;
• motor dysfunction and speech impairment;
• cognitive deficiency and varying degrees of  mental retardation in children .

Diagnostics of the polymicrogyria

The diagnosis of polymicrogyria of the brain is determined based on the presenting symptoms and the result of a neurological examination, including genetic analysis and various imaging modalities.

To date, instrumental diagnostics using  magnetic resonance imaging (MRI) of the brain is considered the most informative .[13]

Electroencephalography is used to evaluate brain function.

Differential diagnosis

Differential diagnosis is carried out with other congenital anomalies of the brain, including pachygyria, schizencephaly, syndromic disorders of cerebral functions, as well as  idiopathic generalized and focal epilepsy in children .[14]

Treatment of the polymicrogyria

With this congenital defect, treatment is aimed at eliminating the symptoms. So, antiepileptic drugs are used to control seizures .

Other methods of treatment: physiotherapy, occupational therapy, speech therapy.

In most cases, therapy is palliative.[15], [16]

Prevention

Given the significant proportion of spontaneous gene mutations leading to the development of this malformation of the cerebral cortex, prevention is considered impossible.

Forecast

In most cases, with polymicrogyria, the prognosis is poor: 87-94% of patients suffer from almost incurable epilepsy with recurrent seizures. Many children with a bilateral anomaly or damage to more than half of the convolutions of one hemisphere die in early childhood.