The Polymicrogyria Is a rare neurological disease that causes a cerebral malformation characterized by excessive cortical folds and shallow furrows. This is an abnormal development of the brain that occurs before birth.
The surface of the brain usually has many folds, called convolutions. In the case of patients with polymicrogyria, the brain Develops too many folds, while being unusually small.
Hence the literal meaning of polymicrogyria: too many (poly) small (micro) folds (-gyria) on the surface of the brain.
There are different types of polymicrogyria, including unilateral polymicrogyria, which would be the mildest form when it only affects a relatively small area of one side of the brain. If it affected both sides, it would be bilateral polymicrogyria.
The symptoms will depend on how much the brain is affected and in particular on those regions that are affected. It usually occurs as an isolated feature, although it can also occur with other brain abnormalities such as the 22q11 deletion syndrome, 2, Adams-Oliver syndrome, Aicardi syndrome or Spectrum disorder Zellweger .
Polymicrogyria can result from both genetic and environmental causes, and may present as an isolated finding or as part of a syndrome.
Finally, the treatment will be based on the symptoms present in each person.
As we mentioned before, the symptoms will depend on the area and the location that is affected, so the symptoms will vary.
Polymicrogyria can occur at any age, from the neonatal period to late adolescence, and its symptoms are quite different according to the different stages of life.
In general the signs of polymicrogyria are as follows:
- Food problems
- Mental retardation
- Cerebral palsy
- Difficulty in speech And swallowing
Cross-eyed or crossed eyes
The following are the symptoms of unilateral and bilateral polymicrogyria:
In the case of unilateral polymicrogyria, with only one part of the brain being affected, the symptoms are usually milder, such as seizures, which can be easily controlled with medication. There are even people with unilateral focal polymicrogyria who have no associated any problems.
In contrast, bilateral forms of polymicrogyria, if they tend to cause more serious neurological problems. Symptoms include recurrent seizures ( epilepsy ), Squinty eyes, speech difficulties, swallowing, delayed development, and muscle weakness or paralysis.
The most serious case would be a generalized bilateral polymicrogyria, which affects the whole brain. This condition causes severe intellectual disability, movement problems, and convulsions that are difficult to control. Symptoms for bilateral polymicrogyria include the following:
-Paralysis of the muscles on both sides of the face, tongue, jaw and throat
- From mild to severe, intellectual disability
-Convulsions and / or epilepsy
Sudden involuntary spasms of facial muscles
Regression of development or loss of previously acquired skills does not occur in general. However, some clinical manifestations (particularly seizures) that appear later in childhood can significantly affect the overall clinical course [Guerrini et al 2003].
Polymicrogyria can result from both genetic and environmental etiologies. It can occur as an isolated finding with no other systemic involvement or as part of a syndrome with multisystem involvement.
As to what is causing the said brain anomaly is still unclear. It appears that intrauterine infection by cigomegalovirus (CMV) could be the basis of a significant percentage of them; In addition, in the last years, a great number of genes that could be involved in the pathophysiology of this type of cerebral malformations are being discovered.
In addition, researchers have identified several environmental and genetic factors that may be responsible for the disease.
Regarding the environmental causes of polymicrogyria, they include certain infections during pregnancy and the lack of oxygen to the fetus called intrauterine ischemia. It can also occur due to toxoplasmosis, syphilis and varicella-zoster.
As for genetic factors, it appears that the condition may be the result of deletions or rearrangements of genetic material from several different chromosomes.
In addition, mutations in an ADGRG1 gene have been found to cause a severe form of the disease called bilateral frontoparietal polymorphism. This gene appears to be critical for the normal development of the outer layer of the brain.
Two forms of polymicrogyria have been localized: bilateral perisliviana on the X chromosome and bilateral frontoparietal polymicrogyria on chromosome 16.
Aicardi syndrome has also been associated with polymicrogyria and other brain malformations including Agenesis of the corpus callosum , Subependymal heterotalia and deficiency of the sickle of the brain. [Barkovich et al., 2001]
Other congenital metabolism errors associated with polymicrogyria include glycine encephalopathy, pyruvate dehydrogenase deficiency, type II glutaric academy, Zelweger syndrome, and neonatal adrenoleukodystrophy. [Harding and Copp 1997].
In general, researchers believe that many other genes are possibly involved in the various forms of presentation of polymicrogyria.
Currently the prevalence is unknown. Researchers believe that, although polymicrogyria in all its forms is a fairly common brain malformation, each individual disorder is rare in the population.
Perisilvian polymicrogyria appears to be the most commonly described syndrome, but its prevalence as that of the other symptoms is still unknown.
In order to establish the diagnosis of polymicrogyria, a series of evaluations are made through different neuroimaging techniques, which gives us detailed information about where the brain anomaly is.
But before proceeding to establish the diagnosis, it is necessary to carry out a series of assessments as:
- The detailed personal history study , As it may point to underlying environmental etiologies such as infections in the uterus or toxicity of a drug during pregnancy.
- Family background , With special attention to learning difficulties , Mental retardation, epilepsy and demoralizing traits that can give us information about the possible mode of inheritance.
- The Karyotype study To identify chromosomal abnormalities. Apart from the problems of orientation, this will help us to identify the loci or more genes involved in the development of polymicrogyria.
- The Creatine kinase serum Should also be measured to rule out the presence of congenital muscular dystrophy.
- In case there are individuals with Peri-vivial polymicrogyria , These should be tested to see if there is a link with Xq28. If such a linkage is confirmed, families may be advised of the inheritance pattern linked to the X chromosome.
Also, patients with frontoparietal polymicrogyria should be examined to see if there is a mutation in the GPR56 gene on chromosome 16q12.2-21. If a mutation is found, the family members will also be examined and therefore the prenatal diagnosis becomes an option.
Usually, the diagnosis of polymicrogyria is made using images from magnetic resonance , Since the Computed tomography Or other imaging methods generally do not have sufficient resolution or adequate contrast to identify small folds.
In particular, MR can demonstrate a cortical surface irregularity suggestive of multiple small folds or an irregular scalloped appearance at the junction of gray matter-white matter; The latter is often more evident, and therefore is what gives rise to such cerebral anomaly. [Raybaud et al 1996]
Before establishing a definitive diagnosis of polymicrogyria, a differential diagnosis must be made, since there are diseases that are accompanied by polymicrogia, including Zellweger's syndrome.
On the other hand, patients with Fukuyama muscular dystrophy may also present polymicrogyria.
In addition to these syndromes, polymicrogyria also needs to be distinguished from pachygria, which is a brain malformation other than polymicrogyria, in which the folds of the surface of the brain are too broad and scarce.
The Lisencephaly (Smooth brain), being the extreme form of pachydermia, should be taken into account, since the grooves in the cortical surface are very little or nothing, resulting in a wide spectrum.
Lissencephaly can be confused with radiolytic polymicrogyria, particularly in images that are low resolution, but the fact of smoothness and lack of irregularity in the grayish-white crossing, together with noticeable increase in cortical thickness, Distinguishes it from lysencephaly.
Treatment plans will vary depending on the severity of the condition and how it manifests in each particular patient.
Treatment is usually symptomatic and includes both seizure medication and special education.
Health areas that are likely to need to be evaluated and assessed include: speech, vision, hearing, mental retardation, and cerebral palsy.
- Orthopedic appliances
Speech therapy for people with language disorders
- Antiepileptic drugs (AEDs) for seizures depending on the type of specific epilepsy
Occupational therapy for people with language disorders
-Surgery for people with spastic motor impairment
As we have seen throughout the article, there is a genetic heterogeneity of polymicrogyria. Many types appear to be inherited as disorders of a single gene, while in some cases the inheritance is multifactorial, with the interaction of several gene modifiers.
Therefore, the prognosis will depend on which area is affected, the location and of course the signs and symptoms it causes.
Those with the mildest forms of polymicrogyria survive into adulthood, while those with the more severe forms may die at an early age as a result of complications such as seizures or pneumonia.
Guerrini et al reported a series of nine patients (two bilateral, seven unilateral) with polymicrogyria and electrical sleep state (ESES) with a favorable prognosis. In a series of 15 patients, Ohtsuka et al confirmed that patients with localized unilateral polymicrogyria tend to have ESES with a relatively favorable prognosis.
Prevention is paramount and for this it is appropriate that parents be educated about common seizure presentations.
Supportive measures, particularly for those who suffer from cerebral palsy due to polymicrogyria, may help prevent the development of secondary complications such as joint contractures and decubitus ulcers.
- Guerrini R, Sicca M, L. Parmeggiani epilepsy and malformations of the cerebral cortex. Epileptic disorders. 2003; 5 Suppl. 2: S9-26
- Barkovich AJ, Simon EM, Walsh CA. Agenesis of the corpus callosum With A Cyst: A Better Understanding and New Classification. Neurology 2001; 56: 220-7
- Harding B, Copp AJ. Malformations. It is: Graham DI, Lantos PL, eds. Neuropathology of Greenfield. 6 ed. London, United Kingdom: Arnold, 1997
- Polymicrogyria: epidemiology, neurological and anatomical factors and clinical evolution of a series of 34 cases. C. Castano de la Mota, M.L. Ruiz-Falcó Rojas, J.J. García Penas, M.L. Calleja Geroa, A. Duat Rodríguez a and M.A. López Pino. Neuropediatrics Service, Infant Child University Hospital, Madrid, Spain
- Polimicrogyria Author: Doctor Laurent Villard 1 Date of creation: October 2002 Update: August 2004 Scientific editor: Professor Gérard PONSOT 1 Genetic medicine and development, INSERM U491, Faculty of Médecine de la Timone, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5 , France.