Polymicrogyria (PMG)
Polymicrogyria (PMG) is a relatively common brain malformation linked to developmental and neurological disorders, including epilepsy and autism, often caused by prenatal factors like infections, with growing evidence suggesting a need for early diagnosis, awareness, and potential preventive treatments.
[Posted on 22 April 2025 by Christopher Gillberg]
"Dedicated to Hera, 10 years old"
Polymicrogyria (PMG) in the brain refers to an overfolding and abnormal layering of the brain's cortex. This causes the surface of the brain to appear irregular. PMG occurs during fetal development due to abnormalities in the later stages of neuronal migration or in the early stages of the so-called cortical organisation. The nerve cells end up "in the wrong place" in the brain.
PMG is one of the most commonly known "malformations" in the brain and has recently, in a larger study from Stockholm, been shown to have a higher frequency than previously believed: at least 2 children per 10,000 births are affected. This means that every year in Sweden, about 20 children are born who can be identified through brain imaging, such as MRI, to have PMG during their development. However, there is likely a significant underreporting, as not all children with symptoms undergo brain imaging. The Stockholm study also showed that almost all of the 109 children had developmental neurological problems/NDD/ESSENCE.
PMG is present in some individuals with 22q11.2DS, but also in many who have undergone cytomegalovirus (CMV) infection or early brain infarction. The causal relationships are often complex and can be influenced by both genetic factors and environmental damage, as well as combinations of both.
As early as 40 years ago, Ed Ritvo and colleagues noted PMG during the autopsy of an individual with autism. Later, Marcelo Berthier found PMG through MRI brain scans in two individuals with Asperger syndrome. In 1990, Joe Piven and his team examined 13 "high-functioning" individuals with autism using MRI, and it was found that 7 of them had abnormalities in the appearance of the cortical brain, 5 of whom had PMG.
Taken together, these now fairly "old" studies show that PMG is relatively common within ESSENCE/NDD.
In recent years, a relatively high frequency of PMG has also been observed in treatment-resistant epilepsy. The connection often seems to be that the child contracted a CMV infection during the fetal stage, which then led to the development of PMG, which in turn greatly increases the risk of epilepsy. At least half of all children with confirmed PMG develop epilepsy during the first few years of life. New onset of epileptic seizures is rare after the age of 10.
When I have travelled around the world and lectured on rare diagnoses, parents of children with PMG – like many parents of children with 22q11.2DS – have expressed concerns about their child developing schizophrenia when they reach adolescence. Several studies have pointed to a significantly increased risk of schizophrenia in 22q11.2DS, possibly especially if PMG is also present. However, the results from our own long-term studies of 22q11.2DS suggest that it is uncommon to develop schizophrenia; rather, (transient?) psychoses during and after the teenage years are relatively common. Early information about the diagnosis and understanding from the child’s close family members is likely a contributing factor to a "good prognosis" in this regard.
Most brain malformations within PMG are caused by damage to the so-called neocortex during the later stages of fetal development and are triggered by infections such as CMV, or by oxygen deprivation, or alternatively by brain hemorrhage with subsequent inflammation in the young nerves and support cells. The connection to 22q11.2DS and other relatively rare genetic syndromes is not yet fully understood. PMG in 22q11.2DS is often particularly pronounced in parts of the temporal lobes and in the right hemisphere, abnormalities that in various studies have been linked to symptoms of autism and different types of speech and language disorders.
In studies on mice with artificially induced PMG, it has recently been observed that treatment with hydrocortisone significantly reduces the risk of both PMG and seizure disorders. It is possible that anti-inflammatory treatment could also be feasible in humans, at least if there is suspicion that the fetus may be on the verge of developing PMG, and the treatment is initiated as soon as possible.
It is urgent to establish systematic research plans in the near future to get closer to understanding PMG, its connection with 22q11.2DS, and, not least, to potentially find relevant, possibly anti-inflammatory (including preventive) treatment methods.
Patients, parents, siblings, other relatives, teachers, physiotherapists, occupational therapists, leisure educators, speech therapists, nurses, and, not least, doctors and psychologists, should be (preferably jointly) trained in the field within the next year.
[This is a blog. The purpose of the blog is to provide information and raise awareness concerning important issues. All views and opinions expressed are those of the writer and not necessarily shared by the GNC.]
