What is hemimegalencephaly?
Hemimegalencephaly is an extremely rare condition where one half of the brain’s cerebral cortex is larger than the other. The neurons in the enlarged half are typically malformed. Cytoarchitecture (how the neurons are stacked) is one type of deformity. It can include various types of cortical dysplasias such as polymicrogyria, pachygyria , and other brain malformations. Often, the corpus callosum is poorly formed or absent. The ventricles of the brain may be enlarged as well due to hydrocephalus .
Types of hemimegalencephaly
● Isolated hemimegalencephaly: Only the cerebral cortex is involved with no associated unilateral body overgrowth, skin involvement, or systemic involvement of the organs;
● Syndromic hemimegalencephaly: Not only is the brain involved, but also the skin and some organs. Conditions such as linear nevus syndrome, “cafe au lait” spots, ash leaf marks , and Hypomelanosis of Ito. Skin involvement may take months or years after birth to appear. Hemihypertrophy , where one half of the body is larger than the other, may also be present. Hemihypertrophy can be mild to severe and can sometimes a risk of tumors of the kidneys and other organs. In rare cases, syndromic hemimegalencephaly can include facial infiltrating lipomatosis, Proteus syndrome, and issues with collagen which may lead to hyperextensible joints and other challenges.
● Total hemimegalencephaly: Includes enlargement of cerebellum and sometimes brain stem. Total hemimegalencpehaly can be isolated or syndromic.
In some cases, hemimegalencephaly can include malformations on the other side of the brain. Sometimes these malformations may take years to find because magnetic resonance imaging (MRI) is unable to detect the malformation until the child is older.
Cause
Hemimegalencephaly is caused by a spontaneous mutation which occurs on the mTOR pathway at approximately the third week of gestation. It is genetic (meaning that it involves genes) but is not hereditary. There are no reported cases of two or more children with hemimegalencephaly in one family.
There is no evidence to show that hemimegalencephaly is caused by poor maternal diet or ingestion of any substance during pregnancy.
Diagnosis
Hemimegalencephaly is very difficult to diagnose in utero. Ultrasound imaging can only detect some, but not all, forms of brain malformations. Because it is a spectrum condition (meaning there is a broad range of presentation, from mild to severe) it can often go undetected in utero.
Seizures
In most cases, hemimegalencephaly will cause the child to have seizures. Seizures can begin in very early infancy and are often drug-resistant. Some children may not have any seizures associated with hemimegalencephaly.
There are many different types of seizures associated with hemimegalencephaly. It is important to note here that seizures in childhood, especially if they begin in early infancy, can be catastrophic to the child’s development. Uncontrolled, they can lead to profound intellectual and developmental impairment, cause development to freeze in time, and damage the developing brain. Stopping seizures as soon as possible is imperative.
Epileptic spasms (formerly known as infantile spasms) is a particularly catastrophic form of childhood epilepsy, can often occur with hemimegalencephaly. Again, it is imperative that infantile spasms are stopped as soon as possible.
A small number of children are able to maintain relative seizure control throughout their lives, but most will have drug-resistant epilepsy that requires hemispherectomy – a type of brain surgery where one half of the cerebral cortex is removed or disconnected from the other side. Sometimes, other resection surgeries may be recommended.
Shorter time seizing prior to surgery is correlated with better developmental outcomes in infants with hemimegalencephaly.
Prognosis
Hemimegalencephaly is a spectrum condition, meaning there is a wide range of functional outcomes that are poorly reported in research literature. Most children with hemimegalencephaly have some level of intellectual disability. Some can attain near normal intellectual development if seizures are controlled. Others may have profound intellectual and motor disabilities. All children with hemimegalencephaly have hemiparesis, a type of cerebral palsy which affects one side of the body, which may range from very mild to severe. Some may have homonymous hemianopsia, a visual impairment where half the visual field is lost. Most are able to walk and talk, but not all. Some may be tube fed while others can eat a normal diet orally. Like any spectrum condition, there are outliers at both ends of the spectrum.
Functional outcomes are closely tied to seizure control and whether the brain malformation is present on both sides of the brain. It is extremely important that the child’s neurologist is proactive in ensuring that the child has no seizures. Epilepsy surgery – most often hemispherectomy/hemispherotomy – should be considered early if the child fails two medications.
In children who have had hemispherectomy/hemispherotomy, early data from our Global Pediatric Epilepsy Surgery Registry shows that 68% eventually speak after surgery. (See Speech and Cognition After Hemispherectomy For Hemimegalencephaly: A Report From The Global Pediatric Epilepsy Surgery Registry presented at the American Epilepsy Society Meeting in 2020.
How young can hemispherectomy be performed?
Hemispherectomy is an extremely delicate and difficult brain surgery which should only be performed by an experience pediatric epilepsy surgeon. The youngest reported case is 41 days; however, we know an infant as young as 28 days has had hemispherectomy surgery for hemimegalencephaly.
Hemispherectomy for hemimegalencephaly is particularly difficult for many reasons: often the blood vessels are malformed, making them difficult to locate and cut during surgery, and can sometimes cause excessive bleeding. Also, the overall brain malformation makes surgery difficult because the familiar landmarks the surgeon uses to identify various structures are often missing. The epilepsy surgeon should not only have experience performing hemispherectomy, but should also be experienced performing hemispherectomy on infants with hemimegalencephaly.
Support Groups
The Hemimegalencephaly Family Support Network is the world’s largest support group for parents of children with hemimegalencephaly. It offers a website and Yahoo! group, but its most active support platform is now found in this closed Facebook group which includes parents from all over the world. To request acceptance into the Facebook group, you must request permission to join the group. Be sure to check your message folders on Facebook (especially the “recent”folder) as administrators will contact you to ask why you want to join the group. Grandparents, siblings, and others may join the group only with the permission of the parents of the child first.
Every two years, there is a national pediatric epilepsy surgery conference in the United States for children of families affected by epilepsy surgery. The hemimegalencephaly group usually has the most attendees at this conference, and often families of children who have not yet had hemispherectomy, or whose seizures are controlled and do not need hemispherectomy, attend this conference so that they can meet other families of children with hemimegalencephaly.
Resources
Hemimegalencephaly is an extremely rare condition. Many neurologists will be unfamiliar with the condition. The International League Against Epilepsy has excellent resources for neurologists which should be reviewed here.
Sources
Seizure and cognitive outcomes of epilepsy surgery in infancy and early childhood
