Hemimegalencephaly & Cortical Dysplasia

Malformations of cortical development (MCD) are increasingly recognized as an important cause of epilepsy and developmental delay. MCD encompass a wide spectrum of focal and diffuse disorders with various underlying genetic etiologies and clinical manifestations. Disruption at various stages of normal cortical development – those of neuronal proliferation, neuroblast migration, and neuronal organization - lead to characteristic MCD.  Focal Cortical Dysplasia (FCD) and Hemimegalencephaly (HME) are both types of MCD, but the association of the two is so close that the malformations are often considered as part of their own spectrum.  Many look at HME as a severe form of cortical dysplasia, though FCD and HME themselves can exhibit a broad range of severity.  The dividing line between an FCD diagnosis and HME diagnosis is not always obvious; therefore it can sometimes be difficult to ascertain a definitive diagnosis.  To learn more about MCD, please view the presentation, Neuroimaging of Seizures: Malformations of Cortical Development, in the column to the right.     

Hemimegalencephly, first described by Sims in 1835 and also known as unilateral megalencephaly, is relatively rare and characterized by the enlargement and malformation of most or all of a cerebral hemisphere.  HME is considered to be a primary disorder of proliferation wherein the neurons that are unable to form synaptic connections are not eliminated but accumulated instead. The affected hemisphere may also have focal or diffuse neuronal and glial cell migration defects, with areas of polymicrogyria, pachygyria, and heterotopias.  The exact pathogenesis of such a complex malformation is still unknown.  Common hypotheses reported in literature are that it occurs due to insults during the second trimester of pregnancy, or as early as the 3rd week of gestation, as a genetically programmed developmental disorder related to cellular lineage and establishment of symmetry.  

HME is classified into three (3) types.  Isolated HME occurs sporadically without hemicorporal hypertrophy or cutaneous or systemic involvement.  Syndromic HME occurs in association with neurocutaneous syndromes or developmental disorders (such as Klippel–Trenaunay-Weber Syndrome, hypomelanosis of Ito, linear sebaceous nevus of Jadassohn, neurofibromatosis, tuberous sclerosis complex, epidermal nevus syndrome, Proteus syndrome) and may occur as hemihypertrophy of all or part of the ipsilateral body.  Total HME, which is the least common, involves enlargement of the same (ipsilateral) half of the brainstem and cerebellum.  No chromosomal abnormalities have been associated with isolated HME and there are no known inheritance patterns.  A gender bias has not been observed in the isolated type, nor has a bias to the left or right hemisphere.    

Symptoms often include:
  • abnormally large head and/or asymmetrical head at birth or in early childhood
  • epileptic seizures, especially soon after birth (although these may be delayed until later in infancy or in more rare cases into early childhood)
  • developmental delay ranging from mild to severe
  • progressive contralateral hemiplegia - a weakness down one side of the body
  • progressive contralateral  hemianopia – blindness in one half of the visual field in both eyes
  • psychomotor difficulties, though not all patients experience these
  • the most common with occurrence rate of 90%

Other possible symptoms of the syndromic forms include facial or limb enlargement and/or skin disorders that are indicative of the particular associated syndrome or developmental disorder.

Prenatal diagnoses have been reported, though most cases go undiagnosed prior to delivery.  Ultra-sound scanning may show asymmetry of the cerebral hemispheres.  Ante-natal MR scan at twenty to twenty-five weeks in specialist units may provide additional information.  Prenatal screening and genetic advice may be optional protocol for future pregnancies. 

Gross pathology of HME correlates with imaging findings of enlargement of the affected cerebral hemisphere.  The brain surface may show pachygyria and polymicrogyria.  Microscopically, nerve cells are larger and less densely packed than in the normal side of the brain, and the number of glial cells is increased.  Areas of polymicrogyria, neuronal heterotopia, and pachygyria occur.  White matter may show areas of poor myelination, cystic change, and gliosis.  Histologically, there is no difference between FCD and HME. However, macroscopically, HME involves the whole hemisphere, whereas FCD is typically more limited. 

Treatments may lessen or alleviate seizures and improve the quality of life for HME patients. In most cases, the first line of treatment is AEDs (Anti-Epileptic Drugs), though current clinical experience indicates that early surgical consideration should be given because of the intractable nature of the seizures associated with HME. Many children undergo and see significant benefit from hemispherectomy surgery.  Hemispherectomy is the most effective treatment to control seizures, and it also seems to provide good results on the psychomotor development when performed early. Some neurologists and neurosurgeons are currently of the thought that the earlier the surgery, the better the outcome in regards to both seizure control and cognitive impairment.  While seizure cessation remains the ultimate goal of this extreme treatment, quality of life improvement scan no longer be ignored as another primary impetus for surgery.  

Focal cortical dysplasia or unilateral cortical dysplasia involves malformation of part of one cerebral hemisphere, without the enlargement associated with HME. Patients, however, present with similar clinical features and require a similar course of management.  FCD is frequently associated with focal epilepsy and about 76% of patients will have drug resistant epilepsy.  The resulting degree of developmental delay varies from mild to severe.    

MRI criteria suggestive of FCD are gyration anomalies, focal thickenings of the cortex, blurring of the grey–white matter junction, and abnormal cortical and subcortical signal intensity.  FCD is classified into types and subtypes based on severity and pathology.   FCD type 1 and its subtypes are considered mild MCD, while more severe forms are labeled as FCD type 2 and subtypes.  Typing based on pathology is as follows: isolated architectural abnormalities (dyslamination) (FCD 1a), additional ‘immature neurons’ or giant neurons (FCD 1b), additional dysmorphic neurons (FCD 2a) and additional balloon cells (FCD 2b).  Some subtypes are thought to originate in the first trimester of gestation due to abnormal cell proliferation, others are believed to emerge later in the third trimester due to abnormal cortical organization. The different times at which the disorders occur may affect the epileptogenicity of FCD and the outcome after surgery. 

Click here to view a classification article on focal cortical dysplasia. 

The Hemi Foundation Cortical Dysplasia Family Network is for families of children who have, or persons with, a cortical dysplasia diagnosis that has led to hemispherectomy surgery or consideration and exploration of hemispherectomy as a treatment option for drug resistant epilepsy due to cortical dysplasia. Because this Network is a Facebook support group of the Hemispherectomy Foundation, members need to have registered or be willing to register with the Hemispherectomy Foundation. The purpose of this Network is to allow Cortical Dysplasia families of the Hemispherectomy Foundation the opportunity to connect for family-to-family support. It's an avenue those families to share successes and worries, to ask questions, to support families that are newer to the CD journey, and so forth.  We hope that you will enjoy this newest diagnosis-specific support avenue. While we understand that we share the hemispherectomy connection with many families, there is often added value in connecting with others that share the same diagnosis that led to this surgery.  
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