What is HME?
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.
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.
[Taken from The Hemispherectomy Foundation website, as authored by Holly Paauwe, Speciality Director for Hemimegalencephaly and Cortical Dysplasia]
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.
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.
[Taken from The Hemispherectomy Foundation website, as authored by Holly Paauwe, Speciality Director for Hemimegalencephaly and Cortical Dysplasia]
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This page and associated links are provided for informational purposes only. The HFSN dose not endorse medical
centers, physicians, particular research or products of any kind. This information and any resources are not intended to substitute or replace the professional medical advice you receive from a physician. The content provided is not designed to diagnose or treat a health problem or disease. Please consult your child's physician with any questions or concerns you may have regarding your child's condition
This page and associated links are provided for informational purposes only. The HFSN dose not endorse medical
centers, physicians, particular research or products of any kind. This information and any resources are not intended to substitute or replace the professional medical advice you receive from a physician. The content provided is not designed to diagnose or treat a health problem or disease. Please consult your child's physician with any questions or concerns you may have regarding your child's condition