Introduction
Hemimegalencephaly is an uncommon neurological condition marked by abnormal enlargement of one side or one-half of the brain, often presenting with varying structural irregularities. This size discrepancy frequently results in seizures, accompanied by cognitive or behavioral issues, typically starting in early infancy, sometimes with infantile spasms. HME can appear as a standalone brain malformation or be associated with other neurodevelopmental syndromes, requiring a thorough diagnostic approach.
What Is Hemimegalencephaly?
Hemimegalencephaly (HME) is a rare congenital brain malformation characterized by abnormal overgrowth in one brain hemisphere. Unlike typical brain development, HME displays extreme asymmetry. Despite an unknown cause, it is categorized as a syndrome due to a specific combination of symptoms. Immunocytochemical studies reveal that HME originates early in neuroepithelium differentiation before neuroblast migration. While it can manifest independently, it is often associated with neurocutaneous syndromes. These syndromes may share a common pathogenesis involving abnormalities in neural crest cell migration and differentiation.
The exact cause remains unknown, with suggested genetic links and potential associations with mutations in the mTOR (mammalian target of rapamycin) pathway.
Seizures are the predominant symptom, though developmental delays, hemianopia (loss of one-half of the visual field), and motor weakness are also present.
Recognition of HME may be triggered by a combination of symptoms such as altered mental status, seizures, enlarged head, and/or abnormal skin pigmentation.
A conclusive diagnosis involves brain MRI (Magnetic Resonance Imaging).
With advancements in fetal imaging, prenatal detection of HME is becoming more prevalent through techniques like ultrasound and MRI.
What Are the Signs and Symptoms of Hemimegalencephaly?
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Hemimegalencephaly is usually diagnosed in neonates due to seizures.
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Seizures in HME persist despite medical intervention and can exceed 50 per day.
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Physical examination may show an enlarged or asymmetrical head shape in children with HME.
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Motor deficits (difficulty while moving) on the side opposite to HME may be noticeable during examination.
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Suspected cases of HME prompt neurologists to order an MRI examination.
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HME may be associated with syndromes like Epidermal Nevus Syndrome (ENS), Proteus syndrome, Klippel-Trenaunay Syndrome (KTS), tuberous sclerosis complex, neurofibromatosis, linear sebaceous nevus syndrome, and Sturge-Weber syndrome.
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Syndromes associated with HME often exhibit skin pigmentation abnormalities identifiable in a physical examination.
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Children with both skin markings and seizures should be further evaluated for HME and other brain malformations.
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Developmental delays.
How Is Hemimegalencephaly Classified?
Hemimegalencephaly is classified as:
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Isolated - Affects one side of the cerebral hemisphere without any associated syndrome.
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Syndromic - It is associated with a syndrome.
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Total - It involves the brainstem, cerebellum, and cerebral hemispheres.
How Does Hemimegalencephaly Occur?
The underlying cause of HME remains unclear. It can be genetic or due to gene mutation.
This disorder arises from an imbalance in cell growth, where one hemisphere of the brain experiences significantly faster growth than its counterpart (hamartomatous overgrowth). It is widely believed that single or multiple gene mutations contribute to this process. Consequently, the enlarged brain’s cortex is malformed (dysplastic), and the white matter exhibits abnormalities. In the enlarged part of the hemisphere, the lateral ventricles (brain spaces) are enlarged in proportion to the lateral ventricle of the smaller hemisphere.
Some state that HME results from fetal brain damage during the first or second trimester of pregnancy, impacting the genetically programmed processes responsible for establishing symmetry and the development of various classes of brain cells.
How Is Hemimegalencephaly Diagnosed and Managed?
Rule out associated syndrome if present. Blood tests may be asked to diagnose a few syndromes. The diagnosis of hemimegalencephaly involves MRI and ultrasound. Seizures are diagnosed by electroencephalography.
Treatment:
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Treatment mostly includes anti-epileptic medications to treat seizures.
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Surgery can be opted in some cases to remove the abnormal hemisphere (hemispherectomy).
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In children with weakness, movement difficulty, and developmental delays, occupational therapy, speech therapy, physiotherapy, vision therapy, special training, and educational support are advised.
What Is the Differential Diagnosis of Hemimegalencephaly?
The differential diagnosis may include:
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Hydrocephalus - Abnormally dilated cerebral spaces that inhibit the normal flow of Cerebrospinal Fluid (CSF). The CSF gets collected in the skull and exerts pressure on the brain tissue. Hydrocephalus can be of various forms: communicating, non-communicating, internal, normal-pressure, and benign hydrocephalus.
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Megalencephaly - Referred to as an abnormally large, heavy, and poorly functioning brain. The head is abnormally large in the early years of an infant. It is more prevalent in males than females.
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Ventriculomegaly - Enlarged fluid spaces in the brain.
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Rasmussen Encephalitis - a chronic inflammatory disease affecting one brain hemisphere.
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Dyke-Davidoff-Masson syndrome - A condition known by hemicerebral atrophy or hypoplasia secondary to brain damage typically in the fetus or early childhood, followed by ipsilateral compensatory osseous hypertrophy and contralateral hemiparesis.
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Sturge-Weber Syndrome - A neurocutaneous syndrome recognized by angiomas involving the face (facial port wine stains), choroid, and leptomeninges.
Conclusion
Hemimegalencephaly is a rare neurological condition characterized by asymmetrical growth in one brain hemisphere. While the precise cause is unclear. It is believed to be caused by genetic mutations or inherited abnormalities leading to hamartomatous overgrowth. It can be associated with syndromes. Some suggest that damage to the fetal brain during early pregnancy disrupts genetically programmed processes, impacting symmetry and the development of different classes of brain cells.
