What Is Hemimegaloencephaly?
Hemimegaloencephaly is a rare developmental disorder in children where one hemisphere or some parts of the brain grow abnormally larger than the rest of the brain. This can result in recurrent seizures and developmental delays in the child’s growth. The range of abnormalities can range from subtle deviations from normal to marked differences. Hemimegaloencephaly can also be explained as a congenital disorder of cortical formation with hamartomatous overgrowths of all or parts of a cerebral hemisphere, resulting in increased proliferation, decreased apoptosis, or both of the developing neurons.
What Are the Different Types of Hemimegaloencephaly?
There are three different types of hemimegaloencephaly, as described by researchers:
Isolated Hemimegaloencephaly: Only the cerebral cortex is involved, with no overgrowths on the skin or systemic organs.
Syndromic Hemimegaloencephaly: Cerebral, cutaneous, and organ system manifestations.
Total Hemimegaloencephaly: This includes enlargement of the entire cerebellum and the brain stem. This can also occur as isolated or in conjunction with syndromes.
Some syndromes associated with syndromic hemimegaloencephaly include epidermal naevus syndrome, Klippel-Trenaunay syndrome, McCune-Albright syndrome, Proteus syndrome unilateral hypomelanosis of Ito, neurofibromatosis type 1, tuberous sclerosis, and CLOVES syndrome (congenital, lipomatous, overgrowth, vascular malformation, epidermal nevi, and scoliosis).
Who Is Susceptible to Hemimegaloencephaly?
Hemimegaloencephaly is a very rare disorder. Hence, prevalence studies have not been done to establish the occurrence rates. However, in the reported cases, hemimegaloencephaly has not shown any gender or racial predominance. In one particular study conducted between 1990 and 2003, 53 percent of the cases were non-syndromic, and 47 percent were associated with a known or suspected genetic syndrome. According to rough estimates, hemimegaloencephaly may occur in one to three patients of about 1000 epileptic children. Hemi-hemimegaloencephaly, or posterior quadrantic dysplasia, is an extremely rare condition, with just one reported case, where just the posterior quadrant of a single hemisphere of the brain is enlarged.
What Is the Cause of Hemimegaloencephaly?
The exact cause of hemimegaloencephaly is poorly understood. This is caused when the cells in one part or hemisphere of the brain grow much more rapidly than the other. This is believed to be a multi-genetic disorder resulting in dysplastic or malformed and abnormal white matter. The lateral ventricle (one of the common empty spaces of the brain) in the enlarged hemisphere is of a larger proportion than in the smaller hemisphere. Hemimegaloencephaly is also believed to have occurred due to damage to the fetal brain during the first or second trimester. The damage affects the genetic programming that establishes symmetry and the development of various classes of brain cells.
What Are the Clinical Features of Hemimegaloencephaly?
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Focal spasms.
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Generalized infantile spasms.
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Developmental delays (delays in performing developmental milestones).
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Hemiparesis (weakness or the inability to move on one side of the body).
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Hemianopia (loss of one-half of a vertical visual field).
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Macrocephaly (large head).
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Raised intracranial pressure.
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Seizures (epilepsy).
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Abnormal skull morphology.
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Cranial asymmetry (asymmetry of the skull bones).
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Focal cortical dysplasia (malformation of cortical development affecting the neocortex).
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Focal motor seizure.
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Polymicrogyria (congenital malformation of the cerebral cortex).
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Psychomotor retardation (slow speed, movement, and cognition).
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Ventriculomegaly (ventricles appear larger than normal).
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Abnormal neuron morphology.
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Atonic seizure (seizures with limp muscles).
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Cranial nerve paralysis (paralysis of the cranial muscles).
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Epileptic spasm (brief events of arm, leg, and head flexion).
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Focal tonic seizure (type of epilepsy).
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Functional motor deficit (functional movement disorder).
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Gliosis (fibrous proliferation of glial cells in injured areas of the central nervous system).
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Gray matter heterotopia (clumps of gray matter in the wrong part of the brain).
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Severe intellectual disability.
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Myoclonus (quick and involuntary muscle jerk).
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Oculomotor nerve palsy (paralysis of the third cranial nerve).
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Optic atrophy (optic nerve shrinkage by the degeneration of retinal ganglion cells).
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Pachygyria (abnormal migration of nerve cells in the developing brain and nervous system).
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Status epilepticus (seizures lasting for more than five minutes).
How Is Hemimegaloencephaly Diagnosed?
In-utero diagnosis of hemimegaloencephaly is difficult; only a few forms of brain malformation can be seen by ultrasound imaging. Suspected cases of hemimegaloencephaly can be further evaluated with MRI (magnetic resonance imaging), and seizures are defined by electroencephalography (EEG).
Radiographic features of hemimegaloencephaly include
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Increased size of lateral ventricles.
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Shallow sulci enlarged gyri.
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Thickened calvaria.
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Contralateral displacement of the posterior falx.
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White matter calcification.
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Developmental venous anomalies.
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Grey matter heterotopia.
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Cortex can be polymicrogyria, lissencephaly, agyria, or pachygyria.
Brain SPECT (single-photon emission computerized tomography) and PET (positron emission tomography) indicate hypermetabolism of tracer in the enlarged hemisphere.
How to Treat Hemimegaloencephaly?
The treatment focuses on controlling epilepsy attacks by means of anti-epileptic drugs. Surgical cases are carefully selected and show up to a 60 percent decline in seizures post-operatively. Contralateral malformations show poorer outcomes.
Functional hemispherectomy is the usual go-to surgery for hemimegaloencephaly. The youngest ever hemispherectomy patient was as young as 28 days. However, hemispherectomy for hemimegaloencephaly is an extremely delicate procedure, often due to malformed blood vessels, making them difficult to identify, isolate, and ligate. Additionally, what makes this difficult is the lack of recognition of familiar landmarks and structures owing to the malformations.
What Is the Differential Diagnosis of Hemimegaloencephaly?
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Gliomatosis cerebri (central nervous system tumor).
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Rasmussen encephalitis (inflammatory neurological disorder affecting one hemisphere of the brain).
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Dyke-Davidoff-Masson syndrome (atrophy or hypoplasia of one cerebral hemisphere secondary to fetal brain injury).
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Sturge-Weber syndrome (port-wine birthmark, leptomeningeal angioma, and glaucoma).
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Neuronal migration anomalies.
Conclusion:
Hemimegaloencephaly is a very rare hamartomatous brain malformation that primarily induces seizures in infants. Although the cause and treatments are not absolute, one of the most delicate surgery carries the answer for improved quality of life in infants through childhood and adulthood. The child may have its own timeline for achieving milestones and its own pace of learning. Parents need to be patient, and therapy should be introduced not just for the child but for the entire family. In-utero recognition is also very difficult, so the parents may not be ready for the upcoming challenge. Newly introduced minimally invasive surgery can stop seizures, and the school for the same includes neurologists, neuro-interventional radiologists, neonatologists, and neurosurgeons. This kind of surgery is available only at a few establishments all over the world.
