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Copyright 2006, 2012
NORD is grateful to Peter Crino, MD, PhD, Director of the PENN Epilepsy Center and Associate Professor of Neurology, Perelman School of Medicine, University of Pennsylvania, for assistance in the preparation of this report.
Hemimegalencephaly (HME) is a rare neurological condition in which one-half of the brain, or one side of the brain, is abnormally larger than the other. The structure of the brain on the affected side may be markedly abnormal or show only subtle changes. In either case, as a consequence of this size and structural differences, the enlarged brain tissue causes frequent seizures, often associated with cognitive or behavioral disabilities. Seizures in association with HME often begin in early infant life including an association with infantile spasms. Hemimegalencephaly may occur as an isolated or sporadic brain malformation or it may be associated with other neurodevelopmental syndromes. Thus, when detected, HME should prompt a search for other syndromic diagnoses.
Anti-seizure medications typically are not effective in controlling seizures in HME and thus, surgery is often recommended to control the seizures. If the affected side is surgically removed (anatomic hemispherectomy) or disconnected from the other brain structures (functional hemispherectomy), the remaining side of the brain may gradually take over the functions normally performed by the affected side.
Any combination of altered mental status, seizures, enlarged head, and /or altered skin pigmentation should prompt consideration of HME. In general, the presence of HME is definitively diagnosed by brain MRI. With the evolution of more widespread fetal imaging including ultrasound and MRI, a number of HME cases are detected prenatally.
HME typically is identified in the neonatal period when the baby develops presents seizures. The seizures usually do not decline in severity or number with medical treatment and in some cases they may exceed 50 or more per day. On physical examination, a child with HME may presents with enlarged head circumference or an asymmetrical head shape. There may be movement or motor deficits on the side opposite to the HME. When these signs are present, the neurologist may suspect the presence of HME and order magnetic resonance imaging (MRI) examination.
HME may occur in association with other syndromes, such as Proteus syndrome, epidermal nevus syndrome, tuberous sclerosis complex (TSC), linear sebaceous nevus syndrome, neurofibromatosis, and Sturge-Weber syndrome which are associated with abnormalities of skin pigmentation that can be detected on physical examination. Any child with these skin markings and seizures should be further evaluated for HME as well as other brain malformations. Hemimegalencephaly may also occur in association with Sotos syndrome and Alexander disease. These syndromes arise as a result of complex genetic activities such as single or multiple gene mutations. The mutations causing these disorders can be inherited or occur randomly during fetal development.
The basic cause(s) of HME is not well understood. The disorder occurs because the cells of one hemisphere of the brain grow much more rapidly than do the corresponding cells of the other half of the brain (hamartomatous overgrowth of one hemisphere). It is widely believed that a single or multiple gene mutations contribute to this process. As might be expected, the cortex of the enlarged brain is malformed (dysplastic) and the white matter is abnormal. One of the common, empty spaces of the brain (lateral ventricle) in the enlarged hemisphere is enlarged in proportion to the lateral ventricle of the smaller hemisphere.
Some clinicians believe that HME occurs as a result of damage to the fetal brain during the first or second trimester of pregnancy that affect the genetically programmed process that establishes symmetry as well as the development of different classes of brain cells.
Hemimegalencephaly is a very rare disorder for which prevalence estimates are not available.
Hydrocephalus is a condition in which abnormally widened (dilated) cerebral spaces in the brain (ventricles) inhibit the normal flow of cerebrospinal fluid (CSF). The cerebrospinal fluid accumulates in the skull and puts pressure on the brain tissue. An enlarged head in infants and increased cerebrospinal fluid pressure are frequent findings but are not necessary for the diagnosis of hydrocephalus. There are several different forms of hydrocephalus: communicating hydrocephalus, non-communicating hydrocephalus or obstructive hydrocephalus, internal hydrocephalus, normal pressure hydrocephalus, and benign hydrocephalus.
Megalencephaly is characterized by an abnormally large, heavy, and poorly functioning brain. The head of an infant affected by megalencephaly is abnormally large in the infant’s early years especially. The mechanism that regulates the brain cell reproduction and multiplication is, for reasons that are poorly understood, thrown out of synchronization so that the number, type and location of brain cells are abnormal. This disorder affects more males than females.
Hemi-hemimegalencephaly (HHM), or posterior quadrantic dysplasia (PQD), is so rare that only one paper on this subject appears in the literature. That paper reviews the clinical features of 19 patients with epilepsy that doesn’t respond to treatment (intractable). Of these, 14 had confirmed hemi-hemimegalencephaly and 5 were dysplastic in quadrants other than the posterior. Fourteen patients were operated upon and, of these, 6 were seizure free for at least two years; 2 had at least an 85% reduction of seizures; 4 had a reduction of at least 50% in seizures; and 2 patients showed no significant change after surgery.
Examination by MRI is usually sufficient to confirm a suspected case of HME. Thus, an MRI examination should be performed as soon as HME is suspected. Seizures are diagnosed and defined by electroencephalography (EEG).
Persistent, intractable seizures are seldom brought under control by means of anti-epileptic medications. Most patients undergo surgery to separate one hemisphere of the brain from the other. The surgical procedure may involve "functional hemispherectomy" in which the nerves and tissue connecting one side of the brain to the other are severed, but the abnormal hemisphere remains within the skull. Complete or anatomic hemispherectomy involves disconnecting one side of the brain from the other and extracting the abnormal hemisphere. These surgeries are typically performed by a neurosurgeon trained in epilepsy surgery.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
Contact for additional information about hemimegalencephaly:
Peter B. Crino MD, PhD
Director, PENN Epilepsy Center
3400 Spruce Street
Philadelphia, PA 19104
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NINDS Megalencephaly Information Page. National Institute of Neurological Disorders and Stroke. Last update:March 9, 2009
www.ninds.nih.gov/disorders/megalencephaly/megalencephaly.htm Accessed on:February 2, 2012.
Cephalic Disorders Fact Sheet. National Institute of Neurological Disorders and Stroke. Last update:September 30, 2012 www.ninds.nih.gov/disorders/cephalic_disorders/detail_cephalic_disorders.htm Accessed on:February 2, 2012.
Report last updated: 2012/02/24 00:00:00 GMT+0