Information on the following diseases can be found in the Related Disorders section of this report:

• Hydrocephalus
• Megalencephaly
• Hemi-hemimegalencephaly or quadrantic dysplasia

Hemimegalencephaly presents first with a large number of seizures during the course of a day. The seizures do not decline in severity or number with medical treatment. In some cases, they may number 50 or more per day. A child with this disorder often presents with a lop-sided (asymmetrical) head, and if untreated, substantial motor deficits. When these signs are present, the neurologist may suspect the presence of hemimegalencephaly and order an MRI examination.

Hemimegalencephaly may occur in association with other syndromes, such as Proteus syndrome, epidermal nevus syndrome, nevus sebaceous syndrome, and Sturge-Weber syndrome. These disorders arise as a result of complex genetic activities. Hemimegalencephaly may also occur in association with disorders that involve only one disturbed gene (monogenetic), such as Sotos syndrome, Alexander disease and neurofibromatosis.

The basic cause(s) of hemimegalencephaly 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). As might be expected, the cortex of the 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 hemimegalencephaly occurs as a result of "insults" to the fetus 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.

The medical literature includes reports on clinical aspects of patients with hemimegalencephaly noted in 44 patients from Japan. Of these: 44 had epileptic seizures, 28 were male and 16 were female, 29 were right brain affected and 15 were left brain affected, 41 were mentally retarded to various degrees, 16 had various neurocutaneous symptoms, and 11 underwent functional hemispherectomy.

Hydrocephalus
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
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)
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.

Diagnosis
Examination by magnetic resonance imaging (MRI) is usually sufficient to confirm a suspected case of hemimegalencephaly. An MRI examination should be given as soon as hemimegalencephaly is suspected.

Treatment
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 hemispherectomy" involves disconnecting one side of the brain from the other and extracting the abnormal hemisphere.

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:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

TEXTBOOKS
Rowland LP, ed. Merritt’s Neurology. 10th ed. Lippincott Williams & Wilkins. Philadelphia, PA. 2000:487.

Sabry MA, Mochida GH, Walsh CA. Genetic disorders of cerebral cortical development. In: Rimoin D, Connor JM, Pyeritz RP, Korf BR. Eds. Emory and Rimoin’s Principles and Practice of Medical Genetics. 4th ed. Churchill Livingstone. New York, NY; 2002:2996, 3016.

JOURNAL ARTICLES
Luders H, Schuele SU. Epilepsy surgery in patients with malformations of cortical development. Curr Opin Neurol. 2006;19:169-74.

Agid R, Lieberman S, Nadjari M, Gomori JM. Prenatal MR diffusion-weighted in a fetus with hemimegalencephaly. Pediatr Radiol. 2006;36:138-40.

Tinkle BT, Schorry EK, Franz DN, Crone KR, Saal HM. Epidemiology of hemimegalencephaly: a case series and review. Am J Med Genet A. 2005;15:204-11.

Sasaki M, Hashimoto T, Furushima W, et al. Clinical aspects of hemimegalencephaly by means of a nationwide survey. J Child Neurol. 2005;20:337-41.

Yu J, Baybis M, Lee A, et al. Targeted gene expression analysis in hemimegalencephaly: activation of beta-catenin signaling. Brain Pathol. 2005;15:179-86

Specchio N, Kahane P, Pasquier B, Tassi L, Guerrini R. Resective surgery for epileptogenic dysembryoplastic neuroepithelial tumor in hemimegalencephaly. Neurology. 2005;65:777-78.

Hung PC, Wang HS. Hemimegalencephaly: cranial sonographic findings in neonates. J Clin Ultrasound. 2005;33:243-47.

Crino PB. Molecular pathogenesis of focal cortical dysplasia and hemimegalencephaly. J Child Neurol. 2005;20:330-36.

Soufflet C, Bulteau C, Delalande O, et al. The nonmalformed hemisphere is secondarily impaired in young children with hemimegalencephaly: a pre- and postsurgery study with SPECT and EEG. Epilepsia. 2004;45:1375-82.

D’Agostino MD, Bastos A, Piras C, et al. Posterior quadrantic dysplasia or hemi-hemimegalencephaly: a characteristic brain malformation. Neurology. 2004;62:2214-20.

FROM THE INTERNET
NINDS Megalencephaly Information Page. National Institute of Neurological Disorders and Stroke. Last updated January 24, 2006. 2pp.
www.ninds.nih.gov/disorders/megalencephaly/megalencephaly.htm

Cephalic Disorders Fact Sheet. National Institute of Neurological Disorders and Stroke. Last updated March 10, 2006. 10pp.
www.ninds.nih.gov/disorders/cephalic_disorders/detail_cephalic_disorders.htm

Cross H. Hemimegalencephaly. Contact a Family. 2006. 2pp.
www.cafamily.org.uk/Direct/h30.html