Hemimegalencephaly

Hemimegalencephaly

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Hemimegalencephaly is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • macrencephaly
  • unilateral megalencephaly

Disorder Subdivisions

  • None

General Discussion

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.

Symptoms

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.

Causes

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.

Affected Populations

Hemimegalencephaly is a very rare disorder for which prevalence estimates are not available.

Standard Therapies

Diagnosis

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).



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 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.

Investigational Therapies

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



Contact for additional information about hemimegalencephaly:



Peter B. Crino MD, PhD

Associate Professor

Director, PENN Epilepsy Center

3400 Spruce Street

Philadelphia, PA 19104

800-789-7366

References

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.



Flores-Sarnat L, Sarnat HB, Dávila-Gutiérrez G, Alvarez A.Hemimegalencephaly: part 2. Neuropathology suggests a disorder of cellular lineage. J Child Neurol. 2003 Nov;18(11):776-85.



Flores-Sarnat L. Hemimegalencephaly: part 1. Genetic, clinical, and imaging aspects. J Child Neurol. 2002 May;17(5):373-84; discussion 384.



INTERNET

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.

Resources

Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Hemispherectomy Foundation

P.O. Box 1239

Aledo, TX 76008

Tel: (817)307-9880

Email: info@hemifoundation.org

Internet: http://www.hemifoundation.intuitwebsites.com/welcome.html



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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