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Malformed Cerebral Hemispheres

By

Stephen J. Falchek

, MD, Nemours/Alfred I. duPont Hospital for Children

Reviewed/Revised Jul 2023
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Topic Resources

Cerebral hemispheres may be large, small, or asymmetric; the gyri may be absent, unusually large, or multiple and small.

In addition to the grossly visible malformations, microscopic sections of normal-appearing brain may show disorganization of the normal laminar neuronal arrangement. Localized deposits of gray matter may be present in regions normally occupied only by white matter (heterotopic gray matter).

Malformations of the cerebral hemispheres may be due to genetic or acquired causes. Acquired causes include infections (eg, cytomegalovirus) and vascular events that interrupt the blood supply to the developing brain.

Before birth, diagnosis is by prenatal ultrasonography, MRI, or both. However, a significant proportion of subtle malformations can be missed by prenatal imaging. After birth, diagnosis is based on presence of associated symptoms described above.

Treatment is supportive, including antiseizure medications, specialized education, and, if needed, therapy.

Holoprosencephaly

Holoprosencephaly spectrum occurs when the embryonic prosencephalon (which becomes the forebrain) does not undergo complete segmentation and cleavage.

The 3 main types of holoprosencephaly, in declining order of severity, are

  • Alobar

  • Semilobar

  • Lobar

Alobar holoprosencephaly is the most severe and is usually fatal. It is characterized by complete failure of cleavage and a single ventricular cavity without any septation.

Semilobar holoprosencephaly is characterized by partial cleavage into hemispheres posteriorly but with a communicating unified ventricular cavity anteriorly.

Lobar holoprosencephaly is characterized by absence of the septum pellucidum (the membrane that separates the front of the 2 lateral ventricles), agenesis of the corpus callosum, fusion of the anterior horns of the lateral ventricles, and possibly fusion of the cingulate gyri.

A fourth, rare type, called middle interhemispheric variant, is characterized by fusion of the posterior frontal and parietal lobes as well as possibly the thalamus but with normal hemispheric differentiation elsewhere.

Rhombencephalosynapsis is a malformation similar to holoprosencephaly but mainly involves the hindbrain (2 Holoprosencephaly references Cerebral hemispheres may be large, small, or asymmetric; the gyri may be absent, unusually large, or multiple and small. In addition to the grossly visible malformations, microscopic sections... read more Holoprosencephaly references ). In rhombencephalosynapsis, there is fusion of the cerebellar hemispheres with partial or complete absence of the vermis (the midline portion of the cerebellum). This malformation can result in aqueductal stenosis and hydrocephalus. Other possible associated abnormalities include forebrain holoprosencephaly, absence of the olfactory bulbs, dysgenesis of the corpus callosum or septum pellucidum, and VACTERL (vertebral anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistula, renal anomalies, and limb anomalies).

Severely affected fetuses may die before birth. After birth, manifestations include seizures, intellectual disability, low muscle tone, and motor delays that affect all modalities of functioning.

Treatment of holoprosencephaly is supportive.

Holoprosencephaly references

  • 1. Hong M, Srivastava K, Kim S, et al: BOC is a modifier gene in holoprosencephaly. Hum Mutat 38(11):1464–1470, 2017. doi: 10.1002/humu.23286

  • 2. Ishak G, Dempsey J, Shaw D, et al: Rhombencephalosynapsis: A hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity. Brain 135(5):1370–1386, 2012. doi: 10.1093/brain/aws065

Lissencephaly

Lissencephaly consists of an abnormally thick cortex, diminished or absent gyral pattern on the surface of the brain, reduced or abnormal lamination of the cerebral cortex, and often diffuse neuronal heterotopias.

This malformation is caused by abnormal neuronal migration, the process by which immature neurons attach to radial glia and move from their points of origin near the ventricle to the cerebral surface. Several single-gene defects Single-Gene Defects Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more may cause this anomaly (eg, LIS1). One X-linked X-Linked Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more gene, DCX, causes familial X-linked lissencephaly in males and another, generally milder, migrational abnormality in females called subcortical band heterotopia. In subcortical band heterotopia, a broad swath of ectopic gray matter in the subcortical white matter resembles a "double cortex" on MRI.

Treatment of lissencephaly is supportive.

Survival depends on seizure severity and the presence of other complications including swallowing dysfunction, apnea, and difficulty clearing oropharyngeal secretions.

Polymicrogyria

Polymicrogyria, in which the gyri are small and overabundant, also involves abnormal neuronal migration. Other common findings include simplified or absent cortical lamination in affected regions, heterotopic gray matter, a hypoplastic or absent corpus callosum and septum pellucidum, and malformations of the brain stem and/or cerebellum.

The structural abnormalities may be diffuse or focal. The most common area of focal involvement is the perisylvian fissure (bilaterally or unilaterally). The term perisylvian syndrome is sometimes used when children present with features of epilepsy, facial and oral motor weakness, prominent speech and language delays, and usually bilateral polymicrogyria in the sylvian fissure region.

Numerous causes of polymicrogyria have been identified, including a number of single-gene mutations (eg, of SRPX2), and primary maternal infection with cytomegalovirus (ie, in which the mother has no prior immunity—see Congenital and Perinatal Cytomegalovirus Infection Congenital and Perinatal Cytomegalovirus Infection (CMV) Cytomegalovirus infection may be acquired prenatally or perinatally and is the most common congenital viral infection. Signs at birth, if present, are intrauterine growth restriction, prematurity... read more Congenital and Perinatal Cytomegalovirus Infection (CMV) ).

Treatment of polymicrogyria is supportive.

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