Disorders of neurogenesis, neuronal maturation, and proliferation are responsible for many severe forms of childhood epilepsy. They may arise in discrete cortical areas or involve widespread brain regions in one or both cerebral hemispheres. While extensive unilateral involvement of one cerebral hemisphere is a relatively uncommon condition, the rare occurrence of a hemispheric malformation is associated with a high rate of morbidity and mortality. Affected children typically manifest cognitive delay, intractable epileptic seizures, and lateralized neurological deficits.

An awareness of the clinical presentations and management (Fig. 36–1) of this unusual group of disorders is an important part of pediatric epilepsy as the frequent association of unrelenting partial seizures and clinical deterioration may prove catastrophic in the first year of life. Prompt recognition of the various underlying causes and aggressive treatment, frequently surgical, are therefore essential.

Hemimegalencephaly is a rare but clinically significant brain malformation characterized by the excessive growth of one cerebral hemisphere. Hemispheric asymmetry may present at birth but typically increases during the first year of life due to progressive hemispheric expansion. Affected infants often appear normal and their head circumference and shape appear unremarkable as the hemisphere enlarges. The classical signs of raised intracranial pressure, bulging fontanel, widening of skull sutures, and the “setting sun sign” are notably absent. Either cerebral hemisphere may be affected.

Three subtypes of hemimegalencephaly are now recognized.

ISOLATED HEMIMEGALENCEPHALY

In the isolated form, unilateral hemispheric enlargement is not associated with somatic hemicorporeal hypertrophy, cutaneous manifestations or other signs of systemic involvement.¹ Isolated hemimegalencephaly accounts for approximately half of all known hemimegalencephaly cases.² Its occurrence is typically sporadic with no known genetic pattern of inheritance.

SYNDROMIC HEMIMEGALENCEPHALY

The second form, syndromic hemimegalencephaly, is associated with one of several well-recognized developmental syndromes, mostly neurocutaneous disorders. All have known patterns of Mendelian inheritance, and systemic involvement is common. Syndromic disorders with hemimegalencephaly include the following disorders.

EPIDERMAL NEVUS SYNDROME

Affected patients manifest cutaneous epidermal nevi that are often unilateral. The linear nevus sebaceous of Jadassohn is commonly associated. Ocular and skeletal abnormalities are frequently noted.

HYPOMELANOSIS OF ITO

This neurocutaneous disorder presents with a linear area of depigmentaion variably associated with hemimegalencephaly ipsilateral or contralateral to the skin lesion. Both macrocephaly and callosal agenesis have been observed in affected children.

INCONTINENTIA PIGMENTI

A disorder characterized by irregular marbled or wavy linear cutaneous pigmentation caused by excess melanin deposition. Cavitary lesions in subcortical white matter and loss of cerebellar cortical neurons are common. Hemimegalencephaly has been described in a portion of patients.

NEUROFIBROMATOSIS-1

Although magalencephaly is particularly frequent in this disorder, hemimegalencephaly is unusual. Neurofibromatosis-1 occurs as an autosomal dominant disorder with frequent multiple organ involvement.

KLIPPEL–TRENAUNAY–WEBER SYNDROME

Vascular nevi in conjunction with hemicorporeal enlargement of osseous and soft tissues characterize this unusual disorder. Contralateral or ipsilateral hemimegalencephaly has been described. Macrocephaly is common.

TUBEROUS SCLEROSIS COMPLEX

An association between tuberous sclerosis complex and hemimegalencephaly has been reported rarely.³ Several overlapping histological features and the tendency for a portion of the hemisphere to calcify in both disorders has led to speculation that hemimegalencephaly may represent a more widespread expression of an underlying process also responsible for tuberous sclerosis.

TOTAL HEMIMEGALENCEPHALY

The third form, so-called “total” hemimegalencephaly, is the rarest subtype and is characterized by unilateral enlargement of the cerebellum and brainstem in conjunction with ipsilateral hemisphere expansion. Total hemimegalencephaly occurs in either an isolated or syndromic form.