HEMIMEGALENCEPHALY

Hemimegalencephaly (HME) or unilateral megalencephaly is an uncommon but major congenital malformation of the brain, characterized by hamartomatous overgrowth limited to one cerebral hemisphere. HME differs from most other cerebral dysgeneses because of its extreme asymmetry, not corresponding to any normal stage of human brain development. HME represents a unique clinicopathological entity with great variation in clinical, neuroimaging and pathological features. No chromosomopathies or causative gene(s) have been identified. HME, therefore, should be regarded as a syndrome because it manifests numerous symptoms and signs and the etiology remains unknown. Neuropathological studies using neuronal and glial markers, show that HME is a genetically programmed early developmental disorder of symmetry and cellular lineage that occurs around the third gestational week, just after gastrulation. The neuroblast migratory abnormalities observed in HME are secondary to both abnormal radial glia and neuroblasts, occurring after the eight week of gestation. The neuropathology of excessive growth in HME also suggests a disturbance in cellular proliferation. HME can occur as an isolated condition or associated with other disorders. Isolated HME is sporadic and the clinical picture is characterized by neurological manifestations only. Associated HME is related in most cases to neurocutaneous syndromes; recognition of this association is essential because of high risk of systemic involvement. The most common are epidermal nevus syndrome, Proteus syndrome, Klippel-Trenaunay syndrome and hypomelanosis of Ito. The association of HME with tuberous sclerosis is uncommon, however, both entities share a similar histopathology. In both the clinical picture and neuroimaging abnormalities three degrees of severity are recognized in HME: mild, moderate and severe. In the associated forms, particularly those related to neurocutaneous syndromes, cutaneous and systemic manifestations are also present. Features of HME in neurocutaneous disorders are related to neural crest and include vascular malformations in skin and other organs, hypo- o hyperpigmented cutaneous lesions that sometimes follow Blaschko lines, lipomas and congenital infiltrating lipomatosis of the face. The diagnosis rests upon neuroimaging and neuropathology, when available. Treatment and prognosis depend on the degree of severity of HME, not the form, whether isolated or associated.