In hemimegalencephaly, one cerebral hemisphere is enlarged and presents with a thick cortex, wide convolutions, and reduced sulci (Figure 1). The potential for structural changes in the seemingly normal hemisphere is of particular importance with respect to planning surgical treatment of epilepsy.
Laminar organization of the cortex is absent, and gray-white matter demarcation is poor. Giant neurons are observed throughout the cortex and the underlying white matter. In about 50% of cases, large, bizarre cells are observed, which have been named balloon cells. In some patients, the structural abnormality is multilobar, usually predominating in the posterior quadrant (posterior temporal and parieto-occipital lobes), but does not affect an entire hemisphere. Hemimegalencephaly is probably an aetiologically heterogeneous condition. Localization of the abnormality to one cerebral hemisphere and the fact that the malformation has always been sporadic can indicate somatic mosaicism. Hemimegalencephaly has been described in the context of different disorders, including epidermal nevus syndrome, Proteus syndrome, hypomelanosis of Ito, neurofibromatosis type 1, and tuberous sclerosis, but occurs most frequently as an isolated malformation.
The clinical and anatomic spectrum of severity is wide, ranging from severe epileptic encephalopathy beginning in the neonatal period to patients with normal cognitive function. The most common presentation is asymmetric macrocrania, hemiparesis, hemianopia, mental retardation, and seizures. The electroclinical features usually include partial motor seizures beginning in the neonatal period, infantile spasms, and often an asymmetric suppression-burst pattern on sleep electroencephalography (EEG). In addition, there is a high mortality rate in the first months or years of life, with status epilepticus being the most important cause of death. Seizure intractability in these patients can usually be established within the first year of life. This is important because major surgical procedures can stop life-threatening seizures and prevent epileptic activity from interfering with physiologic activity of the contralateral, healthy hemisphere. There are indications that the surgical operation (LINK with epilepsy surgery program) should be performed early because in younger children, transfer of functions to the “normal” hemisphere is greater and a better neuropsychologic outcome is more likely, although significantly improved cognitive skills after the procedure have not been uniformly observed.

If you have a child who you think may have this condition and you would like us to review the diagnosis or provide genetic testing please contact us at neuroscience@meyer.it.