Institute of Child Neurology and Psychiatry, University of Pisa, Calambrone, Italy
Malformations of the cerebral cortex (MCC) are often associated with severe epilepsy and developmental delay. About 40% of drug‐resistant epilepsies are caused by MCC. Classification of MCC is based on embryological brain development, recognising forms that result from faulty neuronal proliferation, neuronal migration and cortical organisation. Hemimegalencephaly, an enlarged dysplastic hemisphere, can present as early onset severe epileptic encephalopathy or as partial epilepsy. In focal cortical dysplasia (FCD), MRI shows focal cortical thickening and simplified gyration. Patients have drug‐resistant, often early onset epilepsy. Complete surgical ablation of FCD is accompanied by remission in up to 90% of patients, but may be technically difficult. Tuberous sclerosis (TS) is a multisystemic disorder primarily involving the nervous system; 60% of patients having epilepsy, with 50% having infantile spasms. TS is caused by mutations in the
TSC2 genes; 75% of cases are sporadic.
TSC1 mutations cause a milder disease. Bilateral periventricular nodular heterotopia (BPNH) consists of confluent and symmetric nodules of grey matter along the lateral ventricles. X‐linked BPNH presents with epilepsy in females and prenatal lethality in most males. Most patients have partial epilepsy.
Filamin A mutations have been reported in families and sporadic patients. Lissencephaly (LIS – smooth brain) is a severe MCC characterised by absent or decreased convolutions. Classical LIS is quite rare and manifests with severe developmental delay, spastic quadriparesis and severe epilepsy.
XLIS mutations cause classical lissencephaly in hemizygous males and subcortical band heterotopia in heterozygous females. Thickness of heterotopic band and degree of pachygyria correlate well with phenotype severity. Schizencephaly (cleft brain) has a wide anatomo‐clinical spectrum, including partial epilepsy in most patients. Polymicrogyria (excessive number of small and prominent convolutions) has a wide spectrum of clinical manifestations ranging from early onset epileptic encephalopathy to selective impairment of cognitive functions. Bilateral perisylvian polymicrogyria may be familial. Patients present with facio‐pharingo‐glosso‐masticatory diplegia and epilepsy, which is severe in about 65% of patients.