Overview: FCD is an MCD that is intrinsically epileptogenic. It is one of the most common causes of intractable epilepsy in children and accounts for up to 39% of surgical cases.17,18 The mechanism of epilepsy is still unclear. Possibilities include abnormal firing from the dysplastic neurons rather than from balloon cells,¹⁹ dysfunction of synaptic circuits with abnormal synchronization of the neuronal population, and abnormal organization of the inhibitory interneurons.²⁰ Numerous classifications of FCD have been proposed.^13,21–23 Recently, a consensus classification has been proposed by the International League Against Epilepsy (Table 38-1).²⁴

Imaging: FCD can be located in any cortex of the cerebral hemisphere and can have variable size, from one gyrus to more than one lobe. The MRI features of FCD are increased cortical thickness, blurring of the cortical–white matter junction, increased T2 or FLAIR signal in the cortex and subcortical white matter, high T1 signal in the cortex, and an abnormal sulcation and gyration pattern. Taylor FCD or FCD type IIB more commonly involves the extratemporal cortex and is more likely to demonstrate a high T2 and FLAIR signal that tapers toward the ventricle.21,25,26 Non-Taylor FCD (type I FCD and mild MCDs) is more likely to be located in the temporal lobe and to demonstrate hypoplasia or atrophy of the white matter and mild increased signal. FCD, in particular non-Taylor FCD, is associated with hippocampal sclerosis.²⁷ The MRI appearance of FCD may change with brain maturation. Longitudinal MRI studies in infants with FCD have shown that findings of the early study may be normal but later imaging may demonstrate a high T2 signal in the white matter, a high T1 signal in the cortex, and blurring of the cortical/subcortical white matter junction.²⁸ The high signal in the white matter may be a result of abnormal myelination, either because of the underlying disease or as a result of seizures. Thus even when the MRI findings appear normal in a neonate or an infant with refractory partial seizures or infantile spasm, a repeat study is recommended (Fig. 38-1).²⁸ In contrast to the high T2/FLAIR signal in the white matter of FCD in children, the white matter adjacent to the dysplastic cortex may demonstrate a low T2 and high T1 signal in neonates and infants, which is thought to be secondary to early white matter myelination as a result of repeated seizures.²⁹

Treatment: Good seizure control or a seizure-free outcome is achieved in up to 50% to 70% of patients with FCD after surgical resection of the FCD.30–32 This outcome compares favorably with the outcome of patients who have hippocampal sclerosis³³ and a low-grade neoplasm.³⁴ The reported surgical outcomes of persons with subtypes of FCD are variable. Authors of some studies reported a better surgical outcome in persons with Taylor FCD,^21,35,36 whereas other authors reported better surgical outcomes in persons with other subtypes of FCD, including type I FCD and mild MCD.^37,38 Differences in outcomes of persons with subtypes of FCD may in part be related to the preponderance of type I FCD and mild MCD in the temporal lobe.³⁷

Overview: Hemimegalencephaly is an MCD that is characterized by one hemisphere being larger than the contralateral side. It may be sporadic or it may be associated with a variety of syndromes, including proteus syndrome, epidermal nevus syndrome, hypomelanosis of Ito, linear nevus sebaceous syndrome, neurofibromatosis type I, and tuberous sclerosis. The sporadic form is considered a hemispheric variant of FCD.³⁹ On histology, the appearance is similar to FCD with abnormal gyration of the cortex, dyslamination, blurring of the gray/white matter junction, giant neurons in both gray and white matter, and balloon cells in 50% of cases. The most common clinical presentation is early intractable epilepsy; other clinical presentations include hemiparesis, hemianopia, and mental retardation.

Imaging: The affected hemisphere is larger than the contralateral side. The cortex is dysplastic and thick, with broad gyri and shallow sulci (e-Fig. 38-2). The ipsilateral lateral ventricle may be enlarged. The ipsilateral white matter demonstrates variable signal changes, depending on the age of the patient. Neonates and infants usually demonstrate a high T1 and low T2 signal in the white matter suggestive of early myelination, whereas in older children the white matter shows a low T1 signal and a high T2 signal with associated cystic changes and calcification.^40–42 With recurrent seizures or status epilepticus, the enlarged hemisphere later may become atrophic.⁴³

Treatment and Follow-up: An early functional hemispherectomy or hemispherotomy may be required as a result of severe intractable epilepsy that is refractory to medications.

Overview and Imaging: Tuberous sclerosis complex is an autosomal-dominant neurocutaneous syndrome characterized by multisystem involvement including the brain, eyes, heart, kidney, skin, and lung. Seizures occur in 80% to 90% of patients, and seizures are intractable in 25% to 30% of patients.⁴⁴ Children with medically refractory epilepsy usually have multiple cortical/subcortical tubers that exhibit broad gyri, a thick cortex, and an abnormal signal in the cortex and subcortical white matter. The cortical/subcortical tubers occasionally may demonstrate calcification and cystic degeneration. A combination of structural and functional imaging such as fluorodeoxyglucose (FDG)-PET, ictal/interictal SPECT, and magnetoencephalography can be used to identify the epileptogenic tubers^45–48 (Fig. 38-3). Cerebellar tubers also occur and more commonly are seen in patients with a high cerebral tuber burden. The subependymal nodules often calcify. Another manifestation of tuberous sclerosis complex is subependymal giant cell astrocytomas, which commonly occur near the foramen of Monro.

Overview and Imaging: Sturge-Weber syndrome, or encephalotrigeminal angiomatosis, is a phakomatosis characterized by a facial capillary vascular malformation or “port wine stain” in the territory of the trigeminal nerve, ipsilateral leptomeningeal angiomatosis, and angiomatosis of the choroid of the ipsilateral eye. Seizures usually are the initial neurological manifestation in the first year of life. Children with early onset of epilepsy are more likely to have hemiparesis, status epilepticus, and developmental delay compared with persons whose seizures start later in life.⁴⁹ Imaging findings include leptomeningeal angiomatosis, enlargement of the choroid plexus, parenchymal atrophy, calvarial changes, and calcification (Fig. 38-4). Leptomeningeal angiomatosis and choroid plexus hyperplasia appear earlier in the course of the disease, whereas atrophy and calcification usually are evident later. Contrast-enhanced MRI is considered the most sensitive sequence for depicting leptomeningeal enhancement and revealing subtle bilateral hemispheric involvement, compensatory venous drainage, enlarged choroid plexus in the atria, and cerebellar and eye involvement.^50–52

Treatment: Medical therapy is the first line of treatment for controlling seizures. Surgical lobectomy or hemispherotomy also may be indicated in cases in which seizures are refractory to medical therapy.

Overview and Imaging: Mesial temporal sclerosis is encountered less frequently in children than in adults.53–56 The etiology of hippocampal sclerosis is unknown, but a link with febrile seizures has been suggested.^57,58 Hippocampal sclerosis is characterized by neuronal loss and gliosis in the hippocampus.⁵⁹ MRI features include atrophy and increased T2 and FLAIR signal in the hippocampus (Fig. 38-5).^59–62 Other findings include loss of interdigitations of the hippocampal head,⁶³ atrophy of the ipsilateral mamillary body and fornix,⁶⁴ dilatation of the ipsilateral temporal horn, volume loss of the temporal lobe, and atrophy of the collateral white matter between the hippocampus and collateral sulcus.⁶² Functional imaging with FDG-PET usually reveals hypometabolic activity that is larger than the hippocampus abnormality^65,66 and can identify mesial temporal metabolic abnormalities in patients with normal MRI.⁶⁷

Treatment and Follow-up: In patients who have medically refractory epilepsy, surgery offers good seizure control in 70% to 90% of cases.68–71