Neuroimaging in Pediatric Epilepsy

Overview

Epilepsy is a common pediatric neurologic disorder. In North America, the overall incidence of epilepsy is approximately 50/100,000 per year, highest for children below 5 years of age and the elderly. Children are at higher risk for developing epilepsy than adults. Atypical, idiopathic, and focal epilepsy as well as epileptic syndromes require evaluation with magnetic resonance imaging (MRI). Approximately 30% of children with epilepsy become refractory to medical therapy. In this group of children with refractory focal epilepsy, neuroimaging is critical for identifying an epileptogenic substrate responsible for the epilepsy, particularly in those potentially undergoing surgery. Epilepsy surgery in those with normal MRI has been reported to have poorer surgical outcomes compared with those with an identifiable lesion. Epileptogenic substrates include malformations of cortical development (MCD), developmental tumors, anoxic-ischemic injuries, prior cerebrovascular disease, neurocutaneous syndromes, and Rasmussen encephalitis. Concurrent lesions such as MCD, hippocampal sclerosis, and developmental tumors can occur in approximately 13% to 20% of cases. Another important role of imaging in presurgical epilepsy evaluation is to identify the location of eloquent cortex and white matter tracts.

MRI is the imaging study of choice for identifying an epileptogenic substrate. Higher field strengths such as 3 T is preferred. A dedicated epilepsy protocol is required to improve lesion detection and has been shown to improve seizure-free surgical outcome. The epilepsy protocol in children should include volumetric T1-weighted imaging, and T2-weighted and fluid attenuation inversion recovery (FLAIR) imaging in at least two orthogonal planes covering the entire brain. Additional sequences such as proton density, 3D FLAIR, inversion recovery, and gradient echo/susceptibility-weighted imaging may be helpful. Epilepsy protocols in neonates and infants younger than 1 year require a different set of sequences due to immature myelination and should include volumetric T1-weighted, and axial and coronal T2-weighted images covering the entire brain. FLAIR and proton density images are less helpful in neonates and infants due to lack of myelination. Volumetric imaging section thickness of less than or equal to 1 mm provides excellent gray-white matter contrast, can be reformatted into any orthogonal or nonorthogonal planes, and can be used for anatomic integration of functional data, stereotactic electrode placement, and neuronavigation. In temporal lobe epilepsy, the coronal plane should be acquired perpendicular to the long axis of the hippocampus. Contrast injection does not improve lesion detection but may help with lesion characterization. In cases where an epileptogenic focus is not identified, further evaluation with dedicated higher resolution MRI, image postprocessing, or additional imaging techniques including diffusion tensor imaging, magnetic resonance spectroscopy, functional imaging with interictal positron emission tomography (PET) or ictal/interictal single-photon emission computed tomography (SPECT), and magnetoencephalography (MEG) may help in identifying a lesion or the epileptogenic zone.

Malformations of Cortical Development

MCD are a major cause of drug-resistant epilepsy, in particular focal cortical dysplasia (FCD), hemimegalencephaly, and tuberous sclerosis. Other MCD such as lissencephaly, gray matter heterotopia, polymicrogyria, and schizencephaly are also associated with epilepsy.

Focal Cortical Dysplasia

Overview.

FCD is one of the most common causes of intractable epilepsy in children and accounts for up to 39% of pediatric epilepsy surgical cases. The mechanism of epilepsy is still unclear. Postulated possibilities include abnormal firing from the dysplastic neurons rather than from balloon cells, dysfunction of synaptic circuits with abnormal synchronization of the neuronal population, and abnormal organization of the inhibitory interneurons. A consensus classification has been proposed by the International League Against Epilepsy (ILAE) in 2011 ( Table 38.1 ).

TABLE 38.1

Histopathologic Classification of Focal Cortical Dysplasia

FCD Type I (isolated)	Type Ia: Focal cortical dysplasia with abnormal radial cortical lamination Type Ib: Focal cortical dysplasia with abnormal tangential cortical lamination Type Ic: Focal cortical dysplasia with abnormal radial and tangential lamination
FCD Type II (isolated)	Type IIa: Cortical dyslamination and dysmorphic neurons without balloon cells Type IIb: Cortical dyslamination and dysmorphic neurons with balloon cells
FCD Type III (associated with principal lesion)	With associated lesion Type IIIa: Hippocampal sclerosis Type IIIb: Epilepsy-associated tumors Type IIIc: Vascular malformation Type IIId: Other lesion

Imaging.

FCD can be located in any cortex of the cerebral hemisphere and can have variable size, from one gyrus to more than one lobar involvement. The MRI features of FCD include 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 abnormal sulcation and gyration pattern. Taylor's FCD or FCD type IIB are more likely to demonstrate high T2/FLAIR signal that tapers toward the ventricle. Type I FCD is more likely to demonstrate hypoplasia or atrophy of the white matter and mild increased T2 signal of the white matter. The high T2 signal in the white matter may be secondary to abnormal myelination, either due to the underlying disease or secondary to seizures. FCD, in particular FCD type I, are associated with hippocampal sclerosis. The MR appearance of FCD may change with brain myelin maturation. In patients with focal epilepsy, MR during infancy may be normal, and repeat imaging after the age of 2 years may reveal FCD. Therefore even when the MRI appears normal in an infant with refractory focal seizures, a repeat study is recommended at a later age ( Fig. 38.1 ). 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 low T2 and high T1 signal in neonates and infants. This is postulated to be secondary to early myelination in the white matter from repeated seizures.

Treatment and Follow-up.

Up to 50% to 70% of patients with FCD achieve good seizure control or seizure-free outcome after surgical resection of FCD. This compares favorably with the outcome of patients with hippocampal sclerosis and low-grade neoplasms. The reported surgical outcomes of subtypes of FCD are variable. Some studies reported better surgical outcome in those with Taylor's FCD, while others reported better surgical outcomes in those with other subtypes of FCD, including type I FCD and mild MCD. Differences in outcomes of subtypes of FCD may in part be related to the preponderance of type I FCD and mild MCD in the temporal lobe.

Hemimegalencephaly

Overview.

Hemimegalencephaly is a MCD characterized by one hemisphere being larger than the contralateral side. It may be sporadic or 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. On histology, the appearance is similar to FCD with abnormal gyration of the cortex, dyslamination, blurring of 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 intellectual disability.

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 also demonstrates signal changes that are variable, depending on the age of the patient. Neonates and infants usually demonstrate high T1/low T2 white matter signal, suggestive of early myelination, while in older children, the white matter shows low T1/high T2 signal, suggestive of gliosis, and may be associated with calcification. With recurrent seizures or status epilepticus, the enlarged hemisphere may later become atrophic.

Treatment and Follow-up.

Hemispherectomy or functional hemispherotomy may be required.

Tuberous Sclerosis Complex

Overview and Imaging.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome characterized by multisystem involvement including brain, eyes, heart, kidney, skin, and lungs. Seizures occur in about 80% to 90% of patients and are intractable in 25% to 30%. Children with medically refractory epilepsy usually have multiple cortical/subcortical tubers that exhibit broad gyri, thick cortex, and abnormal signal in the cortex and subcortical white matter. The cortical/subcortical tubers may occasionally demonstrate calcification and cystic degeneration. A combination of structural and functional imaging such as FDG-PET, ictal/interictal SPECT, and MEG can be used to identify the epileptogenic tubers ( Fig. 38.3 ). Cerebellar tubers can also be identified and are more commonly seen in patients with high cerebral tuber burden. The subependymal nodules commonly calcify. Another manifestation of TSC is subependymal giant cell astrocytomas, which commonly occur in the region of the foramen of Monro.