Neuroimaging in the Evaluation of Epilepsy

Naymee J. Velez-Ruiz, MD; Joshua P. Klein, MD, PhD2


Semin Neurol. 2012;32(4):361-373. 

In This Article

Malformations of Cortical Development

Malformations of cortical development (MCD) result from disruptions in the complex process of human brain cortex formation and are highly associated with severe epilepsy (Fig. 2). Modern advanced imaging techniques have improved not only our ability to detect and characterize MCD, but also to identify associated functional abnormalities that are far beyond the visualized structural lesions. The gain in spatial resolution with increasing magnetic field strength (now up to 7T) and subsequent increase in signal-to-noise ratio, can potentially increase the degree of anatomic detail obtained in complex brain malformations.[54] Advances in multichannel coil technology with phased-array surface coil have increased resolution and contrast of the acquired images, with maximum gains in the cortical surface.[54] Recent MR advanced sequences improve image quality and might be helpful in the characterization of MCD. For example, the volumetric T1WI with spatial resolution (SPGR or MPRAGE) allow high-quality multiplanar reconstructions that favor a more accurate diagnosis.[55] Also, volumetric FLAIR can be very sensitive for characterizing white matter involvement.[55] Despite these advances, clinical information is still necessary for guiding the intensive and time-consuming visual search required in the evaluation of volume acquisitions with multiplanar reformats, which are in the order of millimeters. Computer-assisted methods, such as voxel-based morphometry (VBM), may be helpful in the detection of subtle lesions.[56] However, automatic approaches are supplementary to human visual inspection, and typically inaccurate when used in isolation.[54,56]

Figure 2.

Malformations of cortical development. (A,B) Coronal and axial T2- fluid attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) of a 34-year-old right-handed man with frequent convulsive seizures shows left superior temporal gyrus focal cortical dysplasia. There was no mass effect or abnormal enhancement associated with the lesion. (C) Axial T1- magnetization-prepared rapid acquisition gradient echo magnetic resonance imaging (MPRAGE MRI) of a 28-year-old ambidextrous man with episodes of left arm numbness and weakness shows right parietal focal cortical dysplasia (arrow). Note the abnormal cortical thickness. (D,E) Coronal and axial T2-FLAIR MRI of a 28-year-old left-handed man with nonconvulsive seizures, which are each preceded by tingling and tightness in the right face, shows left temporoparietal subependymal and subcortical gray matter heterotopia. (F) Proton density MRI of a 37-year-old right-handed man with complex partial and convulsive seizures shows bilateral polymicrogyria (arrows).

Although conventional MRI with high spatial resolution identifies the malformed cortex in a large number of cases, recent investigations have focused on associated abnormalities in the white matter identified by DTI and tractography.[57] Some studies have shown a reduction in the white matter in the affected hemisphere containing the MCD and more widespread alterations in diffusivity and anisotropy that could be of potential clinical importance if surgery is considered.[58]

Although hypometabolism in interictal 18F-FDG PET studies can help in delineating the epileptogenic region, it appears that this technique does not contribute toward elucidating the underlying etiology when the MCD is not obvious or well defined on MRI. For example, it is not helpful in differentiating focal cortical dysplasias (FCD) from mixed neuronal and glial tumors.[59] The presence of regional interictal hypometabolism, however, may guide the intensive search for a subtle MCD in patients with cryptogenic epilepsy. Unfortunately, the sensitivity of PET in extratemporal epilepsy is lower than in TLE, ranging between 30% and 50%.[32] Nevertheless, when a metabolic abnormality is detected, 18F-FDG PET/MRI coregistration appears to enhance the noninvasive identification and successful surgical treatment of patients with MCD, especially mild focal cortical dysplasia (FCD).[60] SPECT perfusion difference has also been used with the same purpose.

Current data demonstrates the utility of MEG for providing (1) functional concordance for the majority of structural lesions, and (2) useful data for identification of previously unappreciated lesions.[61] These advantages are especially important in the presence of multiple MCD and, in presumed nonlesional cases where a mild MCD (for example, FCD) is suspected. MEG may detect interictal epileptiform activity in up to one-third of EEG-negative patients, especially in the case of lateral cortical epilepsy and/or FCD.[62] In the evaluation of the epileptogenicity of MCD, MEG is considered a valuable complementary tool to EEG.

Another important aspect of the evaluation of MCD in epilepsy is the possibility that regions of malformed cortex might retain a functional role. This likely depends to a significant extent on the severity and distribution of the malformation or on the usual functional role subserved by the affected region of cortex.[63] When epilepsy surgery is being considered, this question is usually addressed with the aid of functional imaging modalities, such as fMRI and MEG.

Some of the MCD with highest epileptogenic potential and radiologic significance are hemimegalencephaly, lissencephaly, schizencephaly, polymicrogyria, heterotopias, and FCD. Each type of MCD is characterized by particular radiologic features that allow its identification and differentiation. An accurate diagnosis is especially important for surgical planning and determination of prognosis.

Hemimegalencephaly is a rare malformation that affects an entire hemisphere. Imaging characteristics are abnormal gyration, thickened cortex, loss of gray white matter differentiation, and signal changes on T2-weighted images.[64] The contralateral hemisphere usually appears normal on imaging. However, this does not exclude the possibility of abnormal pathology, which may be epileptogenic as well.[65]

Polymicrogyria, schizencephaly, and lissencephaly are further forms of MCD characterized by abnormal gyration patterns. In polymicrogyria, there are too many small gyri separated by shallow sulci. In schizencephaly, an abnormal cleft is lined by polymicrogyric cortex. Lissencephaly is characterized by the absence of gyri. In addition to the abnormal gyration patterns, MRI may demonstrate blurring of the gray-white junction and cortical signal abnormalities.[66] Some reports suggest that in this type of MCD, the visualized abnormalities are probably not the most important component of the epileptogenic zone, which may be spatially distributed.[67]

Subcortical and periventricular nodular heterotopias are characterized by the abnormal presence of gray matter in the white matter. These are typically more subtle than the abnormalities in gyration patterns, and histopathologically characterized by an overlying dysplastic cortex.[67] Evaluation by stereo-EEG has shown that ictal activity starts from the overlying cortex, or simultaneously in nodules and cortex.[68] Heterotopias are usually seen as multiple lesions, or in the company of other types of cortical abnormalities. Despite these findings, case series suggest that surgical treatment may be beneficial when the epileptogenic zone is carefully located before surgery.[68]

Focal cortical dysplasia is the most common MCD in epilepsy surgery patients.[69] A study by Kim and colleagues showed a significant relationship between the pathologic grade and the detectability of FCD by brain MRI.[70] FCD are characterized on MRI as focal cortical thickening with hyperintense T2/FLAIR and hypointense T1 signal abnormalities in the underlying white matter, at times with the aspect of a wedge-shaped tail extending radially to the ventricle.[54,71,72,73] Other accompanying imaging findings are focal white matter atrophy, a deep sulcus, and broadening of the gyri adjacent to the FCD.[55] Often, with FCD, the epileptogenic zone is more extensive than the lesion visualized.[72] In fact, at times, the lesion can be quite subtle, and FCD accounts for a significant proportion of patients with intractable focal epilepsy whose MRIs are considered normal.[74,75] Palmini et al proposed a classification of FCD into two types with two subtypes each based on the presence of changes in the cortical architecture and the presence of dysplastic neurons, giant neurons, or balloon cells on histopathology.[76] The discussion of this classification is beyond the scope of this article. However, it is important to mention that current MRI is only moderately sensitive to detect FCD, independently of the type, because 31–41% of patients with FCD type I and 21–33% of patients with FCD type II have no MRI abnormalities.[77,78]