Review Article

Neuroimaging in
Address correspondence to
Dr Fernando Cendes,
Departamento de Neurologia,
FCM, UNICAMP, Campinas,

Investigation of SP, Brazil, 13083-880,

[email protected].
Relationship Disclosure:

Patients With Epilepsy Dr Cendes is a member of the

editorial boards of Neurology,
Epilepsy Research, Epilepsia,
Epilepsy and Behavior,
Fernando Cendes, MD, PhD Arquivos de Neuropsiquiatria,
and Frontiers in Neurology.
Dr Cendes receives research
support from Fundação de
ABSTRACT Amparo à Pesquisa do Estado
Purpose of Review: This review discusses the MRI and functional imaging findings de São Paulo (FAPESP) and
in patients with focal seizures, practical ways to improve the detection of subtle Conselho Nacional de
Pesquisa (CNPq) Brazil.
lesions, and limitations and pitfalls of the various imaging techniques in this context. Dr Cendes is chair of the
Recent Findings: A proper MRI investigation of patients with focal epilepsy Diagnostic Methods
requires the use of specific protocols, selected based on identification of the region Commission of the
International League
of onset by clinical and EEG information. For practical purposes, the focal epilepsies Against Epilepsy.
are divided here into mesial temporal lobe epilepsies and neocortical epilepsies. The Unlabeled Use of
majority of patients with mesial temporal lobe epilepsies associated with hippocampal Products/Investigational
Use Disclosure:
sclerosis undergoing presurgical evaluation will have a clear-cut unilateral atrophic Dr Cendes reports
hippocampus with increased T2 signal and a normal-appearing contralateral hip- no disclosures.
pocampus. Among the several types of neocortical lesions, focal cortical dysplasias * 2013, American Academy
deserve especial attention because these lesions are often missed on routine MRIs. The of Neurology.
focal cortical dysplasias include a gradient of morphologic changes from dysplastic
lesions that can be easily identified by conventional MRI techniques to minor structural
abnormalities with small areas of discrete cortical thickening and blurring of the gray/
white matter interface that often go unrecognized.
Summary: The use of MRI protocols targeted for the study of patients with epilepsy
allows the diagnosis of the etiology of epilepsy in most patients with focal seizures.
However, in a considerable number of patients with epilepsy, MRI results are con-
sidered normal. Although the etiology remains unclear in these cases, the malfor-
mations of cortical development (mainly focal cortical dysplasias) have been identified
as most likely pathologic substrates. The effort involved in trying to increase the
detection of these ‘‘invisible’’ lesions involves the improvement of structural imag-
ing techniques and the combination of metabolic and functional studies, including
18F-fluorodeoxyglucoseYpositron emission tomography (18F-FDG-PET), ictal single-
photon emission computed tomography (SPECT), diffusion MRI, and magnetic reso-
nance spectroscopy (MRS). The methods used to enhance the detection of subtle
cortical abnormalities by improving the structural images have addressed two basic
aspects of the examination by MRI: signal acquisition and imaging postprocessing.

Continuum (Minneap Minn) 2013;19(3):623–642.

INTRODUCTION of seizures, presence or absence of

Epilepsies feature a variety of etiolo- mental retardation, and associated
gies and in most cases are multifacto- diseases, among other factors. Al-
rial.1 Therefore, investigation of the though the advent of CT introduced
underlying causes of epilepsy will unprecedented structural information
depend on the clinical context, espe- about diseases that affect the nervous
cially the type of syndrome, age, types system, no technologic advances were

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 Neuroimaging in Epilepsy

KEY POINTS
h CT scans are indicated more important for the diagnosis of In addition, the logistics of CT make it
in emergent situations the etiology of epilepsies than the easier for unstable patients to be
but are of limited emergence of MRI. imaged as compared to MRI. There-
usefulness for limited fore, this is the ideal imaging exami-
or small lesions, particularly INDICATIONS nation for emergencies. CT can detect
in regions of orbitofrontal All patients with epilepsy should un- most tumors (except for some low-
or medial temporal dergo an MRI except possibly those grade tumors), large arteriovenous
cortex. Focal lesions are with very typical forms of primary and extensive brain malformations,
only seen in 30%. generalized epilepsy (eg, juvenile stroke, and infectious lesions, and is
h A proper MRI investigation myoclonic epilepsy, childhood ab- sensitive for detection of calcified le-
of patients with focal sence) or benign focal epilepsies of sions and bone lesions. CT has low
epilepsies requires the childhood with characteristic clinical sensitivity for detecting small cortical
use of specific protocols and EEG features (eg, benign epilepsy lesions in general and particularly le-
selected based on with centrotemporal spikes, early- sions in the base of the skull, as in the
identification of the
onset childhood epilepsy with occipital orbitofrontal and medial temporal re-
region of onset by
spikes [Panayiotopoulos type]) and gions. Small, low-grade gliomas usually
clinical and EEG findings.
adequate response to antiepileptic drugs are not detected by CT. The overall per-
(AEDs).1,2 centage of success of CT in detecting
There are two basic situations in lesions in focal epilepsies is low, ap-
which to perform neuroimaging in pa- proximately 30%.3
tients with epilepsy. The first applies
to newly diagnosed patients and those MRI
with long-standing epilepsy that has The extraordinary ability of showing
not been properly investigated. The clear differences between gray and
second applies to patients with intrac- white matter and other tissues in the
table epilepsy who are therefore can- brain in MRI is the main difference
didates for surgery.2 Even patients between this technique and x-ray imag-
with long-term focal epilepsy of un- ing modalities, such as CT. MRI has
known etiology should undergo MRI. fundamental importance in the diagno-
Low-grade tumors may be found in sis and treatment of patients with
patients with a history of epilepsy with epilepsy. The introduction of MRI led
more than 20 years’ duration. to major improvement in the diagnosis
Priority should be given to patients and understanding of different epileptic
with focal changes in the neurologic syndromes. MRI allows the characteri-
examination. Emergent imaging (CT or zation of the nature of the lesion and its
MRI) should be performed in patients behavior over timeVthat is, whether
who have new onset of seizures with the lesion is progressive (eg, cancer,
focal neurologic deficits, fever, persis- Rasmussen encephalitis) or static (eg,
tent headache, cognitive changes, and a ischemic lesions, congenital malforma-
recent history of head trauma. Focal tions). Within the context of investiga-
seizures with onset after the age of 40 tion for surgical treatment, identification
years should be considered as a possi- of a lesion closely associated with the
ble indication for an emergency neuro- ictal and interictal EEG abnormalities is
imaging examination. associated with a better prognosis of
postoperative seizure control.4Y6
CT A proper MRI investigation of pa-
CT has the advantages of being avail- tients with focal epilepsies requires
able in most hospitals worldwide and the use of specific protocols selected
having a relatively low operating cost. based on identification of the region
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 KEY POINTS
of onset by clinical and EEG findings. weighted volumetric acquisition with h MRI epilepsy protocols
For practical purposes, the focal epilep- isotropic voxel size of 1 or 1.5 mm in should include a
sies can be divided into mesial temporal order to enable the reconstruction of three-dimensional,
lobe epilepsies (MTLE) and neocortical images in any plane.2,7 Studies dem- T1-weighted volumetric
epilepsies. This distinction is due to the onstrated that more sophisticated acquisition with
relative specificity and consistency of methods of image reconstruction from isotropic voxel size of 1
clinical, MRI, and pathologic findings 3D acquisitions allow a better evalua- or 1.5 mm in order to
(most frequently hippocampal sclero- tion of patients with discrete structural enable the reconstruction
sis) (Figure 3-1 and Figure 3-2) ob- lesions, in particular focal cortical dys- of images in any plane.
served in MTLE (Table 3-1, Case 3-1) plasia (Figure 3-3 and Figure 3-4) h Methods of image
compared to neocortical epilepsies. where the main findings are cortical reconstruction from
The clinical manifestations and EEG thickening, abnormal gyri, and poor three-dimensional
changes in neocortical epilepsies are delineation of the transition between acquisitions allow a
varied, and the pathologic substrate white and gray matter.7Y10 The 3D better evaluation of
patients with discrete
involved in its genesis comprises a images obtained have the characteris-
structural lesions, in
broader range of etiologies (Table 3-2). tics of a volume that can be handled
particular focal cortical
MRI epilepsy protocols should in- on a computer workstation to serve dysplasia where the
clude a three-dimensional (3D), T1- various purposes. Among the methods main findings are
cortical thickening,
abnormal gyri, and poor
delineation of the
transition between
white and gray matter.

FIGURE 3-1 Coronal T1 inversion recovery (A, C) and fluid-attenuated inversion recovery
(FLAIR) (B, D) MRIs showing left hippocampal atrophy associated with change
in morphology and internal structure and hyperintense FLAIR signal (arrows),
all classic signs of hippocampal sclerosis on MRI that were confirmed on postoperative
histopathology. Patient with left mesial temporal lobe epilepsy was seizure free after left
amygdalohippocampectomy.

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 Neuroimaging in Epilepsy

Multiplanar analysis is the interactive

visual evaluation of brain parenchyma,
acquired by volumetric MRI. These
techniques allow the inspection of de-
tails of brain structure through the si-
multaneous analysis of brain in different
planes of section, which is very impor-
tant for the detection of focal cortical
dysplasias (Figure 3-3 and Figure 3-4).

Mesial Temporal Lobe Epilepsy

The acquisitions of MRI in patients
with MTLE need to be optimized for
evaluating the abnormalities in hippo-
campal sclerosis. Thin coronal slices,
perpendicular to the long axis of hip-
pocampus, are essential. Thin slices (ie,
3 mm or less) allow appreciation of
details of the hippocampal anatomy of
normal and abnormal hippocampi. T1-
weighted MRI with high resolution,
particularly with inversion recovery or
other sequences with high-contrast res-
olution between different tissue types,
allow the best images for evaluating
volume, shape, orientation, and hippo-
campal internal structure (Figure 3-1
and Figure 3-2). T2-weighted images,
using fast spin echo (FSE) sequences
and fluid-attenuated inversion recovery
(FLAIR), are fundamental for assess-
ment of signal changes (Figure 3-1 and
Figure 3-2). FLAIR imaging sequences
have shown an accuracy of 97% for
detecting abnormalities associated with
hippocampal sclerosis defined on his-
topathology12,13; however, it should be
FIGURE 3-2 Coronal T1 inversion recovery (A, B) and emphasized that FLAIR images may
fluid-attenuated inversion recovery (FLAIR)
(C) MRIs showing signs of left hippocampal show false abnormal signals in
sclerosis (arrows): hippocampal atrophy and hyperintense hippocampi.14Y16 The presence and
signal on FLAIR MRI at the level of hippocampal head.
Observe the flattening and inclination of the left hippocampus. degree of preoperative MRI signs of
Patient with left mesial temporal lobe epilepsy became seizure hippocampal sclerosis in the ipsilateral
free after left amygdalohippocampectomy.
and contralateral hippocampus are im-
portant for the prognosis of both post-
for postprocessing and analysis of operative seizure control and memory
images with great diagnostic appli- outcome.13,14
cation in epilepsy are the multiplanar Studies demonstrated that MRI
(Figure 3-3)11 and curvilinear recon- volumetry of the hippocampus and
structions (Figure 3-4).7 amygdala is sensitive and specific in the
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TABLE 3-1 MRI Features of Hippocampal Sclerosis Detectable By Visual Inspection

Feature Description
Hippocampal The most specific and reliable feature, hippocampal atrophy, is defined
atrophy by comparing the hippocampal circumference on each side on all available
coronal slices. Small asymmetries can be present because of normal variation
or a tilted position in the scanner, and should not be considered abnormal.
It is important to evaluate the shape of the hippocampus as well. A normal
hippocampus is oval. In the presence of hippocampal sclerosis it becomes
flattened and usually inclined.
Increased T2 signal In isolation, increased T2 signal may be insufficient to diagnose hippocampal sclerosis.
T2 mapping (relaxometry) is an objective method for measuring abnormal T2 signal,
which may be difficult to detect visually.
Loss of internal This is usually associated with atrophy and hyperintense T2 signal. The loss of normal
structure internal hippocampal structure is a consequence of neuronal loss and gliosis with
a collapse of pyramidal cell layers that is characteristic of hippocampal sclerosis.
Other features Asymmetry of the horns of the lateral ventricles (which is variable and may lead to
false lateralization) and atrophy of the anterior temporal lobe (which is nonspecific)
may be present.
Atrophy of the fornix and mammillary body ipsilateral to the hippocampal sclerosis
may also be present.

Case 3-1
A 40-year-old, right-handed man presented with focal seizures since 2 years of age. Seizures were
controlled with antiepileptic drugs (AEDs) until he was 10 years old, when he began having at
least 3 focal seizures per week despite several adequate trials with AEDs; his longest period free of
seizures was 3 months. He described his seizures as rising epigastric sensations (sometimes with fear)
followed by loss of contact with surroundings, staring, oroalimentary automatisms, and sometimes
more complex automatisms such as walking around or taking off his clothes. Rarely, these seizures
evolved to secondary generalization. The patient had no history of head trauma, encephalitis, or
status epilepticus and no family history of seizures. He complained that his memory had been getting
worse over the years.
Routine EEGs showed frequent slow waves and epileptiform sharp waves over both
anterior-midtemporal regions with left-side predominance. Five of his habitual seizures were
recorded on video-EEG monitoring. All had EEG onset over the left anterior-midtemporal region
(maximum at T3) and the first clinical manifestations were coincident with first EEG changes. The
patient’s neuropsychological evaluation showed a significant deficit of verbal and nonverbal memory
and impairment of verbal fluency tests. His MRI showed signs of left hippocampal sclerosis (Figure 3-1).
He underwent a left anterior temporal lobe resection and had a brief focal seizure on the second
day after surgery, after which he remained seizure free on carbamazepine over the next 2 years
until it was discontinued; a few months later he had a generalized seizure and a few focal seizures. He was
put back on medication and remained seizure free at the last follow-up visit 5 years after surgery.
Comment. This patient had a typical history, semiology, EEG changes, and MRI signs of
hippocampal sclerosis. Unfortunately, he spent 30 years with frequent, disabling seizures and was
referred for evaluation for surgical treatment only at age 40. Patients with this clinical picture and
clear-cut MRI findings of unilateral hippocampal sclerosis should be considered for evaluation for
surgery as soon as refractoriness to AEDs is defined.

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 Neuroimaging in Epilepsy

TABLE 3-2 Imaging Investigation in Patients with Suspected Neocortical Lesions

1. Initial screening for patients over the age of 2:

Coronal T1-weighted (3 mm or less)
High-resolution volume (3D) acquisition with isotropic voxel size of 1 to 1.5 mm3 for multiplanar
reconstruction.
Coronal T2 and fluid-attenuated inversion recovery (FLAIR) sequences
Axial FLAIR
Sagittal T1-weighted
2. Initial screening for patients under the age of 2:
Fast spin echo T2-weighted and proton density images
High-resolution volume acquisition
MRI may not reveal cortical lesions, and scans need to be repeated after about 1 year
3. If nothing is found, reexamination by an experienced observer may reveal a subtle lesion such as focal
cortical dysplasia.
Multiplanar reconstruction and reslicing, 3-mm coronal inversion recovery images, thin T2 fast spin
echo sequence, and 3D FLAIR may be helpful at this point.
In the absence of magnetic resonance findings, no imaging technique is specific for dysplasia. In such
cases, cortical dysplasia may be discovered at surgery.
4. If focal findings appear, comparison of ictal and interictal single-photon emission computed
tomography (SPECT) images or positron emission tomography (PET) may add additional information on
the localization of the epileptogenic zone.
Local expertise in performing and interpreting this procedure is important given the complexity of
many cortical dysplasia syndromes.
5. The most common lesions causing neocortical epilepsies are low-grade tumors; malformations of
cortical development; posttraumatic, postischemic, and inflammatory-infectious scars; cavernous
angioma; and arteriovenous malformations.

KEY POINT identification of hippocampal sclerosis Visual MRI interpretation, hippocam-

h The hippocampal MRI in patients with MTLE. However, qualita- pal volumetry, and T2 relaxometry
abnormalities in patients tive visual analysis is also highly sensitive, are useful in detecting hippocampal
with hippocampal
provided that the images are acquired sclerosis.17,18 While MRI is the gold
sclerosis can be bilateral
with an optimized protocol.15,16 Visual standard for in vivo detection of hip-
and sometimes
symmetric, but usually
discrimination of a normal from an pocampal sclerosis, it may fail to de-
are unilateral or with abnormal hippocampus is straightfor- tect mild hippocampal sclerosis that
clear asymmetry. MRI ward when one is clearly normal and the may be found on postoperative histo-
also shows atrophy other is clearly abnormal; however, the pathology. The hippocampal MRI
and signal changes in visual binary paradigm breaks down in abnormalities in patients with hippo-
structures outside of the the presence of bilateral symmetric or campal sclerosis can be bilateral and
hippocampus, usually mild unilateral atrophy (Table 3-1). sometimes symmetric, but usually are
ipsilateral to the side of unilateral or clearly asymmetric. MRI
hippocampal sclerosis. Presurgical Evaluation of Mesial also shows atrophy and signal changes
Temporal Lobe Epilepsy with in structures outside of the hippocam-
Hippocampal Sclerosis pus, usually ipsilateral to the side of
MRI is highly sensitive and specific for hippocampal sclerosis.6
detecting hippocampal sclerosis in
patients with MTLE (Table 3-3) as well Epilepsies Due to Neocortical
as for in vivo diagnosis of other lesions Lesions
that cause MTLE, such as tumors, dys- In patients with suspected neocortical
plasias, and vascular malformations. temporal lobe epilepsy or extratemporal

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FIGURE 3-3 MRI multiplanar reconstruction (MPR) in a patient with frontal lobe seizures due
to focal cortical dysplasia who had previous MRIs considered as negative. Top
row shows nonvolumetric axial T2-weighted and axial and coronal T1-weighted
images with 3-mm thickness. The thicker images (3 mm or more) showed areas with blurring
of cortex in both frontal regions, indicated by the question marks. The blurred cortex on the right
side is a false thickened cortex due to partial volume effect, whereas the area with blurring on
the left frontal lobe is a combination of normal partial volume and an abnormal cortex. This small
area of focal cortical dysplasia in the left frontal lobe was better demonstrated in the MPR
with 1-mm-thick three-dimensional MRI (arrows). MPR allows for more dynamic analyses of
MRI with simultaneous view in different planes and orientation of slices. The three smallest
images on the right side of the figure depict the coordinates of angulation and location (the two
lines on each small image) of the reconstructed images in the other two orientations.The two
lines on the small sagittal image indicate the planes of the coronal and axial reconstructed image
and so on (the position and angle of these lines of reconstruction can be changed by the
examiner allowing a more dynamic analysis of the image). Note the small area with thickened
cortex associated with abnormal gyri and a depression on the overlying surface of the brain
(also referred to as cortical dimple) (arrows). The T2-weighted and fluid-attenuated inversion
recovery (FLAIR) images (not shown) did not show abnormal signal. These changes are
suggestive of focal cortical dysplasia type I or IIA.

epilepsies, subtle structural lesions can be fast and able to provide excellent
be missed unless MRI is performed differentiation of gray and white mat-
with optimal technical quality and ex- ter and spatial resolution. Unfortunately,
pertly interpreted. Correlation with these goals are mutually exclusive
semiology, EEG, and structural and because of limitations imposed by
functional imaging data is essential. basic physical principles of MRI. The
The ideal protocol for MRI investi- sequences should include T1- and T2-
gation in patients with epilepsy should weighted images covering the entire
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 Neuroimaging in Epilepsy

KEY POINTS
h MRI sequences should
include T1- and
T2-weighted images
covering the entire brain
in the three orthogonal
planes, with minimum
slice thickness allowed
by the scanner. The
injection of contrast is
usually unnecessary;
however, it may be
important in situations
when the images
without contrast are not
sufficient for diagnosis
or when a tumoral or
inflammatory lesion is
suspected.
h The use of appropriate
MRI protocols targeted
for the study of patients
with epilepsy allows
the diagnosis of the
majority of patients with
lesional epilepsies.
However, in a
considerable number FIGURE 3-4 MRI curvilinear reconstruction (A, C, and E) in a patient with frontal lobe seizures
and previous MRIs considered as normal. Panel D shows an axial T1-weighted
of patients with image at the level of the abnormality. Note the area with abnormal gyri (H, I, red
epilepsy, the MRI is arrows), a deep sulcus, and a depression on the overlying surface of the brain
considered normal. (G-I, blue arrows) with increased CSF space that is better observed in the curvilinear reconstructions
in the right frontal lobe (A-C, E, F). These abnormalities and the focal cortical-subcortical
Although the etiology blurring become obvious in the curvilinear reconstructions in layers going from 4 mm (A) to
remains unclear in these 12 mm (F) below the surface of the brain. The T2-weighted and fluid-attenuated inversion
cases, the disorders of recovery (FLAIR) images (not shown) did not show abnormal signal. The patient, a 36-year-old
woman, underwent a right frontal resection under electrocorticography and has been seizure
cortical development, free for 4 years. Histopathology showed focal cortical dysplasia type IIA.
mainly focal cortical
dysplasia, have been
identified as the most brain in the three orthogonal planes, that more methods of image recon-
likely pathologic with minimum slice thickness al- struction from 3D acquisitions allow
substrates. lowed by the scanner. The injection of a better evaluation of patients with
contrast (eg, gadolinium) is usually discrete structural lesions, especially
unnecessary; however, it may be im- focal cortical dysplasias (Figure 3-3 and
portant in situations when the images Figure 3-4).
without contrast are not sufficient The use of appropriate MRI pro-
for diagnosis or when a tumoral or tocols targeted for the study of patients
inflammatory lesion is suspected. with epilepsy allows the diagnosis of
The ideal MRI in patients with focal the majority of patients with lesional
epilepsy should include a 3D volumet- epilepsies. However, in a considerable
ric acquisition with thin sections (ie, number of patients with epilepsy, the
less than 2 mm) in order to enable the MRI is considered normal. Although the
reconstruction of images in any plane etiology remains unclear in these cases,
(Table 3-2).8,9,11 Studies have shown the disorders of cortical development,
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 KEY POINT

TABLE 3-3 Imaging of Hippocampal Sclerosis h Focal cortical dysplasia

may be observed in MRI
b MRI examinations as areas
Detects most moderate-to-severe hippocampal sclerosis of cortical thickening,
Abnormalities highly specific to hippocampal sclerosis loss of the interface
Insensitive to epileptogenicity between white and gray
matter, focal atrophy,
b Magnetic Resonance Spectroscopy
Detects metabolic changes in mild-to-severe hippocampal sclerosis and hyperintense signal
in T2/fluid-attenuated
b Interictal Fluorodeoxyglucose Positron Emission Tomography (PET) inversion recovery
Detects metabolic changes in mild-to-severe hippocampal sclerosis (FLAIR) sequences.
Highly sensitive to epileptogenicity, not specific to hippocampal sclerosis
b Ictal Single-Photon Emission Computed Tomography (SPECT)
Highly sensitive to epileptogenicity, not specific to hippocampal sclerosis

mainly focal cortical dysplasia, have been examinations as areas of cortical thick-
identified as the most likely pathologic ening, loss of the interface between
substrates. The effort involved in try- white and gray matter, focal atrophy,
ing to increase the detection of these and hyperintense signal in T2/FLAIR
‘‘invisible’’ lesions involves the im- sequences (Figure 3-3, Figure 3-4,
provement of the signal-to-noise ratio and Figure 3-5).
and contrast resolution between dif- In the current classification, focal
ferent tissue types, structural imaging cortical dysplasias are subdivided into
techniques, and imaging postprocessing.8 three types: type I (no dysmorphic
Among the techniques used to imple- neurons or balloon cells), type II (pres-
ment the image quality, two methods ence of dysmorphic neurons with or
are highlighted: the use of higher mag- without balloon cells), and type III
netic fields (eg, 3 Tesla or higher) and (focal cortical dysplasia associated with
surface coils.19,20 another lesion)9; these in turn have
subdivisions (Table 3-4).
Malformations of Cortical Focal cortical dysplasia type I may
Development present with mild hyperintensity of
Focal cortical dysplasias. Refractory the white matter in T2/FLAIR with loss
epilepsy, particularly in childhood, is of gray/white matter differentiation,
often associated with malformations but in many patients MRI does not
of cortical development, especially show abnormalities in the white matter.
focal cortical dysplasia. Many patients It may present with mild focal increase
have seizures refractory to medication in cortical thickness and abnormal gyrus
and are candidates for surgical treat- in shape and deep sulci, but it may also
ment. However, not all patients with be associated with focal volume loss
malformations of cortical develop- and thin cortex, in particular when the
ment present with refractory epilepsy. temporal lobe is affected.
Focal cortical dysplasia is character- Focal cortical dysplasia type IIB, or
ized by disorganization of the cortical focal cortical dysplasia with balloon
lamination associated with bizarre (ie, cells (which was previously defined as
dysplastic) neurons or cells with eosin- Taylor type dysplasia), is characterized
ophilic cytoplasm and increased vol- by areas of thickening of the cortex,
ume (ie, balloon cells).21 Focal cortical with the blurring of the differentiation
dysplasia may be observed in MRI between the gray/white matter interface,

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 Neuroimaging in Epilepsy

FIGURE 3-5 Coronal T1-inversion recovery (A, B) and coronal (E, F) and axial fluid-attenuated
inversion recovery (FLAIR) images showing typical changes of focal cortical dysplasia
type IIB (arrows). Diagnosis was confirmed in the postoperative histopathology in a
patient with refractory focal seizures with temporal-insular semiology. Note area of cortical
thickening and loss of sharpness of the cortical-subcortical transition (A, B, D-F, blue arrows) and
cortical-subcortical signal changes (increased FLAIR signal and decreased T1 signal) below the area of
cortical thickening that extends toward the ventricle (transmantle sign) (A-C, F, red arrows).

and its main feature is hyperintense to the ipsilateral ventricle ependymal

T2-FLAIR signal in the subcortical white surface (transmantle sign) (Figure 3-5,
matter with wedge shape that extends Table 3-4).9

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 a
TABLE 3-4 Summary Classification and MRI Findings of Focal Cortical Dysplasia

Type of
Focal Cortical
Dysplasia Histologic Characteristics MRI Features
Ia Abnormal radial cortical lamination & Mild hemispheric hypoplasia
Ib Abnormal tangential cortical lamination & Areas with thin cortex
Ic Abnormal radial and tangential & Blurring of the gray/white matter junction
cortical lamination
& Abnormally shaped sulci and sometimes
deep sulci
& MRI results are often negative
& MRI cannot differentiate these subtypes
IIa Dysmorphic neurons without & Gradient of morphologic changes: from
balloon cells dysplastic lesions that can be easily
identified by conventional MRI techniques
to minor structural abnormalities, including
small areas of discrete cortical thickening or
blurring of the gray/white matter interface
that often go unrecognized
& Sometimes subtle hyperintense T2 signal
in the subcortical and deep white matter
IIb Dysmorphic neurons with & Increased T2 or fluid-attenuated inversion
balloon cells recovery (FLAIR) signal in the subcortical
white matter underneath the focal cortical
dysplasia
& Transmantle sign (tapering of abnormal
white matter signal from cortex to
ventricle surface)
& Blurring of the gray/white matter junction
& Increased cortical thickness
& Deep sulci
& Abnormal cortical gyration and sulcation
IIIa Architectural abnormalities & Variable combination of MRI features of
associated with hippocampal focal cortical dysplasia described above
sclerosis and the associated lesion, which is most
IIIb Architectural abnormalities frequently in the same lobe/region
adjacent to tumors
IIIc Architectural abnormalities
adjacent to vascular malformation
IIId Architectural abnormalities adjacent
to lesions acquired early in life
(ie, trauma, ischemic injury, encephalitis)
a
Adapted from Blümcke I, et al, Epilepsia.9 With permission from Wiley Periodicals, Inc. B 2010 International League Against Epilepsy.
onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2010.02777.x/full.

Other malformations of cortical face with the ventricular lumen. The

development associated with epilepsy. cortical tissue is usually abnormal in
Schizencephaly is characterized by a its edges (polymicrogyria); closed-lip
cleft that connects the cortical sur- schizencephaly occurs when the
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 Neuroimaging in Epilepsy

FIGURE 3-6 MRI of four different patients illustrating schizencephaly and polymicrogyria. Axial T2- and T1-weighted and
coronal T1-weighted MRIs from a patient with open-lip schizencephaly (AYC) and axial T1-weighted images from
a patient with closed-lip schizencephaly (DYF); axial T1-weighted image from a patient with bilateral polymicrogyria
(G) and coronal and sagittal T1-weighted image from a patient with left unilateral polymicrogyria (H, I).

edges are juxtaposed, and open-lip neurons reach the cerebral cortex
schizencephaly when the edges are during development but are distrib-
separated (Figure 3-6).22 uted abnormally, resulting in abnor-
Polymicrogyria is characterized by mal small gyri that may appear as
developmental abnormalities where thickened cortex if the MRI is acquired
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FIGURE 3-7 Unilateral periventricular nodular heterotopia (A, arrow) with polymicrogyria in the adjacent cortex; two
patients with bilateral periventricular nodular heterotopia (B, C); a patient with periventricular nodular
heterotopia in the right temporal horn of the ventricle (D, arrow) and a large subcortical heterotopia
extending to the posterior quadrant of the brain (E, F); three patients with different thickness of subcortical laminar
heterotopia (double cortex), from thin and discontinuous bands (G, arrows) to continuous bands (H, arrows, I); three patients
with different degrees of lissencephaly-agyria-pachygyria complex, from pachygyria (J), posterior agyria and anterior pachygyria
(K), and diffuse lissencephaly (L).

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 Neuroimaging in Epilepsy

with low resolution and thick cuts promising the adjacent neocortex.23
(Figure 3-6).22 Subcortical laminar heterotopia (double
Periventricular nodular heterotopia cortex) is characterized by a continu-
is characterized by clusters of ectopic ous or semicontinuous ectopic band of
neurons and can be located at the gray matter below the cortical mantle
periventricular areas (subependymal). (Figure 3-7).9
These nodules consist of mature neu- Lissencephaly-agyria-pachygyria and
rons and glia cells without well-defined subcortical laminar heterotopia repre-
lamellar organization (Figure 3-7). Sub- sent extremes in the spectrum of the
cortical nodular heterotopia is charac- same entity. In lissencephaly-agyria-
terized by nodules of ectopic gray pachygyria the brain has a limited num-
matter that vary in number and size, ber of gyri and sulci, resulting in shallow
sometimes in the posterior peritrigonal sulci and large gyri with thickened
region (vascular border zone), and may cortex or an almost complete absence
extend toward the white matter, com- of sulci in lissencephaly (Figure 3-7).22

FIGURE 3-8 Two patients with left (A, B) and one patient with right (C, D)
hemimegalencephaly. Note the abnormal signal in the white matter, which is
brighter on T2 (A) and darker on T1-weighted images (BYD) of the affected
hemisphere in all patients and variable degrees of pachygyria and hemispheric enlargement.
Periventricular nodular heterotopia is present in panel D.

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FIGURE 3-9 T2-weighted axial MRIs showing multiple cortical tubers (arrows) in a patient
with tuberous sclerosis and epilepsy.

Hemimegalencephaly is character- addition, there are often areas of

ized by hamartomatous growth of part pachygyria, polymicrogyria, heterotopia,
of or the entire cerebral hemisphere. focal cortical dysplasia, and gliosis of
This is visualized on MRI as hemispheric the underlying white matter.22
enlargement, often associated with ip-
silateral ventricular dilatation and clearly Tuberous Sclerosis
abnormal signal in the white matter (hy- The cortical hamartomas or ‘‘tubers’’ are
perintense in T2/FLAIR and hypointense the most characteristic lesions in tuber-
in T1-weighted images) (Figure 3-8). In ous sclerosis complex and may be

FIGURE 3-10 Coronal MRIs showing ganglioglioma in three patients with temporal lobe epilepsy and seizures not
responding to antiepileptic drugs who became seizure free after surgical resection of the lesion. A,
T2-weighted image showing a ganglioglioma in the left amygdala. B, T1-inversion recovery image showing
a small ganglioglioma in the right collateral sulcus (arrow) that was previously missed in an MRI without thin coronal cuts.
C, T2-weighted image showing a ganglioglioma in the left uncal region with a cystic component (arrow). Gangliogliomas
usually have clear limits and are hypointense on T1 (not shown in this figure) and hyperintense on T2-weighted images.
The contrast enhancement is variable from absent to intense, and may present with an annular (ring-enhancing) pattern.
Gangliogliomas should be considered when a poorly defined, slightly enhancing mass is present in the temporal lobes.

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 Neuroimaging in Epilepsy

FIGURE 3-11 Two patients with temporal lobe epilepsy due to oligodendroglioma, one in the right temporal horn of the
ventricle adjacent to the hippocampus (AYC) and the other (DYF) in the right inferior temporal gyrus.
Oligodendrogliomas are nonspecifically hypointense on T1-weighted (D) and hyperintense on
T2-weighted or fluid-attenuated inversion recovery (FLAIR) images (A, E). Occasionally, foci of increased signal on
T1-weighted images (B) reflect intratumoral hemorrhage. Enhancement on CT or MRI is variable (C, F, arrows). On CT,
calcifications are expected and may be shell-like, ringlike, or nodular.

KEY POINT related to focal seizures, often refractory Low-Grade Tumors

h Gangliogliomas, to AEDs; however, not all tubers are Gangliogliomas (Figure 3-10), oligo-
oligodendrogliomas, necessarily epileptogenic. Cortical dendrogliomas (Figure 3-11), and
and dysembryoplastic
hamartomas on CT appear as dark le- dysembryoplastic neuroepithelial tu-
neuroepithelial tumors
sions with broadened gyri in young chil- mors are frequently located in the tem-
are frequently located in
the temporal lobe and
dren; the lesions became progressively poral lobe and may be associated with
may be associated with less dark with age, and these tubers may focal cortical dysplasia (Figure 3-12),
focal cortical dysplasia, be difficult to identify on CT in adults and their most common clinical man-
and their most common unless the tubers are calcified. The MRI ifestation is epilepsy.
clinical manifestation is appearance of tubers also changes with The differential diagnosis of these
epilepsy. myelination. In neonates they are hyper- low-grade tumors in adult patients in-
intense on T1-weighted images and cludes other types of gliomas, in particular
hypointense on T2-weighted images astrocytoma. In children, astrocytoma,
compared to the surrounding white ganglioglioma, gangliocytoma, neuro-
matter. In older children they are hyper- blastoma, and other primitive neuro-
intense on T2-weighted images, with ectodermal tumors may have similar
poorly defined borders (Figure 3-9).22 MRI findings.24

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FIGURE 3-12 Images illustrating dysembryoplastic neuroepithelial tumors. A, B, T1
postgadolinium and T2-weighted images showing a dysembryoplastic
neuroepithelial tumor associated with focal cortical dysplasia (confirmed in the
postoperative histopathology) in the right temporal lobe in a 23-year-old man with refractory
focal seizures since the age of 9. The patient became seizure free after lesionectomy.
C, D, Coronal T1 and axial T2-weighted images showing a dysembryoplastic neuroepithelial
tumor in the right temporal lobe of a 26-year-old woman experiencing seizures since
childhood. She became seizure free after lesionectomy. Dysembryoplastic neuroepithelial
tumors are hypodense in CT scan and may show calcifications. Close to one-third of the cases
show contrast enhancement. In MRI the lesion is often limited to the cortex and is hypointense
on T1 (A, C) and hyperintense on T2 sequences (B, D). There is no peritumoral edema or mass
effect; variable contrast enhancement may be present (A, arrow).

Rasmussen Encephalitis rection of the diffusion of water in each

MRI in Rasmussen encephalitis shows voxel, which can be used to estimate
progressive atrophy of one of the ce- the orientation of white matter tracts.
rebral hemispheres, usually beginning Based on this information, it is possible
in the opercular region (ie, the part to trace major myelinated tracts
of the cerebral cortex that covers the (tractography) offering additional infor-
insula). Many times the cortex presents mation for surgical approach; for exam-
hyperintense signal on T2 and FLAIR ple, it can be used for visualization of
sequences. the optic radiation and for predicting
visual field deficits after surgery.25 In
DIFFUSION TENSOR IMAGING addition, DTI allows obtaining other
AND TRACTOGRAPHY quantitative data (such as fractional
Diffusion tensor imaging (DTI) data anisotropy and diffusivity and connec-
provide information regarding the di- tivity indices) that can indicate integrity

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 Neuroimaging in Epilepsy

KEY POINTS
h N-acetylaspartate or subtle lesions of white matter, nology may allow multislice or 3D proton-
appears to be a dynamic which have research applications.26 MRS acquisitions with whole-brain cov-
marker of epileptogenic DTI clinical applications for epilepsy, erage, with good spatial resolutions.
activity as well as a although promising, are still limited.
marker of neuronal POSITRON EMISSION
density; therefore, MAGNETIC RESONANCE TOMOGRAPHY
N-acetylaspartate SPECTROSCOPY PET images using 18F-fluorodeoxyglucose
abnormalities should be ProtonYmagnetic resonance spectros- (18F-FDG) may demonstrate a focal or
interpreted with caution. copy (proton-MRS) assesses neuronal regional hypometabolism within the ep-
h The major limitation of integrity by quantifying the peak of ileptogenic area, especially in MTLE.26,29
magnetic resonance N-acetylaspartate (NAA), a marker of This hypometabolic area can extend be-
spectroscopy is its neuronal integrity, usually by compar- yond the epileptogenic zone defined by
limited coverage area, ing its concentrations with choline or EEG, or beyond the area of structural
which in current creatine peaks. Unlike MRI, single- damage. This hypometabolism may
practice undermines the
photon emission computed tomogra- represent deafferentation or neuronal
evaluation of patients
phy (SPECT), and positron emission dysfunction, and can ‘‘recover’’ after a
with neocortical epilepsy
without a strong
tomography (PET) techniques, the successful surgery.29,30
suspicion of the location entire brain is not covered by MRS In clinical practice, the additional
of the epileptogenic examinations and usually only a few yield of 18F-FDG-PET in patients with
focus or lesion on MRI. large voxels are included in proton- MTLE and clear video-EEG and MRI
h PET images using MRS.26Y28 The poor signal-to-noise findings is modest, and in most of these
18F-fluorodeoxyglucose ratio of proton-MRS is a technical cases it may be considered unnec-
may demonstrate a limitation for acquisitions including essary.29 However, for patients with
focal or regional small volumes of tissue. In addition, inconclusive video-EEG and MRI re-
hypometabolism within the relatively long time for spectra sults, 18F-FDG-PET is extremely help-
the epileptogenic area, acquisitions makes the quantification ful for presurgical evaluation; it
especially in mesial of spectra in many voxels impractical. provides a correct detection of tempo-
temporal lobe epilepsy. Comparisons with the EEG localiza- ral lobe foci in 66% of these cases, as
This hypometabolic area tion and surgical results have demon- confirmed by depth-EEG studies.30,31
can extend beyond the strated that the reduced signal intensity The focal hypometabolism has been
epileptogenic zone
of NAA can lateralize and localize the useful in predicting seizure control after
defined by EEG, or
epileptogenic focus in patients with surgery for MTLE, as the greater severity
beyond the area of
structural damage.
focal epilepsies, especially MTLE. How- of the hypometabolism (defined either
ever, these changes are often bilateral by quantitative or qualitative methods)
h In clinical practice, the in patients with MTLE.26Y28 Moreover, correlates with better postoperative
additional yield of
the relative concentration of NAA can seizure outcome.32,33
fluorodeoxyglucose-PET
in patients with mesial
normalize after successful surgery for An extratemporal epileptogenic fo-
temporal lobe epilepsy MTLE.27 NAA appears to be a dynamic cus presents a hypometabolism by
and clear video-EEG and marker of epileptogenic activity as well 18F-FDG-PET less frequently.26 How-
MRI findings is modest, as a marker of neuronal density; there- ever, some patients with infantile spasms
and in most of these fore, NAA abnormalities should be may have a regional hypometabolism
cases it may be interpreted with caution.27 that can help in the decision for a sur-
considered unnecessary. The major limitation of MRS is its gical treatment.29
However, for patients limited coverage area, which in current A cost-comparison study showed
with inconclusive practice undermines the evaluation of that the combination of EEG and MRI
video-EEG and MRI results, patients with neocortical epilepsy with- as screening tests, without addition of
18F-fluorodeoxyglucose-
out a strong suspicion of the location of PET, is the most cost-effective screen-
PET is extremely helpful.
the epileptogenic focus or lesion on ing approach for presurgical investiga-
MRI.27,28 Future improvements in tech- tion of epilepsies.34
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 KEY POINTS
SINGLE-PHOTON EMISSION organization of seizures and epilepsies:
Report of the ILAE Commission on h SPECT examinations for
COMPUTED TOMOGRAPHY Classification and Terminology, 2005Y2009. the study of interictal
SPECT examinations for the study of Epilepsia 2010;51(4):676Y685. cerebral blood flow
interictal cerebral blood flow have low 2. Recommendations for neuroimaging of have low accuracy and
accuracy and are of little utility.26 By patients with epilepsy. Commission on are of little utility. By
Neuroimaging of the International League contrast, SPECT studies
contrast, SPECT studies during a seizure Against Epilepsy. Epilepsia 1997;38(11):
using the radiotracer hexamethyl- during a seizure using
1255Y1256.
propylene amine oxime (HMPAO)Y99mTc the radiotracer
3. Bronen RA, Fulbright RK, Spencer DD, et al. HMPAO-99mTc or
or ethyl cysteinate dimer (ECD)Y99mTc Refractory epilepsy: comparison of MR
imaging, CT, and histopathologic findings in
ECD-99mTc can
can identify both temporal and extra-
117 patients. Radiology 1996;201(1):97Y105. identify both temporal
temporal epileptogenic foci, as long as and extratemporal
the radiopharmaceutical is injected as 4. Berg AT, Mathern GW, Bronen RA, et al.
Frequency, prognosis and surgical treatment epileptogenic foci,
soon as possible after the onset of the of structural abnormalities seen with as long as the
seizure during video-EEG monitor- magnetic resonance imaging in childhood radiopharmaceutical is
ing.26,35 Therefore, interictal SPECT is epilepsy. Brain 2009;132(pt 10):2785Y2797. injected as soon as
only indicated for the comparison or 5. Téllez-Zenteno JF, Hernández Ronquillo L, possible after the onset
subtraction from an ictal examination. Moien-Afshari F, et al. Surgical outcomes of the seizure during
in lesional and non-lesional epilepsy: a video-EEG monitoring.
The ictal SPECT is most effective systematic review and meta-analysis.
for MTLE patients, with a sensitivity Epilepsy Res 2010;89(2Y3):310Y318. h To improve the spatial
and specificity between 80% and 97% 6. Cascino GD. Advances in neuroimaging: resolution, functional
if the radiotracer is injected soon after surgical localization. Epilepsia 2001;42(1): images can be
the seizure onset. In extratemporal epi- 3Y12. subtracted (eg, ictal
lepsies, ictal SPECT is much less effec- 7. Bastos AC, Comeau R, Andermann F, et al. SPECT minus interictal
tive and varies with the pathologic Diagnosis of subtle focal dysplastic lesions: SPECT) and coregistered
curvilinear multiplanar reformatting from (eg, the subtracted
substrate and the affected region. In three dimensional magnetic resonance ictal-interictal SPECT,
seizures with rapid spread (eg, frontal imaging. Ann Neurol 1999;46:88Y94.
or a PET image) with
lobe seizures) the major limitation is 8. Bernasconi A, Bernasconi N, Bernhardt BC, a high-resolution
the time required to inject the radio- et al. Advances in MRI for ‘cryptogenic’
anatomical MRI. All
epilepsies. Nat Rev Neurol 2011;7(2):99Y108.
pharmaceutical.26,35 functional images must
It is important to remember that 9. Blümcke I, Thom M, Aronica E, et al. The be interpreted in the
clinicopathologic spectrum of focal
temporal resolution of SPECT is poor; cortical dysplasias: a consensus classification
context of all clinical
images reflect what brain perfusion was proposed by an ad hoc Task Force of the and laboratory data.
approximately 10 seconds after injec- ILAE Diagnostic Methods Commission.
tion. Therefore, SPECT is not indicated Epilepsia 2011;52(1):158Y74.

for seizures less than 15 seconds in 10. Colombo N, Salamon N, Raybaud C, et al.
Imaging of malformations of cortical
duration. development. Epileptic Disord 2009;11(3):
To improve the spatial resolution, 194Y205.
functional images can be subtracted 11. Barkovich AJ, Rowley HA, Andermann F. MR
(eg, ictal SPECT minus interictal SPECT) in partial epilepsy: value of high-resolution
and coregistered (eg, the subtracted volumetric techniques. AJNR Am J Neuroradiol
1995;16(2):339Y343.
ictal-interictal SPECT, or a PET image)
with a high-resolution anatomical 12. Kuzniecky RI, Bilir E, Gilliam F, et al.
Multimodality MRI in mesial temporal
MRI.26,35 All functional images must sclerosis: relative sensitivity and specificity.
be interpreted in the context of all Neurology 1997;49(3):774Y778.
clinical and laboratory data. 13. Arruda F, Cendes F, Andermann F, et al.
Mesial atrophy and outcome after
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