Magnetic resonance (MR) imaging plays a pivotal role in every aspect of the diagnosis and management of temporal lobe epilepsy. Mesial temporal sclerosis (MTS) is the most common epileptogenic lesion in human epilepsy. This review focuses on the 1) normal anatomy of the hippocampus; 2) MR features of MTS and its mimics; 3) functional MR imaging as well as newer modalities such as MR spectroscopy and diffusion tensor imaging; 4) the role of MR in surgery of temporal lobe epilepsy; and 5) other lesions that may cause temporal lobe epilepsy, such as tumors, vascular malformations, and dysplasias. MR techniques are crucial for a complete workup of a patient with seizures because the ultimate goals of treatment are relief from intractable symptoms and prevention of disastrous postresection complications, such as speech and memory loss.
is currently Chief Resident at University of Texas (UT) at Houston.
She graduated with honors and received her MD in 1993 from All
India Institute of Medical Sciences. She later completed her
internship at UT Houston. Dr. Gupta will remain at UT Houston to
begin a fellowship in MR Imaging in 2003.
Magnetic resonance (MR) imaging plays a pivotal role in
every aspect of the diagnosis and management of temporal lobe
epilepsy. Mesial temporal sclerosis (MTS) is the most common
epileptogenic lesion in human epilepsy. This review focuses on
the 1) normal anatomy of the hippocampus; 2) MR features of MTS
and its mimics; 3) functional MR imaging as well as newer
modalities such as MR spectroscopy and diffusion tensor imaging;
4) the role of MR in surgery of temporal lobe epilepsy; and 5)
other lesions that may cause temporal lobe epilepsy, such as
tumors, vascular malformations, and dysplasias. MR techniques are
crucial for a complete workup of a patient with seizures because
the ultimate goals of treatment are relief from intractable
symptoms and prevention of disastrous postresection
complications, such as speech and memory loss.
The International Classification of Epilepsies and Epileptic
Syndromes classifies clinical epilepsy into two broad categories:
idiopathic (primary) and symptomatic (secondary) disorders.
Primary epilepsies are genetically transmitted seizures that are
not associated with other neurological disturbances or structural
pathology and are usually benign. Secondary epilepsies, in
contrast, are seizures resulting from a specific pathologic
substrate that can be genetic or acquired.
Both primary and secondary epilepsies are further divided into
generalized disorders (where the brain is diffusely and bilaterally
involved) and localization-related or focal disorders (seizures
originate from a localized cortical region). Temporal lobe epilepsy
constitutes nearly two-thirds of focal epilepsies
and is responsible for most cases of complex partial seizures.
Temporal lobe epilepsy can be further divided into the following
Mesial temporal lobe epilepsy (MTLE)
: The "pathological substrate" of MTLE is mesial temporal sclerosis
(MTS). In addition to being the lesion most commonly associated
with complex partial seizures (60% to 85% of cases),
it is also the most common structural abnormality in human
Lesional temporal lobe epilepsy
: This category is associated with specific structural
abnormalities, including developmental disorders, neoplasms,
infections, trauma, and immune-mediated disorders, such as
These lesions account for a minority of cases of temporal lobe
epilepsy. They could be located either in the mesial temporal lobe
or more distant neocortical areas with projections on the temporal
Cryptogenic temporal lobe epilepsy
: This category has no associated identifiable structural
abnormalities and is a diagnosis of exclusion.
Mesial temporal lobe epilepsy is not only the most common form
of human epilepsy but is also often medically intractable. However,
it is frequently amenable to surgical treatment with excellent
seizure control. High-resolution magnetic resonance (MR) imaging
and other MR techniques play a pivotal role in patient workup, case
prognostication, treatment planning (including surgery), and
subsequent follow-up. MR technique is also critical in helping to
elucidate the pathophysiology of MTLE.
What is MTS?
Mesial temporal sclerosis is the most common lesion seen in
patients with complex partial seizures. It is characterized by
pyramidal cell loss and astrogliosis in the mesial temporal lobe,
hippocampal formation, amygdala, parahippocampal gyrus, and the
entorhinal cortex. Radiologists must be very familiar with the
detailed anatomy of the mesial temporal lobe in order to guide
patient management accurately, especially surgical resection. The
MR features of MTS are subsequently described.
Anatomy of the mesial temporal lobe
The hippocampus forms an arc running rostrocaudally in the
mesial temporal lobe. The hippocampus has a head (pes hippocampus),
body, and tail. The head has prominent digitations (Figure 1),
whereas the body does not. The superficial portion of the body lies
adjacent to the fimbriae that extend superomedially to form the
thin crura of the fornices, and the tail lies in the floor of the
atrium. The hippocampal sulcus separates the subiculum, which
occupies the medial/superior curvature of the parahippocampal gyrus
(Figure 2). The hippocampus, fornix, and mamillary body are
components of a single limbic circuit (circuit of Papez). The
hippocampal fibers project to the mamillary body via the fornix.
The majority of the fibers come from the subiculum. This circuitry
explains how hippocampal neuronal damage leads to atrophy of the
fornix and mamillary body by wallerian and transneuronal
The hippocampus has two major parts: the cornu ammonis
(hippocampus proper) and the dentate gyrus (which is separated by
the hippocampal sulcus).
The cornu ammonis
(Figure 3) has four sectors: CA1, which is adjacent to the
subiculum; CA2, which is at the superior aspect of the cornu
ammonis; CA3, which is at the curve; and CA4, which is enveloped by
the dentate gyrus. This lamellar pattern of the hippocampus can be
readily identified by MR imaging
(Figure 4). Two different types of MTS can be identified
Classic Amnion horn's sclerosis,
or classic hippocampal sclerosis
which has pyramidal cell loss in CA1, CA3, and in the dentate
hilum, with sparing of CA2; and
end folium sclerosis,
in which only the end folium cells are involved.
Although MTS is a bilateral process, one side is affected more
than the other in 80% of patients. Usually, the more severely
affected side is the origin of the patient's seizures. Cases in
which both sides are equally affected generally respond less
favorably to temporal lobectomy.
MR features of MTS
A small atrophic unilateral hippocampus
(Figure 5) with loss of both the normal architecture and that of
normal digitations of the head. The atrophic hippocampus is bright
on both T2-weighted (T2W) and fluid-attenuated inversion recovery
(FLAIR) images (Figure 6). Visual assessment of size, architecture,
and signal intensity changes is quite sensitive, with the eye being
able to detect asymmetry of 14% or more.
Unilateral atro-phy of the mamillary body
fornix columns (circuit of Papez)
(Figure 5), and the
. In patients who have undergone temporal lobectomy, the frequency
of detection of these signs increases and may represent wallerian
degeneration and deafferentation of the circuit.
Unilateral dilatation of the temporal horn
(a less reliable secondary sign) (Figure 5).
Unilateral atrophy of the collateral white matter bundle
loss of gray-white demarcation in the ipsilateral anterior
. The anterior temporal lobe signal change has been associated with
earlier onset of seizures,
earlier age at antecedent event, and greater seizure load. This
change may be related to the postulated causative initial cerebral
insult rather than the effect of cumulative damage from seizures.
Because the appearance is similar to the immature development of a
temporal lobe, it may represent abnormal myelin or arrested
and suggest maldevelopment as a possible cause of temporal lobe
Anatomic variants that may mimic pathology
A right-handed individual has been shown to have a larger right
hippocampus and amygdala. Left-handed individuals show no
difference in size between the sides.
Similar size variations showing the right hippocampus larger than
the left were found in healthy volunteers by Jack et al.
A mean difference of 0.3 cm
<0.001) was noted.
In the immediate postictal phase, the resulting edema that
involves the hippocampus may hide the underlying atrophy
or mimic disease (encephalitis, neoplasm, etc.).
Standard imaging planes and sequences
A set of sagittal and axial T1-weighted (T1W) spin-echo (SE)
images are obtained initially (repetition time [TR] 500, echo time
[TE] min full). These are useful to define normal anatomy. This is
followed by an axial conventional SE T2W sequence (TR 2500, TE min
full/90), which is sensitive for most pathology. Compared with
conventional SE, foci of hemorrhage are less evident on fast SE
and, in such cases, a gradient-echo sequence may be used. Since the
majority of the lesions are in the temporal lobe, a modified
coronal plane perpendicular to the long axis of the hippocampus
(Figure 7) is the optimal plane for imaging the hippocampi. A set
of such oblique coronal images is obtained through the entire
hippocampus using both FLAIR (TR 10,000, TE 156, T1 2200) and fast
SE T2W (TR 5000, TE 102, echo train length [ETL] 8) techniques.
Fluid attenuated inversion recovery (Figure 6) increases the
conspicuity of parenchymal lesions in the
subcortical/periventricular white matter and hippocampal
formations. On this sequence, signal intensity changes are most
striking; this is related to the increase in tissue-free water that
reflects the underlying astroglial proliferation. However, it has
limited use in children with immature white matter containing
normal areas of hyperintensity.
Finally, an axial three-dimensional (3D) fast spoiled
gradient-recalled acquisition steady-state high-resolution
thin-slice acquisition is obtained using a very short TR and TE.
This provides a strong T1W contrast between the gray and white
The thin (1.5- to 2.0-mm) contiguous slices help detect subtle
cortical mantle and hippocampal migrational anomalies. A 3D T2W
acquisition may be useful in preoperative planning, stereotactic
surgery, or even as a neuronavigational tool. Furthermore, in cases
of focal abnormalities associated with mass effect that are
suspicious for tumors etc., gadolinium-based contrast may be
administered. Both axial and coronal T1W images are then
Other useful and emerging MR techniques
Magnetic resonance spectroscopy (MRS).
This technique is a means for noninvasive chemical analysis of the
brain. Proton spectroscopy is widely used with both single or
multivoxel techniques. It primarily analyzes choline (Cho),
creatine (Cr), and N-acetylaspartate (NAA) levels. In temporal lobe
epilepsy due to MTS, ipsilateral reduction of NAA, increases in Cho
and Cr, and significant reductions in NAA/Cho and NAA/Cr ratios
have been observed.
Lateralization by MRS compares well with hippocampal atrophy seen
on MR imaging and MR volumetry in temporal lobe epilepsy (Figure
8). Decreased NAA activity has been found in cases without
hippocampal atrophy as well. Also, in cases with bilateral changes
on MRS, maximal loss of NAA corresponds to the more severely
affected side on MR imaging. A decline in NAA peak may represent
both neuronal loss and/or neuronal/ glial dysfunction,
whereas the increase in Cho and total Cr concentrations has been
related to gliosis. When discordant results are present (eg,
maximal NAA activity decrease contralateral to MR hippocampal
changes), a dual pathology and a lower probability of successful
surgical outcome may be expected.
Postictal studies may reveal an additional lactate peak reflecting
a phase of anaerobic metabolism (seen within minutes of seizure
onset and persisting for several hours.
Other changes that can be identified are an increased myoinositol
peak in the ipsilateral temporal lobe
correlating with the extent of hippocampal sclerosis. In addition,
patients with MRI-negative temporal lobe epilepsy show an increase
in glutamate-glutamine signal and a less marked decrease in NAA,
when compared with cases of MRI-positive temporal lobe
Volumetric MR imaging.
This is a means of objectively quantifying size. Measuring size can
be accomplished by manually tracing the hippocampus or by using the
grid method. It is particularly useful for patients with anatomical
variants, bilateral hippocampal atrophy, or for those with
unsuspected disease. However, it is not useful in cases with
segmental hippocampal involvement.
The normal, ipsilateral hippocampal volume is approximately 2.8
This is used to quantify the T2 signal in the hippocampus. It
measures the decay in signal intensity at different TEs in a series
of T2W images acquired in the same slice. In MTS, the relaxation
time has proven to be lengthened by 10 milliseconds. The definition
of a normal hippocampus by this method is very precise, and the
diagnosis of MTS does not depend on a side-to-side comparison.
Thus, both cases of mild and bilateral hippocampal sclerosis can be
Diffusion tensor imaging (DTI).
This technique is a noninvasive imaging means to study the
intrinsic diffusion properties of the white matter.
A recent study on white matter
changes in patients with temporal lobe epilepsy
showed lower diffusion anisotropy in ipsilateral white matter
structures like the corpus callosum, external capsule, and internal
capsule. This may relate to a less tightly packed neuronal network
or deficient myelin. Similar changes have been identified by others
in white matter regions beyond the temporal lobe and may represent
global changes of epilepsy. Whether this is the cause or effect of
epilepsy is yet to be determined.
Functional MR imaging (fMRI).
This method uses the blood-oxygen-level dependent contrast
technique. Deoxyhemoglobin is paramagnetic and can be detected on
T2W images as low or decreased signal intensity. In contrast,
oxyhemoglobin is diamagnetic and exerts little effect. Thus, when
with contiguous nonstimulated areas, an activated cortex has
increased metabolism and blood flow and corresponding higher signal
intensity. The principal application of fMRI lies in the
preoperative localization of the motor strip, memory, and language
cortex. In this aspect, it produces information complementary to
the intracarotid amobarbital Wada's test.
Before temporal lobectomy, fMRI can be used to locate regions
responsible for memory and speech (Broca's and Wernicke's areas),
ie, the eloquent cortex. It can also identify the seizure focus
(since declarative memory depends on the integrity of the mesial
temporal lobe region, and the seizure focus is usually deficient in
Its potential clinical value in studying the effects of long-term
drug treatments, such as carbamazepine, in patients with epilepsy
is being evaluated.
The future holds great promise with newer methods on the horizon.
The sensitivity of the magnets has improved and MR microscopy has
been experimented with to trace the circuit of Papez using
manganese (Mn2+) injected subcutaneously (a potential MR contrast
agent). Watanabe and colleagues
were able to delineate the principal cell layers of the hippocampal
formation (CA2 and CA3) and dentate gyrus in living mice. At
present, these techniques are not applicable to human imaging.
Other pathologic substrates seen in temporal lobe
Pathologic substrates account for a minority of cases of
temporal lobe epilepsy. However, high-resolution MR imaging is
vital to their diagnosis and surgical treatment.
Focal cortical dysplasias are the most common disorders causing
developmental epilepsy (Figure 9). The MR hallmark is a
macroscopically thickened cortex (normal thickness is 4 mm).
Neuronal heterotopia is another common cause that may be nodular or
laminar in appearance (Figure 10). Other associated lesions are
hemimegalencephaly, schizencephaly, lissencephaly (agyria), and
pachygyria (broad flat gyri).
Neurocutaneous syndromes (phacomatosis)
In patients with tuberous sclerosis, cortical tubers cause
seizures, and those with Sturge-Weber syndrome (encephalotrigeminal
angiomatosis) have a pial angioma that represents a developmentally
impaired venous outflow abnormality.
Most venous angiomas and capillary telangiectases are clinically
silent. However, approximately 50% of patients with arteriovenous
malformations (Figure 11) and cavernous hemangiomas may experience
seizures. Epileptogenesis in cavernous angiomas is attributed to
irritation and compression from mass effect and exposure of brain
tissue to blood breakdown products and associated gliosis.
Seizures associated with neoplasms are usually of recent onset.
Gliomas, most commonly astrocytomas (Figure 12), account for nearly
80% of the primary neoplasms presenting with seizures. Pleomorphic
xantho-astrocytomas are rare tumors typically seen in the temporal
lobes of children with a history of seizures. Both gangliogliomas
(Figure 13) and dysembryoplastic neuroepithelial tumors are also
associated with pediatric seizures and have a predilection for the
Other tumors, such as meningiomas and cerebral metastases, are
related to late-onset or elderly seizure/epilepsy cases.
Seizures are common in patients with acute cerebral infections
(viral encephalitis and bacterial and aseptic meningitis) as well
as those with brain abscesses, aspergillosis, and other fungal
infections. Patients developing acute central nervous system
infections before 4 years of age have a higher propensity to
develop hippocampal sclerosis. In certain parts of the world,
cysticercosis and tuberculosis are leading infectious causes of
seizures in general.
MR imaging in surgery of epilepsy
The goal of resective epilepsy surgery is the complete resection
(disconnection) of the epileptogenic zone with preservation of the
eloquent cortex. The operative strategy is influenced by the
presumed pathology (provided by MR imaging) and by the extent and
location of the lesion. Historically, invasive recordings were
required before most epilepsy surgeries, but indications have
dramatically changed since the introduction of high-resolution MR
imaging, since it uncovers structural lesions in a high percentage
of cases. No invasive recordings are required before performing a
temporal lobectomy in patients who are MRI-positive for MTS and
have concordant interictal and ictal surface electroencephalogram
(EEG) recordings, functional imaging, and clinical findings.
Invasive testing is needed if there is evidence of bilateral MTS,
if there are discordant results, and/or if EEG and additional
neuroimaging techniques have been unable to lateralize the culprit
epileptogenic zone. Once depth (Figure 14) or subdural (Figure 15)
electrodes are used to lateralize the lesion, they can be seen
clearly on MR imaging. Both their placement (occipital temporal or
orthogonal temporal) and associated complications (hemorrhage,
infection, infarction, gliosis, etc.) can then be accurately
Currently, at least three surgical techniques are in common use
: Selective microsurgical resection (as in MTS, subpial resections,
etc.); functional hemispherectomy (frontal/ temporal lobectomy);
and corpus callosotomy (Figure 16).
MR techniques play a pivotal role in the complete workup of
patients with temporal lobe epilepsy. While MR imaging provides
morphologic details, newer techniques like MRS, volumetric MR, T2
relaxometry, and even fMRI can help assist and confirm the
epileptogenic focus. Accurate localization of the focus helps
accomplish the ultimate goal of treatment, ie, surgical resection
with the preservation of the eloquent cortex and preventing or
predicting devastating memory and speech complications. To achieve
this, a solid foundation in anatomic knowledge of the mesial
temporal lobe and the most common lesion, mesial temporal
sclerosis, is key. The future is even more exciting as the
anticipated growth of MR techniques, especially MR microscopy, may
help unravel the molecular and histopathologic substrates of
The author is grateful to Larry A. Kramer, MD, for reviewing the
manuscript and providing both the images and guidance. Special
thanks to Sandra A.A. Oldham, MD, for her encouragement and
support. The author is also grateful to Daniel A. Klepac for
technical assistance with the images.