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Cortical dysplasia in temporal lobe epilepsy Magnetic resonance imaging correlations.

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Cortical Dysplasia in Temporal Lobe Epilepsy:
Magnetic Resonance Imaging Correlations
Ruben Kuzniecky, MD,”Julio H. Garcia, MD,f Edward Faught, MD,” and Richard B. Morawetz, MD1‘
Cortical dysplasia has been documented in histological specimens surgically removed for treatment of refractory
temporal lobe epilepsy. We studied 10 patients with cortical dysplasia and complex partial seizures who underwent
temporal lobectomy. Magnetic resonance imaging revealed abnormalities in 5 of the patients who had microscopically
detectable major abnormalities. Magnetic resonance imaging revealed an abnormal cortical-white matter architectonic
pattern in 2 patients with moderate cortical dysplasia. I n the remaining 3 patients, magnetic resonance imaging
findings were unremarkable. These observations suggest that magnetic resonance imaging is sensitive in the d e t e d o n
of certain dysplastic lesions in temporal lobe epilepsy. Preoperative identification of these abnormalities by magnetic
resonance imaging may permit early and optimal surgical treatment in patients with refractory epilepsy.
Kuzniecky R, Garcia JH, Faught E, Morawetz RB. Cortical dysplasia in temporal lobe epilepsy:
magnetic resonance imaging correlations. Ann Neurol 1991;29:293-298
Temporal lobectomy is an effective, yet underused,
method of treatment for most patients with medically
resistant temporal lobe epilepsy [ 1). Although electroencephalographic (EEG) information remains crucial in
defining the epileptogenic area, there is considerable
controversy regarding the techniques used to identify
the epileptogenic focus. The presence of abnormalities-on-imaging procedures, in congruence with electrographic and other localizing data, often permits a
rational decision for surgical treatment. Computed tomographic (CT) scanning is usually unrevealing in patients with temporal lobe epilepsy [2-4). Magnetic resonance imaging (MRI) is unquestionably superior to
CT scanning in the detection of small epileptogenic
structural lesions such as tumors or small vascular malformations [5 , 6). Although controversial evidence exists [7), we have reported that with appropriate techniques, MRI is sensitive in detecting mesial temporal
sclerosis [ S ] , which is present in about 60% of patients
with temporal lobe epilepsy fs]. More recently, with
further refinement of our techniques, we have demonstrated hippocampal atrophy in association with other
abnormalities in patients with mesial temporal sclerosis
Over the past several years, many studies have described a variety of histological abnormalities in temporal lobe epilepsy [10-12]. In 1971, Taylor and colleagues [ 13) reported on the histological abnormalities
found in surgical specimens removed from a group of
patients with intractable partial epilepsy. They described “cortical dyslamination” associated with abnorFrom the Univcrsity of Alabama at Birmingham Epilepsy Center,
Deparrments of *Neurology, ?Neurosurgery, and $Pathology,
University of Alabama at Birmingham, AL.
mal giant neurons. They termed this abnormality “focal
cortical dysplasia” and ascribed ir to a developmental
malformation. More recently, this pathological entity
has been revived and expanded to include mild forms
of cortical and subcortical neuronal derangements
114-17). In recent studies, we reported on the usefulness of MRI in the diagnosis and management of various epileptic disorders caused by developmental migration disorders {18, 19). In this report, we describe the
MRI findings in a group of patients with histological
focal dysplasia of the temporal lobe and complex partial
Ten patients were entered into this study. They were selected
from a group of consecutive patients who underwent temporal lobe resections for medically intractable temporal lobe
epilepsy at the University of Alabama at Birmingham Epilepsy Center (Birmingham,AL). The patients were selected
on the basis of ( I ) a histological verification of cortical dysplasia and (2) a high-quality preoperative MRI scan of the brain.
All patients were evaluated with prolonged EEG-video monitoring (scalp = 10; intracranial electrodes = 7) and neuropsychological studies including bilateral intracarotid sodium
Amytal testing. All patienrs had CT scans with and without
contrast agents (GE 9800, General Electric, Milwaukee,
MRI Studies
The MRI examinations were performed on two different units. A Picker (Cleveland, OH) operating at a field
strength of 0.5 T and a Siemens Magneton GBS-2
(Erlangen, Germany) operating at a field strength of
Received May 30, 1990, and in revised form Aug 10. Accepted for
publication Sep 9. 1990.
Address correspondence to Dr Kuzniecky, Deparcment of Neurology, UAB Station, Birmingham, AL 35294.
Copyright (0 1391 by the American Neurological Association
1.5 T were used. Spin-echo sequences with echo times
(TE) of 25 to 100 msec and repetition times (TR) of
2,000 to 2,500 msec were performed in the axial and
coronal planes. T1-weighted images were obtained
with T R of 50 msec and TE of 15 msec in 3 patients.
Three patients underwent repeated studies in both
units. Gadolinium-diethylenetriamine pentaacetic acid
(DTPA)-enhanced MRls were performed in 3 patients.
Coronal and axial images with a T R of 70 msec and
TE of 20 msec were obtained after the administration
of 0.2 ml/kg of intravenous gadolinium-DTPA.
Clinical Feuturex
Age at onset (yr)
Full scale IQ
Seizure frequency
Partial complex seizures
Secondary generalization
4.1 (range, 0.7-13 years)
90 (range, 70-112)
8.8 per month (range, 6-20 months)
10 patients
8 patients
able pregnancy and birth histories. There were 6 females and 4 males aged 7 to 41 years (mean, 24
years). Additional information is presented in the
Histological Studies
The surgical resection was done by the subpial aspiration technique. The resection included a standard, en
bloc neocorticectomy, sparing the superior temporal
gyrus. This technique has been described in detail elsewhere 1201. The mesial temporal structures including
uncus, amygdala, and anterior hippocampal formation
were also resected. Because of the surgical technique
used, the middle and inferior temporal gyri were the
best available anatomical structures for histological examination. After gross examination, the specimens
were fixed in a buffered aldehyde and embedded in
paraffin. Histological sections were stained with hematoxylin-eosin and cresyl violet (Nissl). Axons were
demonstrated by silver impregnation (Sevier-Munger
technique). All specimens were reacted with antisera
for glial fibrillary acidic protein and neuron-specific
enolase. In some patients, additional immunohistochemical reactions included antiserum for synaptophysin.
The histological diagnosis was done following the
criteria established by previous studies 113-17). All
tissue sections were examined and arbitrarily classified
into two groups. Group 1 consisted of tissue sections
with mild dysplastic changes and Group 2 included
specimens with severe dysplasia. This subdivision was
based on the degree of histological abnormalities found
on the specimens. The abnormalities were graded from
slight to severe as follows: (A) multiple clusters of 5 to
10 neuronal aggregates in white matter (high-power
field), (Bj changes in orientation of neurons with poor
cortical lamination, ( C ) cortical dyslamination without
giant neurons, (Dj neuronal clustering with bare areas
within cortex, (E) cortical dyslamination with abnormal
giant neurons and large reactive astrocytes. Specimens
with abnormalities A, B, or C, or any Combination of
A, B, and C, were classified in Group 1. Specimens
with additional abnormalities such as D and E were
included in Group 2.
Clinical Features
Febrile convulsions were identified by history in 4 patients as a possible eciological factor. All had unremark294 Annals of Neuroloev Vol 29 No
March 1991
Electroencephalographic Studies
Scalp EEG recordings showed predominantly unilateral temporal lobe interictal abnormalities in 8 patients.
In 1 patient, bilateral independent but predominantly
unilateral epileptiform abnormalities were recorded. In
the remaining patient, secondary bilateral synchronous
spike and wave discharges in conjunction with a temporal focus were observed. The distribution of epileptiform discharges revealed that most abnormalities were
located over anterior-lateral temporal and frontal neocortex and less frequently over the mesial sphenoidal
electrodes. Intracranial studies were performed in 7 of
the 10 patients (6 epidural electrodes, 1 foramen ovale
electrode). In 3 patients, predominantly mesial EEG
ictal onsets were observed; in another 3 patients, the
ictal pattern was widespread over the lateral temporal
neocortex; and in the last patient, a unilateral widespread predominantly frontotemporal pattern was observed. The interictal and ictal EEG studies indicated
a left temporal focus in c) of the 10 patients.
MRI Ahnormalities
MRI studies revealed abnormalities in 7 of the 10 patients. The pattern of changes was variable between
patients but was restricted to one of the temporal
lobes. In 4 patients, the MRI abnormalities consisted
of nonhomogeneous increased signal-intensity lesions
within the anterior temporal, inferior and middle temporal gyri, and extending into the white matter. In 2
of these patients, the lesions extended into the mesial
structures. T1-weighted images demonstrated an abnormal organization of the cortical and white matter
pattern in certain patients (Fig 1). These abnormalities
were clearly detected in the T2-weighted images (Figs
2A, 3A). Gadolinium-enhanced scans did not reveal
any changes in these patients (Fig 2B).
In 2 patients, the MRI abnormalities were characterized by increased signal-intensity lesions on the inferior
temporal gyrus with limited extension into the adjacent
mesial temporal structures. The lesions were nonhomogeneous, without mass-effect, and with the cortex
focally thickened (Fig 4A). The MRI in the seventh
patient revealed a less-defined cortical-white matter
circumscribed abnormalities in 2 of the 5 patients (see
Fig 4 A , B).
Fig 1. (A,B) TI -weighted image demomtrates an abnormal cortical white matter organization. Note thick gyrus and white matter
pattern i n the 1eJt anterior temporal lobe (arrows).
architectonic pattern in the affected temporal lobe,
with a minimally increased abnormal signal intensity
from the cortex (Fig 4B).
M R I Pathological Correlations
Based on pathological subgroups, 5 patients were classified in Group 2 (see Figs 2C, 3B). In this group, MRI
revealed pronounced abnormalities in all patients (see
Figs 2A, 3A). The remaining 5 patients were classified
in Group 1. MRI correlation in this group revealed
Fig 2. (A)Magnetic resonance irnaging-T2-~~eightedsequence
showing increased signal in the Left anterior temporal lobe. (B)
Gadolinium-diethylenetriamine pentaacetir acid scan oJthe same
tecpatient produced no abnormal mhanctmnt. (C) Micro~~ropiition showing a cluster of neurons i n deep white matter. (Hematoxylin-eoJin; original magnification, x 400.) Other abnormalities
included cortical &lamination with bare areas within cortex.
patients underwent temporal lobe resections as
previously described. Follow-up ranged from 6 to 40
months, with a mean of 24 months. Six patients have
been seizure free since surgery. Three patients have
had 3 greater than 80% reduction in frequency of attacks. One patient was seizure free for 8 months, but
seizures have recurred. Postoperatively, 1 patient developed a mild hemiparesis that has improved.
The term cortical dysplasia was first introduced by Taylor and colleagues in 1971 [13], but it was Roncoroni
{Zl} who made the first comments on the relation between epilepsy and maturational brain disturbances.
Over the last several years, numerous studies have described neuronal microdysgenesis in patients with primary generalized epilepsy {22) and partial epilepsies
{ 15- 17). Several quahtative studies have reported focal cortical dysplasia and milder forms of dysplasia
in patients with refractory complex partial seizures
[l4-16, 233. More recently, quantitative studies have
revealed increased neuronal microdysgenesis in patients with temporal lobe epilepsy than in age-matched
controls { 171. Our patients represent examples of mild
to severe cortical dysplasia. We specifically excluded
specimens with minimal degrees of neuronal ectopia
because, without cell-density counts, the significance of
these findings is questionable. Hippocampal pyramidal
ectopic neuronal aggregates were present in one speci-
Kuzniecky et al: Dysplasia, MRI, and Temporal Lobe Epilepsy
Fi g 3. (Aj Magnetic resonance imaging-T2-weighted image
showing a nonhomogeneous high-intensity J.ignal lesion in the left
mesial and anterior temporal lobe. (B) Example of one of the several
abnomzalities in this patient; cortical dyslamination including
large neurons and astrocjites. (Hematoxylin-eosin;original magnification, x 400.)
Fig 4. (AJMagnetic resonance imaging (MRl)-T2-~eightedimage revealing a well circumscribed high-intensity abnomality in
the left posterior mesial temporal lobe with extension into white
matter (arrows). (Bi MRI-T2-weighted image, axial. The normal right temporal lobe cortical-white mutter definition is indistinct in comparison with contralateralside. Loss of u?hite matter
digitations ir noted (arrows).
men. In another 2 patients, structural abnormality was
not found in the mesial structures. Because of the limitations imposed by the surgical technique, which preclude preservation of topographical relations, we
cannot make meaningful comments on the exact
distribution of the dysplastic changes among gyri. The
data derived from MRI, however, makes it plausible
that the histological abnormalities are more extensive
in some patients and circumscribed in others.
MRI revealed abnormalities in 7 of our patients.
Nonhomogeneous high-signal-intensity lesions were
296 Annals of Neurology Vol 29 No 3 March 1991
detected in 5 patients; however, variability was observed with some lesions extending into the white matter, whereas others were more localized (see Fig 4A).
In some patients, the temporal cortical ribbon appeared thick. T2-weighted images provided best visualization of the lesions. Gadolinium-DTPA added no information to the images, suggesting but not excluding
nonneoplastic lesions. The normal cortical-white matter architectonic pattern of the temporal lobe was affected in some of our patients. This abnormality consisted of poor whiteigray matter demarcation with focal
thickening of the cortex (see Fig 1). The significance
of these findings was controversial at first, but became
consistent when several MRIs revealed similar abnormalities. Furthermore, temporal lobe atrophy was not
seen in these patients.
Consideration of the specificity of the MRI findings
in our patients is important. Previous studies reported
nonspecific high-intensity signals from the mesial structures in patients with temporal lobe epilepsy. Pathological correlations demonstrated a variety of histological
abnormalities ranging from mesial temporal sclerosis
to small tumors [S-7). More recently, however, our
studies have shown that certain distinctive imaging
findings have emerged in these patients. It is now clear
that mesial temporal sclerosis, the most common
pathological abnormality in temporal lobe seizures, is
distinguished by the presence of hippocampal atrophy
associated with increased signal intensity on T2-weighted images [ 5 , 91. Small structural lesions may appear
as high-intensity abnormalities, however, other features such as calcifications and variable mass-effect are
usually present, and we have observed the absence of
focal atrophy or temporal horn dilatation in these patients. Although variable nonspecific high-intensity ab-
Fig 5 . Mild dysplaJia in a patient with n o w 1 magnetic resonance imaging: neuronal clustering and dyslamination in hjier
I-II of the neocortex. (Hematoxylin and eosin; originul rnagnz3cation, x 400.1
normalities were observed among our patients, certain
imaging features such as an abnormal corticalwhite matter architectonic pattern and the presence of
gyral thickening may suggest the underlying pathological substrate. Further studies are necessary to confirm
these preliminary observations.
In this study, we attempted to correlate the histological observations with the MRI abnormalities. It is
important to mention, however, that because of the
surgical technique, limited histological material was
available for study, and therefore, accurate correlation
was not possible. We found a moderate correlation
between the severity of dysplastic features in the histological specimens and the MRI findings. Patients with
severe dysplastic lesions (Group 2) (see Figs 2, 3) had
major MRl abnormalities, whereas, patients with mild
to moderate dysplasia (Fig 5 ) correlated with more subtle and restricted lesions on imaging or with normal
MRIs (3 patients with group 1 histology had normal
MRIs). The preceding findings are expected. Tl-
weighted images were best to demonstrate the abnormal cortical-white pattern. T2-weighted images demonstrated abnormal increased intensity signal lesions,
however, in those patients with major histological
changes. The abnormality on T2-weighted scans may
be related to increased water content in the abnormal
cells, which consequently induces an increase in the T 2
relaxation time.
Previous studies have suggested an unfavorable postoperative outcome for patients with cortical dysplasia.
Bruton [l 1) recently reviewed 249 patients with temporal lobectomy; cortical dysplasia was found in 8 patients (3.2%), and the outcome was unfavorable in all.
In Taylor’s original publication 1 131, however, only 1
of the 5 patients who underwent temporal lobectomy
failed to improve, whereas the other 4 had experienced
seizure relief. Goldring [24} and others {25}, as well
as our data, suggest a more favorable clinical outcome
in most patients with temporal lobe epilepsy and cortical dysplasia who are treated surgically.
MRI has made a significant impact on the investigation and management of candidates for epilepsy surgery [ 5 , 6, 18, 261.In addition to being more sensitive
than CT scanning in the detection of small epileptogenic structural lesions, MRI has the ability to demonstrate mesial temporal sclerosis in the vast majority of
patients with temporal lobe epilepsy if the appropriate
imaging techniques are used 15, 91. MRI has shown to
be very valuable in the investigation of developmental
abnormalities of the brain often associated with severe
epilepsy [19, 27-29]. We previously reported on the
ability of MRI to detect focal cortical dysplasia in patients with developmental Rolandic lesions [ 181. Others have also reported abnormal MR images in isolated
patients with cortical dysplasia of extratemporal origin
[30, 31). Chugani and colleagues [32} recently reported 5 patients with cryptogenic infantile spasms and
focal dysgenesis. MRI revealed subtle abnormalities in
1 patient. Although the pathological data was limited
by the surgical technique, the present study suggests
that MRI is sensitive in the detection of certain dysplastic lesions in the temporal lobes. Furthermore, we have
found that the present MRI resolution permits identification of lesions with moderate to severe histological
abnormalities but not of those patients with mild neuronal and cortical abnormalities (Group 1).
The preoperative identification of dysplastic lesions
by MRI is important because these histological changes
have been found consistently in brain specimens surgically removed for the treatment of refractory partial
epilepsy [16-18]. These findings are, perhaps, most
important if one considers that these epileptogenic developmental lesions are highly resistant to medical
treatment and are common in the pediatric population
[18, 24, 27, 33, 341. Visualization of these lesions by
MRI should allow early diagnosis and surgical interven-
Kuzniecky et al: Dysplasia, MRI, and Temporal Lobe Epilepsy 297
tion in children with refractory focal epilepsy. In those
patients without obvious MRI abnormalities, although
not diagnostically specific, positron emission tomography (PET) may reveal functional metabolic disturbance
in the regions of cytoarchitectonic abnormalities, as
suggested by Chugani et al(32). As noted in their study
[ 3 2 ) and demonstrated in some of our patients, however, subtle MRI abnormalities such as an abnormal
cortical-white matter architectonic pattern may be
present and may be easily overlooked. Studies combining MRI, PET, and microscopy are necessary to define
the usefulness and the limitations of each technique
and to understand the biology of these developmental
Presented in part at the 42nd Annual Meeting of the American
Academy of Neurology, Miami, FL, May 1990.
We thank Yvonne Zelenka K. for her helpful criticism, and Or S.
Berkovic for reviewing the manuscript.
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correlation, dysplasia, cortical, magnetic, imagine, temporal, resonance, epilepsy, lobel
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