Case report

A case of epilepsy in multiple sclerosis:
Three-dimensional double inversion recovery
sequences revealed cortical dysplasia

The Neuroradiology Journal
0(00) 1–4
! The Author(s) 2017
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DOI: 10.1177/1971400917697732
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Domenico S Zimatore1, Mirko Trentadue1, Marco Castellaro2,
Monica Ferlisi3, Enrico Piovan1 and Massimiliano Calabrese4

Abstract
In epileptic patients with multiple sclerosis (MS), cortical lesions have been suggested to cause seizures. In brain magnetic
resonance imaging (MRI), double inversion recovery (DIR) sequences are generally used to evaluate MS cortical disease
burden. We present the case of a woman, diagnosed with MS, suffering from drug-resistant partial seizures initially
attributed to MS. The patient underwent many MRI exams, but only by means of high-resolution three-dimensional DIR
sequences was a focal cortical dysplasia discovered. The MRI findings and FDG-PET/CT supported the diagnosis. This case
recommends the use of DIR sequences both in patients with suspect epileptogenic lesions not detected with routine MRI
protocols and in epileptic patient with MS, before ascribing seizures to MS.

Keywords
Multiple sclerosis, epilepsy, cortical dysplasia, double inversion recovery (DIR), magnetic resonance imaging

Introduction
In patients with multiple sclerosis (MS) suffering from
epilepsy, cortical lesions have been suggested to cause
seizures.1 Double inversion recovery (DIR) sequences
allow MS cortical burden evaluation, since they
increase the contrast among the grey matter (GM),
the cerebrospinal fluid (CSF) and the white matter
(WM): MS cortical plaques appear hyperintense on
DIR.2 Dysplastic cortex and cortex with a pathological
increase of water content (e.g. oedema, post-critical
alterations) also appear hyperintense on DIR.3 We present the case of a woman diagnosed with MS and suffering from drug-resistant partial seizures. All the
conventional magnetic resonance imaging (MRI) performed failed to demonstrate an area of cortical dysplasia which was discovered by DIR sequences.

After two years, the patient also suffered episodes of
upper and lower limbs dysesthesia and disequilibrium/
step hesitation/lateropulsion not associated each other.
So she underwent to a new brain MRI that showed an
increase in WM lesions with the characteristic pattern of
MS. The presence of anomalous PEVs and CSF oligoclonal bands supported a diagnosis of relapsing remitting
MS. A therapy with interferon-beta-1a was established,
and since then, the clinical course of MS (EDSS 0) as well
as WM lesions on MRI have remained stable.
Nevertheless, the patient continued to complain of
transitory episodes of visual disturbance (left hemianopsia, visual hallucinations) until she suffered a generalised seizure. Even though an electroencephalogram
(EEG) appeared normal, gabapentin was prescribed
as an anti-epileptic. During the following years, no

1

Case report
A 32-year-old woman with left hemianopsia underwent
to brain MRI which demonstrated a subtle corticalsubcortical FLAIR hyperintensity in the right medial
occipital gyrus, initially interpreted as migrainous
infarction. The same MRI showed some WM lesions
also interpreted as migraine related. Despite this
hypothesis, the hemianopsia recovered completely
after one week. Subsequent MRI exams did not show
signs of a previous occipital infarction.

Neuroradiology, Department of Diagnostics and Pathology, Azienda
Ospedaliera Universitaria Integrata Verona, Italy
2
Department of Information Engineering, University of Padova, Italy
3
Division of Neurology; Azienda Ospedaliera Universitaria Integrata Verona,
Italy
4
Neurology Section, Department of Neurological and Movement Sciences,
University of Verona, Italy
Corresponding author:
Domenico Sergio Zimatore, Neuroradiology, Department of Diagnostics and
Pathology, Azienda Ospedaliera Universitaria Integrata Verona, Piazzale
Aristide Stefani, 1-37126 Verona, Italy.
Email: dszimatore@hotmail.it

2
more generalised seizures were reported, but visual
symptoms persisted. Therefore, therapy was changed
to sodium valproate and carbamazepine.
At the age of 43, the patient presented to our institution for a routine control, during a period free from
visual disturbances, and underwent a 3 Tesla MRI
exam (Figure 1), including three-dimensional (3D)
DIR, FLAIR, T2-weighted and T1-weighted sequences.
For the first time, DIR images (especially with coronal
reformatting) clearly showed a thickened and hyperintense cortex in the right lateral parieto-occipital region,
a subtle subcortical hyperintensity (less clearly detectable on FLAIR) and a blurring of the GM/WM

The Neuroradiology Journal 0(00)
junction (confirmed on T1-weighted imaging).
Perfusion showed a focal reduction of the cerebral
blood volume (CBV) and MR spectroscopy (MRS)
demonstrated a small reduction of N-acetylaspartate,
with a slight increment of choline, without significant
inversion of Cho/NAA ratio, in the lesion site.
During another MRI exam, performed a few days
after a period of persistent visual disturbances (one
week duration), DIR sequences showed cortical hyperintensity and thickening also in the right medial occipital region, just next to the lateral parieto-occipital
cortical thickening previously reported (Figure 2(a)
and (b)). This new alteration disappeared completely

Figure 1. First MRI examination at our institution (3 Tesla MRI scanner). DIR images show thickened and hyperintense right lateral
parieto-occipital cortex, more evident on coronal reformatting, associated with subtle subcortical hyperintensity (arrows (a) and (d)).
These findings are less evident on 3D FLAIR (arrows (b) and (e)). 3D Gradient Echo T1-weighted images confirm cortical thickening
(arrowheads (c)) and show blurring of the grey matter/white matter junction (arrowheads (f)). Multivoxel spectroscopy demonstrates
slight choline increment and N-acetylaspartate reduction without significant inversion of Cho/NAA ratio in the lesion site (g). DIR images
show cortical (arrow (h)), iuxtacortical (arrowheads (h)), periventricular (empty arrows (h) and (i)), subcortical (dashed arrow (i)) and
infratentorial (empty arrowheads (i)) multiple sclerosis lesions.
MRI: magnetic resonance imaging; DIR: double inversion recovery.

Zimatore et al.

3

Figure 2. Second 3 Tesla MRI examination. DIR coronal image shows thickening and hyperintensity in the right medial occipital cortex
(arrows (a)), in addition to the well-known right lateral parieto-occipital lesion (arrowheads (a)). On FLAIR images, the same alterations
are less evident (arrows and arrowheads (b)). At follow-up (third 3 Tesla MRI examination, two months later), the medial occipital
alteration disappeared, resulting in an area of focal atrophy with relative overrepresentation of the cortical spaces (arrows (c) and (d)) and
dilation of the occipital horn of the lateral ventricle (dashed arrow (c) and (d)). At the same examination, the right lateral parieto-occipital
cortical thickening persisted (arrowheads (c) and (d)). A cerebral FDG-PET/CT (arrowheads (e) and (f)) clearly shows glucidic hypometabolism confined to the right lateral parieto-occipital cortex. An interictal electroencephalogram shows an irregular theta activity with
sharp waves in the right parietal region (g).
MRI: magnetic resonance imaging; DIR: double inversion recovery.

two months later, resulting in an area of mild focal
atrophy. On the contrary, the right lateral parieto-occipital cortical thickening was unmodified (Figure 2(c)
and (d)). A FDG-PET/CT demonstrated glucidic hypometabolism confined to this site (Figure 2(e) and (f)).
Interictal EEGs showed an irregular activity in the right
parietal region (Figure 2(g)).
After this episode, the patient started therapy with
levetiracetam. So far (about one year ago), no new
visual disturbances have been described.

Discussion
With regard to the interpretation of the stable lesion in
the right lateral parieto-occipital cortex, we excluded
the outcomes after a past ischemic event because neither malacia nor localised atrophy was found. A lowgrade cortical tumour was also excluded because the
alteration lacked mass effect. The hypothesis of a
large cortical demyelinating lesion suited the

contemporary diagnosis of MS. However, to our knowledge, such a lesion does not fit any morphological
aspect of MS cortical plaques described.4 Genetic
exams excluded CADASIL and MELAS.
Finally, we assumed the lesion as a focal cortical
dysplasia (FCD) whose typical MRI findings are represented by cortical thickening (especially type II),
blurring of the GM/WM junction (type I and II,
especially type II), WM volume reduction (especially
type I), hyperintensity on long-TR images and
hypointensity on T1-weighted imaging (especially
type II).5 A T2-weighted hyperintensity involving
the GM and the underlying WM up to the ventricle
(transmantle sign) is the hallmark of FCD type IIb.6
Abnormalities of the gyration and of the sulci associated with segmental/lobar hypoplasia up to atrophy
can also be found (especially FCD type I).6,7 Other
pathologies possibly associated to FCD8 (e.g. hippocampal sclerosis, developmental tumours) were not
found.

4
In absence of a clear transmantle sign, we interpreted
the MRI alteration as a FCD type IIa (Taylor’s FCD
without balloon cells).6,8,9 MRS findings were non-specific but reflected a neuronal/glial cell dysfunction suitable to FCD.7 Unfortunately, no MRS was performed
during or some hours after epileptic seizures to search
for the presence of lactate, as some authors suggest that
seizures activates anaerobic glycolysis in neuronal
migration disorders.10,11 EEG confirmed an abnormal
pattern in the region of the cortical anomaly showed by
MRI. Clinically, the patient suffered from visual hallucinations, a hallmark of occipital epilepsy which can be
caused by FCD.12 The FDG-PET/CT hypometabolic
pattern was also consistent with our hypothesis.7
The transient right medial occipital alteration was
interpreted as cortical oedema consequent to persistent
partial seizures. The anatomic location of such oedema
was consistent with the left visual disturbance of which
the patient complained and probably corresponds to
the area of migrainous infarction initially hypothesised. MRI detects reversible pathological findings
in 20–70% of patients after generalised or partial seizures (post-ictal oedema).13 DIR sequences, which are
dedicated to cortical pathology, appeared useful to
document this finding. The subsequent focal widening
of the cortical sulci, observed in the same area, could
be the consequence of a neuronal loss due to persistent
seizures.13
Regarding therapy, the patient continued interferonbeta administration because it was effective in MS control, even if it has been reported a possible increased
risk of seizures related to this drug.14 However, the
therapy for epilepsy was changed to Levetiracetam,
since recent findings in an animal model suggest the
possible efficacy of Levetiracetam to treat the drugresistant epilepsy associated with FCD.15
Our patient had undergone many conventional MRI
scans, but only by using high-resolution 3D DIR acquisition with multiplanar reconstructions was the subtle
lesion in the lateral right occipito-parietal cortex identified. Moreover, DIR depicted transitory cortical alterations related to the seizure.

Conclusions
Even without a histologic confirmation, this case highlights the usefulness of DIR sequences to improve sensibility towards both inflammatory and dysplastic
cortical lesions, and the use of DIR is recommended
in patients with suspect epileptogenic lesions not
detected with routine MRI protocols. In patients with
MS suffering from drug-resistant epilepsy, before
ascribing seizures to MS, it is mandatory to exclude a
better explanation.
Acknowledgement
Thanks to Virginia Munerati, MD, for providing the patient’s
EEG examinations.

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Funding
The authors received no grant from any funding agency in the
public, commercial or not-for-profit sectors.

Conflict of interest
The authors declared no potential conflicts of interest with
respect to the research, authorship and/or publication of this
article.

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