Epilepsy and Behçet's disease: Cortical and hippocampal involvement in
Lívia Almeida Dutraa,⁎, Pedro Braga-Netoa, José Luiz Pedrosoa, Bruno de Vasconcelos Sobreira Guedesd,
Larissa Teles de Souzaa, Célio Roberto Gonçalvesc, Alexandre Wagner Silva de Souzab,
Alberto Alain Gabbaia, Orlando Graziani Povoas Barsottinia
aDepartment of Neurology and Neurosurgery, Universidade Federal de São Paulo — UNIFESP, Escola Paulista de Medicina, Brazil
bDepartment of Medicine, Rheumatology Division, Universidade Federal de São Paulo — UNIFESP, Escola Paulista de Medicina, Brazil
cDepartment of Medicine, Rheumatology Division, Universidade de São Paulo, Brazil
dRadiology Department, Faculdade de Ciências Médicas da Santa Casa de São Paulo, Brazil
a b s t r a c t a r t i c l e i n f o
Received 31 March 2011
Received in revised form 24 June 2011
Accepted 28 July 2011
Available online 19 August 2011
Complex partial seizure
Objective: To describe clinical, radiological and electrophysiological findings in epileptic neuro-Behçet's (NBD)
Methods: A retrospective review of 178 medical records of Behçet's disease patients was conducted in Brazil.
Information on gender,ethnicity/skincolor,ageatsymptomonsetandageatonsetofneurologicmanifestations,
type of seizures, clinical manifestation of the disease, use of antiepileptic drugs and immunosupressors was
collected from medical records of all epileptic NBD patients. Brain MRI, cerebrospinal fluid (CSF) analysis and
electroencephalograms (EEG) were assessed.
Results: Forty NBD cases were identified, of which seven patients (17%) presented epilepsy. In five patients
seizures occurred during an acute exacerbation of the disease, and in one patient they occurred six months after
complex partial seizures. The EEG showed temporal involvement in three patients and frontal in one.
Hippocampal lesions were identified in three patients and cortical lesions in five. All patients had good response
to antiepileptic drugs and are seizure-free, except for one who developed refractory seizures.
Conclusions: Brazilian NBD patients showed a high prevalence of epilepsy, mainly complex partial seizures,
occurring at any phase of the disease. Epileptic NBD patients may have cortical and hippocampal lesions that
could explain the occurrence of epilepsy.
© 2011 Elsevier B.V. All rights reserved.
Behçet's disease (BD) is a multisystemic inflammatory disorder of
unknown etiology characterized by recurrent oral aphthous ulcers,
genital ulcers, ocular inflammation and skin lesions. There may be also
involvement of the central nervous system (CNS), gastrointestinal tract
and large vessels. Genetic and environmental factors are implicated in
the pathogenesis of BD and its prevalence is significantly higher in the
ancient Silk Route, which extends from eastern Asia to Mediterranean
The frequency of CNS involvement in BD is very variable. Three
prospective studies reported that 5.3% to 14.3% of BD patients have
neurological involvement. Parenchymal brain disease is the most
common manifestation, particularly involving the brain stem and basal
ganglia, and may be accompanied by meningeal inflammation. Non-
brain venous sinus and occasionally to arterial vasculitis [2,3]. The type
and frequency of systemic neurologic manifestations of BD seem to be
seen in those of Japanese descent [3,4]. Although epileptic seizures were
rare in a large series including Turkish NBD patients, its frequency was
approximately 20% in Caucasian and Japanese NBD patients [3–6].
Brazil is a South American country with a multiethnic population
Western countries . The aim of this study was to determine the
frequency of epilepsy in Brazilian patients with NBD and to describe its
clinical, radiological and electrophysiological features.
2. Materials and methods
the two largest tertiary hospitals in the city of São Paulo, southeastern
Brazil, was performed between February 2009 and July 2010. Forty NBD
Journal of the Neurological Sciences 309 (2011) 1–4
⁎ Corresponding author at: R. Pedro de Toledo, 650 Vila Clementino, São Paulo, SP,
04039-002, Brazil. Tel.: +55 11 5575 5240; fax: +55 11 5081 5005.
E-mail address: firstname.lastname@example.org (L.A. Dutra).
0022-510X/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
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patients were identified. Information on gender, ethnicity/skin color, age
at symptom onset and age at onset of neurologic manifestations, type of
seizures classified according to the Commission on Classification and
Terminology of the International League Against Epilepsy , clinical
manifestation of the disease, use of antiepileptic drugs and immunosu-
pressors was collected from medical records of allepileptic NBDpatients.
Cerebrospinal fluid (CSF) analysis results and electroencephalogram
(EEG) findings were assessed whenever available. Brain magnetic
The present study was approved by Institutional Review Board at
Among 178 patients with BD evaluated in this study, forty (23%)
presented neurologic manifestations of BD such as parenchymal CNS
disease or cerebral venous thrombosis (CVT). Most of those manifesta-
tions were brainstem involvement, seizures, aseptic meningitis and optic
neuropathy. Although aseptic meningitis is considered an atypical NBD
manifestation, patients with aseptic meningitis were included in the
cohort because our unpublished data support that aseptic meningitis is
more frequent in Brazilian patients. We found six cases among 40 NBDs,
Seven (17%) patients presented seizures and were considered
epilepticbecause of recurrentseizures.Noneof them had prior epilepsy
and all patients required antiepileptic medication. EEG was repeated at
least twice in each patient. All patients met the International Study
Group for Behçet's Disease criteria .
The mean age at the onset of NBD symptoms was 34.42±11.5 years.
The patients had presented recurrent oral ulceration before neurologic
manifestation for a mean 9.71±11.28 years. Twopatients had NBD prior
to BD diagnosis. Four patients were female, only one was Caucasian, and
the remaining seven patients were of mixed ethnicity/skin color. All
patients presented recurrent aphthous and genital ulcers (bipolar ulcers)
and five had erythema nodosum.
Five patients presented parenchymal CNS disease such as
brainstem involvement (four cases) and epilepsy (one case). Two
presented CVT. The mean time of follow-up was 9.25±5.49 years.
Table 1 shows the demographic and clinical characteristics of NBD
patients with epileptic manifestation.
Five patients had complex partial seizures, one presented motor
partial seizure and one generalized tonic–clonic seizure. Patient 1
presented seizures without provoking factors six months after an
episode of meningoencephalitis. Seizures occurred during an acute
neurological event in five patients.
The EEG revealed focal epileptiform discharges in four patients;
discharges were seen in the temporal lobe in three of them and in the
frontal lobe in one of them. Despite a normal EEG in patients 4, 6 and 7,
they had recurrent seizures and cortical lesions.
Brain MRI scans obtained at neurologic manifestation revealed
structural abnormalities in all patients studied. Hippocampal lesions
were identified in three patients and cortical lesions in five patients
(Fig. 1). All hippocampal lesions were evident with brainstem
involvement. When brain MRI scans obtained during the year of
2010 were compared to previous results, it was observed that four
cortical lesions and two hippocampal lesions remained.
CSF results were available from five patients and four of them
showed inflammatory findings.
Of the seven epileptic patients, 62% received cyclophosphamide,
and 25% chlorambucil. All patients received colchicine for cutaneous
symptoms and 62% received azathioprine during the follow-up
period. None of them received cyclosporin at any time.
The most prescribed drug for seizure control was carbamazepine
(Table 1). Patient 3 who had epilepsy as the sole NBD manifestation
Epidemiological and clinical data of Behçet's disease (BD) patients with epileptic manifestations.
Age at the onset of NBD
Time interval between
ulcers and NBD onset
3531 484818 38 23
3 22800 278
Seizures during neurologic
Semiology of seizures
Nausea, deja vu,
SW L TR
jamais vu followed
SW R parasagital region
R foot, followed by GTCS
movements in arms,
loss of consciousness
ILAE Seizure Classification
Foci in R TR
in L TR
Pons, MES, R frontal
MRI findingsPons, thalamus,
CBZ 600 mg
R thalamus and
CBZ 1200 m,
LMT 200 mg,
CLB 20 mg
CBZ 400 mg
Pons, MES hippocampus
OXC 900 mg
Frontal lesionParietal venous infarction
CBZ 600 mgPB 100 mg CBZ 400 mg
127 cells , 62 p
52 cells 58 p
32 cells 29 p
940 cells 51 p
1 cell 16 p
F: female; M: male; DVT: deep venous thrombosis; e nodosum: erythema nodosum; BRAINSTEM: brainstem involvement; CVT: cerebral venous thrombosis; NA: not available; CPS:
complex partial seizure; MPS: motor partial seizure; GTCS: generalized tonic–clonic seizure; L: left; R: right; SW: slow waves; FR: frontal region; TR: temporal region; MES:
mesencephalon; CBZ: carbamazepine; OXC: oxcarbazepine; TPM: topiramate; PB: phenobarbital; LMT: lamotrigine; CLB: clobazam; CFA: cyclophosphamide; AZA: azathioprine;
CHLOR: chlorambucil; PEN: penicillin; p: protein.
L.A. Dutra et al. / Journal of the Neurological Sciences 309 (2011) 1–4
developed refractory seizures and severe psychiatric manifestations.
However, six patients had good response to antiepileptic drugs and
remained seizure-free with proper medication.
There aresignificant ethnic differences inNBD clinicalexpressionand
the frequency of epilepsy varies among several populations [3–5]. The
frequency of epilepsy was 2.2% in Turkish NBD patients whereas it
was 27% in Caucasians. No seizures were reported in Caribbean BD
prevalence of seizures in Brazilian NBD patients was similar to that
reported in Caucasian patients.
Despite the neurologic involvement that is more common in male BD
previous study of 106 BD patients from Brazil and studies conducted in
the United States and Western European countries [3,6,7,11,12]. Indeed,
we found 23 females in our unpublished cohort of 40 NBD cases,
atypical manifestations of the disease, such as optic neuropathy (15%),
demyelinating syndrome (5%), peripheral neuropathy (7.5%) and
seizures. According to our results, 12.5% of patients with parenchymal
CNS disease presented seizures, whereas two patients among three with
CVT presented seizures. This will be discussed elsewhere.
and the diagnosis of BD may be explained by the low threshold for
Turkey and Japan are more familiar with the disease, and even minor
systemic presentations are considered part of the disease manifestations
before the onset of neurological symptoms [4,5]. Patients may present
NBD after years of recurrent oral ulcerations. The presence of minor
mucocutaneous symptoms for long periods does not mean the disease is
The largest series of epileptic BD patients found that seizures were
generalized, not related to acute neurologic manifestations, probably
secondary to seizure provoking factors . In contrast, most of our
cases consisted of complex partial seizures with focal epileptogenic
EEG occurring at the onset of typical neurological manifestations of
BD. This finding has been corroborated in case reports that described
complex partial seizures and even myoclonic jerks in NBD [13–15].
The use of cyclosporin could be related to the occurrence of seizures
due to neurotoxicity, mainly causing posterior reversible encepha-
lopathy [16,17]. However, none of the patients studied received this
immunosuppressant. In general NBD patients with epilepsy respond
well to antiepileptic medication and become seizure-free, but there
are reports of refractory cases [10,13,14,18]. Our results support this
view as most of our patients have remained seizure-free for a
reasonable follow-up period.
epileptic NBD patients. The involvement of the temporal and frontal
cortices has been previously described, sometimes mimicking herpetic
encephalitis [13–15,18–22] or multiple sclerosis, especially when
cortical–subcortical regions are affected . The involvement of other
CNS regions beyond brainstem is a poor prognostic factor . We
speculate that temporal lobe involvement represents a spread of the
inflammatory process to small vessels that supply the mesial temporal
that seizures are a result of the hypoxia induced by the inflammatory
pathogenesis of NBD, that lead to massive release of the excitatory
neurotransmitter glutamate [22,25]. The mechanisms of ischemia-
induced epileptogenesis are not well understood, however studies in
vitro demonstrated that glutamate injury produced a permanent
epileptiform phenotype in surviving neurons .
The reversibility of lesions in parenchymal CNS disease was
observed in earlier publications, supporting the venous-inflammatory
pathophysiology . However, our radiologic follow-up showed that
in most of our patients, cortical and hippocampal lesions remained.
This might suggests that arterial vessels are involved in the
occurrence of cortical and hippocampal lesions.
Although three patients presented hippocampal lesions, discharges
from the temporal region were detected in only one of them. It is
possible that hippocampal lesions are not symptomatic in all cases.
Despite advances in the pathogenesis of BD, its cause remains
uncertain. It is believed that BD is caused by an autoimmune vasculitic
process triggeredbyan infectious orenvironmentalagentingenetically
predisposed individuals [13,27]. HLA-B51 is the mostconsistent marker
of genetic susceptibility to BD along the Silk Route, with a stronger
association found in Turkish and Japanese patients compared to
Caucasians . Unfortunately we were not able to perform HLA-B51
testing in this study.
A limitation of this study was that videoelectroencephalogram
recordings were not available from three patients with abnormal MRI
and normal EEG. However, based on the findings of seizure
recurrence, cortical lesions and description of seizure semiology, it
was clear that these patients were epileptic.
Although this report shows data of a retrospective review of only
because they allowed to describe three patterns of epilepsy in NBD. The
first pattern is the occurrence of epilepsy during an acute neurologic
in the quiescent phase of the disease; and the third one is the
Fig. 1. A: Frontal lesion in an epileptic NBD patient. Second image. B: FLAIR MRI sequence showing bilateral hippocampal involvement.
L.A. Dutra et al. / Journal of the Neurological Sciences 309 (2011) 1–4
manifestation of epilepsy in patients with the progressive form of NBD Download full-text
when there are signs of cognitive and behavioral disturbances without
acute parenchymal CNS disease or cerebral venous thrombosis.
In conclusion, we described complex partial seizures among Brazilian
NBD patients occurring during any phase of the disease. Patients with
NBD and seizures may have cortical and hippocampal lesions that could
explain the occurrence of epilepsy. Therefore, on the onset of epilepsy in
NBD patients, one should look for symptomatic lesions. These results
should be verified in larger series from countries with higher prevalence
The authors thank their colleagues at the Rheumatology Division,
especially Dr. Gonçalves and Dr. Souza, for their enthusiastic support
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