Krysl, David

Marusic, Petr

Senolt, Ladislav

Zamecnik, Josef

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Seizure 22 (2013) 80–82Case report
Chronic repetitive nonprogressive epilepsia partialis continua due to
rheumatoid meningitis
David Krysl a,*, Josef Zamecnik b, Ladislav Senolt c, Petr Marusic a
aDepartment of Neurology, 2nd Faculty of Medicine, Charles University in Prague, University Hospital Motol, Prague, Czech Republic
bDepartment of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague, University Hospital Motol, Prague, Czech Republic
c Institute of Rheumatology and 1st Faculty of Medicine, Charles University in Prague, Czech Republic
Contents lists available at SciVerse ScienceDirect
Seizure
jou r nal h o mep age: w ww.els evier . co m/lo c ate /ys eizA R T I C L E I N F O
Article history:
Received 9 August 2012
Received in revised form 11 October 2012
Accepted 13 October 2012
Keywords:
Status epilepticus
Rheumatoid arthritis
Meningitis
Magnetic resonance1. Introduction
Our case report describes a patient with recurrent episodes of
epilepsia partialis continua (EPC) due to rheumatoid meningitis
(RM). RM is an uncommon complication of rheumatoid arthritis
(RA) and even rarer cause of seizures. It frequently occurs in
patients with little or no systemic symptoms of RA, which may lead
to a thorough and time-consuming differential diagnostic work-
up. To our knowledge, occurrence of EPC was not yet described in
this condition. Brain biopsy analysis is mandatory for diagnosis;
not only to give evidence of chronic lymphocytic ﬁbroproductive
leptomeningitis, but also to rule out leptomeningeal metastases
and other causes of chronic meningitis (especially tuberculous
meningitis and neurosarcoidosis). Although difﬁcult to diagnose,
RM has a favorable prognosis due to its rapid response to
glucocorticoid therapy. Therefore, brain biopsy should not be
delayed, especially in cases with characteristic magnetic resonance
ﬁndings.
2. Case report
Our case is a 62-year-old male with a ten-year history of
rheumatoid arthritis (RA). The diagnosis of RA was based on the
American College of Rheumatology 1987 revised classiﬁcation
criteria. The dominating features at disease onset were presence of* Corresponding author at: University Hospital Motol, V Uvalu 84, 150 06 –
Prague 5, Czech Republic. Tel.: +420 22443 6865.
E-mail addresses: dkrysl@gmail.com, David.krysl@fnmotol.cz (D. Krysl).
1059-1311/$ – see front matter  2012 British Epilepsy Association. Published by Else
http://dx.doi.org/10.1016/j.seizure.2012.10.006symmetric arthritis of hand joints involving more than three joint
areas and positivity of serum rheumatoid factor (RF). The disease
was mild and initially treated with chloroquine for two years.
Sustained drug-free clinical remission was achieved thereafter.
Medical history of the patient was otherwise unremarkable.
At the age of 60, he was admitted to a regional hospital due to
recurrent episodes of epilepsia partialis continua (EPC) involving
his right leg and subsequent spread to the right hemibody. After
unsuccessful trial of benzodiazepines, the seizures were stopped
with a load of phenytoin (PHT). Brain magnetic resonance imaging
(MRI) showed increased T2 signal of the leptomeninges over the
right frontal lobe as well as the medial part of the left hemisphere.
In the latter region, gadolinium enhancement of the leptomeninges
was seen (see Fig. 1A and B). T2 signal increase over the right leg
motor and sensory area was primarily considered as a sign of
luxury perfusion in the left anterior cerebral artery territory, and
the etiology of EPC was presumed to be ischemic.
One month later, the patient was referred to our institution due
to another episode of EPC involving the right leg. Laboratory
ﬁndings on admission showed markedly increased transaminase
levels, which slowly normalized after PHT discontinuation. Follow-
up MRI showed similar ﬁndings as the ﬁrst examination. Magnetic
resonance venography ruled out thrombosis of superior sagittal
sinus. Cerebrospinal ﬂuid (CSF) sample showed normal protein
values (245 mg/l), no inﬂammatory cells and no oligoclonal bands
(OCB). No atypical cells were reported from CSF cytoﬂowmetry.
Polymerase chain reaction (PCR) for common viral pathogens was
negative, as well as antibody tests for Lyme disease and syphilis.
Chest X-ray was normal. Electroencephalography (EEG) demon-
strated intermittent slow activity bilaterally in the frontotemporal
regions, slightly more pronounced on the left side. Levetiracetam
(LEV) was started. Gradual dose escalation of LEV was needed due
to repeated seizures, including another episode of EPC in the right
leg lasting several hours. Seizure freedom was ﬁnally achieved
with LEV daily dose of 2250 mg. A whole-body 18F-ﬂuorodeoxy-
glucose positron emision tomography combined with whole-body
computed tomography (FDG-PET/CT) was performed, ruling out an
occult neoplasm. However, hypermetabolism in several joints and
lymph nodes was found, consistent with the diagnosis of RA with
subclinical disease activity.
Six month after symptom onset, a follow-up CSF analysis
showed normal total protein (345 mg/l) and normal cell count.vier Ltd. All rights reserved.
Fig. 1. Evolution of MRI changes in time. FLAIR sequence is shown in the upper row, the corresponding T1 gadolinium enhanced images in the lower row. (A and B, onset)
Increased signal of sulci can be seen in the right frontal and especially left fronto-parietal cortex close to the midline and mild post-contrast enhancement within falx cerebri.
(C and D, 24 months) Increased signal is now visible over both frontal cortices; mild post-contrast enhancement of falx cerebri can still be seen. (E and F, 30 months, following
glucocorticoid treatment): resolution of signal changes and of gadolinium enhancement.
D. Krysl et al. / Seizure 22 (2013) 80–82 81Isoelectric focusing demonstrated two OCB in the CSF (no bands
were present in serum). At this stage, brain biopsy was planned.
However, second follow-up MRI showed regression of signal
changes and due to this ﬁnding, together with patient’s seizure
freedom, the biopsy was deferred.
After six months of clinical stabilization, the patient experi-
enced another focal motor seizure with secondary generalization
and LEV daily dose was increased to 3000 mg. Follow-up MRI (one
year after symptom onset) showed progression of leptomeningeal
T2 signal increase, namely over left parietal, but also over both
frontal cortices (see Fig. 1C and D). Concurrently, the patient
developed psychiatric symptoms including episodes of mania,
confusion, and aggression. EEG ruled out nonconvulsive status
epilepticus (SE). Another proposition for brain biopsy was declined
by the patient. A third CSF sample was taken, showing mild
increase of cell count (32 cells/3 ml, with 45% lymphocytes, 48%
monocytes and 7% polymorphonuclear leucocytes). No OCB was
found in the CSF or serum. PCR for Mycobacterium tuberculosis
was negative. Western blott for well-characterized onconeural
antibodies (anti-Hu, Yo, Ri, Ma, CV2, and amphiphysin) in the
serum was negative, as well as follow-up serology of Lyme disease.
The patient’s psychiatric symptoms improved after introduction of
olanzapine and gradual switch from LEV to carbamazepine.
Almost two years after the onset of symptoms, the patient
consented to brain biopsy. A small sample of the leptomeninges
with the adjacent cortex was taken from the right frontal lobe,
guided by the signal changes on another follow-up MRI.
Histopathologically, the leptomeninges revealed chronic ﬁbropro-
ductive inﬂammation with predominantly perivascular lympho-
cytic inﬁltration. To a lesser extent, the lymphocytic inﬁltration
was observed also in the adjacent cortex with perivascular
accentuation. Glial ﬁbrillary acidic protein (GFAP) immunohis-
tochemistry showed mild gliosis of the cortex (Fig. 2). Nogranulomas, vascular changes or a tumor were observed in the
biopsy. In the clinical context, the diagnosis of chronic rheumatoid
meningitis (meningoencephalitis) was established.
Glucocorticoid therapy was started (initial daily dose of
prednisone 60 mg was followed by rapid tapering to a daily dose
of 10 mg). Follow-up MRI showed almost complete regression of
leptomeningeal signal changes (see Fig. 1E and F). The patient was
clinically free of symptoms and reported less fatigue. Additional
test for RF in the CSF was negative.
The patient was referred to an outpatient rheumatology clinic.
There were no clinical symptoms of joint inﬂammation, pain,
tenderness or stiffness. Laboratory investigations revealed normal
acute phase reactants; however, RF and anti-CCP antibodies were
signiﬁcantly elevated with titer 1:320 (cutt-off value 1:80) and
760 U/ml (normal range 0–25), respectively. Subsequent radio-
graphic examination of the hands, wrist and feet showed erosions
at both ﬁfth metatarsophalangeal joints and periarticular osteo-
porosis of hands. Alternative systemic rheumatic diseases were
excluded.
Although the patient maintained drug-free clinical remission
for several years, his RA relapsed while tapered to low-dose
glucocorticoid treatment (5 mg prednisone daily). Nevertheless,
the patient’s neurological and psychiatric status remained excel-
lent allowing for successful gradual withdrawal of olanzapine. He
is still treated with carbamazepine and is seizure free for more than
one year.
3. Discussion
Rheumatoid meningitis (RM) is a rare condition and a very rare
cause of seizures.1,2 Epileptic seizures occur in approximately 21%
of patients with RM, more frequently in those with predominant
leptomeningeal involvement.1Although mental status change was
Fig. 2. Histopathology. (A) Hematoxylin–eosin stain showing marked ﬁbrous thickening of leptomeninges (delineated by arrows). (B) The lymphocytic inﬁltration was present
both in the leptomeninges and in the perivascular regions of the adjacent cortex (arrows). (C) CD3 immunohistochemistry demonstrating that the inﬂammatory inﬁltrate consists
predominantly of T lymphocytes. (D) Mild gliosis of the adjacent cortex was evident in GFAP immunohistochemistry. Scale bar = 80 mm (A) and 50 mm (B–D).
D. Krysl et al. / Seizure 22 (2013) 80–8282reported as the most common symptom of RM,1 it is not clear how
many cases are attributable to nonconvulsive SE. In our patient, the
episode of psychiatric disturbance was not caused by non-convulsive
SE. Apart from the direct effect of leptomeningeal involvement, it
could have been caused by antiepileptic medication (LEV).
Other frequent symptoms of RM include hemiparesis, cranial
neuropathy and headache. Atypical syndromes, such as progres-
sive supranuclear palsy-like clinical picture with vertical gaze
palsy, dementia and frequent falls have been reported.3
MRI ﬁndings include regional T2 signal increase of subarach-
noid space and mild leptomeningeal gadolinium enhancement.4
Although characteristic, these ﬁndings are not speciﬁc for RM. CSF
ﬁndings in RM are normal, or show unspeciﬁc elevation of protein
or mild increase of cells. Usefulness of measuring RF in the CSF was
suggested by some authors,5 however, RF was not detected in the
CSF in our case, despite using a sample taken in the highly active
stage of the disease prior to corticosteroid treatment.
The case shows that RM may occur in patients with RA who
have mild or no systemic inﬂammatory involvement. This may
cause diagnostic difﬁculties. We may speculate that in our patient,
low grade subclinical joint inﬂammation observed on FDG-PET/CT
may have contributed to the development RM.
The neuropathological evidence of chronic lymphocytic ﬁbro-
productive leptomeningitis (and, to a lesser extent, lymphocytic
inﬁltration of the adjacent brain cortex) in the context of RA will lead
to correct diagnosis when all other causes of chronic meningitis are
excluded (especially tuberculous meningitis, neurosarcoidosis and
leptomeningeal metastases). Drug-induced aseptic meningitis (i.e.
following ibuprofen treatment) remains an important differential
diagnostic option. Recently, cases of RM induced by TNF-a
antagonist adalimumab have also been described.5
No guidelines are available for the treatment of RM. However,
most reports showed efﬁcacy of glucocorticoids.1,6–8 Promising
results with rituximab have also been published.9In summary, RM is an important consideration in patient with
RA and de novo onset of seizures or SE, especially if characteristic
MRI ﬁndings are present. Due to multiple differential diagnostic
considerations, a brain biopsy analysis is mandatory for diagnosis.
Because of rapid response of the disease to glucocorticoids, biopsy
should not be delayed.
Conﬂict of interest
None of the authors has any conﬂict of interest to disclose.
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Chronic repetitive nonprogressive epilepsia partialis continua due to rheumatoid meningitis 

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Chronic repetitive nonprogressive epilepsia partialis continua due to rheumatoid meningitis

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