Journal of the Neurological Sciences 348 (2015) 274–276

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Journal of the Neurological Sciences
journal homepage: www.elsevier.com/locate/jns

Letter to the Editor

Nonconvulsive status epilepticus (NCSE) may have heterogeneous
presentations and differential diagnosis may be particularly difficult because clinical signs coupled with periodic EEG pattern are most often
subtle or non-specific. Moreover, few cases of NCSE have been previously described as the presenting symptom of sporadic Creutzfeldt–Jakob
disease (sCJD) [1,4,5,7]. We describe a patient with a NCSE strongly,
but erroneously, suggestive of a probable sCJD.

Clinical presentation, EEG pattern, MRI abnormalities and CSF
findings were suggestive of probable sCJD according to several CJD
diagnostic criteria [8], rather than a NCSE associated with an old stroke.
The patient was discharged at day 10 on oral valproate (1200 mg/die)
treatment with gradual improvement of the motor deficit and behavioral changes, although visual misperceptions and cognitive impairment (Mini Mental State Examination, MMSE 18/30) persisted. At six
months of follow-up, the patient appeared oriented without neurological signs or cognitive impairment (MMSE 28/30) and diagnostic tests
were performed once again. EEG recording showed a symmetric background activity without epileptiform discharges (Fig. 1D). Brain MRI
did not reveal the previously detected abnormalities (Fig. 1H–I) and
CSF detection of 14-3-3 and tau proteins was negative. Therefore, the
definitive diagnosis was symptomatic NCSE, induced by previous right
temporal–occipital ischemic stroke.

2. Case report

3. Discussion

A 66-year-old right handed man was referred to our clinic because of
the onset, three months before, of progressive cognitive decline, gait
ataxia with falls and sporadic visual hallucinations. His medical history
was notable for hypertension and a right temporal–occipital ischemic
stroke occurred one year before without neurological sequelae. At the
admission, he displayed a waxing and waning mental status, ocular
motor apraxia, left beating nystagmus and left-sided hemiparesis. A
brain computed tomography (CT) scan documented right temporal–
occipital hypodensity due to the previous stroke, without new lesions.
During the neurological examination the patient exhibited a tonic–
clonic generalized seizure followed by confusion and psychosis. VideoEEG monitoring (continuously performed for 12 hour periods each day)
showed an asymmetry of background activity with pseudo-periodic
high voltage discharges of spikes and bi-triphasic sharp waves on the
right posterior regions, recurring every 1–2 s and lasting 300–500 ms,
that were not interrupted by external stimulations (Fig. 1A) and that
were persisting during sleep. EEG pattern was simultaneously accompanied by left forced eye and head deviation. Infusion of intravenous diazepam 20 mg did not modify either the EEG pattern or clinical context
(Fig. 1B). Then, intravenous valproate was administered at doses of
800 mg in bolus followed by 1200 mg/24 h infusion, with gradual decrease of epileptic discharge frequency up to their disappearance within
two days (Fig. 1C). Motor deficit, as well as oculomotor apraxia started
improving, whereas recurrent nocturnal episodes of psychomotor agitation requiring antipsychotic medications persisted. Blood tests were
unremarkable. At admission day 1 MRI showed restricted diffusion in
right temporal–parietal–occipital cortex and ipsilateral pulvinar on
diffusion-weighted images (DWI) and subtle T2 prolongation only in
the right pulvinar on T2-fluid attenuated inversion recovery (FLAIR)
(Fig. 1E–F–G). The CSF analysis performed on day 2 from admission
revealed high levels of tau protein (1018 pg/mL) and a positive 143-3 protein measured by western blot. Additionally, methioninemeethionine (MM) at codon 129 or the prion protein gene was
detected.

Our case represents the first report of symptomatic NCSE resembling sCJD and highlights a high risk of misdiagnosis due to several
factors.

Symptomatic nonconvulsive status
epilepticus erroneously suggestive of
sporadic Creutzfeldt–Jakob disease

1. Introduction

http://dx.doi.org/10.1016/j.jns.2014.11.012
0022-510X/© 2014 Elsevier B.V. All rights reserved.

3.1. Clinical presentation
Firstly, our patient exhibited three months of subacute cognitive
decline, stroke-like hemiparesis, a convulsive seizure, and ocular and
psychiatric disturbances which mimicked sCJD onset.
3.2. EEG findings
In general, EEG is helpful in making a specific diagnosis when taken
in context with the clinical history, even though the underlying etiologies may be various. It is noteworthy that the EEG hallmark of sCJD
consists of periodic sharp-wave complexes (PSWC) that may occur
lateralized, mainly in the early stages and in patients with MM homozygosity [4,5,12]. In our patient, the first EEG monitoring showed PSWCs
on the right posterior regions accompanied by forced head and eye deviation and that were not attenuated by external stimuli, suggesting a
NCSE. On the other hand, benzodiazepine treatment failed to modify
ictal EEG pattern as it usually occurs in non-epileptic encephalopathies
including CJD. The latter hypothesis was also corroborated by the
prompt electrical improvement by AEDS without subsequent clinical
changes [4,5]. At the beginning, the epileptiform EEG pattern was consistent with NCSE and we hypothesized that it may be an onset form
of sCJD, as previously reported in literature [4,5]. Further investigations
were less conclusive, presenting considerable overlapping features.
3.3. MRI findings
It has long been suggested that acute DWI changes may play a prominent role in diagnosing sCJD, even in the early phase of the disease

Letter to the Editor

275

Fig. 1. EEG extracts in a bipolar longitudinal montage. Asymmetry of background activity with pseudo-periodic high voltage discharges of spikes and bi-triphasic sharp waves on the right
posterior regions, recurring every 1–2 s and lasting 300–500 ms, not interrupted by external stimulations (A). Acute infusion of intravenous diazepam 20 mg did not modify the EEG pattern (B). Intravenous valproate was administered at doses of 800 mg in bolus followed by 1200 mg/24 h infusion, with gradual decrease of epileptic discharges frequency (C). EEG performed six months later showed symmetric background activity without epileptiform discharges (D). MRI scan: At admission day 1 diffusion weighted (DW) study demonstrated
bright signal on isotropic images (E) and dark signal on ADC map (F) indicating restricted diffusion throughout the right temporal–parietal–occipital cortex (arrows) and ipsilateral
pulvinar (white and black arrowheads respectively). Axial fluid-attenuated inversion recovery (FLAIR) image showed subtle T2 prolongation only in the right pulvinar (white arrowhead)
(G). Six months later, no signal abnormalities were noted (H, I).

and before the typical EEG periodic pattern appearance [11]. The involvement of cortical and pulvinar regions has been described in both
sCJD and symptomatic SE [9]. These MRI abnormalities induced by
periictal vasogenic and cytotoxic edema may completely normalize
within weeks in SE [3] and they may disappear later in sCJD [9,11].
Therefore, in our case the reversible radiological findings did not allow
to clearly discriminate SE from sCJD. Such finding was compounded
by clinical and EEG data leading us to suspect CJD.

3.4. CSF findings
Currently, the 14-3-3 protein is considered a useful marker for
supporting the diagnosis of probable sCJD. Rarely, a first positive
test may become negative with a second lumbar puncture in sCJD patients with long disease duration (N 1 year), severe brain atrophy, or
under anesthetic therapy [10], but none of these events occurred in
our case. Hamlin et al. [6] have recently reported that tau protein

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Letter to the Editor

might be more suitable than 14-3-3 in diagnosing sCJD because of
higher specificity. Both tau and 14-3-3 proteins tend to increase
with disease progression in sCJD, but they may transiently increase
in symptomatic SE due to any extensive neuronal damage, as probably occurred in our case [6]. In fact, several studies hypothesized that
the occurrence of 14-3-3 isoforms within CSF may be induced by
acute neurological insults and, notably, that their presence can also
be a biomarker of acute seizure damage. Moreover, it has been
recently demonstrated that 14-3-3 overexpression may confer protection against seizure-induced neuronal death in the mouse
hippocampus [2].
4. Conclusions
In conclusion, our case supports previous evidence of overlapping
features in NCSE and sCJD and shows that diagnosis can be tricky,
even matching several diagnostic findings. In the light of this case
report, we wonder whether a refinement of diagnostic criteria might
be needed in order to avoid overdiagnosis of sCJD, also taking in consideration the usefulness of repeating MRI with FLAIR and DWI and CSF
analysis.

[9] Ohe Y, Hayashi T, Deguchi I, et al. MRI abnormality of the pulvinar in patients with
status epilepticus. J Neuroradiol 2014;41(4):220–6.
[10] Schrooten M, De Vooght W, Weckhuysen S, Van Paesschen W, Van Damme P. Normalization of 14-3-3 in CJD. Acta Neurol Belg 2008;108(2):64–6.
[11] Vitali P, Maccagnano E, Caverzasi E, et al. Diffusion-weighted MRI hyperintensity
patterns differentiate CJD from other rapid dementias. Neurology 2011;76(20):
1711–9.
[12] Wieser HG, Schindler K, Zumsteg D. EEG in Creutzfeldt–Jakob disease. Clin
Neurophysiol 2006;117(5):935–51.

Maria Albanese
Fabio Placidi
Andrea Romigi
University of Rome “Tor Vergata”, Department of Systems Medicine,
Neurophysiopathology Unit, Epilepsy Center, Rome, Italy
Tommaso Schirinzi
University of Rome “Tor Vergata”, Department of Systems Medicine,
Neurology Unit, Rome, Italy
Claudio Liguori
Angela Marchi
University of Rome “Tor Vergata”, Department of Systems Medicine,
Neurophysiopathology Unit, Epilepsy Center, Rome, Italy

Sources of funding
The authors declare no financial support.
Conflict of interest
None of the authors have potential conflicts of interest to be
disclosed.
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Francesco Garaci
Roberto Floris
University of Rome “Tor Vergata”, Department of Diagnostic Imaging,
Molecular Imaging, Interventional Radiology and Radiotherapy, Rome, Italy
University of Rome “Tor Vergata”, Department of Biomedicine and
Prevention, Rome, Italy
Nicola Biagio Mercuri
University of Rome “Tor Vergata”, Department of Systems Medicine,
Neurophysiopathology Unit, Epilepsy Center, Rome, Italy
Fondazione Santa Lucia IRCCS, Rome, Italy
Maria Grazia Marciani
University of Rome “Tor Vergata”, Department of Systems Medicine,
Neurology Unit, Rome, Italy
Francesca Izzi⁎
University of Rome “Tor Vergata”, Department of Systems Medicine,
Neurophysiopathology Unit, Epilepsy Center, Rome, Italy
Corresponding author at: University of Rome “Tor Vergata”, Department
of Systems Medicine, Neurophysiopathology Unit, Epilepsy Center, Viale
Oxford 81, 00133 Rome, Italy. Tel.: +39 06 20902107.
E-mail address: fraizzi@tin.it.
1 September 2014