(2022) 22:421
Le Soudéer et al. BMC Pediatrics
https://doi.org/10.1186/s12887-022-03460-6

Open Access

CASE REPORT

Shigella‑associated mild encephalitis
with reversible splenial lesion in Hospital Center
Delafontaine, Saint‑Denis, France: a case report
Louise Le Soudéer, Jeanne Truong, Julie Le Gal and Simon Escoda*

Abstract
Background: Mild encephalitis with reversible splenial lesion of the corpus callosum (MERS) is a clinical/radiological
syndrome characterized by hyperintense signal changes in the splenium of the corpus callosum visible on diffusion
weighted imaging (DWI) in the brain Magnetic Resonance Imaging (MRI) associated with various neurological symptoms. Progression is usually favorable with disappearance of the MRI brain lesion and regression of clinical symptoms
over a few days to a few weeks. The exact pathophysiology remains unclear. MERS can be associated with various
pathogens.
Case presentation: We report here a paediatric case of MERS associated with Shigella flexneri infection. A five-yearold boy with no relevant past medical history presented with symptoms such as headache, fever, profuse diarrhea
and hallucinations.
A brain Magnetic Resonance Imaging performed on Day 2 of the symptoms revealed hyperintense signal changes
of the splenium of the corpus callosum in T2 FLAIR sequence. This infection had a favorable outcome after antibiotic
therapy. No further recurrence of symptoms was observed and a follow-up clinical examination eight weeks later was
normal. A follow-up brain Magnetic Resonance Imaging three months after discharge was also normal and the hyperintense signal changes of the splenium of the corpus callosum had disappeared completely.
Conclusions: MERS is a clinical/radiological syndrome with a generally good prognosis.
We believe that this is the first description of a case of Shigella-associated MERS.
It is useful to know about this condition to help distinguish it from acute disseminated encephalomyelitis.
Keywords: Case report, Paediatric, Shigella, MERS
Background
Mild encephalitis with reversible splenial lesion of the
corpus callosum (MERS) is a clinical/radiological syndrome. It is not a rare condition in a paediatric setting.
As an example two cases have been recorded in our hospital over an 18-month period (2019–2020).
*Correspondence: simon.escoda@ch-stdenis.fr
Service de Pédiatrie, Centre Hospitalier Delafontaine, 93200 Saint‑Denis,
France

We present here a case of MERS in a five-year-old boy
associated with Shigella flexneri infection. We believe
that this is the first description of a case of Shigella-associated MERS.
Case presentation

A five-year-old boy with no relevant past medical history was admitted to Delafontaine Hospital Center,
Saint-Denis, France, with insomnia-causing headache,
fever and profuse diarrhea without mucous or blood
over a 24-h period. He also presented with temporal

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(2022) 22:421

and spatial disorientation, obtundation and hallucinations that started a few hours prior to Attendances and
Emergency Department (A&E) admission. These symptoms lasted 24 h after temperature came back to normal. No specific contagion, no recent travel or contact
with animals were reported. The vaccinations of the
child were not up to date according to the French vaccination schedule.
When admitted to paediatric A&E, his vital signs
were: temperature 38.8 °C, heart rate 140 beats/min,
respiratory rate 30 breaths/min, oxygen saturation 98%
at ambient air and blood pressure, 106/77 mmHg. He
was confused, disoriented in time and space and suffering from visual hallucinations. The rest of the clinical
examination, particularly neurological, was normal.
The blood count was normal. The serum electrolytes showed: a slight hyponatremia (serum sodium,
132 mmol/L) and an inflammatory syndrome: C-reactive protein, 118 mg/L and procalcitonin, 4.51 ng/mL.
Liver function tests were normal. Blood cultures were
negative after five days. Cerebrospinal fluid (CSF) analysis revealed: 1 leucocyte/mm3 per 6 red blood cells/
mm3; protein concentration, 0.16 g/L and CSF versus blood glucose ratio > 0.6. The direct CSF examination was negative and cultures were sterile after five
days. PCR for Herpes Simplex Virus 1 and 2, varicella
and enterovirus in the CSF were negative. Stool virology (rotavirus, adenovirus) was negative while the stool
culture identified the presence of Shigella flexneri.
Given the SARS-CoV-2 pandemic context, tests for
Paediatric Inflammatory Multisystem Syndrome were
performed, which included an echocardiography, troponin and NT-pro-BNP. The results all came back
normal. Nasal PCR and SARS-CoV-2 serology were
negative.
A non-enhanced brain scan (CT) showed no evidence
of intracranial lesion. A brain MRI performed on Day 2
of the symptoms revealed hyperintense signal changes
on diffusion weighted imaging (DWI) sequences of the
splenium of the corpus callosum (SCC), and diffusion
sequences with a restriction of the apparent diffusion
coefficient (ADC) (Fig. 1). However in our case there
were no hyperintense signal changes in T2 Fluid Attenuated Inversion Recovery (FLAIR).
The initial electroencephalogram (EEG) performed on
Day 2 also revealed greater slow wave activity in the right
frontal and temporal leads, consistent with encephalitis.
Given the encephalopathic symptoms, intravenous
treatment with cefotaxime and acyclovir at meningeal
doses was rapidly initiated on the day of admission.
Acyclovir was discontinued after receiving a negative CSF PCR for herpes simplex virus. The dose of
cefotaxime was rapidly reduced to 100 mg/kg/d due to

Page 2 of 5

the negative direct CSF examination. Antibiotic treatment was continued for three days to treat the Shigella
infection.
The inflammatory syndrome reduced during hospitalization, with C-reactive protein of 93 mg/L at Day 5.
The clinical condition of the patient improved during
hospitalization with complete regression of neurological symptoms. The condition of the patient was normal
at Day 4 post-admission and he was discharged after six
days in hospital.
No further recurrence of symptoms was observed and
a follow-up clinical examination eight weeks later was
normal.
A follow-up EEG four weeks after discharge was
normal.
A follow-up brain MRI three months after discharge
was also normal and the SCC hyperintense signal
changes had disappeared completely.

Discussion and conclusions
MERS is a clinical/radiological syndrome first described
by Tada et al. In 2004 [1]. Its radiological presentation
is established on the basis of a brain MRI: SCC hyperintense signal changes on T2 FLAIR and DWI sequences.
The apparent diffusion coefficient (ADC) of the lesion is
decreased on ADC maps, and iso- to hypo-intense signals
may appear on T1-weighted imaging sequences without
enhancement after injection of a contrast agent [1–3].
MERS has been widely described in case reports and
case series around the world, initially first in Japan. The
clinical symptoms of MERS described in the literature
are varied and affect the central nervous system: disturbed consciousness, behavioral disorders, incoherent
speech, seizures, drowsiness, headaches, hallucinations,
and more rarely ataxia, motor deficits and blindness.
There could be also more general symptoms such as
fever, cough, vomiting and/or diarrhea.
No specific biological criteria defining MERS have
been established. Pleocytosis and hyponatremia have
been reported inconsistently [1, 2, 4]. Pleocytosis was not
observed in our case: however, mild hyponatremia was
reported and was rapidly corrected with the resolution
of the symptoms. An inflammatory syndrome is often
identified.
There is a frequent but not universal association
between MERS and hyponatremia. The principal cause of
hyponatremia mentioned so far is the syndrome of inappropriate antiduretic hormone secretion (SIADH). Interleukin 6 (IL-6) which increases during inflammation, may
have a key role in the pathophysiology of SIADH. Indeed,
it is recalled that it can stimulate the hypothalamus and
pituitary gland and induce vasopressin release leading to
hyponatremia [5, 6].

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Page 3 of 5

Fig. 1 This is the legend from a figure from the study. a. Brain MRI performed on day 2 of the symptoms. Hyperintense signal changes of the SCC
are visible on Diffusion-weighted imaging sequence. b. Brain MRI performed on day 2 of the symptoms. No hyperintense signal changes of the SCC
are visible on T2W/FLAIR image. c. Brain MRI performed on day 2 of the symptoms. Reduction of ADC is visible on ADC maps

The possible etiologies for MERS are large. Historically, reversible MRI lesions in the SCC were described
in patients using anti-epileptic drugs [7]. Anti-epileptic
drugs and their rapid withdrawal or toxic levels were
thought to be the cause of the splenial lesion although it
is difficult to strongly impute the antiepileptic drugs over
the effect of frequent seizures in epileptic patients [8].
The principal hypothesis is that antiepileptic drugs may
interact with fluid balance system (arginine-vasopressin)
and cation channels. If antiepileptic drugs concentration changes rapidly, this might disturb the fluid balance
system, causing a syndrome of inappropriate antidiuresis that leads to hyponatremia and finally to brain

edema. However this hypothesis cannot explain why
the splenium of the corpus callosum is the preferential
localization.
Reversible MRI lesions in the SCC have also been
described in high-altitude disease, cerebrovascular disease or vasculitis (Kawasaki disease), metabolic disturbances (hypoglycemia, Machiafava-Bignami disease) [9]
or infectious diseases.
The list of MERS-associated pathogens identified
includes viruses such as rotavirus [1, 2], cytomegalovirus
[10], adenovirus [11], influenza A/B virus [12], herpesvirus 6 [13] and Epstein Barr virus [14], as well as bacteria such as Mycoplasma pneumonia [4], Salmonella [15],

Le Soudéer et al. BMC Pediatrics

(2022) 22:421

Listeria monocytogenes [16], Escherichia coli [17], Klebsiella pneumoniae [18] and Enterococcus faecalis [19]. It
is known that Shigella-associated infections are sometimes associated with neurological symptoms such as seizures, drowsiness, hallucinations and, more rarely, severe
and fatal encephalopathy [20, 21]. However, the association with MERS had never been mentioned so far.
As described in our clinical case, most MERS patients
recover within a few days with a favorable prognosis and
the brain MRI usually reverts to normal within a month.
However, a poor clinical outcome has been reported in
some cases, without a clear explanation. In addition,
in some of the cases described, the SCC lesion did not
revert on a subsequent brain MRI after one month [22,
23]. Two types of radiological MERS have been described
in the literature [24]. Type I is an isolated SCC lesion,
whereas type II is described as an extensive lesion,
encompassing the entire corpus callosum and sometimes
the white matter. Although radiological lesions are usually reversible within a few weeks, some cases of Type II
MERS have reported clinical neurological sequelae and
radiological lesions persisting for over a month [4, 25].
At present, the exact pathophysiological mechanism of MERS is not fully understood. The most commonly described hypothesis is cytotoxic edema caused
by cytokine release, as high density of cytokine receptors is observed in the SCC [3]. Indeed, it is well known
that pro-inflammatory cytokines such as IL-1 and IL-6
are usually released due to endothelial damage. Theses
cytokines lead to activate receptors such as N-methylD-aspartate (NMDA), aquaporines 4 (AQP4) at the surface of astrocytes and neurons. It could result in an influx
of water into these cells (cellular swelling). As there is a
higher density of cytokine and AQP4 receptors in the
neurons, astrocytes and oligodendrocytes of the corpus
callosum, this localisation is more likely to be exposed to
cytotoxic edema when cytokine release occurs.
Cytotoxic edema is characterized by the intracellular accumulation of fluid and sodium, which results in
cell swelling. It is generally known to lead to irreversible
lesions and cellular death, such as cytotoxic edema in
ischemic strokes. However, MRI shows a reversible lesion
on diffusion-weighted imaging, separating these lesions
from persistent ischemia [3].
The primary differential diagnosis of MERS appears
to be acute disseminated encephalomyelitis (ADEM)
[1]. ADEM is described as an inflammatory disorder
usually occurring after infection or vaccination and
characterized by multifocal demyelination of the central nervous system. Its clinical presentation may be
similar to MERS: seizures, altered consciousness, focal
neurological signs. Symptoms develop over a few days
to weeks after the start of the suspected triggering

Page 4 of 5

element. Despite the similar presentation, ADEM can
be severe and in some cases, including acute necrotizing encephalitis lead the children to death. MRI
shows hyperintense asymmetric signal in T2 FLAIR
sequences, most commonly in white matter but sometimes also in the thalami and basal ganglia. Areas of
enhancement are described in T1-weighted images
with gadolinium contrast. In acute stages the lesions
may show diffusion restriction on diffusion-weighted
sequences.
As seen in MERS, CSF pleocytosis is common in
ADEM. Assessment of intratecal antibodies synthesis
through oligoclonal bands can be also informative since
there are some cases of ADEM that shows oligoclonal
bands in the CSF [26].
Unfortunately we did not search for oligoclonal bands
in the CSF of our patient.
Treatment of ADEM is via high-dose intravenous
corticosteroids. Lesions may develop over weeks to
months and only disappear after several months,
although white-matter lesions can sometimes become
permanent. Children commonly recover completely
usually over 4–6 weeks but in some cases they may suffer from cognitive and/or physical deficits. Nevertheless
long-term clinical and radiological follow-up of ADEM
is important. Sometimes another episode of ADEM can
occur more than 3 months following the initial condition and is referred to as multiphasic ADEM.
MERS is a clinical/radiological syndrome with a generally good prognosis. The pathophysiological mechanism
is still unclear. It is useful to know about this condition
to help distinguish it from ADEM. MERS can be associated with various pathogens. We report here a paediatric
case of MERS associated with Shigella flexneri infection,
which had a favorable outcome after antibiotic therapy.
Abbreviations
ADC: Apparent diffusion coefficient; ADEM: Acute disseminated encephalomyelitis; A&E: Attendances and emergency department; CSF: Cerebrospinal
fluid; CT-Scan: Computerized-tomography scan; DWI: Diffusion weighted
imaging; EEG: Electroencephalogram; FLAIR: Fluid attenuated inversion recovery; IL-6: Interleukin-6; MERS: Mild encephalitis with a reversible splenial lesion
of the corpus callosum; MRI: Magnetic resonance imaging; PCR: Polymerase
chain reaction; SIADH: Syndrome of inappropriate antidiuretic hormone secretion; SCC: Splenium of the corpus callosum.
Acknowledgements
We would like to thank all the staff in the Pediatric Department of Centre
Hospitalier Delafontaine and IPAC traductions for their help in the achievement of the case report.
Authors’ contributions
LLS drafted the initial manuscript and collected data. Drs JT and JLG reviewed
and revised the manuscript. Dr SE conceptualized and designed the study,
and critically reviewed the manuscript for important intellectual content. All
authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Le Soudéer et al. BMC Pediatrics

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Funding
No funding was secured for this study.
Availability of data and materials
The dataset supporting the conclusions of this article is included within the
article.

Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Written informed consent was obtained from the parents for publication of
this case report.
Competing interests
The authors have no example conflicts of interest to disclose.
Received: 19 December 2021 Accepted: 30 June 2022

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