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\begin{document}

\title{Transient Bilateral blindness due to mild encephalopathy with reversible
splenial lesion (MERS): a case report}



\author[1]{Shima Shekari}%
\author[2]{Farima Farsi}%
\author[1]{Farah Ashrafzadeh}%
\author[3]{Shima Imannezhad}%
\author[3]{Ahmad Niazi}%
\author[3]{Samane Kamali}%
\affil[1]{Mashhad University of Medical Sciences Ghaem Hospital}%
\affil[2]{Mashhad University of Medical Sciences Faculty of Medicine}%
\affil[3]{Mashhad University of Medical Sciences}%


\vspace{-1em}



  
  \date{June 02, 2024}


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\textbf{Abstract}

\textbf{Background:} Mild encephalitis/encephalopathy with a reversible
splenial lesion (MERS) is a rare clinical-radiological being defined by
the magnetic resonance imaging (MRI) finding of a reversible lesion in
the corpus callosum. The most significant neurological symptoms are
disturbance of consciousness and abnormal and delirious behavior.

\textbf{Case presentation:} A seven-year-old male patient with a history
of fever and cough was admitted to our hospital due to sudden-onset
bilateral blindness. His physical examination showed confusion, fever,
and delirious behavior with no focal neurological and meningeal
irritation signs. The electroencephalogram showed diffuse slowing in
favor of mild encephalopathy. Magnetic resonance imaging of the brain
showed a signal alteration in the splenium of the corpus callosum and
Magnetic Resonance Angiography (MRA) was normal. This finding was
suggestive of a reversible cytotoxic lesion. Empiric antiviral treatment
was initiated and the symptoms improved completely.

\textbf{Conclusion:} Sudden blindness was reported as an initial symptom
of MERS in a few children. Until now, there is no evidence of effective
treatment methods. Nevertheless, MERS diagnosis provides pediatricians
with beneficial prognostic information in order to convince patients and
their families about the good outcome of this disease.

\textbf{Keywords:} Reversible encephalopathy, Bilateral blindness,
Corpus callosum

\textbf{Introduction}

Tada et al. first determined the concept of mild
encephalopathy/encephalitis with a reversible splenial lesion (MERS) as
an uncommon clinical-radiological syndrome in 2004{[}1, 2{]} which is
mostly reported in East Asian populations {[}3{]}. It usually develops
in children below sixteen-years-old and only occasionally in adults
{[}4{]}. Infections are considered as the main trigger of the disease;
the major pathogens associated with MERS are viruses, such as influenza
virus (A and B) {[}3{]}. Non-infectious conditions related to reversible
splenial lesions are seizures, antiepileptic drug withdrawal, metabolic
disturbances, and renal or hepatic dysfunction {[}5{]}. To date, a
common pathophysiological mechanism explaining selective splenial
involvement has not been found. However, there are several hypotheses on
MERS pathogenesis, including intramyelinic edema, hyponatremia, axonal
damage, and oxidative stress {[}6{]}. MERS is typically characterized by
a prodromal illness consisting of fever, cough, and digestive tract
symptoms followed one to seven days later by encephalopathy {[}7, 8{]}.
The neurological features of MERS include disturbance of consciousness,
abnormal speech, delirious behavior, headache, agitation,
disorientation, seizures, facial nerve paralysis, and nuchal rigidity;
however visual disturbances are rare symptoms of this syndrome. The most
common neurological symptom described in the literature is delirious
behavior with altered consciousness, which may present as akinetic
mutism {[}5, 9{]}. On MRI, MERS is almost always associated with a
transient splenial lesion that is slightly hyperintense on T2- weighted
images and isointense to slightly hypointense on T1-weighted images, and
that shows reduced diffusion without contrast enhancement during the
acute period of the disease. A classification of MERS based on MRI data
was proposed; In MERS type 1, the lesions are limited to the splenium
(ovoid or band shaped), as observed in our case report, whereas in MERS
type 2 the lesions are not limited to the splenium {[}10, 11{]}.
Clinical and radiological outcome is usually favorable with clinical
improvement occurring within one to two days, while radiologic
improvement within 10 days-4 months. Usually, raised serum inflammatory
markers (white cell count and C-reactive protein) in the absence of CSF
inflammation can be found in children diagnosed with MERS, supporting
the hypothesis that this syndrome is an infection-associated
encephalopathy rather than an encephalitis {[}7{]}. At the moment, No
high-level evidence on the therapeutic approaches is available.
Methylprednisolone pulse therapy and intravenous immune globulin (IVIG)
are recommended for patients with infectious encephalopathy, regardless
of pathogen or clinical-radiological syndromes {[}8{]}. Here we describe
a case of MERS in an Iranian seven-year-old male patient, with a
cytotoxic lesion in the SCC11Splenium of the corpus callosum detected by
MRI and the unusual clinical presentation of acute bilateral blindness.

\textbf{Case presentation}

A previously healthy seven-year-old child was admitted to our hospital
due to sudden-onset bilateral blindness. One day prior to admission, he
suddenly developed a fever of 39 \selectlanguage{ngerman}°C, cough, and loss of appetite. He was
examined by his pediatrician and azithromycin and intravenous fluid
therapy was prescribed due to suspected streptococcal pharyngitis.
Although treatment with azithromycin and oral antipyretics was started,
he still had a fever of 38 °C. On the day of admission, he experienced
all at once a non-episodic bilateral blindness and delirium. The
symptoms were continuous and therefore, he was admitted to the hospital
emergency department. His family history was unremarkable. On physical
examination, the patient was agitated associated with encephalopathy
feature and his general condition was not good. The boy was
collaborative during the medical evaluation, although his responsiveness
was slightly impaired. Neither focal neurological signs nor meningeal
irritation signs were observed.

Chemistry panel and urine analysis showed no abnormalities except for a
highly elevated level of CPK22Creatine phosphokinase (569 U/L), slightly
elevated level of AST33Aspartate aminotransferase (47 U/L), and mild
hyponatremia (134 mEq/L). The presence of blindness prompted an
ophthalmologic evaluation, including a fundus oculi examination that was
negative.

On the following day, the electroencephalogram (EEG) showed diffuse
slowing waves in favor of mild encephalopathy. The child's neurologist
observed mild increase in deep tendon reflex (DTR) but no significant
focal neurological deficit was detected.

The child was then admitted to perform a brain MRI and a lumbar
puncture, in order to exclude acute cerebral vascular accident and the
presence of viral encephalitis, cerebral abscesses, or other cerebral
inflammatory lesions, such as acute disseminated encephalomyelitis
(ADEM).

Brain MRI was done four hours after admission and restriction in the
corpus callosum was seen in diffusion-weighted imaging(DWI), with
correlation in Apparent Diffusion Coefficient (ADC MAP), suggesting an
abnormal diffusion restriction and a reversible cytotoxic lesion (Figure
1) Without any abnormal intensity in other views and T1-W.

Treatment against suspected meningitis with intravenous ceftriaxone (100
mg/ Kg once a day), vancomycin (15 mg/ Kg every 6 h), acyclovir (10 mg/
Kg every 8 h) and dexamethasone (0.2 mg/Kg every 8 h) was initiated,
while waiting for the results of the polymerase chain reaction (PCR)
search for neurotropic viruses, bacteria and fungi in the cerebral
spinal fluid (CSF) and peripheral blood. Antibacterial therapy was
suspended because the blood and CSF44Cerebrospinal fluid culture was
negative. A nasal swab for metapneumovirus virus was positive but this
data did not change patient's management.

Collateral findings detected by MRI were arachnoid cyst in the posterior
fossa and abnormal signal intensity in the maxillary and ethmoid
sinuses. The child was in good general condition without apraxia. As a
result, he was discharged after 6 days of admission and treatment with
acyclovir and dexamethasone. After four days, a follow-up brain MRI was
repeated, showing a complete normalization of the signal alteration in
the SCC (Figure 2). The EEG was also repeated, showing a complete
normalization of the pattern. The child was in good general condition,
without neurological deficits.

\textbf{Discussion and conclusions}

In our case, the unusual main neurological symptom was acute bilateral
blindness, which appeared after one day with symptoms suggestive of
viral infection (low-grade fever, nonproductive cough). The slight
metapneumovirus positivity detected by PCR in the oropharynx and
nasopharynx remains a result of uncertain interpretation within the
clinical picture of this patient.

In this case, there are several reasons why metapneumovirus was not
strongly considered in the etiology. Sometimes, a slight metapneumovirus
positivity by PCR may also be found in patients without related
symptoms. The seven-year-old child presented with non-specific symptoms,
which could be attributed to a variety of viruses, and metapneumovirus
disease usually occurs in winter and autumn. Furthermore, in this case,
the PCR search for metapneumovirus in the CSF was not done.

EEG abnormality was diffuse slowing in favor of mild encephalopathy and
MRI imaging showed lesions limited to the splenium, which was
restriction in DWI with correlation in ADC map (MERS type 1).

With regard to laboratory findings, our patient had highly elevated
level of CPK, slightly elevated level of AST and mild hyponatremia at
hospital admission. However, this result only provides a limited
contribution to the clinical presentation.

Our patient was treated with intravenous therapy against suspected
meningitis and herpes virus until the culture and viral PCR search for
neurotropic in the blood and CSF was found to be negative. In addition,
the patient received corticosteroid therapy for five days with low dose
of dexamethasone. To date, there is no evidence of an effective
treatment for patients with MERS, and the prognosis.

In children, MERS shows a wide spectrum of clinical presentations
however, visual disturbances are rare symptoms of this syndrome. Most of
the MERS cases show a favorable outcome regardless of treatment. The
early recognition of this condition in children with encephalopathy may
limit unnecessary and potentially toxic treatments. Moreover, MERS
diagnosis allows pediatricians to reassure patients' families about the
good outcome of this disease.

\begin{enumerate}
\tightlist
\item
  \textbf{Author contributions:} Farima Farsi: writing-original draft
  (equal), conceptualization (equal); Shima Shekari: writing-original
  draft (equal), conceptualization (equal); Farah Ashrafzadeh: review
  and editing (equal), supervision (equal); Shima Imannezhad: review and
  editing (equal), visualization (equal); Ahmad Sohrab Niazi: review and
  editing (equal), data curation (equal); Samane Kamali: data curation
  (equal).
\item
  \textbf{Compliance with ethical standards}
\item
  \textbf{Acknowledgements:} The authors would like to express their
  gratitude to Mashhad University of Medical Sciences. The authors
  declare that there is no conflict of interest.
\item
  \textbf{Data availability statement:} The data, supporting this study,
  are available upon reasonable request from the corresponding author.
\item
  \textbf{Patient consent statement:} Informed consent was taken from
  the patient and his family, that information about him would be
  published in a journal.
\end{enumerate}

\textbf{References}

\begin{enumerate}
\tightlist
\item
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\item
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\end{enumerate}\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/figure-1-mers/figure-1-mers}

\end{center}
\end{figure}\selectlanguage{english}
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\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/figure-2-mers/figure-2-mers}

\end{center}
\end{figure}

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