EXPERIMENTAL AND THERAPEUTIC MEDICINEMERS associated with bacterial translocation in a pediatricpatient with congenital portal vein hypoplasia: A case report
GEORGE IMATAKA1, TAKESHI YAMAGUCHI2, JUNPEI ISHII1, KEI OGINO2,KENTARO OKAMOTO2,3, TAKASHI TSUCHIOKA2 and SHIGEMI YOSHIHARA1
Departments of 1Pediatrics and 2First Surgery, Dokkyo Medical University, Shimotsuga, Tochigi 321‑0293;
3
Department of Pediatric Surgery, Tokyo Medical and Dental University, Tokyo 113‑8510, Japan
Received October 6, 2017; Accepted December 8, 2017
DOI: 10.3892/etm.2018.6532
Abstract. A case of mild encephalitis/encephalopathy witha reversible splenial lesion (MERS) in a female child who
developed bacterial translocation from a congenital portal vein
hypoplasia is reported. The patient was diagnosed as having
portal hypertension after examinations and laboratory results
showing splenomegaly and thrombocytopenia at the age of1 year. The patient required three endoscopic variceal liga‑tion (EVL) surgeries before the age of 9 due to developmentof multiple esophageal varices. After the second and thirdEVL procedures, she developed septicemia, possibly due tobacterial translocation associated with the administration ofgeneral anesthesia. The day after the third EVL, the patientpresented with high fever and neurological disturbances(altered consciousness). Magnetic resonance imaging detected
abnormal intensities in the corpus callosum ampulla andcerebral white matter, which suggested a diagnosis of MERS
type 2. Considering this clinical course, the possible associa‑tion between bacterial translocation and MERS in a patientwith congenital portal vein hypoplasia and portal hypertension
is discussed.
Introduction
Mild encephalitis/encephalopathy with a reversible spleniallesion (MERS) is a type of acute encephalitic encephalopathy
as reported by Tada et al (1). The characteristic magnetic
resonance imaging (MRI) findings of MERS include revers‑
ible lesions of the splenium of the corpus callosum that
resolved spontaneously within one week in most cases (2).
In recent years, diffusion weighted images (DWIs) of MRICorrespondence to: Dr George Imataka, Department of Pediatrics,

Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga,Tochigi 321‑0293, JapanE‑mail: geo@dokkyomed.ac.jp

Key words: mild encephalitis/encephalopathy with a reversible

splenial lesion, bacterial translocation, endoscopic variceal ligation,congenital portal vein hypoplasia, portal hypertension

have become widespread, and reports have increased onincidences of MERS related to various conditions. The
clinical course of MERS is generally mild, when comparedto other types of acute encephalopathy, and it depends on
the severity of the subjacent condition. The pathogenesis
of MERS has been known to involve a variety of differentmechanisms and includes cases associated with the use ofanti‑epileptic drugs (3,4), cases accompanying acute moun‑tain sickness (5), and others associated to microbial infections(mycoplasma (6), legionella (7), dengue fever (8), rubella (9),rotavirus (10), HHV‑6 (11), Influenza virus type A (12),and others). Thus, MERS is recognized as a uniqueclinico‑radiological encephalitis/encephalopathy syndrome
associated with diverse pathological conditions. However, tothe best of our knowledge, this is the first instance whereinbacterial translocation has been implicated as a causative
mechanism. Herein, we report the case of a 9‑year‑old girlwho had complicated esophageal varices due to congenital
portal vein hypoplasia and developed a bacterial infection
with abdominal pain and neurological abnormalities that led
to a diagnosis of MERS.
Case report
Our pediatric patient was born following a normal delivery at
37 weeks of gestation. Her birth height was 43.3 cm and herweight was 2,090 g. There were no delays in motor develop‑
ment and the girl started walking at the age of 1. No family
history of major diseases was reported.
One year after her birth, the girl was reported to suffer fromfrequent epistaxis episodes. Medical examinations performedat the local hospital showed she had thrombocytopenia andsplenomegaly. She was referred to our university hospital at
the age of 1 year and 3 months; X‑ray images showed evidenceof an expansion of the mediastinum, which led us to suspect
the presence of a mediastinal tumor. A chest computed tomog‑
raphy (CT) scan revealed a low‑density area in the hepatic
portal section, and a tentative diagnosis of portal hyperten‑sion was made. After that, the patient underwent abdominal
ultrasound and contrast CT examinations, and abnormalitiesof the portal vein running through the liver were recognized.
Multiple esophageal varices were also confirmed by uppergastrointestinal contrast radiographic images. Overall, the2

IMATAKA et al: MERS WITH BACTERIAL TRANSLOCATION IN CONGENITAL PORTAL VEIN HYPOPLASIA

patient was diagnosed as having idiopathic portal hyperten‑sion caused by congenital portal hypoplasia.
At 3 years of age, contrast CT examination showed exac‑
erbation of the esophageal varices from the lower portionof the esophagus to the cardia of the stomach. The portalvein was undergoing a cavernous transformation from thesplenoportal junction. The images revealed a splenic veinaneurysm. Additionally, the left kidney was atrophic due tothe progressing splenomegaly. Therefore, a pediatric surgeon
performed an endoscopic variceal ligation (EVL) surgery at
multiple sites that were deemed as prone to bleeding.
A second EVL surgery for recurrent esophageal varices wasperformed under general anesthesia when the patient was 6 years
and 8 months. The day after the EVL surgery, the girl experienced
a sudden high fever (>40˚C). Paralysis of the intestinal tract due
to general anesthesia and the existing portal vein hypoplasia
were suspected as resulting in secondary bacterial translocationand sepsis. The blood culture test collected from the elbow vein
produced a negative result. An attempt to obtain blood directlyfrom the portal vein proved impossible. Nevertheless, a course ofantibiotics and gamma globulin therapy were promptly adminis‑
tered and the infectious symptoms subsided.
Later, at the age of 9 years and 6 months, the patient under‑
went a third EVL surgery under general anesthesia once again
for esophageal varices. This time, cephem antibiotics (ceftri‑axone sodium hydrate; CTRX) were prescribed prophylacticallyand immediately after the surgical procedure. Nevertheless, thenext day after the EVL surgery, the girl developed a 40˚C fever.
She was hospitalized in the city hospital but her consciousness
level reduced by the evening of the same day. Thus, she wastransferred to our university hospital. Blood examinations
showed the following values: White blood cells 3,200x109/l,
hemoglobin 10.4 g/dl, Plt 2.3x104/µl, sodium 130 mEq/l, CRP
7.39 mg/dl, and procalcitonin 26.34 ng/ml. Sepsis and acuteencephalopathy due to bacterial translocation after the EVL
surgery were suspected. The cell count of cerebral spinal fluid
collection was 42/µl. A head CT showed no remarkable changes.
Her MRI images, nonetheless, revealed abnormal signal inten‑
sities mainly at the splenium of the corpus callosum and bothsides of white matter using contrast (Fig. 1). So the patient
was diagnosed as having a MERS type 2, which was probably
precipitated by bacterial translocation. The antibiotic treatment
with CTRX was switched to penem (panipenem; PAPM/BP)
and 5 days of gamma globulin therapy with 3 days of steroid
pulse treatment. After 24 h of the last treatment dosage, the feverprevailed but at a lower temperature. On the second day after
the aforementioned treatments, DWIs of MRI showed marked
improvement (Fig. 1), a finding that was in agreement with thetypical course of MERS. Nevertheless, many abnormal spots
suspected to be due to micro-bleeding were apparent (Fig. 2). On
the third day after the treatment, her neurological symptoms andfever had completely disappeared. Regarding the publication ofthis case report, the patient's parents consented in advance to theformal form prepared by the Ethics Organization Committee ofDokkyo Medical University Hospital (Tochigi, Japan).
Discussion
The clinical course of this pediatric case is very interesting.
Initially, the patient manifested symptoms of portal

Figure 1. Brain MRI upon hospital admission. Top panels: (DWI) of abnormal
signal intensities from MRI were mainly in the corpus callosum and in bothsides of the white matter before treatment. Lower panels: DWI signal intensi‑ties on MRI improved two days after treatment. DWI, diffusion weighted
image; MRI, magnetic resonance imaging.

Figure 2. Brain magnetic resonance imaging after MERS resolution. Microbleeding of small vessels was recognized following the fat suppression
method of short T1 weighted inversion recovery images after treatment.
MERS: mild encephalitis/encephalopathy with a reversible splenial lesion.

hypertension due to congenital portal defects. Between
infancy and childhood, formation of a collateral circulation
pathway to compensate for portal vein deficits was observed,
complicating the situation with dangerous esophageal
varices from the left gastric vein. In addition, pancytopenia
accompanied by marked reduction of platelet cells was

EXPERIMENTAL AND THERAPEUTIC MEDICINE

observed as a result of spleen hyperfunction. Under suchcircumstances, any gastroenteritis is likely to bring bacteria
and toxic substances from the intestinal tract directly into thegeneral circulation system, which can lead to septicemia andencephalopathy from the translocated bacteria. On the otherhand, in cases where bacterial translocation is suspected andin cases where antibiotics are already being administered, thecausative bacteria are rarely detected.
In the course of our case, fever and abdominal pain, seen
as symptoms of gastroenteritis, evolved to develop neuro‑
logical speech disturbances with altered consciousness. An
emergency MRI then led to the diagnosis of MERS. The clin‑
ical course of MERS has been previously reported to include
a febrile state with alterations of speech and conscious‑
ness (13). These symptoms are considered part of febrilederilium (14). However, the fever in our patient was moreconsistent, one having an infectious origin due to its onset
timing and the results of the initial blood tests at hospitaliza‑
tion, which were consistent with a septicemia. The possibilityof disseminated intravascular coagulation (DIC) syndrome
was difficult to rule out in our patient due to the impossibilityof distinguishing it from the original low platelet counts andpancytopenia from the underlying spleen hyperactivity. The
treatment chosen for the patient included antibiotics andgamma globulin therapy and steroid pulses for MERS withsepsis and possible DIC syndrome. The diagnosis of MERS
was further confirmed by the fast improvement of splenialabnormalities on the MRI re‑examination after 2 days oftreatment. And the efficacy of the administered treatment
was clear with a complete resolution of the patient's symp‑
toms 3 days after treatment.
Bacterial translocation occurs when abnormal proliferationof intestinal bacteria coupled with impairment of the intes‑
tinal mucosa defense function leads to an extremely serious
systemic infection. In those instances, intestinal bacteria
penetrate the broken barrier of intestinal mucosal epithelium
and migrate to the whole body via blood and lymph flow. Suchcases generally ensue on fasting patients with acute gastro‑
enteritis or some kind of intestinal chronic disease that leads
to abnormally slow intestinal flow, accumulation of bacteria,
and altered defense function of the intestinal mucosa. In
our patient, portal hypertension and slowed intestinal tractmovements due to anesthesia probably led to edema of theintestinal mucosa and deterioration of the lymphatic vessel
flow, which together allowed the translocation of intestinalbacteria that ultimately reached the central nervous system.
Recent advances in the pathogenesis mechanisms of bacterialtranslocation point to the effects of direct invasion of bacte‑rial cells throughout the body as well as severe inflammatory
reactions caused by inflammatory cytokines released during
phagocytosis in the broken intestinal mucosa. As such, there
have been reports of MERS from bacteremia with toxic
shock syndrome (15), and MERS associated with acute focal
bacterial nephritis caused by Enterococcus faecalis related tomarked elevation of interleukin 6 (16). Our case of MERS isalso related to bacterial infection triggered by bacterial trans‑
location, which caused symptoms of bacteremia or sepsis andacute encephalopathy.
The clinical course of MERS varies among patients,
and a clear mechanism of onset has not yet been elucidated.

3

Nevertheless, it is interesting to note that severe bacterial
infections due to bacterial translocation may be at play inthe multiple cases of MERS in childhood associated withviral infections that run a clinical course similar to the one
described here. We believe that our report represents a modelcase of bacterial translocation leading to MERS.
Acknowledgements
Not applicable.
Funding
No funding was received.
Availability of data and materials
The datasets used and/or analyzed during the current study areavailable from the corresponding author on reasonable request.
Authors' contributions
GI, TY, JI, KOg, KOk and TT designed the study and drafted
the manuscript. GI, JI and SY collected the clinical andimaging data and analyzed the serological data. TY, Kog,
Kok and TT operated and collected surgical and anatomical
information of the patient. SY collected information on themedical history of the patient, interpreted blood test data anddecided the fluid therapy treatment. All authors have read andapproved the final manuscript.
Ethics approval and consent to participate
Regarding the publication of this case report, the patient's
parents consented in advance to the formal form preparedby the Ethics Organization Committee of Dokkyo Medical
University Hospital (Tochigi, Japan).
Patient consent for publication
Consent was obtained from the parents of the patient for publi‑
cation of data.
Competing interests
The authors declare that they have no competing interests.
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