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Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with Mycoplasma pneumoniae infection
© Yuan et al. 2016
Received: 9 December 2015
Accepted: 10 May 2016
Published: 26 May 2016
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by transient mild symptoms of encephalopathy and a reversible lesion in the splenium of the corpus callosum on magnetic resonance imaging (MRI). It is often triggered by infection. The common pathogens of MERS are viruses, especially influenza virus. However, Mycoplasma pneumoniae (M.pneumoniae) are relatively rare pathogens for MERS.
Here we report two paediatric cases of M.pneumoniae infection-induced MERS. The diagnosis of M.pneumoniae infection was established based on polymerase chain reaction (PCR) and specific serum antibodies (IgM). Both of the two patients presented with mild encephalopathy manifestations and recovered completely within a few days. The initial MRI showed a lesion in the central portion of the splenium of the corpus callosum, which completely resolved on the seventh and eighth day after admission for case 1 and case 2. Lumbar puncture was performed in both patients, which revealed no pleocytosis. In case 1, the patient had hyponatremia, peripheral facial nerve paralysis, and rash. To the best of our knowledge, it is the first MERS case associated with peripheral nerve damage. In case 2, interleukin-6(IL-6) was moderately increased in the cerebrospinal fluid (CSF). It suggested that IL-6 may play a role in the pathogenesis of M.pneumoniae-induced MERS.
Our study enriches the available information on the pathogens of MERS and provides valuable data for better understanding of this syndrome.
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome, which was first reported by Tada et al. in 2004  and further enriched by Takanashi et al . The most common clinical feature is a neurological dysfunction, including delirious behavior, consciousness disturbance, and seizures, all of which recover completely within 1 month . Typical magnetic resonance imaging (MRI) findings of MERS include damage to the splenium of the corpus callosum in the acute phase, and sometimes damage spread to the whole corpus callosum and adjacent white matter. The corpus callosum connects the two cerebral hemispheres, and the splenium is located in the corpus callosum backend. The high-signal lesions are typically symmetrical and notable without enhancement on T2- and diffusion-weighted sequences, especially on the diffusion-weighted sequence. Lesions on the MRI images often disappear in 1 week or a few weeks [1, 2].
MERS may affect adults and children. Its pathogenesis is not clear and often triggered by infection. The most common pathogen is influenza virus A and B, and others include rotavirus, measles virus, adenovirus, Streptococcus, and Escherichia coli . Mycoplasma pneumoniae (M.pneumoniae) infection-related MERS is rare [4–6], and MERS has not been previously mentioned in the literature among M.pneumoniae-related central nervous system (CNS) dysfunction . Here, we report 2 cases of M.pneumoniae infection-induced MERS to enrich the available information on the pathogens of MERS and the pathogenic spectrum of M.pneumoniae-related CNS dysfunction.
A 9-year-old male patient was admitted to the hospital because of fever for 2 days, and headache, vomiting, mouth drooping on the right side, and rash for 1 day. Physical examination showed a body temperature of 38.7 °C and otherwise normal vital signs. Red maculopapular rashes that faded under pressure were scattered all over the body. Neurological examination showed poor mental status and obvious lethargy. Cranial nerve examination revealed mouth drooping on the right side, incomplete eyelid closure and shallow nasolabial sulcus on the left side because of the left peripheral facial paralysis, which is known to be associated with M.pneumoniae infection. Meningeal irritation and bilateral Babinski’s signs were negative.
After admission, treatment included acyclovir (10 mg/kg 8 hourly) for herpes viruses infection before the M.pneumoniae infection was confirmed, mannitol (5 ml/kg 8 hourly) for reduction of intracranial pressure, dexamethasone(0.4 mg/kg/d) for reduction of facial nerve swelling, and methycobal (1000 mg/d) for facial nerve paralysis. After M.pneumoniae infection was confirmed, azithromycin (10 mg/kg/day) was administered for 5 days. The symptoms improved significantly. Two days after admission, the patient no longer had lethargy, headache, vomiting, and had normal body temperature. Four days after admission, the patient showed improvement in mouth drooping on the right side, incomplete eyelid closure, and stabilization of the rash. Seven days after admission, his serum sodium was 135 mmol/L and his EEG was normal. Re-examination of the cranial MRI, he had normal MRI signals in the corpus callosum (Fig. 1c, d). Ten days after admission, the patient was discharged with excellent mental status, no obvious mouth drooping, substantially restored ability to close the left eyelid, and no rash.
A 12-year-old male patient was admitted to the hospital because of fever for 6 days, and headache, dizziness, vomiting, and cough for 4 days. Physical examination showed a body temperature of 38 °C and otherwise normal vital signs. The breath sound in the right lower lung was low. Neurological examination showed poor mental status and obvious lethargy. Cranial nerve examination did not reveal abnormal findings. Meningeal irritation and bilateral Babinski’s signs were negative.
After admission, acyclovir (10 mg/kg 8 hourly) was used for herpes viruses infection. After M. pneumoniae infection was confirmed, azithromycin (10 mg/kg/day) was administered for 5 days. Mannitol (5 ml/kg 8 hourly) was used to decrease the intracranial pressure. Two days after admission, the patient showed an improvement in disturbed consciousness and reduced headaches, dizziness, and vomiting. Three days after admission, the patient had normal mental status, normal body temperature, and apparent cough relief. Eight days after admission, the patient was discharged with excellent mental status, no obvious cough, normal EEG findings, and no abnormal MRI signals in the corpus callosum (Fig. 2c, d).
MERS is characterized by acute mild symptoms of encephalopathy occurring during an acute inflammatory disease process. Brain MRIs show characteristic changes in the corpus callosum, and recovery occurs without special treatment. MERS is divided into type 1 (damage limited to the splenium of the corpus callosum on MR images) and type 2 (damage spread to the entire corpus callosum or adjacent white matter or both) . Type 1 MERS is more common.
Pathogens of MERS in the literature
No. of patients
Pathogens of MERS (no. of patients)
Hoshino et al. 
Influenza (53), rotavirus (18), mumps virus (6), HHV-6 (3), bacterial infection (5)
Unknown (22), influenza A/B (6/4), mumps virus (4), adenovirus (3), rotavirus (3), streptococcus (3), Escherichia coli (3)
Tada et al 
Unknown (10), influenza A (1), adenovirus (1), mumps virus (1), VZV virus (1)
Ka A et al. 
Unknown (3), influenza B (1), adenovirus (1), CMV virus (1), Salmonella (1)
Bulakbasi et al. 
Influenza A (5)
Ganapathy et al. 
Influenza B (2)
Takanashi et al. 
Kawasaki desease (4)
The pathogenesis of MERS remains unclear. Possible mechanisms include transient intramyelinic edema, interstitial axonal edema, and inflammatory infiltration due to a myelin specific neurotoxin released by the pathogen [1, 2, 11], thus resulting in the transiently reduced diffusion seen on MRI. Takanashi et al.  suggested that the process of MERS may involve hyponatremia. Hyponatremia reduces the intracellular osmotic pressure in the splenium of the corpus callosum to facilitate free water entry, leading to transient cerebral edema. In the present study, the early serum sodium level was 127 mmol/L in case 1 and normal in case 2. In addition, the serum sodium level in the case of type 2 MERS reported by Zhao et al.  was also within the normal range. It suggests the possible but not essential involvement of hyponatremia in the pathogenesis of M.pneumoniae-induced MERS. Some other investigators have suggested the involvement of cytokines. Mori et al.  found that the CSF level of IL-6 increased significantly in a child with rotavirus-related MERS, while serum level of interleukin-1β, IL-6, interleukin-8, and tumor necrosis factor-α also increased in MERS children with Kawasaki disease , suggesting that the pathogenesis of MERS may involve the activation of the immune system. In the present study, IL-6 was moderately increased in the CSF of patient 2, but was not assessed in the serum and CSF of patient 1. Accordingly, we speculate that IL-6 may be involved in M.pneumoniae-induced MERS, but verification of more cases is needed.
MERS, especially type 2 MERS, should be distinguished from other leukoencephalopathies such as acute disseminated encephalomyelitis (ADEM), reversible posterior leukoencephalopathy syndrome (RPLS), and hereditary leukoencephalopathy. In particular, ADEM has clinical manifestations similar to those of MERS during its early stage. However, their MRI findings are different. In ADEM, lesions are distributed asymmetrically and most obvious in the T2-weighted sequence; diffusion is not restricted; enhancement can be observed after use of contrast agents, and the corpus callosum is less likely involved. On the contrary, in MERS, the corpus callosum is often involved symmetrically; the white matter damage is also symmetrical, and diffusion is significantly restricted without enhancement . Through differential diagnosis, MERS can be diagnosed in a timely and precise manner to avoid overtreatment.
In conclusion, we reported two paediatric cases of type I MERS with coinciding M. pneumoniae detection. Our study enriches the available information on the pathogens of MERS and provides valuable data for better understanding of this syndrome. Recognizing this syndrome early in children can avoid overtreatment and provide reassurance about the good prognosis of the disease.
ADEM, acute disseminated encephalomyelitis; CNS, central nervous system; CSF, cerebrospinal fluid; EEG, electroencephalogram; IL-6, interleukin-6; MERS, clinically mild encephalitis/encephalopathy with a reversible splenial lesion; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; RPLS, reversible posterior leukoencephalopathy syndrome.
The authors would like to thank Mrs Yan Cheng for excellent technical support.
Availability of data and materials
All the data supporting our findings are contained within this article.
Gao F, Xia ZZ and Jiang PF contributed to the study design, and Yuan ZF drafted the manuscript. Yu YL, Xu L and Mao SS helped to draft the manuscript. Shen J helped to draft the manuscript and helped to treat the patients. All authors read and approved the final manuscript.
The authors declare no competing interests.
Both patients’ parents provided written informed consent for the publication of the case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
The study was conducted in accordance with Declaration of Helsinki and ethically approved by the Ethics Committee of the Children’s Hospital of Zhejiang University School of Medicine.
This study was supported from the Grants of the Natural Science Fundation of Zhejiang Province (LY14H090007), the Zhejiang Health Bureau Fund (2014KYA126) and the Population and Family planning fund of Zhejiang Province (2014kyb335).
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