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BMC Neurology

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Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) in adults-a case report and literature review

  • Junliang Yuan1,
  • Shuna Yang1,
  • Shuangkun Wang2,
  • Wei Qin1,
  • Lei Yang1 and
  • Wenli Hu1Email author
Contributed equally
BMC NeurologyBMC series – open, inclusive and trusted201717:103

https://doi.org/10.1186/s12883-017-0875-5

Received: 3 August 2016

Accepted: 9 May 2017

Published: 25 May 2017

Abstract

Background

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinico-radiological entity characterized by the magnetic resonance imaging (MRI) finding of a reversible lesion in the corpus callosum, sometimes involved the symmetrical white matters. Many cases of child-onset MERS with various causes have been reported. However, adult-onset MERS is relatively rare. The clinical characteristics and pathophysiologiccal mechanisms of adult-onset MERS are not well understood. We reviewed the literature on adult-onset MERS in order to describe the characteristics of MERS in adults and to provide experiences for clinician.

Methods

We reported a case of adult-onset MERS with acute urinary retension and performed literature search from PubMed and web of science databases to identify other adult-onset MERS reports from Januarary 2004 to March 2016. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then we summarized the clinico-radiological features of adult-onset MERS.

Results

Twenty-nine adult-onset MERS cases were reviewed from available literature including the case we have. 86.2% of the cases (25/29) were reported in Asia, especially in Japan. Ages varied between 18 and 59 years old with a 12:17 female-to-male ratio. The major cause was infection by virus or bacteria. Fever and headache were the most common clinical manifestation, and acute urinary retention was observed in 6 patients. All patients recovered completely within a month.

Conclusion

Adult-onset MERS is an entity with a broad clinico-radiological spectrum because of the various diseases and conditions. There are similar characteristics between MERS in adults and children, also some differences.

Keywords

Mild encephalitis/encephalopathy with reversible splenial lesionAdult-onset MERSEncephalitisEncephalopathyCorpus callosumReversible plenial lesion

Background

Tada et al. first identified the concept of mild encephalitis/encephalopathy with reversible splenial lesion (MERS) as a rare clinico-radiological syndrome in 2004 [1, 2]. In general, patients with MERS presented with mild central nervous system symptoms such as consciousness disturbance, seizures and headache and recovered completely within a month [1, 3]. MERS is divided into two types according to the lesion location. MERS type I, the typical form, most involves a singular lesion in the midline of the splenium of the corpus callosum (SCC), while MERS type II most commonly presents lesions in the symmetrical cerebral white matter or the anterior aspect of the corpus callosum with similar signal manifestations [4, 5]. The typical magnetic resonance imaging (MRI) features are transient high-signal-intensity on T2-weighted images (T2WI), fluid-attenuated inversion recovery images (FLAIR), and diffusion-weighted images (DWI), decreased apparent diffusion coefficient (ADC) value of the lesion on ADC maps, and hyper-isointense signals on T1-weighted imaging (T1WI) sequences without contrast enhancement [1, 4, 6]. Previous studies have identified that MERS can be triggered by infection including influenza virus [7], rotavirus [8], mumps virus [9], Mycoplasma pneumoniae [10] or Legionella pneumophila [11]. In addition to infection, MERS has also been reported to be associated with the administration of antiepileptic drugs [1214].

Many child-onset MERS cases have been reported, most in Asia, especially Japan [1, 15]. However, adult-onset MERS is relatively rare. Here we reported a case of adult-onset MERS with acute urinary retention. It has been speculated that the characteristics of MERS in adults are different from that in children. So we utilized this opportunity to review the literature on adult-onset MERS in order to describe the clinico-radiological features and establish a clinical position of the disease.

Methods

Case presentation

A previously healthy 37-year-old man was admitted to our hospital due to a 9-day history of headache and vomiting. Ten days prior to admission, he suddenly developed a fever of 40 °C, diarrhea and headache. After taking oral antipyretics, he still had a fever of 38–39 °C. Three days before admission, his body temperature returned to normal. Two days before admission, he suffered acute urinary retention and was treated by temporary transurethral catheterization at another hospital. One day before admission, he came to our hospital for acute urinary retention and the catheter was kept. Neurological examination revealed nuchal rigidity positive. Chemistry panel and urine analysis showed no abnormalities except for an elevated blood white cell counts (10.99 × 109/L), C-reactive protein level (9.41 mg/L) and decreased serum sodium (131.8mml/L). Routine immunological screening and tumor markers were negative. Lumbar puncture showed an elevated cerebrospinal fluid (CSF) pressure of 190mmH2O. CSF examination demonstrated an increase in white blood cells (97/ul) and protein content (124 mg/dl). The CSF etiological examination was negative. Oligoclonal bands, IgG index and myelin basic protein were within the normal ranges in CSF. Paraneoplastic antibodies were negative. Cranial MRI scans taken on the day after admission showed abnormal signals in SCC, which was hyperintense on T2WI and DWI imaging, decreased on ADC, isointense on T1WI with no contrast enhancement (Fig. 1). The plain and enhancement spinal cord MRI showed no obvious abnormalities. He received intracranial pressure reduction, antiviral, anti-inflammatory and experimental anti-tuberculosis. His urinary retention and fever resolved within 10 days. The follow-up MRI scan taken 14 days after the initial examination showed previous lesion disappeared (Fig. 2). He was discharged home without neurological complications. The final diagnosis was MERS with acute urinary retention.
Fig. 1

Initial cranial MRI of the patient. The lesion in the midline of SCC was hyperintensity on DWI (a) and T2WI (c), decreased ADC value (b), isointense signals on T1WI (d), and no contrast enhancement (e)

Fig. 2

Follow up cranial MRI. The follow up cranial MRI showed no lesion on any sequence (a: DWI, b: ADC, c: T2WI)

Literature search and selection

To better understand the characteristics of adult-onset MERS, we performed a literature search to identify other reports (reviews, case reports or case series) from Januarary 2004 to March 2016, using the PubMed and web of science databases with the following terms, ‘mild encephalitis/encephalopathy with reversible splenial lesion’/‘MERS’/‘reversible splenial lesion’. All pertinent English language articles were retrieved. A hand-search by reviewing the reference sections of the retrieved articles was also performed. The non-English language articles, child-onset MERS reports and not getting full-text articles were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline on selection process.

Data extraction

Two investigators collected data from the selected articles. The following information were extracted: last name of the first author, country where the study was performed, the reported patient’s age, gender, CNS symptoms, neurological examination, etiology, auxiliary examination, therapy and outcome.

Results of literature review

A total of 435 articles between Januarary 2004 and March 2016 were identified by preliminary electronic literature search and hand search. The selection process was presented in Fig. 3. The characteristics of the included cases were presented in Table 1 and Table 2.
Fig. 3

Flow diagram of studies selection process

Table 1

Information of 29 adult-onset MERS cases

Reported by, location, reference

Case no.

Sex, age (years)

symptomsis

Neurological examination

Etiology

Beijing Chaoyang Hospital, China

1

M, 37

Fever, UT

cervical rigidity (+)

NQ

Tada et al. [1] Japan

2

F, 59

Fever, vertigo, lethargy

NS

NQ

3

F, 18

Fever, seizure, delirium

NS

NQ

4

M, 19

Fever, cough, delirium, seizure

NS

NQ

5

F, 25

Fever, vesicular, headache, drowsiness, nausea

NS

VZV

6

M, 22

Fever, hallucination, delirium

NS

NQ

Jun-ichi et al. [22] Japan

7

M, 31

Headache, fever, drowsiness, disorientation, memory disturbance

drowsiness, disorientation, memory disturbance

NQ

Jeong-Seon et al. [6] Korea

8

M, 59

Dysarthria, drowsiness,fever

Normal

NQ

Nida Tascilar et al. [27] Turkey

9

F, 26

Fever, headache, phonophobia, photophobia, dizziness, UT

Neck stiffness (+), positive Kernig’s sign, right truncal and gait ataxia

NQ

Makiko et al. [28] Japan

10

F, 23

Fever, headache, UT

Unsteady gait, patellar tendon reflexes, plantar reflexes, abdominal wall reflexes diminished

NQ

Henning Vollmann et al. [29] Germany

11

M, 42

Fever, vomit, headache

Mild ataxia, disturbance of gait

Tick-bites

Dimitri Renard et al. [30] France

12

M, 43

Stuporous state

GCS E4M5V2, mutism, persistent hiccup

Anti-Yo rhombenceh- halitis

Shingo Mitraki et al. [31] Japan

13

M, 29

Consciousness disturbance

Drowsy, disoriented

pneumonia

Hideki Shibuya et al. [10] Japan

14

M, 30

Fever, consciousness disturbance

Glasgrow coma scale: E4V1M6

Mycoplasma- pneumoniae

Balasubramanyam Shankar et al. [32] India

15

F, 28

Fever, vomiting, paresthesia

Drowsy, neck rigidity, up going plantar reflex

NQ

Soon Young Ko et al. [33] Korea

16

M, 30

Fever, alalia

dysarthra

Nonfulminant hepatitis A

Makoto Hibino et al. [34] Japan

17

F, 24

Fever, diarrhea, abdominal pain, weakness of right upper extremity

Right-side hemiparesis, hemianesthesia, Chaddock (+)

adenovirus

Yuji Tomizawa et al. [11] Japan

18

M, 49

Fever, gait difficulty

Wide-based gait, fine postural tremors, mildly exaggerate deep tendon reflexes

Legionella pneumophila- serogroup 2

Robert M et al. [35] America

19

M, 41

Fever, headache, delirium, consciousness disturbance, tremor, gait instability, paresthesias, UT

Slow thought, mild difficulty finding words, intention tremor of the left arm, dysmetria of lower extremities, broad-based gait

ipilimumba

Jing Jing Pan et al. [36] China

20

F, 18

Fever

(−)

NQ

21

M, 26

Fever, acute UT

Nuchal rigidity (+)

NQ

22

F, 23

Fever, headache, disturbance of consciousness

Kerning (+)

C-section

23

M, 21

Fever, headache, acute UT, intestinal obstruction

Kerning (+)

NQ

Shuo Zhang et al. [37] China

24

F, 26

Headache, fever, seizure, somnolence

Somnolence

Mycoplasm-a

25

F, 34

Dizziness, fever, somnolence

Somnolence

Mumps virus

26

M,25

Headache, fever, cognitive impairment, behavioral disorders, confusion

Cognitive impairment, behavioral disorders, confusion

Herpes simplex virus

Eylem Degirmenci et al. [38] Turkey

27

M, 27

Headache, apathy, nausea, vomiting

Bilateral papilledema, mildly altered mental status

NQ

Naila Alakbarvova et al. [39] Turkey

28

M, 46

Headache, vomiting, nausea, diarrea, abdominal pain, generalized tonic-clonic seizure

Confusing with time disorientation

Amanita phalloides intoxication

Matthias Gawlitza et al. [40] Germany

29

F, 28

disorientated

Disorientated, confusion

Hemolytic uremic syndrome

M male, F female, UT urinary retention, NS no statement, NQ no required, VZV varicella zoster virus

Table 2

Auxiliary examination and treatment of 29 adult-onset MERS cases

Case no.

Initial examination

Treatment

WBC (109/L)

CRP (g/L)

Serum sodium (mmol/L)

CSF WBC (106/L)

MRI

EEG

1

10.99

9.41

131.8 (hyponatremia)

97

SCC

NE

mannitol, low dose methylprednisolone, ACV, anti-tuberculosis

2

NS

NS

NS

500

SCC

Slow BA

ACV, antibiotics

3

NS

NS

NS

17

SCC

Slow BA and spikes

PB, PSL

4

NS

NS

NS

Normal

SCC

Slow BA

ACV, PHT, PSL

5

NS

NS

NS

NE

SCC

NE

ACV

6

NS

NS

NS

Normal

SCC

Slow BA

ACV, antibiotics, PSL

7

18.8

17.0

NS

253

Entire CC and peripheral WM

NS

antibiotics

8

normal

normal

normal

normal

SCC and frontal WM

NS

No specific therapy

9

normal

normal

normal

408

SCC

normal

Ceftriaxone, ACV, ampicillin, catheterization

10

normal

normal

normal

normal

SCC, WM

NS

Methylprednisolone pulse, PSL, catheterization

11

NS

normal

132 (hyponatremia)

33

SCC

NS

Ceftriaxone, ACV, symptomatic therapy of headache and fever

12

NS

normal

133 (hyponatremia)

6

SCC, frontoparie-tal WM, putamina, thalami

Diffuse slowing wave

Antiepileptic treatment, methylprednisolone pulse, immunoglobulin treatment

13

elevated

elevated

NS

normal

Entire CC

NS

methylprednisolone pulse, immunoglobulin treatment

14

NS

NS

NS

NS

SCC

NS

Levofloxacin

15

NS

NS

NS

60

SCC, bilateral WM

Slow activity, frontal sharp wave

Empirical corticosteroids and ACV

16

3.48

NS

138

NS

SCC

abnormal

hemodialysis

17

normal

12.21

normal

NE

SCC

NS

No specific therapy

18

elevated

22.9

130

3

SCC

NS

Antibiotics

19

normal

normal

normal

128

SCC

NS

oral PSL and methylprednisolone pulse

20

6.08

normal

137.0

90

SCC

abnormal

methylprednisolone pulse, oral PSL

21

7.10

normal

130.2

100

SCC, insula, caudate nucleus

abnormal

Oral methylprednisolone and PSL

22

11.20

normal

138.6

12

SCC

abnormal

Oral methylprednisolone and PSL

23

8.20

normal

126.5

80

SCC

abnormal

Oral PSL

24

NS

NS

NS

3

SCC

Occipital slow waves

Mannitol, diazepam, macrolides antibiotics and moxifloxacin

25

NS

NS

NS

7

SCC

Occipital slow waves

Interferon, ribavirin

26

NS

NS

NS

112

SCC

Occipital slow waves

Ganciclovir, mannitol, antibiotics

27

normal

normal

normal

150

SCC

NS

Acetazolamide, antibiotics, oseltamivir

28

17.8

NQ

normal

normal

SCC

NS

Risperidone, clozapine, venlafaxine and diazepam, antipsychotic and intoxication treatment

29

NS

NS

NS

NS

SCC

NS

eculizumab

WBC white blood cell, CRP C-reactive protein, CSF cerebrospinal fluid, EEG electroencephalography, NE no examined, NS no statement, BA basic activity, ACV acyclovir, PB Phenobarbital, PSL prednisolone, PHT phenytoin, WM white matters

Of the 29 adult-onset MERS patients, 11 were from Japan, 8 from China, 3 from Turkey, 2 from Germany, 2 from Korea, 1 from France, 1 from India and 1 from America. From a geographical point of view, 86.2% of the countries were in Asia (25/29), especially in Japan (11/29).

The age of onset varied between 18 and 59 years old, with an average of 31. Twelve patients were females (41.38%) with a 12:17 female-to-male ratio. Fifteen patients had identified causes, including 5 virus infections, 3 pneumoniae, and 1 mycoplasma infection. One patient developed MERS due to Amanita phalloides toxication, one because of tick-bites. One patient had emotional and behavioral changes presenting with auditory hallucinations within 10 days after C-section.

Fever had preceded or simultaneously presented with neurologic symptoms in 24 patients. Twelve patients complained of headache while having MERS, and disturbance of consciousness was observed in 15 cases. Seizure occurred in 4 cases, and acute urinary retention in 6 patients. 75.9% of the patients (22/29) had an isolated lesion in the splenium of the corpus callosum. Six patients had lesions in both splenium and extracallosal. One patient had lesions in the entire corpus callosum. Lumbar punctures were performed in 23 patients, 15 of which had elevated CSF WBCs. Sixteen patients had their serum sodium reported, 6 of which had decreased levels. EEG was performed in 23 patients, 14 of which were abnormal.

The patients were treated with antiviral therapy, antibiotics, corticosteroids, IVIG, intravenous osmotic diuretic and isotonic fluid. Thirteen patients received corticosteroids therapy, 5 of which received a methylprednisolone pulse therapy. No case resulted in neurological sequelae.

Discussion

We reported a previously healthy 37-year-old man who suffered MERS associated with acute urinary retention. A lesion in the SCC resulting in acute urinary retention has rarely been reported. We considered acute disseminated encephalomyelitis (ADEM) being the main differential diagnosis. In comparison with the lesions in MERS which show no contrast enhancement and usually disappear quickly [1], the corpus callosum lesions in ADEM are usually asymmetrical, contrast-enhancing, extend to the white matter and spinal cord [16], and resolve over weeks to months. Our patient’s cranial MRI showed an isolated abnormal signal in the SCC with no contrast enhancement. His spinal cord MRI showed no obvious abnormalities. The follow-up MRI scan revealed normalized findings within two weeks. So the patient was diagnosed as MERS instead of ADEM.

At first, a reversible isolated SCC lesion on MRI was diagnosed as MERS [1]. Recent studies suggested additional similar lesions in the cerebral white matter and anterior aspects of the corpus callosum in some encephalitis/encephalopathy patients should also been regarded as MERS (type 2 MERS) [4, 5]. Since the radiologic range of MERS had been expanded, patient no.7, 8, 10, 12, 15, 21 and 29 were included in the literature review.

Similar to child-onset MERS, most adult-onset MERS patients were also reported in Asia, including Japan, China and India. Interestingly, the majority cases were reported in recent five years. The phenomenon may be related to ethnics and social factors, as well as lack of diagnostic awareness and criteria before 2011. The common neurological manifestations of MERS in adult were headache and disturbance of consciousness. However, disturbance of consciousness and seizures were the most common neurological symptoms in children [15]. We suspect that it is related to children’s immature central nervous system and blood brain barrier.

The pathogenesis of MERS is still unknown. There are several hypotheses, including intramyelinic edema, axonal damage, hyponatemia, and oxidative stress [1, 17, 18]. High signal intensity on DWI and decreased ADC values of white matter have been observed in MERS. The possible explanation for this is intrmyelinic edema resulting from separation of myelin layers [19, 20] and local infiltration of inflammatory cells [1, 3]. In this review, we found that more than half (15/23) cases had elevated white cells in the CSF. A previous small sample study reported that patients with MERS has an elevated IL-6 and IL-10 levels in CSF, however, the sample is not enough for any conclusions to be drawn [17]. ADC may return to normal within a week if the intramyelinic edema or inflammatory infiltrate resolves quickly. Takanashi et al. [21] reported that most patients with MERS had mild hyponatremia with a mean serum sodium level (131.0 ± 4.1 mmol/L) lower than that of the healthy group. Our review revealed that 6/16 MERS patients had hyponatremia upon admission. All these indicate that hyponatremia might be a possible cause of MERS. Taken all together, MERS is a rare syndrome with unclear pathogenesis. None of the existing hypotheses explains why MERS specially involves the site splenium.

In any patients presenting with symptoms of encephalitis/encephalopathy who are found to have lesions in the white matter, ADEM should be included in the differentials [1, 4, 22, 23]. ADEM is a post-infectious inflammatory disorder which can present with seizures, focal neurological signs or altered mental status days to weeks after the presumed infections [24]. MRI with contrast shows various enhancements of the lesions in ADEM depending on the stages of the acuity [24]. Other differential diagnoses include posterior reversible encephalopathy syndrome (usually hypertension-related and has subcortical white matter lesion), multiple sclerosis (characteristic relapsing-remitting course), Marchiafava-Bignami disease (often seen in alcoholism), ischemia (usually irreversible and has vascular territory distributions), diffuse axonal injury (head trauma-related), lymphoma (positive contrast enhancement), and extrapontine myelinolysis (happens with electrolyte abnormality) [25].

Even though the evidence of methylprednisolone pulse therapy and IVIG’s efficacy on MERS is still lacking, they are recommended for patients with infectious encephalopathy regardless of the pathogen or clinicl-radiological syndromes [26]. In this review, only five MERS patients were treated with methylprednisolone pulse therapy and two with IVIG treatment. However, all patients without methylprednisolone pulse therapy or IVIG recovered clinically completely, which suggests that those treatments may not be necessary.

Conclusion

In conclusion, we reported a case of an adult-onset MERS with acute urinary retention. Taken together with the previously reported cases, we suggest that MERS in adults is an entity with a broad clinico-radiological spectrum and the prognosis is good. From a geographical point of view, most adult-onset MERS patients were also reported in Asia. The common neurological manifestations were headache and disturbance of consciousness. There are similar characteristics between MERS in adults and children, also some differences.

Abbreviations

ADC: 

Apparent diffusion coefficient

ADEM: 

Acute disseminated encephalomyelitis

CSF: 

Cerebrospinal fluid

EEG: 

Electroencephalogram

MERS: 

Mild encephalitis/encephalopathy with reversible splenial lesion

SCC: 

Splenium of the corpus callosum

Declarations

Acknowledgment

None.

Funding

This work is supported by National Natural Science Foundation of China (Grant No. 81271309) and Beijing Municipal Administration of Hospitals’ Youth Programme (QML20150303).

Availability of data and materials

The datasets supporting the conclusions of this article are included within the article.

Authors’ contributions

JLY provided the adult-onset MERS case. WLH conceived and designed the experiments. SNY performed the literature search and drafted the manuscript. SKW performed the studies selection process. WQ and LY collected data from the selected articles. All authors have read and approved the final manuscript to be published.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

The patient agreed his medical records, images to be published.

Ethics approval and consent to participate

This study has been approved by the Medical Ethical Research Committee of Beijing Chaoyang Hospital Affiliated to Capital Medical University. The patient gave consent to participate in this study.

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Authors’ Affiliations

(1)
Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University
(2)
Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University

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