Case study
Mild encephalopathy with reversible splenial lesion: An important differential of encephalitis

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Abstract

Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by a transient mild encephalopathy and a reversible lesion in the splenium of the corpus callosum on MRI. This syndrome has almost universally been described in children from Japan and East Asia. Here we describe seven cases of MERS occurring in Caucasian Australian children from one centre seen over a 3 year period. All patients had a fever-associated encephalopathy (n = 7), which presented with confusion (n = 4), irritability (n = 3), lethargy (n = 3), slurred speech (n = 3), drowsiness (n = 2) and hallucinations (n = 2). Other neurological symptoms included ataxia (n = 5) and seizures (n = 1). These symptoms resolved rapidly over 4–6 days followed by complete neurological recovery. In all patients, MRI performed within 1–3 days of onset of encephalopathy demonstrated a symmetrical diffusion-restricted lesion in the splenium of the corpus callosum. Three patients had additional lesions involving other parts of the corpus callosum and adjacent periventricular white matter. These same three patients had mild persisting white matter changes evident at followup MRI, while the other patients had complete resolution of radiological changes. A potential trigger was present in five of the seven cases: Kawasaki disease, Salmonella, cytomegalovirus, influenza B and adenovirus (all n = 1). Elevated white cell count (n = 4), elevated C reactive protein (n = 5) and hyponatremia (n = 6) were commonly observed. CSF was performed in four patients, which showed no pleocytosis. This case series of MERS demonstrates this condition occurs outside of East Asia and is an important differential to consider in children presenting with acute encephalopathy.

Introduction

Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome which was first proposed by Tada et al.1 in 2004 and further expanded by Takanashi et al.2 It is typically characterized by a prodromal illness consisting of fever, cough, vomiting or diarrhoea, followed 1–7 days later by encephalopathy. Common neurological symptoms include behavioural change, altered consciousness and seizures.2 These symptoms resolve rapidly over days without treatment and there is typically complete neurological recovery. Magnetic resonance imaging (MRI) during the acute episode reveals a lesion in the splenium of the corpus callosum, sometimes also extending to other areas of the corpus callosum and adjacent parenchymal white matter. The lesions are typically symmetrical and show T2 hyperintensity with corresponding diffusion restriction and no contrast enhancement. These changes resolve completely or near completely on follow up imaging within days to weeks.1, 2

The underlying pathogenesis of MERS is unknown. Takanashi et al. proposed an infectious trigger in their case series of 54 Japanese patients with MERS.2 A recent systematic review by Garcia-Monco et al. revealed multiple other potential causes of reversible splenial lesions, however infectious related MERS remains the most common cause of reversible splenial lesions in childhood.3

MERS is a condition that has largely been described in case reports and case series from East Asia and Japan. To our knowledge, there have been less than 10 published cases of MERS occurring children outside of Japan and East Asia.4, 5, 6, 7, 8 In this study, we describe the findings of seven Caucasian Australian children who presented with MERS over a 3 year time period, demonstrating this to be an important clinical entity outside of East Asia.

Section snippets

Methods

Patients with possible MERS were identified by reviewing the neurology departmental database of inpatient consultations and by directly contacting the neurologists at the Children's hospital at Westmead. We performed a full retrospective chart review of the patients referred for the study. We collected information about ethnicity, past medical history, clinical features, medications, treatment, investigations and outcome. We reviewed all neuro-imaging in conjunction with the paediatric

Results

Seven patients presenting over a 3-year period (2010–2013) were included. All patients were Caucasian with median age of five years (range 3–9). Three patients had a pre-existing medical problems (Table 1). The other children were previously well with normal neurodevelopment.

All seven patients had non-specific symptoms of acute infection prior to encephalopathy onset: fever (n = 7), vomiting (n = 5), cough/coryza (n = 4), abdominal pain (n = 2), headache (n = 2) and diarrhoea (n = 1). One child

Discussion

We report seven cases of MERS in Caucasian Australian children to emphasise the existence of this syndrome outside of East Asia, and increase awareness of this clinical entity as a diagnosis to consider in a child presenting with acute encephalopathy. The clinical findings of our patients were similar to previously reported MERS patients, except that seizures only occurred in one of the seven patients, whereas it has been reported to occur in 33% of a large case series of Japanese patients.2

Conflict of interest

No author reports a conflict of interest.

Acknowledgements

We would like to thank participants of the childhood encephalitis surveillance studies ongoing at the Children's Hospital at Westmead.

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