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Abstract
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicoradiologic syndrome diagnosed by temporary hyperintense lesion in the area, including the splenium of the corpus callosum, on diffusion-weighted imaging and neuropsychiatric symptoms that recover without sequelae. MERS is rare in adults, especially elderly people. We herein report a man in his 60s diagnosed with MERS caused by Legionella pneumonia. He completely recovered with only the administration of levofloxacin and azithromycin despite the risk factors of an advanced age, medical history of untreated hypertension, bilateral spontaneous pneumothoraxes, smoking and drinking habits and pulmonary emphysema. To our knowledge, this is the oldest case of MERS due to Legionella pneumonia and extremely old among total MERS cases. Our research revealed that Legionella species are the most common pathogens of adult-onset MERS, while viruses are the main causative factors in children. This case helps clarify the features of MERS in high-risk adults.
- Infection (neurology)
- Pneumonia (infectious disease)
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Background
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicoradiologic syndrome characterised by distinctive MRI findings and central nervus system manifestations with a good prognosis.1 2 The MRI finding of MERS is a reversible lesion with transiently reduced diffusion in the corpus callosum involving at least the splenium of the corpus callosum (SCC).1 Common neurological symptoms are delirious behaviour, consciousness disturbance and seizures,1 with headache, somnolence, ataxia, dysarthria and blurred vision also observed.3 Both SCC lesions on MRI and neuropsychiatric manifestations completely disappear typically within a month.1 2 MERS is predominantly caused by a viral infection and is mainly seen in children,1 2 with adult-onset MERS cases being relatively uncommon and elderly-onset cases quite rare. The features of adult-onset MERS have barely been explored.
We here report a case of Legionella pneumonia-associated MERS in elderly man. In connection with this case, we discuss differences in the aetiology of MERS between children and adults and highlight interesting common features of MERS and Legionnaires’ disease that may help clarify the pathophysiology of both diseases.
There are no competing interests relevant to this report for any authors.
Case presentation
A man in his 60s visited our hospital because of a feeling of weakness in both lower limbs for the last 3 days. He had gone to a hot spring facility 5 days before the visit. His medical history was bilateral spontaneous pneumothoraxes and untreated hypertension. He did not have a family doctor and was on no other regular medications apart from vitamin tablets. He was a current 40 pack/year smoker and had an alcohol intake of 300 mL of shochu and 350 mL of beer daily.
He did not have a high fever, but our initial observation revealed a temperature of 39.1°C. Other vital signs were a blood pressure of 198/94 mm Hg, heart rate of 115 bpm, respiration rate of 22/min and oxygen saturation was 95% on room air. An ECG showed 109 bpm, unregular rhythm and atrial fibrillation. A neurological examination revealed mild disturbance of consciousness (Japan Coma Scale I-1, Glasgow Coma Scale E4V4M6), dysarthria, kinetic tremor in both hands and a gait disorder. His manner of speaking was slightly unsmooth. He demonstrated inattentiveness and was also slightly hyperactive. He was able to follow commands mostly, but delirious behaviour, such as removing his oxygen mask was observed. He did not show any response to specific stimuli.
Investigations
His blood test showed a severe inflammatory response, elevated liver enzymes, electrolyte abnormalities and CK 1551 IU/L. Legionella pneumophila (subtype 1) urinary antigen was positive (table 1). Meanwhile, sputum culture of Legionella pneumophila was negative.
Laboratory data on admission
Initial chest X-ray showed consolidation in the right lower lobe. Chest CT also showed consolidation in the right inferior lobe and pulmonary emphysema in both lungs (figure 1). Given these findings as well as the urinary positivity for Legionella pneumophila antigen, he was diagnosed with Legionella pneumonia and admitted. To examine his consciousness disorder, head CT and MRI were performed on the admission day. Head CT findings were normal. MRI of the brain revealed an abnormal hyperintensity in the SCC on diffusion-weighted imaging (DWI). The same area also showed slight hyperintensity on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) imaging. MR angiography did not show any obvious abnormality abnormalities (figure 2A–C). An apparent diffusion coefficient map was not performed. Patients with Legionnaires’ disease often present with a high fever, headache, altered mental status and leukocytosis. Once Legionnaires’ disease has been diagnosed, a cerebrospinal fluid (CSF) test is not very informative for the treatment, so we did not perform a CSF test. Electroencephalography was also unexamined.
Chest X-ray and chest CT on admission. (A) Chest X-ray. Consolidation in the right inferior lobe. (B) Chest CT. Consolidation in the right inferior lobe.
Head MRI on admission and day 21. (A–C) Head MRI on admission day. (A) DWI. Abnormal hyperintensity in the SCC. (B) T2WI. Mild hyperintensity in the SCC. (C) Fluid-attenuated inversion recovery (FLAIR). Mild hyperintensity in the SCC. (D–F) Head MRI on day 21. (D) DWI. Abnormal hyperintensity in the SCC disappeared. (E) T2WI. Hyperintensity in the SCC disappeared. (F) FLAIR. Hyperintensity in the SCC disappeared. SCC, splenium of the corpus callosum; T2WI, T2-weighted imaging.
Differential diagnosis
Cerebral infarction was excluded because both the clinical symptoms and abnormal hyperintense lesion in the SCC on DWI and T2WI disappeared 21 days after hospitalisation. In cases of cerebral infarctions, neurological symptoms usually persist to some extent, and T2WI normally shows hyperintension on day 21.
Brain tumour was excluded because the hyperintense lesion on head MRI completely disappeared.
Mycoplasma pneumonia can cause both pneumonia and MERS. However, L. pneumophila antigen was positive in the patient’s urine. His imaging and laboratory findings and history of visiting a hot spring profoundly indicated Legionella pneumonia.
Treatment
We administered 500 mg/day of levofloxacin from hospital days 1 to 8 and 500 mg/day of azithromycin from days 2 to 11. His neuropsychiatric symptoms had resolved on day 5. He recovered from Legionella pneumonia and discharged on day 13. Atrial fibrillation was temporary, so we did not administer anticoagulants.
Outcome and follow-up
Twenty-one days after admission, we performed follow-up MRI of the brain. The hyperintense lesion in the SCC had resolved on DWI, T2WI and FLAIR imaging (figure 2D–F). We then diagnosed him with MERS. No neurological abnormalities were observed for 6 months after discharge.
Discussion
We encountered a man in his 60s with MERS caused by Legionella pneumonia. The disease concept of MERS was first proposed by paediatricians in Japan.2 It mainly develops in children,1 2 where the main cause is viral, and its prognosis is good.1 2 4 We summarised the aetiology of child-onset MERS in several articles we found using the PubMed search engine (see: figure 3A and online supplemental table 1A).2–9
Supplemental material
Etiology of child-onset and adult-onset MERS. (A) Etiology of child-onset MERS.2–9 Number of patients: 248, age range: 0–18 years old. Details in online supplemental table 1A. Coinfection cases included. (B) Etiology of adult-onset MERS, including our case.3 7 9–16 Number of patients: 71, age range: 19–75 years old, Mean age: 38.7 years old. Details in online supplemental table 1B. These were drawn by SK. MERS, mild encephalitis/encephalopathy with a reversible splenial.
Adult-onset MERS, by contrast, is relatively rare, and its main pathogen remains unclear. We also summarised the aetiology of MERS in adults to compare the findings with those in children. In our research, 70 cases of MERS among adult males and females aged 19 and older were reported. Among the 71 cases of adults, including our present case, 27 (38.0%) were caused by bacteria, 16 (22.5%) were caused by viruses, 8 (11.3%) were caused by non-infectious sources and 20 (28.2%) were unidentified. Non-infectious sources include Anti-Yo rhombencephalitis, ipilimumab, C-section, tick-bites, amanita phalloides intoxication, haemolytic uraemic syndrome, acute urinary retention and new-onset refractory status epilepticus. The age range was 19–75 years old, and the mean age was 38.7 years old (see figure 3B and online supplemental table 1B).3 7 9–16
Accordingly, it is possible that adult-onset MERS is more likely to be triggered by bacteria than child-onset cases. Indeed, we found 16 cases of Legionella-associated MERS (mean age: 49.3 years old).3 7 10 11 In contrast, no child-onset MERS by Legionella species (spp) have been reported. Consequently, Legionella spp appear to be the most common pathogens of MERS in adults. Our case is the oldest one of Legionella-associated MERS and the third-oldest among all 71 total MERS cases we found in our research. The present patient completely recovered with only the administration of antibacterial drugs, despite his risk factors, including an elderly age, smoking history and emphysema. This suggests that MERS retains its reversible characteristic even in high-risk elderly people, so clinicians can select watchful waiting for neurological symptoms and SCC lesions on brain MRI in order to administer the most appropriate treatment for primary illness.
However, several MERS cases in adults were accompanied by severe disease, with intractable cases and one death reported.12 13 A man in his 70s who developed MERS due to COVID-19 died of respiratory failure despite the improvement of his neurological symptoms.13 While some adult cases match with MERS findings, there are some differences between adult and paediatric cases with respect to main causative agents, maturity of the brain, underlying health conditions, etc. It is thus possible that neurological abnormalities and hyperintense lesions in the SCC on DWI in mature adults and immature children have differing clinical significance.
Considering that bacteria are the main pathogens of MERS in adults, the imaging and clinical findings may reflect the severity of inflammation. It is difficult to distinguish whether or not the altered mental status is actually related to a brain pathophysiology that causes abnormal callosal signals or reflects a systemic cause of encephalopathy. Once again, it should be noted the fact that the main cause of adult MERS is Legionnaires’ disease, an extremely severe bacterial infectious disease with a death rate of 5%–10% overall and 40%–80% in untreated immunosuppressed patients.17 While the prognosis of MERS is considered to be good, we need to carefully treat the primary illness, manage the general condition and perform cautious observation for neuropsychiatric manifestations and MRI lesions to confirm that the condition is truly reversible. More cases should be gathered to clarify the details of adult-onset MERS, especially elderly cases cases.
Incidentally, the pathophysiology of MERS is unclear. Several mechanisms, such as intramyelinic oedema,2 inflammatory infiltrate,2 electrolyte abnormality18 and oxidative stress,19 have been suggested, but why lesions arise in the SCC remains unclear, especially since the symptoms of MERS, including delirious behaviour, consciousness disturbance and seizures, cannot be induced by impairment of the SCC.
Here, we considered about the developmental mechanism of neurological abnormalities of MERS and the common points with Legionnaires’ disease. Hyponatraemia is sometimes observed in both adult-onset and child-onset MERS cases.3 18 Hyponatraemia and neurological abnormalities, such as impaired consciousness, are common in Legionnaires’ disease too, although the mechanism remains unclear.20 21 In our case, both hyponatraemia and some neurological abnormalities, including disturbance of consciousness, were observed. Elevation of serum interleukin-6 (IL-6) levels was reported in several child-onset cases of MERS.3 IL-6 is considered to induce an increase in vasopressin secretion via a non-osmotic pathway and cause hyponatraemia.22 Lipopolysaccharides, components of the outer membrane of Gram-negative bacteria, including Legionella spp, induce IL-6 secretion.22 Only a few cases of MERS have been evaluated for IL-6, but considering the physiology, IL-6 may be increased in adult Legionella-associated MERS cases. We; therefore, hypothesise that IL-6-induced vasopressin secretion may be involved in the pathogenesis of both MERS and neurological abnormalities of Legionnaires’ disease. Further investigations are required to elucidate the details of adult-onset MERS and Legionnaires’ disease.
Patient’s perspective
I totally recovered. I am happy that I can enjoy my life healthily again.
Learning points
As described in this case report, a patient with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) caused by Legionella pneumonia recovered without sequel with only administration of antibacterial drugs, despite risk factors such as an elderly age, smoking history and emphysema.
Although MERS mainly develops in children, with the most common pathogens being viruses, adult-onset MERS tends to be caused by bacteria, and the most frequent pathogens are Legionella species.
When clinicians suspect MERS, the primary illness should be carefully treated, and watchful waiting for neurological symptoms and MRI findings can be practised.
As observed in this case, unexplained hyponatraemia and neuropsychiatric abnormalities are common symptoms in both MERS and Legionnaires’ disease, so interleukin-6-induced hyponatraemia may be related with both diseases.
Ethics statements
Patient consent for publication
References
Supplementary materials
Supplementary Data
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Footnotes
Contributors SK wrote the original draft of the manuscript. RH treated the patient, reviewed and edited the manuscript. HAU reviewed and edited the manuscript. All authors approved the final version of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.