Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with febrile urinary tract infection
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- Okamoto, T., Sato, Y., Yamazaki, T. et al. Eur J Pediatr (2014) 173: 533. doi:10.1007/s00431-013-2199-9
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Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc-dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2-weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection. Conclusion: In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered.
KeywordsBacteriaFebrile urinary tract infectionMERSPyelonephritisSystemic lupus erythematosus
List of abbreviations
clinically mild encephalitis/encephalopathy with a reversible splenial lesion
magnetic resonance imaging
systemic lupus erythematosus
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is characterized by magnetic resonance imaging (MRI) of a reversible isolated lesion with transiently reduced diffusion in the splenium of the corpus callosum . The most common clinical manifestation is a neurological disorder, such as delirious behavior, consciousness disturbance, and seizures. Most patients with MERS clinically recover completely within 1 month . Influenza virus types A and B are the most common pathogens of MERS. However, bacterial infection has also been reported as pathogens in a few patients with MERS and not in patients with other classifications of acute encephalopathy, such as acute necrotizing encephalopathy and acute encephalopathy with biphasic seizures and late reduced diffusion . We report here the first patient with MERS associated with febrile urinary tract infection.
A 15-year-old Japanese girl was admitted to the hospital with severe periorbital and pedal edema. She also had a butterfly shadow, oral ulcer, and joint pain. A peripheral blood examination showed thrombocytopenia (platelets, 66 × 109/l), hypoproteinemia (serum total protein, 33 g/l), hypoalbuminemia (serum albumin, 6 g/l), and hypercholesterolemia (total cholesterol, 13 mmol/l). Her serum creatinine level was normal (41.5 μmol/l). Immunological studies were positive for anti-nuclear antibody with a titer of 1:640 in a peripheral pattern, anti-smooth muscle antibody of 0.22 U/l (normal range, 0.0–0.0059 U/l), anti-U1 ribonucleic protein antibody of 0.15 U/l (normal range, 0.0–0.012 U/l), and anti-single-stranded DNA antibody of 0.035 U/l (normal range, 0–0.025 U/l). Serum complement levels were low, with C3 of 0.49 g/l (normal range, 0.86–1.6 g/l), C4 of 0.1 g/l (normal range, 0.17–0.45 g/l), and CH50 of 22.3 kU/l (normal range, 31.5–48.4 kU/l). Sediment contained 20–29 red blood cells and cellular casts per high-power field, and urinalysis showed proteinuria at a concentration of 34,010 g/l and urinary protein to creatinine ratio of 27 g/gCr. Based on these findings, she was diagnosed with systemic lupus erythematosus (SLE) with nephrotic syndrome. Renal biopsy findings showed a minor glomerular abnormality under light microscopy. By immunofluorescence study, granular depositions of IgG and C3 along the peripheral capillaries were observed, and electron microscopy showed subepithelial deposits. With prednisolone and tacrolimus, she achieved complete remission after 8 months.
At the age of 17 years, the patient has not had recurrence of MERS with sustained remission of lupus.
Pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in the literature
No. of patients
Pathogens of MERS in the literature (no. of patients)
Hoshino et al. 
Influenza (53), rotavirus (18), mumps virus (6), HHV-6 (3), bacterial infection (5)
Takanashi et al. 
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)
Bulakbasi et al. 
Influenza A (5)
Ganapathy et al. 
Influenza B (2)
Takanashi et al. 
Kawasaki disease (4)
About the pathogenesis of MERS, there are several hypotheses such as intramyelinic edema, hyponatremia, axonal damage, and oxidative stress [6, 8, 10, 12]. However, the exact reason for the development of MERS in patients with bacterial infection, as well as our patient, is unknown. Serum proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, and tumor necrosis factor-alpha are elevated in patients with acute pyelonephritis [4, 9], and Kawasaki disease, by which MERS is also complicated . Therefore, activation of the immune system is likely to be associated with the pathogenesis of MERS. Although our patient did not appear to have flaring of lupus, lupus was possibly associated with the pathogenesis of MERS in our patient because the pathogenesis of SLE also appears to be associated with activation of the immune system and oxidative stress [2, 14].
Because of the prolonged headaches, nausea, and vomiting, further examinations were carried out following detection of MERS in our patient. In patients with acute pyelonephritis, clinical findings included varied gastrointestinal signs and symptoms, such as diarrhea, vomiting, and nausea . Furthermore, neurological manifestations, such as irritability and seizures, are also possible clinical findings in pyelonephritis . Therefore, at the onset, it is difficult to determine whether there are typical clinical findings in pyelonephritis or complications of MERS in patients with pyelonephritis. However, if gastrointestinal and neurological features are prolonged after improving pyelonephritis, clinicians should consider the possibility of MERS.
We would like to thank Dr. Kohsuke Kudo and Dr. Hideaki Shiraishi for their contribution to diagnosis and management of our patient.
Conflict of interest
The authors declare no conflict of interest.
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