Recurrent acute focal bacterial nephritis presenting with meningitis-like symptoms and discordant occurrence of MERS in a late-adolescent male

Abstract

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is usually reported in children with viral infections; bacterial triggers such as acute focal bacterial nephritis (AFBN) are uncommon. We describe a physically mature 16-year-old male with two episodes of AFBN presenting with high fever, severe headache and meningeal signs but essentially normal cerebrospinal fluid (CSF) findings. During the first episode, brain magnetic resonance imaging (MRI) showed a type 1 splenial lesion consistent with MERS, and contrast-enhanced abdominal computed tomography (CT) demonstrated right-sided AFBN. Serum and CSF interleukin-6 (IL-6) were markedly elevated with mild hyponatremia. Symptoms resolved and the splenial lesion disappeared after intravenous ceftriaxone followed by oral antibiotics. Six weeks later, the patient developed recurrent AFBN in the same renal region with a similar clinical presentation and comparable elevations of serum and CSF IL-6; however, repeat brain MRI showed no splenial or other callosal lesions. He recovered fully after a prolonged six-week course of oral antibiotics. This two-episode observation expands the demographic spectrum of AFBN-associated MERS and suggests that IL-6 elevation alone may not be sufficient to induce a splenial lesion; additional transient susceptibility of the splenium and/or osmotic factors may be required.

Introduction

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by transient signal changes in the splenium of the corpus callosum (SCC) and usually favorable neurologic outcome [1]. It predominantly affects children and young adults, most often during viral infections such as influenza or rotavirus, or in association with Mycoplasma pneumoniae infection [2]. Typical manifestations include fever, seizures, impaired consciousness, and mild meningeal signs, whereas marked cerebrospinal fluid (CSF) pleocytosis or direct central nervous system (CNS) invasion are uncommon [1], [3].

Pro-inflammatory cytokines, particularly interleukin-6 (IL-6), together with hyponatremia, are thought to contribute to transient cytotoxic edema in the SCC in MERS and related encephalopathy syndromes [4], [5], [6]. Among bacterial infections, acute focal bacterial nephritis (AFBN) has been recognized as an emerging trigger of MERS, especially in young children, where high cytokine and chemokine levels in serum and CSF plus hyponatremia have been proposed as key pathogenic factors [4], [5], [7]. AFBN itself is a localized renal parenchymal infection that lies between acute pyelonephritis and renal abscess and is increasingly recognized as an under-diagnosed cause of prolonged febrile urinary tract infection in children [8]. In some AFBN cases, neurological manifestations, including seizures or meningitis-like symptoms, have been described together with reversible splenial lesions [4], [5], [7].

However, AFBN-associated MERS in physically mature adolescents is rare, and recurrent AFBN with meningitis-like presentation and discordant occurrence of MERS in the same individual has, to our knowledge, rarely been reported. Such a longitudinal two-episode course provides an opportunity to explore how systemic inflammatory signals, including IL-6, interact with transient CNS vulnerability and systemic water balance to generate or spare reversible splenial lesions within the broader spectrum of cytotoxic lesions of the corpus callosum (CLOCCs). Here, we describe a late-adolescent male with two AFBN episodes presenting with meningitis-like symptoms, in whom type 1 MERS occurred only during the first episode despite similarly elevated IL-6 levels in both serum and CSF in each episode.

Case

A previously healthy, physically mature 16-year-old Japanese male (height 175 cm, weight 75 kg) presented with several days of high-grade fever and throbbing headache. He had no significant past medical, family, or psychosocial history and was not taking any regular medications. On admission, he was alert and oriented but appeared mildly ill. Neurological examination revealed neck stiffness and painful limitation of neck flexion, without seizures, focal neurological deficits, or impaired consciousness, which raised suspicion of CNS infection and meningitis. He reported no urinary symptoms, abdominal pain, or flank pain at that time.

Initial laboratory tests showed leukocytosis with neutrophilia (white blood cell count 17,550/μL; neutrophils 87.7%) and elevated C-reactive protein (CRP 14.0 mg/dL). Serum sodium (Na) was mildly decreased (131.6 mmol/L), while serum potassium and glucose were within or only slightly below the reference ranges. CSF analysis was essentially normal, with a cell count of 2/μL, protein 33 mg/dL, and glucose 79 mg/dL. CSF cultures were negative. Serum IL-6 was markedly elevated at 120 pg/mL, and CSF IL-6 was also elevated at 77.6 pg/mL. Urinalysis revealed mild pyuria and bacteriuria despite the absence of urinary complaints. Key clinical, laboratory, cytokine, imaging, and microbiological findings from both episodes are summarized in Table 1.

Table 1.

Comparison of clinical, laboratory, cytokine, imaging, and microbiological findings between Episode 1 and Episode 2.

Category	Variable	Episode 1	Episode 2
Clinical findings	Fever	38–39 °C	38–39 °C
	Headache / Meningeal signs	Present	Present
	Neck stiffness	Positive	Positive
	Neck flexion test	Positive	Positive
	CVAT	Right-sided, positive	Right-sided, mild
Blood tests	WBC (/μL)	17,550	18,630
	Neutrophils (%)	87.7	92.4
	CRP (mg/dL)	14.0	15.0
	Sodium (mmol/L)	131.6	133.5
	Potassium (mmol/L)	3.1	2.9
	Glucose (mg/dL)	126	117
	Calculated serum osmolality (mOsm/kg)	274	277
CSF findings	Cell count (/μL)	2	2
	Protein (mg/dL)	33	30
	Glucose (mg/dL)	79	69
Cytokines	IL-6 (serum, pg/mL)	120	150
	IL-6 (CSF, pg/mL)	77.6	63.1
Imaging	Brain MRI	type 1 MERS (SCC lesion)	Normal (no SCC lesion)
	Abdominal CT	AFBN (right kidney)	Recurrent AFBN (same location)
Microbiology	Urine Gram stain	Gram-negative rods	Gram-negative rods
	Urine culture	Enterococcus spp. (+1), contaminant	E. coli (+3)
	Blood culture	Negative	Negative
	CSF culture	Negative	Negative
Treatment and outcome	IV antibiotics	Ceftriaxone (2 g/day x 7 days)	-
	Oral antibiotics	TMP-SMX x 7 days	Amoxicillin/Clavulanate (Augmentin) + Amoxicillin (Sawacillin), then de-escalated to Amoxicillin monotherapy
	Neurologic sequelae	None	None

Abbreviations: AFBN, acute focal bacterial nephritis; CVAT, costovertebral angle tenderness; CSF, cerebrospinal fluid; IL-6, interleukin-6; SCC, splenium of the corpus callosum; MRI, magnetic resonance imaging.

Calculated serum osmolality was derived as 2 x Na (mmol/L) + BUN (mg/dL)/2.8 + glucose (mg/dL)/18.

Brain magnetic resonance imaging (MRI) demonstrated a sharply demarcated hyperintense lesion confined to the splenium of the corpus callosum on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI), with corresponding hypointensity on apparent diffusion coefficient (ADC) mapping, consistent with type 1 MERS (Fig. 1A-C). To search for a systemic infectious focus, non-contrast abdominal computed tomography (CT) was performed and showed increased perinephric fat attenuation around the right kidney. Targeted re-examination then revealed clearly positive right-sided costovertebral angle tenderness (CVAT). Urine Gram stain demonstrated Gram-negative rods, whereas urine culture grew Enterococcus spp. (+1), which was interpreted as probable contamination given the Gram-stain findings, absence of urinary symptoms, and subsequent course. Contrast-enhanced CT on the following day demonstrated a poorly enhancing wedge-shaped lesion in the right renal parenchyma, confirming AFBN (Fig. 2B).

Fig. 1.

Brain MRI showing a reversible splenial lesion (white arrows), consistent with clinical recovery. At admission: (A) FLAIR and (B) diffusion-weighted imaging (DWI) demonstrate a hyperintense lesion in the splenium of the corpus callosum (white arrows). (C) Apparent diffusion coefficient (ADC) map reveals a corresponding hypointense signal, indicating cytotoxic edema. At follow-up: (D-F) The FLAIR, DWI, and ADC sequences show complete radiological resolution of the lesion (white arrows).

Fig. 2.

Coronal CT images demonstrating acute focal bacterial nephritis (AFBN) in Episode 1 and recurrent AFBN in Episode 2. (A) Non-contrast CT during Episode 1 showing right-sided perinephric fat stranding (arrow), suggestive of renal parenchymal inflammation. (B) Contrast-enhanced CT during Episode 1 demonstrating a poorly enhancing wedge-shaped lesion in the right renal parenchyma (arrow), consistent with AFBN. (C) Contrast-enhanced CT during Episode 2 showing a recurrent wedge-shaped hypoperfused lesion in the same location (arrow), consistent with recurrent AFBN.

The patient was treated with intravenous ceftriaxone (2 g/day) for 7 days, followed by oral trimethoprim-sulfamethoxazole (80/400 mg, two tablets twice daily) for 7 days. Fever, headache, and meningeal signs rapidly resolved without complications. Follow-up brain MRI performed two weeks after symptom onset demonstrated complete disappearance of the splenial lesion (Fig. 1D-F). He was discharged in good clinical condition without neurological sequelae.

Approximately six weeks after completing therapy, he re-presented with recurrent fever (38–39 °C) and headache. As in the first episode, he had neck stiffness, a positive neck-flexion test, and mild right-sided CVAT, but no confusion, seizures, or focal neurological deficits. Laboratory tests again showed leukocytosis (18,630/μL; neutrophils 92.4%) and elevated CRP (15.0 mg/dL). Serum sodium was at the lower end of normal (133.5 mmol/L). CSF findings remained essentially normal, with a cell count of 2/μL, protein 30 mg/dL, and glucose 69 mg/dL, and CSF cultures were negative. IL-6 levels were again markedly elevated in both serum (150 pg/mL) and CSF (63.1 pg/mL). In both episodes, nasopharyngeal tests for influenza A and B and for SARS-CoV-2 were negative, and there were no respiratory or gastrointestinal symptoms suggestive of a concurrent viral infection.

Abdominal contrast-enhanced CT revealed a recurrent wedge-shaped, poorly enhancing lesion in the same region of the right kidney, consistent with recurrent AFBN (Fig. 2C). Urine culture grew Escherichia coli (+3) with a fully susceptible antimicrobial profile, whereas blood and CSF cultures remained negative. Given his stable general condition, the second episode was treated with oral amoxicillin/clavulanate (Augmentin) plus amoxicillin (Sawacillin), followed by de-escalation to amoxicillin monotherapy after confirmation of susceptibilities. Oral antibiotic therapy was continued for a total of six weeks to ensure eradication of the recurrent focal renal infection. Brain MRI performed on the day of admission, one day after fever onset, was completely normal with no splenial or other callosal lesions. His fever and headaches resolved promptly without neurological deterioration, and he recovered fully with no residual neurological deficits or further recurrences during follow-up.

Discussion

MERS is characterized by transient, reversible signal abnormalities in the splenium of the corpus callosum, most often in children with viral infections, and type 1 lesions confined to the splenium generally have a benign clinical course [1], [2], [3]. AFBN, a localized renal infection between acute pyelonephritis and renal abscess, has more recently been recognized as a bacterial trigger of MERS, mainly in young children [4], [5], [7], [8]. In reported AFBN-associated MERS cases, patients typically present with fever and non-specific systemic symptoms, and a subset also show seizures, impaired consciousness, or meningitis-like signs together with splenial lesions [4], [5], [8]. Our case adds to this literature by documenting AFBN-associated type 1 MERS in a physically mature late-adolescent male, followed by a second episode of AFBN in the same renal region with similar meningitis-like symptoms but no evidence of MERS. This longitudinal two-episode course widens the demographic and clinical spectrum of AFBN-associated MERS and allows intra-individual comparison of factors that may precipitate or spare reversible splenial lesions.

Clinically, both episodes initially mimicked meningitis because of high fever, headache, and meningeal signs, yet CSF findings were essentially normal and CSF cultures remained negative in each episode. In the first episode, brain MRI disclosed a typical type 1 MERS lesion, prompting systematic evaluation for an extracranial infectious focus, and AFBN was identified on abdominal imaging despite the absence of overt urinary symptoms. In the second episode, the patient again had AFBN with fever and meningitis-like signs, but brain MRI was completely normal without splenial or other callosal lesions, and the episode was managed as AFBN-associated fever with meningitis-like features. This pattern indicates that AFBN in adolescents can present with meningitis-like symptoms, with or without concomitant MERS, and that AFBN explained the fever and meningitis-like manifestations in both episodes in this patient. Without brain MRI in the first episode, the reversible splenial lesion and its discordant behavior in the second episode would likely have remained unrecognized.

A notable feature of this case is the similarly marked elevation of IL-6 in both serum and CSF during the two AFBN episodes, despite MERS occurring only in the first. Cytokine and chemokine elevation, particularly IL-6, has been implicated in AFBN-associated MERS and related para-infectious encephalopathy syndromes [4], [5]. Previous reports have emphasized high IL-6 levels as a potential marker linking systemic infection to transient CNS dysfunction in this context [4], [5], [8]. IL-6 can act at the blood-brain barrier and at circumventricular organs, modulate astrocytic function, and promote endothelial activation and oxidative stress. In our patient, however, the discordant MRI outcomes despite comparable IL-6 elevations suggest that IL-6 largely reflected the burden of systemic bacterial infection and that an IL-6 surge alone was not sufficient to induce a splenial lesion. Rather, these paired episodes support a threshold-plus-susceptibility model in which MERS development depends not only on the intensity of systemic cytokine signalling but also on transient, episode-dependent vulnerability within the splenium. Such vulnerability could be shaped by short-lived changes in astrocytic excitability, microglial activation, or local perfusion that were present during the first episode but not during the second, although these possibilities remain speculative.

Systemic inflammatory cytokines such as IL-6 may also interact with whole-body water balance. IL-6 and other mediators can promote non-osmotic arginine vasopressin release, enhancing aquaporin-2 (AQP2)-mediated water reabsorption in the renal collecting ducts and predisposing to mild hypotonic hyponatremia. Even modest reductions in serum sodium in this setting may increase the osmotic drive for water entry into the brain. In the splenium, which is rich in aquaporin-4 (AQP4)-expressing astrocytic endfeet [6], [9], such conditions could facilitate transient cytotoxic edema in the presence of systemic inflammatory stress. Although we did not directly measure serum or urine osmolality or urinary sodium and cannot establish definite syndrome of inappropriate antidiuretic hormone secretion (SIADH), an IL-6-driven, SIADH-like milieu may have contributed to creating a vulnerable background for MERS during the first episode.

Reversible splenial lesions, including those seen in MERS, are increasingly conceptualized within the broader spectrum of cytotoxic lesions of the corpus callosum (CLOCCs) [9]. CLOCCs can occur in association with diverse systemic insults-such as infections, metabolic disturbances, antiepileptic drug withdrawal, and high-altitude exposure-through converging mechanisms that include cytokine-mediated endothelial dysfunction, blood-brain barrier disturbance, excitotoxicity, oxidative stress, and AQP4-dependent water shifts [6], [9]. Experimental data showing worse cytotoxic edema with AQP4 overexpression and improved outcome in AQP4-knockout mice after ischemia further support the idea that water channel regulation modulates this spectrum [10]. Within this framework, our case suggests that AFBN-associated MERS reflects a transient intersection of systemic inflammatory cytokines, including IL-6, and osmotic factors with a dynamically vulnerable splenium, rather than direct CNS infection or classic meningitis. The absence of CSF pleocytosis, normal CSF protein and glucose, and negative microbiological studies in both episodes reinforce a para-infectious, cytokine-mediated mechanism.

This report has several limitations. It describes a single patient, so unmeasured factors differing between episodes-such as subtle changes in blood pressure, hydration status, other cytokines, or the timing of imaging-cannot be excluded. IL-6 was measured only once per episode, and other potentially relevant mediators (e.g., TNF-α, IL-1β) and advanced CSF or permeability imaging studies were not obtained [5]. We also lacked detailed quantitative assessment of water balance disturbances, which would have allowed a more precise characterization of osmotic status. In addition, a comprehensive urological evaluation for vesicoureteral reflux or structural abnormalities was not performed, although no further recurrences have been observed to date. Larger series of AFBN-associated MERS and mechanistic studies will be needed to clarify how systemic cytokine profiles, osmotic status, and CNS susceptibility interact over time to determine whether a reversible splenial lesion emerges.

Conclusion

This case illustrates non-convulsive type 1 MERS associated with AFBN in a physically mature late-adolescent male, followed by a second AFBN episode with similar meningitis-like presentation and similarly elevated serum and CSF IL-6 levels but no radiologic evidence of MERS. The paired episodes suggest that IL-6 elevation largely reflected systemic bacterial infection and that MERS emerged only when inflammatory stress coincided with transient, episode-dependent splenial susceptibility within the broader CLOCCs spectrum, potentially influenced by water-balance factors. Clinically, AFBN accounted for the fever and meningitis-like symptoms during both episodes in this patient, whereas a reversible splenial lesion was present only in the first episode and would likely have remained undetected without brain MRI. AFBN in adolescents may therefore occasionally present with meningitis-like features, with or without concomitant MERS, and recognition of this association may help to contextualize similar cases in which neuro-meningeal symptoms accompany renal parenchymal infection.

List of abbreviations

AFBN: Acute focal bacterial nephritis

ADC: Apparent diffusion coefficient

AQP2: Aquaporin-2

AQP4: Aquaporin-4

CLOCCs: Cytotoxic lesions of the corpus callosum

CSF: Cerebrospinal fluid

CVAT: Costovertebral angle tenderness

DWI: Diffusion-weighted imaging

FLAIR: Fluid-attenuated inversion recovery

IL-6: Interleukin-6

MERS: Mild encephalitis/encephalopathy with a reversible splenial lesion

MRI: Magnetic resonance imaging

SCC: Splenium of the corpus callosum

SIADH: Syndrome of inappropriate antidiuretic hormone secretion

CRediT authorship contribution statement

Kazuki Ocho: Investigation, Writing – review & editing. Tsutomu Ishikawa: Investigation, Writing – review & editing. ISHIKAWA HISASHI: Conceptualization, Investigation, Supervision, Writing – original draft, Writing – review & editing.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

Ethical approval was not required for this case report according to institutional policy.

Sources of funding

This research received no specific grant from any funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.