Posterior reversible encephalopathy syndrome associated with Rickettsia conorii infection: a rare case report

Highlights

• •Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder characterized by headaches, seizures, and visual symptoms.
• •Rickettsia conorii is an infectious cause of PRES.
• •Rickettsial infections should be considered in atypical cases of PRES.
• •Intravenous ciprofloxacin may be an alternative when doxycycline cannot be administered.

Abstract

Objectives

Posterior reversible encephalopathy syndrome (PRES) is an uncommon but serious neurological complication characterized by headache, seizures, visual disturbances, and altered mental status, and associated with parieto-occipital vasogenic edema on neuroimaging. Rickettsial infections have rarely been reported as triggers of PRES.

Methods

In this report, we describe the case of a 26-year-old man with rickettsial infection in Iran who developed a diffuse petechial rash, acute kidney injury, recurrent seizures, and bilateral cortical blindness.

Results

Brain magnetic resonance imaging revealed extensive parieto-occipital hyperintensities consistent with PRES. An indirect immunofluorescence assay demonstrated a fourfold rise in immunoglobulin M titers against Rickettsia conorii from 1:24 to 1:96, confirming acute R. conorii infection.

Conclusion

This case highlights R. conorii as a rare infectious cause of PRES and underscores the importance of early recognition and empiric treatment in endemic settings.

Introduction

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological condition characterized by acute to subacute neurological disorders such as headache, seizures, altered consciousness, and visual disturbances. It is predominantly associated with posterior vasogenic edema on magnetic resonance imaging (MRI). The pathophysiological mechanisms of PRES involve disruption of the blood-brain barrier due to endothelial injury, autoregulation failure, and systemic inflammatory stress [1]. While this syndrome is classically linked to severe hypertension, eclampsia, and immunosuppressive therapy, it is increasingly being recognized that infectious and inflammatory triggers also play an important role [1,2].

Rickettsial infections are among the most important vector-borne diseases, causing a wide range of clinical symptoms and signs and posing a substantial public health concern. Among the various species of the Rickettsia genus, Rickettsia conorii (causative agent of Mediterranean spotted fever [MSF]) has the most extensive global distribution. MSF is a tick-borne disease that is mostly transmitted to humans by Rhipicephalus sanguineus sensu lato. It is endemic to parts of the Mediterranean Basin, the Middle East, and South Asia [3]. There has been a recent increase in the reported cases of MSF in Iran, particularly in the eastern and northeastern parts of Iran [4,5].

Patients with MSF usually present with fever, rash, and sometimes an eschar, potentially leading to multisystem involvement via widespread vasculitis [3]. Neurological complications of MSF observed in some patients include meningitis, encephalitis, acute disseminated encephalomyelitis, and cranial neuropathy [6]. PRES following rickettsiosis is extremely rare, with only one case reported in India that was associated with spotted fever group rickettsiosis [7].

We report a young man with serologically confirmed R. conorii infection who presented with meningoencephalitis, acute kidney injury, diffuse vasculitic rash, and cortical blindness, in whom MRI findings were consistent with PRES. This case expands the clinical spectrum of rickettsial infections and provides further insight into the pathogenetic link between rickettsial endothelial injury and PRES.

Case presentation

A 26-year-old previously healthy male conscript soldier (resident of Mashhad City in northeastern Iran) was admitted to a local hospital with a 5-day history of fever, chills, and progressive weakness. On examination, he was febrile and tachycardic with a diffuse petechial and vasculitic rash involving the trunk, abdomen, and back (Figure 1). Laboratory tests showed severe thrombocytopenia and markedly elevated serum creatinine levels, and despite repeated hemodialysis sessions, renal function continued to deteriorate. Therefore, the patient was referred to our tertiary care center and admitted to the nephrology ward.

Figure 1.

A diffuse petechial and vasculitic rash on the trunk, abdomen, and back of the patient.

During hospitalization, his condition worsened with recurrent generalized tonic–clonic seizures, bilateral visual loss, and decreased level of consciousness, necessitating transfer to the intensive care unit. He remained febrile and received empiric intravenous meropenem and vancomycin. Brain MRI revealed extensive bilateral parieto-occipital hyperintensities on T2-weighted and fluid-attenuated inversion recovery sequences, consistent with PRES (Figure 2). Cerebrospinal fluid analysis showed an aseptic meningitis profile with elevated protein levels, mild pleocytosis, and negative bacterial and viral cultures. Transthoracic echocardiography revealed an ejection fraction of 15%, suggestive of myocarditis.

Figure 2.

Brain magnetic resonance imaging findings in a patient with a hemorrhagic variant of posterior reversible encephalopathy syndrome. (a) Axial T2-weighted image showing extensive hyperintense vasogenic edema predominantly involving the subcortical white matter of the parieto-occipital regions, with relative sparing of the cortical ribbon. (b) Axial T2-weighted section at a lower level shows similar edema within the bilateral cerebellar hemispheres and brainstem (predominantly in the pons). (c) Sagittal T2-weighted image further highlighting posterior-predominant white matter edema extending into the cerebellum with no significant mass effect. (d) Axial gradient-recalled echo/susceptibility-weighted imaging sequence revealing multiple punctate hypointense foci suggestive of microhemorrhages, supporting a hemorrhagic pattern of posterior reversible encephalopathy syndrome.

Given the triad of fever, meningoencephalitis, and diffuse vasculitic rash with negative microbiological cultures, an infectious disease consultation was requested. Based on the MRI findings, epidemiological background, and exanthematous presentation, R. conorii infection was suspected. Blood samples were sent to the Research Centre for Emerging and Reemerging Infectious Diseases at the Pasteur Institute of Iran for molecular and serologic testing. Due to severe encephalopathy and inability to tolerate oral therapy, intravenous ciprofloxacin was initiated. Antiepileptic therapy, hemodialysis, and supportive management were continued, and dexamethasone was added to treat possible autoimmune vasculitis.

The initial indirect immunofluorescence assay (IFA) was positive for immunoglobulin M (IgM) antibodies (dilution of 1:24) against R. conorii. Molecular testing was negative for Rickettsia. The patient was transferred to the infectious disease ward. Over the subsequent days, his renal function normalized, his fever subsided, and his level of consciousness returned to baseline. The seizures did not recur, and his visual acuity progressively improved. After 2 weeks, repeat IFA demonstrated a fourfold rise in the IgM titer from a dilution of 1:24 to a dilution of 1:96, confirming acute R. conorii infection. Upon discharge, the patient was afebrile and neurologically intact and experienced full recovery of both visual and renal functions. A follow-up brain MRI performed 3 weeks after the initial study showed near-complete resolution of the edema with residual focal hemorrhagic transformation in the occipital lobe (Figure 3).

Figure 3.

Follow-up brain magnetic resonance imaging obtained 3 weeks after the initial study in the same patient. (a) Axial T2-weighted image showing near-complete resolution of previously extensive parieto-occipital white matter hyperintensities with a residual focal heterogeneous lesion in the left occipital lobe demonstrating mixed signal intensity suggestive of late subacute hemorrhage. (b) Corresponding axial T1-weighted image reveals a hyperintense component within the same occipital lesion, consistent with blood degradation products. (c) Sagittal T2-weighted image confirming the localized hemorrhagic cavity within the left occipital region with surrounding gliotic changes and no new areas of vasogenic edema.

Discussion

This case represents an exceptionally rare presentation of R. conorii infection manifesting as PRES. This syndrome is characterized by vasogenic edema caused by endothelial dysfunction and impaired cerebral blood flow regulation [6]. Rickettsiae are obligate intracellular organisms with endothelial cell tropism that cause inflammation, apoptosis, and microvascular injury [6,8]. The overlap in the pathogenic mechanisms between rickettsial vasculitis and PRES supports a possible causal link.

Neurological manifestations of rickettsioses are uncommon but may include meningoencephalitis, seizures, meningitis, encephalitis, acute disseminated encephalomyelitis, mental disturbance, myelitis, hallucinations, confusion, facial nerve palsy, cerebral infarction, and visual disturbances [6]. PRES has only been reported once in relation to spotted fever group rickettsiosis, but the species of Rickettsia was unknown, and treatment included doxycycline [7]. In our patient, R. conorii infection was serologically confirmed, with a fourfold increase in IFA IgM titers.

Doxycycline remains the treatment of choice for rickettsial infections. However, oral administration may not be feasible in patients with impaired consciousness or gastrointestinal dysfunction. In our patient, intravenous ciprofloxacin was administered because of altered mental status, which resulted in rapid clinical improvement. Although fluoroquinolones are not routinely recommended as first-line therapy, early reports demonstrated the successful use of ciprofloxacin in MSF [9]. Experimental studies have shown that ciprofloxacin exerts a deleterious effect on R. conorii-infected endothelial cells by up-regulating toxin–antitoxin modules, providing mechanistic support for its antimicrobial activity [10]. Our patient’s favorable response aligned with these observations, suggesting that fluoroquinolones may serve as effective alternatives when doxycycline is contraindicated or impractical.

This case reinforces the importance of considering rickettsial infections in patients with PRES who present with fever and vasculitis, particularly in endemic areas. Conversely, new-onset seizures, encephalopathy, or cortical blindness in rickettsial fever should prompt urgent neuroimaging to evaluate for PRES. Prompt initiation of effective empiric therapy while awaiting serologic confirmation remains essential, as delay in treatment is associated with increased morbidity.

Conclusion

Rickettsia conorii infection can rarely cause PRES via endothelial injury and systemic vasculitis. This report underscores the need for increased clinical suspicion of rickettsial etiologies in patients with atypical presentations of PRES. Intravenous ciprofloxacin may be a viable therapeutic option when standard doxycycline therapy cannot be administered.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval

The Research Ethics Committee of Mashhad University of Medical Sciences approved this case report (IR. MUMS. REC.1404.269). Informed consent was obtained from the patient, who signed the consent form. Consent was obtained from the patient for publication of all forms of personally identifiable data, including biomedical and clinical data and identifying information/images.

Data availability

Publicly available data have been included in this manuscript.

CRediT authorship contribution statement

Hamidreza Naderi: Writing – review & editing, Writing – original draft, Supervision, Investigation, Conceptualization. Alireza Sedaghat: Writing – review & editing, Investigation. AbouSaleh Sobhi: Writing – review & editing, Investigation. Mohammadreza Seyedzadeh: Writing – review & editing, Investigation. Hamidreza Mirzaei: Writing – review & editing, Investigation. Parsa Aryanpour: Writing – review & editing, Investigation. Saber Esmaeili: Writing – review & editing, Writing – original draft, Supervision, Methodology, Investigation, Conceptualization.

Declaration of competing interest

The authors have no competing interests to declare.