Posterior reversible encephalopathy syndrome in adult acute post-streptococcal glomerulonephritis

Abstract

Posterior reversible encephalopathy syndrome is characterized by abnormal white matter findings and neurological symptoms. However, it is clinically rare and can easily be misdiagnosed. Herein, we describe a case of posterior reversible encephalopathy syndrome in an adult patient with acute post-streptococcal glomerulonephritis, confirmed by renal pathology and magnetic resonance imaging, and provide diagnostic suggestions for clinicians.

Introduction

The typical manifestations of acute glomerulonephritis caused by streptococcal infection are hematuria, proteinuria, hypertension, and edema. There are few reports of acute post-streptococcal glomerulonephritis (APSGN) also involving the central nervous system. Posterior reversable encephalopathy syndrome (PRES) is a rare manifestation.^1–3 It is a complex disease that is characterized by abnormal white matter findings and neurological symptoms such as headache, epilepsy, and visual, consciousness, and mental disorders. If diagnosed in time and treated appropriately, its clinical and imaging symptoms can be rapidly alleviated. Previous case reports of APSGN complicated with PRES have all occurred in children. ⁴ Moreover, such cases are not well-known by most clinicians and are easy to misdiagnose. Here, we report a case of PRES in an adult APSGN patient that was confirmed by pathology; this report will be a useful resource for recognizing this disease. The reporting of this study conforms to CARE guidelines (for CAse REports). ⁵

Case report

A previously healthy 22-year-old woman presented with oliguria and double lower limb edema for 5 days. She was admitted to West China Fourth Hospital of Sichuan University in October 2023. On admission, she denied any history of sore throat, cough, arthralgias, or skin disease. Physical examination revealed blood pressure of 126/76 mmHg, heart rate of 102 beats/minute, and respiratory rate of 22 breaths/minute. Both lower limbs displayed slight edema. Other physical examinations, including of the heart, lung, abdomen, and nervous system, were normal.

Laboratory tests results were as follows. Renal and hepatic evaluations showed increased blood urea nitrogen (14.2 mmol/L) and serum creatinine (187.7 µmol/L), decreased serum albumin (21.5 g/L), and normal electrolytes. Urinalysis revealed proteinuria +++, 70 white blood cells/high-power field, and 335 red blood cells/high-power field. A quantitative urine protein analysis demonstrated protein excretion of 2.68 g/24 hours. Furthermore, the following values were noted: hemoglobin 10.6 g/dL, hematocrit 35.8%, white blood cells 15.9 × 10⁹/L, platelets 77 × 10¹²/L, erythrocyte sedimentation rate 15 mm/hour, C-reactive protein 26 mg/L; complement component C3 < 0.0583 g/L (normal range 0.785–1.52 g/L), C4 0.101 g/L (normal range 0.145–0.36 g/L), antistreptolysin O titer 180 IU/mL (normal range 0–200 IU/mL). Immunochemical assays including anti-nuclear antibody, extractable nuclear antigen, anti-glomerular basement membrane antibodies, and anti-neutrophil cytoplasmic antibodies were negative. Renal ultrasound imaging showed renal parenchyma impairment.

Using the Kidney Disease: Improving Global Outcomes guidelines, the patient was classified as having acute kidney injury (stage 2). We obtained patient consent for treatment. She was treated with furosemide (20 mg/day); her urine increased continuously to more than 2000 mL/day in 4 days and her renal dysfunction improved. However, 5 days after admission, she developed headache, consciousness disturbance, and seizures that lasted for about 1 minute. Physical examination indicated blood pressure of 132/84 mmHg and pupils that were equal in size and reacted to light. Heart, lung, and abdominal examinations were normal. Her deep tendon reflexes were hyperactive; muscle strength of the left and right limbs was level IV to V. Hoffmann, Babinski, and meningeal irritation signs were negative. Because the patient recovered quickly without discomfort, no special treatment was administered. On day 12 after admission, similar symptoms occurred three times, each lasting 1 minute. After being treated with phenobarbital (100 mg three times/day), 20% mannitol (250 mL daily), and diazepam (10 mg daily) for 3 days, the symptoms were relieved and no recurrence was observed.

Cranial magnetic resonance imaging (MRI) was performed to investigate the neurological causes of seizures. The MRI findings revealed multiple edemas in the cortex and subcortical areas of the bilateral cerebral hemispheres, which was consistent with PRES (Figure 1). The patient also underwent renal biopsy to identify the cause of her kidney injury. Renal pathology demonstrated intracapillary proliferative glomerulonephritis with typical subepithelial depositions of hump-like immune complex (Figure 2). Optical microscopy showed the proliferation of endothelial cells and mesangial cells as well as the infiltration of neutrophils and monocytes. Immunofluorescence examination revealed the presence of C3 and immunoglobulin G in the “hump” and granular deposition along the capillaries. No cellular or fibrous crescents were observed.

Figure 1.

Magnetic resonance imaging findings showing multiple high signals (white arrows) in the cortex and subcortical areas of the bilateral cerebral hemispheres on fluid-attenuated inversion recovery images.

Figure 2.

Renal electron microscopic pathology showing a typical subepithelial deposition of hump-like immune complex (white arrow).

The patient was eventually diagnosed with APSGN in combination with PRES. On day 15 after admission, her treatment was discontinued because the neurological symptoms did not recur. On discharge, her renal function and C3 levels had returned to within normal ranges. At the 1-year follow-up, her renal function was completely normal and no neurological sequelae persisted. No markers of kidney damage, including proteinuria, albuminuria, or hematuria, were present during the follow-up.

Discussion

PRES was first described in 1996. ⁶ The most common clinical symptoms and signs include headache, confusion, vomiting, seizures, and visual disturbances. PRES is associated with renal diseases (APSGN, chronic renal failure, and kidney transplantation), pregnancy, eclampsia, immunosuppressive therapies (cyclosporine, tacrolimus, rapamycin, and rituximab), and autoimmune diseases (lupus nephritis, scleroderma, and anti-neutrophil cytoplasmic antibodies-related vasculitis). ⁷ APSGN in combination with PRES has been reported in children; however, no cases have previously been reported in adults, especially with pathologically confirmed APSGN. Our case seems to be the first to describe APSGN-induced PRES based on renal pathology.

There are two theories regarding the pathophysiology of PRES. The main theory involves hypertension and cerebral hyperperfusion caused by hypertension because most patients with PRES have elevated or fluctuating blood pressure at onset. However, approximately 15% to 20% of patients with PRES have normal or low blood pressure.^8–10 The second theory involves endothelial dysfunction caused by circulating endogenous or exogenous toxins. ¹¹ In the present case, no abnormal blood pressure was noted during the entire disease course. In view of our patient's low complement levels and hypoproteinemia, we inquired about her medical history in detail. The patient recalled that she had experienced a skin infection that manifested as the peeling of multiple toes with interphalangeal exudation 1 month earlier; the infection recovered without any treatment after several days. However, renal pathology, clinical manifestations, and laboratory examinations strongly suggested that the patient was infected with streptococcus. Our finding that the patient had an infection but no hypertension before PRES onset suggests that endothelial injury is indeed an important inducing factor of PRES.

APSGN comprises a wide spectrum of etiologies. Addressing the relationship between skin infections and kidney injuries is a key challenge. As much as possible, clinicians should look for evidence of infection during the diagnosis and treatment of APSGN. Interestingly, APSGN and hemolytic uremic syndrome (another disease with kidney damage) have three shared features: streptococcal infection, kidney injury, and PRES.^12,13 Streptococcus may destroy target tissues by producing a large number of toxins or stimulating the host to produce antibodies. Moreover, it has been reported that streptococcus may directly invade the blood–brain barrier or adhere to endothelial cells attacking cerebral microcirculation.^14,15 Evidence from previous reports and the present case therefore supports the theory that streptococcal infection and endothelial cell injury can lead to PRES.

Generally speaking, clinicians rarely actively suspect PRES when encountering neurological symptoms such as epilepsy, meaning that radiological findings are of great diagnostic importance. When identified and treated in time, PRES can be completely reversed. Clinicians should therefore improve their understanding of PRES to avoid misdiagnosis and mistreatment. Findings from our case suggest that MRI examination should be strongly recommended to check for PRES in patients with renal damage, regardless of whether blood pressure is high.