Posterior reversible encephalopathy syndrome (PRES) was initially described by Hinchey et al. in 1996 in a retrospective series of 15 patients with headache, seizures, altered mental status, high blood pressure, and unique MRI findings that disappeared on subsequent imaging after controlling blood pressure [
The exact incidence of PRES is unknown, commonly being mistaken for acute stroke. Some authors have reported in their case series predominance in young female patients (75%) particularly when being associated with autoimmune disorders, such as Systemic Lupus Erythematous (SLE) with nephritis [
A 22-year-old woman with history of Systemic Lupus Erythematous (SLE) complicated with chronic kidney disease (CKD) secondary to lupus nephritis [ISN-RPS class IV-G (A)] presented with generalized tonic-clonic seizures and uncontrolled hypertension. Vitals signs at presentation were as follows: blood pressure of 180/148 mmHg; heat rate of 140 per minute. She was afebrile and somnolent but responsive to verbal stimuli and oriented in time, place, and person with no evidence of apparent focal deficits. She had no body rashes, ulcers, hair loss, joint tenderness, or swelling. The rest of the physical examination was unremarkable.
Laboratory tests on presentation were remarkable for anemia, thrombocytopenia, elevated lactate dehydrogenase, and a reticulocyte count of 3.3% (Table
Laboratory data.
Variable | Reference range, adults | On admission | Third hospital day | Sixteenth hospital stay | At discharge |
---|---|---|---|---|---|
White cells (per mm3) | 3,500–11,000 | 29,000 | 14,500 | 8,900 | 8,800 |
Hemoglobin (g/dl) | 12–16 (women) | 9.6 | 7.7 | 7.7 | 8.9 |
Hematocrit (%) | 36–46 | 30.6 | 23.9 | 22.4 | 26.3 |
Platelets (per mm3) | 150,000–440,000 | 95,000 | 45,000 | 143,000 | 131,000 |
Carbon dioxide (mEq/L) | 24–30 | 12.6 | 24.8 | 29.5 | 21 |
Urea nitrogen (mg/dl) | 5–26 | 54 | 45 | 47 | 59 |
Creatinine (mg/dl) | 0.1–1.5 | 2.3 | 2.2 | 5.3 | 2.9 |
Albumin (g/dL) | 3.5–5.5 | 2.4 | 2.3 | 2.5 | 3.3 |
Lactate dehydrogenase (U/L) | 100–210 | 1,144 | 418 | 393 | |
Total bilirubin (mg/dl) | 0.1–1.2 | 0.2 | 0.3 | 0.3 | 0.3 |
Erythrocyte sedimentation rate (mm/hr) | 0–20 | 36 | |||
C-reactive protein (mg/L) | 0–5 | 64.9 | |||
Complement C3 (mg/dl) | 90–180 | 80 | |||
Complement C4 (mg/dl) | 10–40 | 28.5 | |||
ADAMTS13 activity | ≥67% | 82% | |||
Direct Coombs test | Negative | Negative | Negative |
She was diagnosed presumptively with thrombotic thrombocytopenic purpura (TTP) due to anemia, thrombocytopenia, and schistocytes on peripheral smear. Plasma exchange and prednisone were started as the mortality rate without early treatment in TTP is very high. Additional testing was pursued to rule out other causes.
Further tests showed antinuclear antibody 1 : 1280 with speckled pattern; antibodies including anti-Smith, RNP, dsDNA, and histone were also positive. Lupus anticoagulant and cardiolipin antibody were negative.
Electroencephalogram (EEG) was with no epileptiform discharges. First brain MRI showed extensive areas of high signal intensity in the subcortical white matter of both parietooccipital regions, as well as in the frontal lobes and right basal ganglia/capsular region and the head of the caudate nucleus on the left (Figures
The initial MRI (images (a)–(c)) showed typical holohemispheric involvement: axial view in FLAIR (see (a), (b)) and T2-weighted (see (c)) images with extensive areas of high signal intensity in the subcortical white matter of both parietooccipital regions, including frontal lobes. Second MRI (images (d)–(f)) performed 2 weeks later with no signal abnormality within the brain parenchyma on FLAIR (see (d), (e)) and T2-weighted (see (f)) images.
She completed a ten-day course of plasma exchange but continued to have low platelets, anemia, and worsening kidney function. ADAMTS13 assay level returned back to normal (82%) and also paroxysmal nocturnal hemoglobinuria panel was negative. At this time, after an interdisciplinary team meeting, a decision was made to perform a kidney biopsy. She was considered to have very high risk of the procedure due to persistent thrombocytopenia, anemia, and high risk of bleeding; but this was thought to be essential in order to clarify the diagnoses which at this time were mainly lupus nephritis versus atypical hemolytic uremic syndrome. Nicardipine IV infusion was continued for a more stable and tight blood pressure control. Patient received one dose of complement based therapy with eculizumab one day before the kidney biopsy (day 14 of hospitalization). The kidney biopsy showed diffuse endocapillary and extracapillary proliferative and membranous lupus nephritis (ISN-RPS class IV-G+V), new changes with endothelial swelling secondary to severe hypertension, but no evidence of thrombotic microangiopathy (Figure
Renal biopsy with crescent formations (image (a)). Immunofluorescent findings (image (b)) of diffuse granular mesangial and glomerular capillary wall staining for IgG, IgM, IgA, C3, and C1; tubular basement membrane and arteriolar staining for IgG, IgM, and C3; vessel wall staining for IgG, IgM, and C3. Arterioles with focal luminal obliteration and concentric intimal fibroplasia (image (c)). Moderate fibrosis (image (d)). Findings consistent with lupus nephritis and severe hypertension.
Second MRI of the head was performed weeks later which confirmed reversal of the brain lesions seen on the first MRI (Figures
Unfortunately her kidney function did not improve, requiring permanent renal replacement therapy. She required renal replacement therapy for a brief period for optimizing her volume status. Her BP medications were optimized, requiring maximum doses of labetalol, nifedipine, clonidine, and minoxidil. She was transferred to acute rehabilitation service where she had multiple episodes of seizures due to uncontrolled BP secondary to poor medication compliance. Third MRI performed showed diffuse bilateral peripheral cortical and subcortical signal abnormalities including the posterior fossa and cerebellum. She left the hospital without completing rehabilitation and unfortunately was lost to follow-up.
This case raises awareness of PRES in the differential diagnosis of acute stroke. Most of the presentations of PRES are straightforward, but in some patients with confounding factors the diagnosis is not obvious. This is especially true when the patient presents with acute or chronic manifestation of their underlying disease or is on a medication that can predispose to PRES, making the diagnosis challenging.
PRES can occur with variable degrees of hypertension regardless of its etiology. A rapid rise in blood pressure is a greater risk for development of PRES than the degree of hypertension itself [
Despite a plethora of information on PRES in general, there is a paucity of data in those with established chronic kidney disease (CKD), even though these patients have a high preponderance of risk factors.
Autoimmune disorders: Systemic Lupus Erythematous, antiphospholipid syndrome, polyarteritis nodosa, cryoglobulinemia, thrombotic thrombocytopenic purpura, scleroderma, polyangiitis, antiglomerular basement membrane antibody disease, rheumatoid arthritis, Sjögren syndrome, Crohn’s disease, ulcerative colitis, autoimmune hepatitis, type 1 diabetes mellitus, Grave’s disease, Hashimoto thyroiditis, and neuromyelitis optica [ Essential hypertension Preeclampsia and eclampsia [ Acute or chronic renal failure and dialysis (55%)[ Septicemia and severe infections (predominantly gram positive organisms) [ Immunosuppressive therapy (despite normal levels): cisplatin, cyclosporine, tacrolimus, intravenous globulin, rituximab, methotrexate, bevacizumab, sunitinib, and sorafenib [ Others: blood transfusion, contrast exposure, hypercalcemia, cocaine, and methamphetamine
The incidence has been variably reported, with a study from Ireland showing an occurrence of 0.84% [
The pathophysiology of PRES is not fully understood and two theories are proposed [
PRES was initially described in a case series [
Brain imaging is essential in the diagnosis of PRES. Typically seen are asymmetric cortical and subcortical white matter edema in the posterior cerebral hemispheres not confined to a single vascular territory [
It is imperative not only to correctly identify PRES as an entity but also to identify the underlying cause(s) that are triggering this syndrome.
Diagnostic approach for the evaluation of possible PRES in patients with baseline autoimmune disease. It needs more than 2 criteria present for kidney biopsy. MRI: magnetic resonance; MAP: mean arterial blood pressure; PRES: posterior reversible encephalopathy syndrome; BP: blood pressure; TIA: transient ischemic attack.
There is no specific treatment for PRES. Prompt and moderate lowering of blood pressure along with removal of the underlying cause is the mainstay of treatment. Delay in diagnosis and treatment can result in cerebral infarction or hemorrhage with persistent neurologic damage and chronic seizures. There are no established guidelines for BP reduction, but aiming for an initial 20% reduction in MAP is usual [
The prognosis is favorable and most patients will recover with prompt treatment [
In our patient, the initial presentation was very complicated and posed a diagnostic and therapeutic dilemma. In addition despite atypical features and presenting with 2 of the adverse prognosticators, there was no
Posterior reversible encephalopathy syndrome should be included as a differential diagnosis in any cause of headache, acute confusional state, seizure, and acute stroke. It must be recognized and treated timely because of the potential reversibility in the early stages. Physicians must have high suspicion for unusual presentations. In patients with AKI or CKD as in our patient, having a low threshold for performing kidney biopsy is helpful when the diagnosis is obscure.
The authors current address is as follows: Jacobi Medical Center, The Albert Einstein College of Medicine, 1400 Pelham Parkway South, Bronx, NY 10461, USA.
The authors declare that they have no competing interests.