Posterior reversible encephalopathy syndrome in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome

Abstract

Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurologic condition associated with systemic lupus erythematosus (SLE). This study aimed to demonstrate the risk factors and clinical outcome of PRES in patients with SLE.

Fifteen patients with SLE were diagnosed with PRES by characteristic clinical manifestations and magnetic resonance imaging (MRI) features from 2000 to 2012. Clinical profiles and outcomes were assessed for this study population. Additionally, 48 SLE patients with neurologic symptoms who underwent brain MRI were included for comparative analyses.

The median age and duration of SLE in patients with PRES was 27 and 6.1 years, respectively. Comparison between patients with and without PRES revealed significant differences in the presentation of hypertension and seizure, lupus nephritis with renal insufficiency, treatment with high-dose steroid and cyclophosphamide, recent transfusion, and lupus activity measured by SLE disease activity index. Renal failure was the single independent factor with a high odds ratio of 129.250 by multivariate analysis. Of 15 patients, four experienced relapse and two died of sepsis during hospitalization.

Our results suggest that lupus nephritis with renal dysfunction and other related clinical conditions can precede the occurrence of PRES in patients with SLE. It is important to perform early brain imaging for a timely diagnosis of PRES when clinically suspected.

Keywords

Posterior reversible encephalopathy syndrome systemic lupus erythematosus lupus nephritis renal failure renal insufficiency

Introduction

Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome, is a clinico-radiological syndrome characterized by brain imaging that includes vasogenic edema and clinical symptoms of hypertension, headache, and seizure. Since Hinchey and colleagues categorized this syndrome in 1996,¹ the number of cases has been increasing with the advent of neuroimaging techniques and clinicians’ awareness of PRES. Previous studies have suggested that PRES develops in association with hypertension, renal disease, autoimmune disorders, and treatment with cytotoxic drugs.^1–4

Systemic lupus erythematosus (SLE) is one of the predisposing conditions related to PRES, particularly when accompanied by lupus nephritis.^4–9 However, SLE is an uncommon autoimmune disease in which the occurrence of PRES is even rarer. This rarity makes it difficult to clarify the clinical course of PRES in patients with SLE, and there are some inconsistencies between the studies performed with case reports. Furthermore, it is challenging to distinguish PRES from other neuropsychiatric manifestations of SLE,^10,11 since SLE patients can present various neurologic manifestations encompassing neuropsychiatric lupus and other neurologic complications due to metabolic or infectious causes.

Clinical suspicion and early neuroimaging are required for a timely diagnosis because management of PRES, which is mainly supportive, differs from immunosuppressive therapy or other specific treatment for neuropsychiatric complications of SLE. The present study aimed to elucidate the clinical features predicting the development of PRES and to demonstrate the clinical course of PRES.

Methods

Patients and controls

We retrospectively reviewed the medical records of patients with SLE who were admitted to Seoul St. Mary’s Hospital, tertiary care university hospital and referral center, between January 2000 and December 2012. Of the 740 patients who fulfilled the 1997 updated version for classification of SLE,^12,13 15 with PRES were identified. PRES was diagnosed using a multidisciplinary approach based on clinical symptoms and typical brain imaging. Forty-eight age- and sex-matched control subjects were recruited from SLE patients with neuropsychiatric problem other than PRES. Diagnoses in the control group were systematically determined by the clinical course, and laboratory and radiological tests. The control group was composed of 19 patients with neuropsychiatric lupus, 10 with cerebral infection, four with migraine, two with benign intracranial hypertension, two with seizure disorder, two with fibromyalgia, two with headache secondary to upper respiratory infection, and seven with other causes. The study population was entirely Korean.

All included patients underwent brain magnetic resonance imaging (MRI) to evaluate neurologic symptoms including seizure and/or headache. This study protocol was approved by the Institutional Review Board of Seoul St. Mary’s Hospital.

Clinical and laboratory profiles

The following conditions were assessed for the 15 patients with PRES: demographic characteristics such as age, sex, and disease duration, clinical features, laboratory profiles, current treatment for SLE, management and clinical outcomes of PRES. Of laboratory tests, anti-double-stranded DNA (anti-dsDNA) antibody was measured using enzyme-linked immunosorbent assay (ELISA) (anti-dsDNA ELISA kit, GENESIS, Leicester, UK), and anti-DNA antibody was determined by the Farr assay. Lupus disease activity was evaluated with the SLE Disease Activity Index (SLEDAI).¹⁴ Additionally, modified SLEDAI, excluding neuropsychiatric manifestations, was calculated, as PRES frequently accompanies neurologic symptoms. Clinical and laboratory profiles were compared between patients with and without PRES to assess risk factors for PRES.

Statistical analysis

Differences in continuous variables between the patients with and without PRES were analyzed by the Mann Whitney U test. Fisher’s exact test was used to compare categorical data. We performed multivariate logistic regression using forward stepwise selection to determine the independent risk factors for PRES. Variables with p ≤ 0.10 in a univariate analysis were included in a multivariate analysis. A p value < 0.05 was considered statistically significant. All data were analyzed using SAS 9.1 software (SAS Institute, Inc, Cary, NC, USA).

Results

Patient characteristics

The clinical characteristics of the patients with lupus who were diagnosed with PRES are summarized in Table 1. All 15 patients were women, and the age of PRES onset ranged 17 to 51 years. Three patients developed PRES several days after the initial diagnosis of SLE for other symptoms reflecting a lupus flare. All patients except one presented with seizure and hypertension, and five patients complained of a visual disturbance. Patient 3, with a history of bipolar disorder, complained of headache and psychosis. Of 14 patients with lupus nephritis, six were treated with renal replacement therapy. Ten patients received a blood transfusion within five days before the occurrence of PRES, and the transfusion was performed within 24 hours in five patients. In accordance with high disease activity measured by the SLEDAI score, high-dose glucocorticoid therapy and immunosuppressive agents were used to manage SLE.

Table 1

Clinical characteristics of 15 SLE patients with PRES

Patient	Sex	Age	Duration of SLE (years)	Neurologic symptoms	Lupus nephritis	Dialysis	BP (mmHg)	Dose of prednisolone (mg/day)	Immuno suppressant	Transfusion^a	SLEDAI	Lesions in brain MRI
1	F	50	14.9	SZ, blindness	Yes	PD	150/100	60	MZ	Yes^b	13	O (B)
2	F	17	0 (15 days)	HED, SZ	Yes	No	200/100	125	CYP, MZ	Yes	45	O/T (B)
3	F	29	5.8	HED, psychosis	No	No	100/60	60	None	No	17	O/P/F (B)
4	F	23	9.0	SZ	Yes	HD	170/120	30	MMF	No	14	O/P/T/F (B)
5	F	41	4.6	HED, SZ	Yes	No	190/95	12.5	CYP	No	24	O/P/T/F/Cbll/BG/CC (B)
6	F	25	11.5	SZ	Yes	HD	180/100	62.5	CYP	No	21	O/P/T/F (B)
7	F	38	10.9	HED, SZ blurred vision	Yes	HD	170/90	40	None	Yes^b	26	O/P (B)
8	F	27	6.1	HED, SZ, blurred vision	Yes	No	220/120	250	CYP	Yes^b	30	O/P (B)
9	F	25	3.0	HED, SZ	Yes	HD	170/100	50	CYP	Yes^b	33	O/P/T/F/Cbll (B)
10	F	24	15.7	HED, SZ, blurred vision	Yes	No	180/100	40	CYP	Yes	20	O/P/T/F (B)
11	F	23	6.3	HED, SZ	Yes	HD	160/100	250	None	Yes	21	BG (B), Cbll/CC (L)
12	F	34	18.6	SZ	Yes	No	180/120	50	CYP	Yes^b	26	O/P/T/F/Th (B)
13	F	51	0 (3 days)	SZ	Yes	No	160/100	40	None	Yes	34	O/P/T/F/BS (B)
14	F	44	0 (5 days)	HED, SZ, blurred vision	Yes	No	180/90	125	IVIG	No	25	O/P/T/F(B), Cbll(R)
15	F	21	3.3	SZ	Yes	No	170/100	125	MMF	Yes	27	O/P/F (B)

SLE: systemic lupus erythematosus; PRES: posterior reversible encephalopathy syndrome; BP: blood pressure; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index; MRI: magnetic resonance imaging; SZ: seizure; HED: headache; PD: peritoneal dialysis; HD: hemodialysis; MZ: mizoribine; CYP: cyclophosphamide; MMF: mycophenolate mofetil; IVIG: intravenous immunoglobulin; O: occipital; T: temporal; P: parietal; F: frontal; Cbll: cerebellum; BG: basal ganglia; CC: corpus callosum; Th: thalamus; BS: brainstem; B: bilateral; L: left; R: right.

Transfusion within five days before occurrence of PRES.

These five patients received blood transfusion within 24 hours before occurrence of PRES.

Table 2 shows the laboratory profiles of the 15 patients with PRES. Serum creatinine was >1.5 mg/dl in 12 patients and serum albumin was below the normal range in all 15 patients. The levels of complement and anti-dsDNA and/or anti-DNA antibody reflected lupus flare in most patients with PRES. The test for antiphospholipid (aPL) antibody was positive in five patients.

Table 2

Laboratory profiles of 15 SLE patients with PRES

Patient	Cr (mg/dl)	Albumin (mg/dl)	C3^a (mg/dl)	C4^a (mg/dl)	Anti-dsDNA^b (IU/ml)	Anti-DNA^c (IU/ml)	Hb (g/dl)	WBC (10⁶/l)	PLT (10⁹/l)	aPL
1	7.43	2.39	59.1	11.3	9.8	0.44	12.4	7170	18	LA pos
2	1.85	2.3	23	3.7	223.2	26.54	8.6	12410	51	Neg
3	0.60	3.2	35.3	7.53	400	—	11.9	1990	105	Neg
4	2.78	3.09	94.6	21.9	—	48.01	11	15960	109	Neg
5	1.82	2.8	40	12.9	245.6	23.83	11.5	11460	178	Neg
6	5.14	3.0	40	11.9	324.7	62.55	9.3	4630	40	LA pos
7	2.08	2.08	120	22.5	10	1.05	10.5	5800	250	LA pos
8	3.92	2.94	47.2	8.63	400	720.39	10.4	12130	181	Neg
9	4.29	3.4	64	9.4	28.9	—	9.3	10710	72	aCL pos
10	2.10	3.0	71.2	31.9	54	1.2	8.2	3560	274	Neg
11	2.55	2.3	55.3	8.39	46	22.2	13.7	19780	219	aCL pos
12	1.79	2.7	43	6.06	53	—	9.7	14270	100	Neg
13	0.83	2.34	15.6	5.3	400	—	8	3780	19	Neg
14	1.91	2.28	31.4	6	39	2.89	12.9	8330	56	Neg
15	0.77	2.7	38	6.7	26.2	6.19	10.7	18760	202	Neg

SLE: systemic lupus erythematosus; PRES: posterior reversible encephalopathy syndrome; Cr: creatinine; Anti-dsDNA: anti-double-stranded DNA; Hb: hemoglobin; WBC: white blood cell; PLT: platelet; aPL: antiphospholipid antibody; LA: lupus anticoagulant; pos: positive; neg: negative; aCL: anticardiolipin antibody.

Reference ranges for C3 and C4 are 76–139 mg/dl and 12–37 mg/dl, respectively.

Reference range is below 100 IU/ml.

Reference range is below 7 IU/ml.

Risk factors for PRES

Clinical and laboratory characteristics were compared between patients with and without PRES (Table 3). Age, sex, and disease duration were similar between the two groups. A significant difference was observed in the presentation of hypertension and seizure. Renal involvement, treatment with high-dose steroid and cyclophosphamide, and a recent transfusion were more frequently detected in patients with PRES. Serum creatinine was higher in the PRES group than that in the group without PRES. The median SLEDAI score of lupus patients with PRES was 25 (range 13 to 45), higher than that in the control group. The SLEDAI score excluding neuropsychiatric manifestations showed similar results.

Table 3

Comparison of SLE patients with or without PRES

Clinical and laboratory profiles	PRES (n = 15)	Non-PRES (n = 48)	p value
Age (years)	27 (17–51)	30 (18–57)	0.821
Women, n (%)	15 (100)	45 (93.8)	1.000
Duration of disease (years)	6.1 (0–18.6)	6.6 (0–22.9)	0.846
SBP at presentation (mmHg)	170 (100–220)	120 (90–160)	<0.0001
Seizure, n (%)	14 (93.3)	12 (25.0)	<0.0001
Lupus nephritis, n (%)	14 (93.3)	20 (41.7)	0.001
Current dose of prednisolone (mg/day)	60 (12.5–250)	10 (0–60)	<0.0001
Cyclophosphamide therapy, n (%)	7 (46.7)	2 (4.2)	<0.0001
Transfusion, n (%)	10 (66.7)	1 (2.1)	<0.0001
Positivity of aPL, n (%)	5 (33.3)	17 (35.4)	1.000
Hemoglobin (mg/dl)	10.5 (8–13.7)	11.0 (4.4–15.6)	0.410
Platelet (10⁹/l)	105 (18–274)	153 (3–345)	0.129
ESR (mm/hr)	11 (2–54)	29 (2–120)	0.054
CRP (mg/dl)	0.77 (0.03–5.84)	0.52 (0.01–24.7)	0.904
C3 (mg/dl)	43.0 (15.6–120.0)	64.1 (20.3–230.0)	0.052
C4 (mg/dl)	8.6 (3.7–31.9)	13.9 (5.4–64.8)	0.091
Anti-DNA Ab (IU/ml)	22.20 (0.44–720.39)	12.62 (0.03–1029.97)	0.614
Serum creatinine (mg/dl)	2.08 (0.6–7.43)	0.77 (0.44–3.18)	<0.0001
Albumin (mg/dl)	2.7 (2.08–3.4)	3.4 (2.17–4.4)	<0.0001
SLEDAI	25 (13–45)	12 (0–29)	<0.0001
mSLEDAI	17 (5–22)	5 (0–22)	<0.0001

SLE: systemic lupus erythematosus; PRES: posterior reversible encephalopathy syndrome; SBP: systolic blood pressure; aPL: antiphospholipid antibody; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; SLEDAI: Systemic Lupus Erythematosus Activity Index; mSLEDAI: modified Systemic Lupus Erythematosus Activity Index.

As presented in Table 4, the occurrence of PRES was preceded by multiple clinical factors, which appeared to be statistically significant in the univariate analysis. Nevertheless, renal insufficiency was the single independent factor revealed in the multivariate analysis. The odds ratio for developing PRES was 129.250 (95% confidence interval, 13.121–1273.183) and was considerably high in lupus patients with renal failure.

Table 4

Factors preceding the diagnosis of PRES

Univariate		Multivariate
Factors	OR (95% CI)	p value	OR (95% CI)	p value
HBP at presentation (SBP ≥ 140 mmHg)	82.000 (9.257–726.383)	<0.0001
Seizure at presentation	42.000 (4.984–353.904)	0.001
Lupus nephritis	19.600 (2.380–161.398)	0.006
High-dose steroid therapy	98.000 (10.840–885.970)	<0.0001
Cyclophosphamide therapy	20.125 (3.527–114.844)	0.001
Transfusion	94.000 (9.879–894.451)	<0.0001
Renal insufficiency (Cr ≥ 1.5 mg/dl)	129.250 (13.121–1273.183)	<0.0001	129.250 (13.121–1273.183)	<0.0001
Hypoalbuminemia (Alb ≤ 2.5 mg/dl)	3.905 (1.056–14.436)	0.041
Higher SLEDAI (score ≥ 15)	10.833 (2.189–53.619)	0.004

PRES: posterior reversible encephalopathy syndrome; OR: odds ratio; CI: confidence interval; HBP: high blood pressure; SBP: systolic blood pressure; Cr: creatinine; Alb: albumin; SLEDAI: Systemic Lupus Erythematosus Activity Index.

Treatment and clinical outcomes

The management of patients after PRES and their clinical outcomes are shown in Table 5. The main therapeutic modalities for PRES were to control blood pressure and suppress seizures. Multiple agents were required to lower blood pressure in most patients with PRES, and six different classes of antihypertensive medications were prescribed to Patient 9 after one episode of relapse. Thirteen patients were treated with anticonvulsive drugs. Of two patients who did not take anticonvulsants, one had a second attack of seizure, whereas the other patient improved without recurrence.

Table 5

Treatments and clinical outcomes of 15 SLE patients with PRES

Patient	Antihypertensive	Anticonvulsant	Steroid	Time to recovery (days)	Relapse	Sequelae
1	CCB	Oxcarbazepine	Increased	2	None	None
2	CCB, BB, DU	Oxcarbazepine	Increased	14	Twice	None
3	None	Lorazepam	Continued	NA	None	NA
4	CCB, BB, ARB, DU	Phenytoin	Increased	1	None	None
5	CCB, BB, ARB, DU	Valproic acid	Increased	7	None	None
6	CCB, BB, ARB, DU	Carbamazepine	Increased	6	None	None
7	CCB	None	Increased	3	Once	None
8	CCB, BB, DU	None	Increased	8	None	None
9	CCB, BB, ARB, DU Hydralazine, doxazosin	Levetiracetam	Continued	14	Once	None
10	CCB, ARB, DU	Phenytoin/oxcarbazepine	Increased	14	Once	None
11	CCB, BB, ARB, DU	Valproic acid	Increased	1	None	None
12	BB	Phenytoin	Increased	NR	None	Death
13	ARB	Valproic acid	Increased	2	None	None
14	CCB, BB, ARB, DU	Valproic acid	Continued	2	None	None
15	CCB, BB, ARB, DU	Levetiracetam	Increased	14	None	None

SLE: systemic lupus erythematosus; PRES: posterior reversible encephalopathy syndrome; CCB: calcium channel blocker; BB: beta blocker; DU: diuretics; ARB: angiotensin-converting enzyme receptor blocker; NA: not accessible; NR: not resolved.

Four patients experienced relapse of seizures, and one (Patient 12) did not recover from PRES. Patient 12 remained unconscious after onset of PRES until death. The resolution of PRES was not established in Patient 3 who had been diagnosed previously with bipolar disorder, because psychosis, one of the presenting manifestations, continued thereafter. Two patients (Patients 1 and 12) died of sepsis during hospitalization.

Discussion

The advance of neuroimaging techniques and the accumulation of case reports have enabled a further understanding of PRES during the last decade. However, PRES in association with lupus is still uncommon to characterize the clinical features distinct from other neuropsychiatric manifestations of SLE.

The present study shows similarity to prior studies in terms of the clinical manifestations and the preceding features of PRES. As described in earlier cases, most of our patients complained of headache and visual disturbance, and presented with suddenly increasing blood pressure and seizure. Lupus nephritis with renal dysfunction, hypoalbuminemia, treatment with high-dose steroid, and cyclophosphamide therapy were predisposing conditions for PRES as reported previously.^6,7,9,10,15

The clinical features that appeared significant for the development of PRES are closely interrelated. As expected, the renal function of patients with lupus nephritis deteriorated, and high-dose steroid and/or cyclophosphamide were used to manage the nephritis. Therefore, we evaluated the independent factors for the development of PRES in patients by using a multivariate analysis. As a result, renal failure, as defined by elevated creatinine, was the only significant factor in our study. The association between renal insufficiency and PRES has been described extensively.^1,2,16–19 The pathogenic mechanism of PRES is considered to be vasogenic edema caused by hypertension with autonomic dysregulation and disruption of the blood-brain barrier. ^1,11,20 Considering the increased incidence of fluid retention and resulting elevated blood pressure in patients with renal failure, hypertension would be one of the common pathways. High-dose steroid therapy and blood transfusions also lead to volume expansion, accounting for one of the preceding factors for PRES.

Despite the close connection with hypertension, several reports are available regarding development of PRES in SLE patients with normal blood pressure.^21,22 In our series, Patient 3 was normotensive. We concluded that the neurologic manifestation of Patient 3 was PRES by typical MRI findings, although the clinical features were distinct from the other patients. A case of PRES without hypertension suggests that the vasogenic edema can be derived from endothelial injury. SLE is a systemic autoimmune disease in which organ damage is mediated by autoantibody production and immune complex formation. The blood-brain barrier can be damaged by immune-mediated attack in patients with SLE.^13,23 Four patients in our series were suspected to have vasculitis of the central nervous system when brain MRIs were reviewed. This presumption is supported by higher lupus activity measured by the SLEDAI score in the PRES group. In addition, four of 13 patients, excluding two patients who had not recovered from PRES (30.8%), experienced a recurrent attack of PRES despite supportive care. For a similar reason, there is an opinion that although immunosuppressive therapy is predisposed to PRES, immunosuppressive agents are required to reverse PRES after failure of symptomatic treatment.⁸ The association of PRES with autoimmune disease is quite apparent, but the relevant pathophysiology remains to be explained. Thus further investigation is required to explore the mechanism of how lupus affects the development of PRES.

Some dissimilarities with the prior studies were observed in our cases. Several reports have suggested an association between aPL and PRES,^15,24 but we found no statistical difference in aPL positivity between patients with and without PRES. Our patients with PRES were relatively older than earlier cases in which PRES developed in mostly adolescent or young adults <40 years.^7,9,25

Some limitations of our study should be mentioned. First, the clinical records of the patients were collected retrospectively. The treatment for PRES was not standardized, and a follow-up MRI was not possible in most patients. Thus, the impact of therapeutic modalities could not be evaluated, and the resolution of PRES was only determined clinically but not confirmed radiologically. Second, this study had defects stemming from its small sample size. Considering the low incidence of PRES in patients with SLE, a multicenter study would overcome this weakness. Nevertheless, the present study is composed of a relatively large number of patients with SLE and PRES, and to our knowledge, this is the only case-control study on the development of PRES.

In summary, PRES with underlying SLE is being increasingly encountered. Some preceding clinical features of PRES were apparent when lupus patients presented with neuropsychiatric manifestations. Our results indicate that lupus nephritis, particularly when accompanied by renal dysfunction, is one of the most significant risk factors for PRES. As an early diagnosis of PRES is essential for proper management involving control of blood pressure, it is important to be aware of PRES and to perform brain imaging when this syndrome is clinically suspected.

Footnotes

Funding

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

Conflict of interest

The authors have no conflicts of interest to declare.

References

Hinchey

Chaves

Appignani

. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500.

Fugate

Claassen

Cloft

Kallmes

Kozak

Rabinstein

. Posterior reversible encephalopathy syndrome: Associated clinical and radiologic findings. Mayo Clin Proc 2010; 85: 427–432.

Bartynski

. Posterior reversible encephalopathy syndrome, part 1: Fundamental imaging and clinical features. AJNR Am J Neuroradiol 2008; 29: 1036–1042.

Zhou

Hao

. The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: A retrospective series of 24 patients. J Neuroimaging 2011; 21: 219–224.

Magnano

Bush

Herrera

Altman

. Reversible posterior leukoencephalopathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum 2006; 35: 396–402.

Leroux

Sellam

Costedoat-Chalumeau

. Posterior reversible encephalopathy syndrome during systemic lupus erythematosus: Four new cases and review of the literature. Lupus 2008; 17: 139–147.

Barber

Leclerc

Gladman

Urowitz

Fortin

. Posterior reversible encephalopathy syndrome: An emerging disease manifestation in systemic lupus erythematosus. Semin Arthritis Rheum 2011; 41: 353–363.

Fujieda

Kataoka

Odani

. Clinical features of reversible posterior leukoencephalopathy syndrome in patients with systemic lupus erythematosus. Mod Rheumatol 2011; 21: 276–281.

Varaprasad

Agrawal

Prabu

Rajasekhar

Kanikannan

Narsimulu

. Posterior reversible encephalopathy syndrome in systemic lupus erythematosus. J Rheumatol 2011; 38: 1607–1611.

10.

Ishimori

Pressman

Wallace

Weisman

. Posterior reversible encephalopathy syndrome: Another manifestation of CNS SLE? Lupus 2007; 16: 436–443.

11.

Mak

Chan

Yeh

. Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: A challenging clinical dilemma. Rheumatology (Oxford) 2008; 47: 256–262.

12.

Tan

Cohen

Fries

. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

13.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

14.

Bombardier

Gladman

Urowitz

Caron

Chang

. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35: 630–640.

15.

Baizabal-Carvallo

Barragán-Campos

Padilla-Aranda

. Posterior reversible encephalopathy syndrome as a complication of acute lupus activity. Clin Neurol Neurosurg 2009; 111: 359–363.

16.

Onder

Lopez

Teomete

. Posterior reversible encephalopathy syndrome in the pediatric renal population. Pediatr Nephrol 2007; 22: 1921–1929.

17.

Ishikura

Ikeda

Hamasaki

. Nephrotic state as a risk factor for developing posterior reversible encephalopathy syndrome in paediatric patients with nephrotic syndrome. Nephrol Dial Transplant 2008; 23: 2531–2536.

18.

Gao

Liang

Liu

. Isolated pons involvement in posterior reversible encephalopathy syndrome in a patient with chronic renal insufficiency: Case report and literature review. Clin Neuroradiol 2012; 22: 341–344.

19.

Nakabou

Kai

Maeshima

Kanamasa

. Hypertensive encephalopathy in patients with chronic renal failure caused by stopping antihypertensive agents: A report of two cases. Clin Exp Nephrol 2010; 14: 256–262.

20.

Bartynski

. Posterior reversible encephalopathy syndrome, part 2: Controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol 2008; 29: 1043–1049.

21.

Kur

Esdaile

. Posterior reversible encephalopathy syndrome—an underrecognized manifestation of systemic lupus erythematosus. J Rheumatol 2006; 33: 2178–2183.

22.

Shin

Choi

Bae

Lee

Song

. Reversible posterior leukoencephalopathy syndrome in systemic lupus erythematosus with thrombocytopenia treated with cyclosporine. J Clin Rheumatol 2005; 11: 164–166.

23.

Abbott

Mendonca

Dolman

. The blood-brain barrier in systemic lupus erythematosus. Lupus 2003; 12: 908–915.

24.

Bandettini di Poggio

Murdaca

Puppo

Primavera

. Antiphospholipid syndrome and reversible posterior leukoencephalopathy syndrome. Semin Arthritis Rheum 2010; 40: e9–e10.

25.

Muscal

Traipe

de Guzman

Myones

Brey

Hunter

. MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus. Pediatr Radiol 2010; 40: 1241–1245.