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Manuscript Accepted Early View Article

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Early View Article: Online published version of an accepted article before publication in the final form.

Journal Name: International Journal of Case Reports and Images (IJCRI)

doi: To be assigned

Early view version published: October 4, 2017

How to cite the article: Joshua Sunny George, Shahil Mehta, Patricia Calvo.

Post-Operative Posterior Reversible Encephalopathy Syndrome (PRES) as

Initial Presentation of Systemic Lupus Erythematosus. International Journal

of Case Reports and Images (IJCRI). Forthcoming 2017.

Disclaimer: This manuscript has been accepted for publication. This is a pdf file of the Early View Article. The Early View Article is an online published version of an accepted article before publication in the final form. The proof of this manuscript will be sent to the authors for corrections after which this manuscript will undergo content check, copyediting/proofreading and content formatting to conform to journal’s requirements. Please note that during the above publication processes errors in content or presentation may be discovered which will be rectified during manuscript processing. These errors may affect the contents of this manuscript and final published version of this manuscript may be extensively different in content and layout than this Early View Article.


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TYPE OF ARTICLE: Case Report 1

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TITLE: Post-Operative Posterior Reversible Encephalopathy Syndrome (PRES) as 3

Initial Presentation of Systemic Lupus Erythematosus 4

5

AUTHORS: 6

Joshua Sunny George1, B.S. 7

Shahil Mehta1, B.A. 8

Patricia Calvo1, M.D 9

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AFFILIATIONS: 11

1University of Miami Miller School of Medicine, Miami, FL, U.S.A 12

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CORRESPONDING AUTHOR DETAILS 14

Joshua Sunny George 15

82 Gordon Drive, Troy, Michigan, U.S.A., 48098 16

Email: [email protected] 17

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Short Running Title: An Unusual Presentation of Lupus 19

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Guarantor of Submission: The corresponding author is the guarantor of 21

submission. 22

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SUMMARY 32

Posterior reversible leukoencephalopathy syndrome (PRES) is a syndrome 33

consisting of neurological symptoms including headaches, visual changes, and 34

seizures. PRES often occurs in the setting of uncontrolled hypertension secondary to 35

a variety of conditions including but not limited to pregnancy, eclampsia, drug toxicity 36

and autoimmune conditions such as systemic lupus erythematosus (SLE). Diagnosis 37

is often confirmed by characteristic findings on neuroimaging studies including 38

edema in the posterior cortical white matter; however, findings are not restricted to 39

strictly posterior or reversible lesions. It is still debated whether PRES can be 40

considered as a neuropsychiatric manifestation of SLE. The central theories of 41

PRES pathophysiology in SLE patients focus on interruption of neurovascular 42

autoregulation and subsequent vasogenic edema. Although the majority of these 43

findings are reversible, if not identified and treated, complications such as infarction, 44

cerebral hemorrhage, or cytotoxic edema may occur, increased morbidity and 45

mortality. Our patient was a 25 year old woman with a past medical history of severe 46

endometriosis who underwent total abdominal hysterectomy and bilateral salpingo-47

oophorectomy (TAH-BSO). The procedure was completed successfully without any 48

complications. Post-operatively, the patient experienced hypertension, which she 49

never had prior to hospitalization. On post-op day five, the patient experienced vision 50

changes and a seizure episode and was diagnosed with PRES based on findings on 51

T2 and FLAIR MRI studies. She was discharged several days later on anti-52

hypertensive medications but with no formal diagnosis as to the cause. Several 53

months later, she returned to the emergency room with complaints of arthralgias 54

which led to further outpatient workup and eventual diagnosis of SLE. We suspect 55

that the patient had undiagnosed SLE prior to her surgery which put her at increased 56

risk for PRES. Most cases of PRES in SLE occur after lupus diagnosis and are 57

related to either increases in disease activity or immunosuppressive therapy. This 58

case is unique in that our patient’s neuropsychiatric symptom of PRES occurred 59

post-operatively and was the initial manifestation that led to her diagnosis of SLE. 60

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ABSTRACT 64

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Introduction 66



seizures often occurring in the setting of uncontrolled hypertension. Diagnosis is 69

often confirmed by characteristic findings on neuroimaging studies. 70

71

Case Report 72

We present a case of a 25 y/o African American woman with a history of chronic 73

pelvic pain secondary to recurrent endometriosis presenting with chief complaints of 74

fever and pelvic pain. She was treated with laparoscopic ablation three months prior. 75

Workup revealed bilateral tubo-ovarian abscesses and the patient underwent total 76

abdominal hysterectomy and bilateral salpingo-oophorectomy. Postoperatively, the 77

patient had new onset hypertension which eventually lead to a seizure episode. The 78

patient was transferred to the ICU, started on Nicardipine and Keppra and her 79

hypertension improved within several hours. Neuroimaging findings on MRI revealed 80

lesions in the occipital and parietal lobes consistent with PRES. Outpatient workup 81

conducted several months afterwards uncovered a diagnosis of systemic lupus 82

erythematosus, leading us to conclude that the post-operative hypertensive 83

emergency and PRES were secondary to undiagnosed SLE. 84

85

Conclusion 86

The rare complication of PRES has been described in a variety of settings including 87

SLE in which endothelial dysfunction of the intracerebral vasculature leads to 88

characteristic PRES symptoms. Patients, especially those in the post-operative 89

setting covered by multiple specialty providers, with new onset hypertension and 90

neurological symptoms should warrant further workup as they may indicate 91

underlying etiologies such as SLE or other described risk factors for PRES. 92

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Keywords: Posterior reversible encephalopathy syndrome, total hysterectomy, 94

systemic lupus erythematosus, hypertension 95


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INTRODUCTION 96



seizures often occurring in the setting of uncontrolled hypertension [1]. Diagnosis is 99

often confirmed by characteristic findings on neuroimaging studies. PRES has been 100

reported in association with systemic lupus erythematosus (SLE) and is thought to 101

be related to disease activity [2]. There have been several case series published 102

regarding patients with SLE and PRES; the majority of patients were previously 103

diagnosed and were on immunosuppressive therapy at the time of their PRES 104

episode [3]. We describe a patient with no prior history of hypertension who 105

experienced uncontrolled hypertension, vision changes, and seizure in the post-106

operative setting after a total abdominal hysterectomy and bilateral salpingo-107

oophorectomy (TAH-BSO). Imaging and clinical findings led to a diagnosis of PRES. 108

She recovered appropriately after several days and was discharged without an 109

etiology for her new onset hypertension. It was not until several months later that 110

outpatient workup led to an underlying diagnosis of SLE. 111

112

CASE REPORT 113

A 25 year old woman with a past medical history of severe endometriosis status post 114

laparoscopic ablation and recent IUD placement presented to the hospital with 115

debilitating abdominal pain, a fever of 39.3 C, and tachycardia. On admission, she 116

also complained of chest pain and difficulty swallowing medication, feeling as 117

though, “the pills are getting stuck.” This led to intravenous (IV) administration of 118

medications, including an IV PPI for possible pill esophagitis secondary to 119

doxycycline. Pelvic ultrasound demonstrated large bilateral complex adnexal masses 120

and labs showed a normal WBC and anemia with a hemoglobin of 7.6 and a 121

hematocrit of 22%. All other laboratory studies were within normal limits. The patient 122

requested definitive treatment for her symptoms and consented for TAH-BSO. Two 123

units of packed red blood cells were given to the patient prior to surgery. The surgery 124

was performed without any complications and a Jackson Pratt drain was placed in 125

the RLQ. During surgery, the patient was confirmed to have bilateral tubo-ovarian 126

abscesses. 127


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On post-operative day one, the patient was tachycardic with a heart rate of 100 128

beats per minute and blood pressure of 156/111. Oral labetalol was ordered for the 129

patient to control her tachycardia and blood pressure. Of note, she had no prior 130

history of hypertension. She also continued to have difficulty swallowing pills which 131

persisted throughout her hospital course. On postoperative day 2, the patient had a 132

normal heart rate and blood pressure; however, she developed acute kidney injury 133

with oliguria, which was corrected with IV fluids. For the following two days, the 134

patient’s blood pressure began to rise so the dose of labetalol was increased and 135

oral amlodipine was started. On postoperative day five, the patient developed 136

worsening tachycardia and hypertension with a maximum blood pressure of 182/118 137

during the day. She also complained of a new onset persistent headache and blurry 138

vision. Labetalol was discontinued, clonidine was started and the dosage of 139

amlodipine was increased. Later that day, the patient had one episode of vomitus 140

and complained of worsening vision changes. She then experienced a seizure 141

episode which lasted less than 3 minutes and was followed by a period of post-tictal 142

confusion. Blood pressure was measured at 175/114 during the code rescue for the 143

seizure. She denied any seizure history or family history of seizures. The patient 144

was transferred to the ICU and Keppra (UCB Pharma Inc., Smyrna, Georgia, U.S.A.) 145

was given for seizure prophylaxis and a nicardipine drip was started to control for her 146

hypertension. 147

MR brain angiography and MRI of the brain without contrast were ordered for further 148

evaluation. MR brain angiography showed no evidence of thrombosis. MRI of the 149

brain without contrast showed edema signal changes in a cortical and subcortical 150

distribution in both the subdural cortices, temporal cortices, in the right frontal and 151

parietal cortex (Figure 1). There was mild reversal on diffusion. These imaging 152

findings in context of the clinical picture suggested the diagnosis of posterior 153

reversible encephalopathy syndrome. Following the seizure episode, further inquiry 154

was made into the cause of uncontrolled hypertension during the patient’s hospital 155

stay. At the time, it was thought to be that the patient was not compliant with her oral 156

hypertension medications during her hospital course as she had continued 157

discomfort when swallowing pills. 158


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During the remaining four days of the hospitalization, the patient did not experience 159

any further neurological symptoms and had a negative EEG. She had a CT brain 160

completed without contrast which showed no acute intracranial hemorrhage and loss 161

of normal gray-white matter cortex along the frontal, parietal and occipital cortex and 162

subcortical distribution, greater on the right side. She was weaned off of the 163

nicardipine and transitioned to an oral medication regimen of amlodipine, 164

chlorthalidone, and lisinopril. By this time, her ability to swallow oral medication 165

improved. She was discharged on amlodipine, chlorthalidone, and lisinopril for blood 166

pressure control and Keppra for seizure prophylaxis. She was encouraged to follow 167

up with her primary care and to return within a month for further imaging studies. 168

The patient did not follow up for imaging; however, two months later, she was seen 169

in the emergency department (ED) on two separate occasions with a chief complaint 170

of arthralgias. At the first visit, she was discharged from the ED on corticosteroids 171

with the diagnosis of arthralgias secondary to an adverse reaction from Lupron shot 172

she had received months prior to treat her endometriosis. She was referred to a 173

rheumatologist at this time. To note, the patient was anemic at this time with 174

hemoglobin and hematocrit at 9.3/ 28.2 and CRP and ESR were noted to be 175

elevated. She returned to the ED a week later with the same complaint, stating that 176

her appointment to see the rheumatologist was not for several weeks. She was 177

discharged again the same day with the same diagnosis. She was seen by her 178

primary care physician later that month who eventually diagnosed her with SLE. She 179

was found to have positive laboratory tests for ANA, anti-Smith, anti-dsDNA. She 180

was started on a regimen of mycophenolate mofetil, hydroxychloroquine, and 181

prednisone and her symptoms resolved. Further neurological workup at 6 months 182

included MRI sequences of T2 FLAIR, diffusion and ADC, and T1 with and without 183

contrast. Imaging appeared unremarkable with no lasting changes from prior PRES 184

episode. In addition, she had a normal EEG and no further seizure episodes or any 185

other clinical signs of neurological changes. 186

187

DISCUSSION 188

Posterior reversible leukoencephalopathy syndrome (PRES) was first described by 189

Hinchey et al as a recognizable pattern of headache, altered mental status, seizure, 190


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and vision loss [1]. Other sequelae of intracranial hypertension may be present as 191

well, contributing to the high variability in clinical presentation [4]. PRES is often 192

found with characteristic findings on neuroimaging studies including edema in the 193

posterior cortical white matter. Although named as such, findings again may be 194

variable and diagnosis is not restricted to strictly posterior or reversible lesions [5-6]. 195

PRES has been described in the literature in association with pregnancy, eclampsia, 196

drug toxicity and autoimmune conditions such as systemic lupus erythematosus 197

(SLE), as was the case for our patient. The underlying pathophysiology is focused 198

around the “endothelial hypothesis” and high blood pressure [7-8]. These theories 199

purport an inciting factor for sustained or uncontrolled hypertension leading to 200

endothelial dysfunction and loss of nitric oxide production. This results in subsequent 201

vasogenic edema which is found on imaging studies. 202

Although our patient’s course was diagnosed relatively quickly and resolved without 203

complication, PRES identification in the acute setting is important for preventing 204

associated morbidity. In a retrospective study of severe PRES, Legriel et al reported 205

increased prevalence of status epilepticus and unfavorable functional outcome 206

based on Glasgow Outcome Score [9]. Time to control of causative factor was found 207

to be an independent predictor of 90 day functional outcome, highlighting the 208

importance of recognition of clinical presentation and intervention [10-11]. In this 209

case, delays in diagnosis of the patient were due to confounders in her clinical 210

presentations. Our patient experienced hypertension preoperatively which was 211

thought to be caused by pain from her chief complaint. This condition along with the 212

medication noncompliance secondary to suspected pill esophagitis disguised the 213

underlying cause of the patient’s hypertension emergency, her undiagnosed SLE. 214

Because the clinical course was relatively benign after the seizure episode as blood 215

pressure was switched to intravenous management and anti-epileptics were started, 216

no further workup for new onset hypertension was completed. She was simply 217

diagnosed with secondary hypertension. Closer follow up on a telemetry/ICU floor 218

was helpful in monitoring vital signs postoperatively and may be suitable for 219

recommendation for all patients undergoing procedures with general anesthesia [12]. 220

Comparing our case to a review of case series pertaining to SLE and PRES revealed 221

similarities in most common presenting symptoms, age of onset, and brain lobes 222


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affected [2]. The unique component of this presentation is that PRES was the initial 223

finding of SLE and that the onset occurred in the post-operative setting. The majority 224

of PRES cases reported come after patients have already been diagnosed with SLE 225

and started on immunosuppressive therapy. PRES onset is related to increase in 226

disease activity and can signal the need for adjustments of immunosuppressive 227

therapy to control lupus activity [2, pp2133]. There are also other reports of PRES 228

occurring after TAH; however, in those cases, PRES was attributed to other causes 229

such as rapid correction of anemia and incomplete pain control [13-14]. 230

231

CONCLUSION 232

PRES is a rare complication has been described in a variety of settings including 233

SLE. The underlying endothelial dysfunction from lupus disease activity is suspected 234

to contribute to the interruption of neurovascular autoregulation, placing patients at 235

an increased risk for vasogenic edema and clinical symptoms. Multi-specialty care 236

teams working together in the post-operative setting should take note of patients with 237

new onset hypertension and neurological symptoms such as seizures as they may 238

be indicators of underlying autoimmune processes such as SLE or other described 239

risk factors for PRES. Early detection and management may lead to proper workup 240

and treatment at an earlier clinical disease state, which may lead to better long term 241

outcomes for patients. 242

243

CONFLICT OF INTEREST 244

The authors declare no conflicts of interest. 245

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REFERENCES 247

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posterior leukoencephalopathy syndrome. N Engl J Med. 1996; 334(8):494-249

500. 250

2. Budhoo A, Mody G. The spectrum of posterior reversible encephalopathy in 251

systemic lupus erythematosus. Clin Rheumatol. 2015; 34(12):2127-34. 252

3. Shaharir S, Remli R, Marwan A, Said M, Kong N. Posterior reversible 253

encephalopathy syndrome in systemic lupus erythematosus: pooled analysis 254


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4. Richards C, Mcmurray R, Criman E, Clark M, Gillern S. An unusual 257

presentation of a rare disease: posterior reversible encephalopathy syndrome 258

following abdominal sepsis. J Surg Case Rep. 2016; 2016(11). 259

5. Canney M, Kelly D, Clarkson M. Posterior reversible encephalopathy 260

syndrome in end-stage kidney disease: not strictly posterior or reversible. Am 261

J Nephrol. 2015; 41(3):177-82. 262

6. Fitzgerald R, Santoro J, Hinduja A, Samant R, Kumar M, Angtuaco E. PRES 263

and Epilepsy: A Potential Long-Term Consequence of a "Reversible" 264

Syndrome. Neurologist. 2017; 22(2):41-43. 265

7. Bartynski W. Posterior reversible encephalopathy syndrome, part 2: 266

controversies surrounding pathophysiology of vasogenic edema. AJNR Am J 267

Neuroradiol. 2008; 29(6):1043-9. 268

8. Marra A, Vargas M, Striano P, Del Guercio L, Buonanno P, Servillo G. 269

Posterior reversible encephalopathy syndrome: the endothelial hypotheses. 270

Med Hypotheses. 2014; 82(5):619-22. 271

9. Legriel S, Schraub O, Azoulay E, Hantson P, Magalhaes E, Coquet I, et al. 272

Determinants of recovery from severe posterior reversible encephalopathy 273

syndrome. PLoS ONE. 2012; 7(9):e44534. 274

10. Kozak O, Wijdicks E, Manno E, Miley J, Rabinstein A. Status epilepticus as 275

initial manifestation of posterior reversible encephalopathy syndrome. 276

Neurology. 2007; 69(9):894-7. 277

11. Servillo G, Bifulco F, De Robertis E, Piazza O, Striano P, Tortora F, et al. 278

Posterior reversible encephalopathy syndrome in intensive care medicine. 279

Intensive Care Med. 2007; 33(2):230-6. 280

12. Apfelbaum J, Hagberg C, Caplan R, Blitt C, Connis R, Nickinovich D, et al. 281

Practice guidelines for management of the difficult airway: an updated report 282

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13. Hong S, Jung J, Ryu H, Kwon D, Park M. Posterior reversible encephalopathy 285

syndrome following rapid correction of anemia. Neurology Asia 2013; 286

18(4):423. 287

14. Sato N, Machida H, Kodaka M, Nishiyama K, Komori M. Perioperative 288

posterior reversible encephalopathy syndrome in a patient with no history of 289

hypertension: a case report. JA Clinical Reports. 2016; 2(38). 290

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FIGURE LEGEND 292

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Figure 1: Axial views on T2 FLAIR revealed: A) patchy areas of increased signal 294

with slight involvement of the right frontal lobe and posterior parietal lobe right 295

greater than left B) along the cortex in the right temporal and occipital lobes and the 296

left occipital lobe C) in the cerebellar areas in the distribution of the posterior cerebral 297

circulation D) coronal view of increased FLAIR signal changes typical in PRES. 298

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FIGURE 317

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Figure 1: Axial views on T2 FLAIR revealed: A) patchy areas of increased signal 322

with slight involvement of the right frontal lobe and posterior parietal lobe right 323

greater than left B) along the cortex in the right temporal and occipital lobes and the 324

left occipital lobe C) in the cerebellar areas in the distribution of the posterior cerebral 325

circulation D) coronal view of increased FLAIR signal changes typical in PRES. 326

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