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Current Neurology and Neuroscience Reports
Published in: Current Neurology and Neuroscience Reports 8/2023

28-06-2023 | Posterior Reversible Encephalopathy Syndrome

Posterior Reversible Leucoencephalopathy Syndrome: Case Series, Comments, and Diagnostic Dilemma

Authors: Jasodhara Chaudhuri, Sagar Basu, Mrinal K Roy, Ambar Chakravarty

Published in: Current Neurology and Neuroscience Reports | Issue 8/2023

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Abstract

Purpose of Review

To report a series of patients with clinical and radiological features suggestive of posterior reversible encephalopathy syndrome (PRES) related to diverse etiologies emphasizing its pathophysiological basis.

Recent Findings

Posterior reversible encephalopathy syndrome (PRES) may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury induced by ischemia from a vasoconstrictive response to rising blood pressure or toxins/cytokines. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. Diagnosis of PRES in some circumstances can be challenging and structural imaging may not be sufficient to distinguish it from other differential diagnostic considerations like ADEM. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Such techniques are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease.

Summary

Eight patients with PRES resulting from different etiologies varying from pre-eclampsia/eclampsia, post-partum headache with seizures, neuropsychiatric systemic lupus erythematosus, snake bite, Dengue fever with encephalopathy, alcoholic liver cirrhosis with hepatic encephalopathy, and lastly reversible cerebral vasoconstriction syndrome (RCVS). Additionally, a diagnostic dilemma between PRES and acute disseminated encephalomyelitis (ADEM) was notable in one patient. Some of these patients did not have or only very transiently had arterial hypertension. PRES may underlie the clinical conundrum of headache, confusion, altered sensorium, seizures, and visual impairment. PRES need not necessarily be always associated with high blood pressure. Imaging findings may also be variable. Both clinicians and radiologists need to familiarize themselves with such variabilities
Literature
1.
Truwit CL, Denaro CP, Lake JR, DeMarco T. MR imaging of reversible cyclosporin A-induced neurotoxicity. Am J Neuroradiol. 1991;12:651–9.PubMedPubMedCentral
2.
Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. Am J Roentgenol. 1995;165:627–31.CrossRef
3.
Hauser RA, Lacey DM, Knight MR. Hypertensive encephalopathy. Magnetic resonance imaging demonstration of reversible cortical and white matter lesions. Arch Neurol. 1988;45:1078–83.CrossRefPubMed
4.
Rail DL, Perkin GD. Computerized tomographic appearance of hypertensive encephalopathy. Arch Neurol. 1980;37:310–1.CrossRefPubMed
5.
Jones-Muhammad M, Warrington JP. Cerebral blood flow regulation in pregnancy, hypertension, and hypertensive disorders of pregnancy. Brain Sci. 2019;9:224–39.CrossRefPubMedPubMedCentral
6.
7.
•• Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334(8):494–500. https://​doi.​org/​10.​1056/​NEJM199602223340​803. One of the first articles to describe the syndrome of PRES and its pathophysiology. Reversible, predominantly posterior leukoencephalopathy may develop in patients who have renal insufficiency or hypertension or who are immunosuppressed. The findings on neuroimaging are characteristic of subcortical edema without infarctionCrossRefPubMed
8.
•• Raman R, Devaramane R, Jagadish GM, Chowdaiah S. Various imaging manifestations of posterior reversible encephalopathy syndrome (PRES) on magnetic resonance imaging (MRI). Pol J Radiol. 2017;82:64–70. https://​doi.​org/​10.​12659/​PJR.​899960. A detailed radiological study. The involvement of the parieto-occipital, frontal and temporal lobes is common in PRES. Occasionally, there may be an involvement of the basal ganglia, cerebellum and brainstem, with or without hemorrhage and restricted diffusion. Radiologists should be aware of the typical and atypical imaging manifestations of PRES in order to make an accurate diagnosisCrossRefPubMedPubMedCentral
9.
•• Je F, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015;14:914–25. A diagnosis of PRES should be considered in the setting of acute neurological symptoms in patients with renal failure, blood pressure fluctuations, use of cytotoxic drugs, autoimmune disorders, or eclampsia. Characteristic radiographic findings include bilateral regions of subcortical vasogenic oedema that resolve within days or weeks. The presence of haemorrhage, restricted diffusion, contrast enhancement, and vasoconstriction are all compatible with a diagnosis. In most cases, PRES resolves spontaneously and patients show both clinical and radiological improvements. The range of symptoms that can comprise the syndrome might be broader than usually thoughtCrossRef
10.
•• Anderson RC, Patel V, Sheikh-Bahaei N, CSJ L, Rajamohan AG, Shiroishi MS, Kim PE, Go JL, Lerner A, Acharya J. Posterior reversible encephalopathy syndrome (PRES): pathophysiology and neuro-imaging. Front Neurol. 2020;11:463. https://​doi.​org/​10.​3389/​fneur.​2020.​00463. Posterior reversible encephalopathy syndrome (PRES) represents a unique clinical entity with non-specific clinical symptoms and unique neuroradiological findings. This syndrome may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injuryCrossRefPubMedPubMedCentral
11.
Garg RK, Kumar N, Malhotra HS. Posterior reversible encephalopathy syndrome in eclampsia. Neurol India. 2018;66:1316–23.CrossRefPubMed
12.
Jones-Muhammad M, Warrington JP. Cerebral blood flow regulation in pregnancy, hypertension, and hypertensive disorders of pregnancy. Brain Sci. 2019;9:224–39.CrossRefPubMedPubMedCentral
13.
Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol. 2014;10(8):466–80.CrossRefPubMedPubMedCentral
14.
•• Chakravarty A, Chakrabarti SD. The neurology of eclampsia: some observations. Neurol India. 2002;50:128–35. An early report on the neurological and radiological findings in eclampsia and a detailed discussion on the pathogenesis of the conditionPubMed
15.
16.
• Delgado ME, Del Brutto OH. Case report: Reversible posterior leukoencephalopathy in a venomous snake (Bothrops asper) bite victim. Am J Trop Med Hyg. 2012;86(3):496–8. Unusual case report of PRES induced by snake biteCrossRefPubMedPubMedCentral
17.
18.
Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am. J. Neuroradiol. 2008;29:1043–9.CrossRefPubMedPubMedCentral
19.
Tam CS, Galanos J, Seymour JF, et al. Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol. 2004;77:72–6.CrossRefPubMed
20.
• Largeau B, Boels D, Victorri-Vigneau C, Cohen C, Gandonnière CS, Ehrman S. Posterior reversible encephalopathy syndrome in clinical toxicology: a systematic review of published case reports. Front Neurol. 2020; https://​doi.​org/​10.​3389/​fneur.​2019.​01420. This study highlights that comorbidities such as chronic hypertension and kidney failure were less frequent than in patients with other PRES etiologies. Imaging analysis did not highlight a specific pattern for poisoning-induced PRES. Although less described, PRES in the context of poisoning, which shares most of the clinical and radiological characteristics of other etiologies, is not to be ignored.
21.
22.
23.
24.
•• Magro-Checa C, Steup-Beekman GM, Huizinga TW TW, van Buchem MA, Ronen I. Laboratory and neuroimaging biomarkers in neuropsychiatric systemic lupus erythematosus: where do we stand, Where To Go? Front Med. 2018;5:340. This article critically reviews the current state of knowledge on laboratory and neuroimaging biomarkers in NP-SLE, discusses the factors that need to be addressed to make these biomarkers suitable for clinical application, and suggests potential future research paths to address important unmet needs in the NP-SLE fieldCrossRef
25.
26.
27.
Liu B, Zhang X, Zhang FC, Yao Y, Zhou R, Miao-Miao Xin MM, Wang LQ. Posterior reversible encephalopathy syndrome could be an underestimated variant of “reversible neurological deficits” in Systemic Lupus Erythematosus. BMC Neurol. 2012;12:152.CrossRefPubMedPubMedCentral
28.
• Nisar T, Alchaki AR, Feinstein E. A rare case of cyclophosphamide-induced posterior reversible encephalopathy syndrome in a patient with anti-GBM vasculitis, and review of current literature. Case Rep Neurol Med. 2019;2019:5. https://​doi.​org/​10.​1155/​2019/​2418597. A case of cyclophosphamide-induced PRES in a patient with anti-glomerular basement membrane (Anti-GBM) positive vasculitis. In the acute setting, PRES can be challenging to distinguish from cerebral venous sinus thrombosis or cerebral vasculitis based on clinical presentation. Neuroimaging with magnetic resonance imaging (MRI) of the brain along with a vessel imaging, can help reach the diagnosisCrossRef
29.
30.
31.
•• Mackay M, Tang CC, Vo A. Advanced neuroimaging in neuropsychiatric systemic lupus erythematosus. Curr Opin Neurol. 2020;33(3):353–61. https://​doi.​org/​10.​1097/​WCO.​0000000000000822​. Study design issues related to patient selection (non-NPSLE vs. NPSLE syndromes, SLE disease activity, medications) are critical for biomarker development. Regional and network structural and functional changes identified with advanced brain imaging techniques in patients with non-NPSLE may be further developed as biomarkers for cognitive and mood disorders attributable to SLE-related mechanismsCrossRefPubMedPubMedCentral
32.
33.
Barber CE, et al. Posterior reversible encephalopathy syndrome: an emerging disease manifestation in systemic lupus erythematosus. Semin Arthritis Rheum. 2011;41:353–63.CrossRefPubMed
34.
• Sheikh-Bahaei N, Acharya J, Rajamohan A, Kim PE. Advanced imaging techniques in diagnosis of posterior reversible encephalopathy syndrome (PRES). Front Neurol. 2020;11:165. https://​doi.​org/​10.​3389/​fneur.​2020.​00165. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Other techniques, such as susceptibility weighted imaging (SWI) improves detection of hemorrhage which has prognostic role. CT or MR Perfusion as well as Single-Photon Emission Computed Tomography (SPECT) are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease.CrossRefPubMedPubMedCentral
35.
Kuhn JH, Peters CJ. Arthropod-borne and rodent-borne virus infection. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, editors. Harrison's principles of internal Medicine, vol. 2. 19th ed. New York: McGraw-Hill; 2015. p. 1318–9.
36.
Sawant Y, Birajdar S, Doshi H, et al. posterior reversible encephalopathy (PRES) in a child with severe dengue. J Trop Pediatr. 2020;66(3):322–6.CrossRefPubMed
37.
•• Trivedi S, Chakravarty A. Neurological complications of dengue fever. Curr Neurol Neurosci Rep. 2022;22(8):515–29. An uptodate review of the neurological manifestations of Dengue fever including their pathogenesisCrossRefPubMedPubMedCentral
38.
39.
40.
41.
Mai NTH, Phu NH, Nghia HDT, et al. Dengue-associated posterior reversible encephalopathy syndrome. Vietnam. Emerg Infect Dis. 2018;24(2):402–4.CrossRefPubMed
42.
•• Cudalbu C, Taylor-Robinson SD. Brain edema in chronic hepatic encephalopathy. J Clin Exp Hepatol. 2019;9(3):362–82. This review explores the different methods used to measure brain edema ex vivo and in vivo in animal models and in humans with chronic HE. In addition, an in-depth description of the main studies performed to date is provided. The role of brain edema in the neurological alterations linked to HE and whether HE and brain edema are the manifestations of the same pathophysiological mechanism or two different cerebral manifestations of brain dysfunction in liver disease are still under debate. In vivo MRI/magnetic resonance spectroscopy studies have allowed insight into the development of brain edema in chronic HECrossRefPubMedPubMedCentral
43.
44.
45.
Elizabeth J, Ramy S, Ishita D, Kristina K, Sharma R. PRES in alcoholic hepatitis: hepatic encephalopathy a common theme: 1778. Am J Gastroenterol. 2016;111:S852–3.CrossRef
46.
•• Kumar G, Taneja A, Kandiah PA. Brain and the liver: cerebral edema, hepatic encephalopathy and beyond. Hepatic Critical Care. 2017:83–103. https://​doi.​org/​10.​1007/​978-3-319-66432-3_​8. Occurrence of brain dysfunction is common in both chronic liver disease as well as acute liver failure. While brain dysfunction most commonly manifests as hepatic encephalopathy is chronic liver disease; devastating complications of cerebral edema and brain herniation syndromes may occur with acute liver failure. Ammonia seems to play a central role in the pathogenesis of brain dysfunction in both chronic liver disease and acute liver failure. In this chapter we outline the pathophysiology and clinical management of brain dysfunction in the critically ill patients with liver disease
47.
•• de Boysson H, , Parienti JJ, Mawet J, et al Primary angiitis of the CNS and reversible cerebral vasoconstriction syndrome: a comparative study. Neurology 2018;91:e1468-e1478.This study confirms that careful analysis of clinical context, headache features, and patterns of brain lesions can distinguish PACNS and RCVS within the first few days of admission in most cases. However, diagnosis remains challenging in a few cases.CrossRefPubMed
48.
•• Singhal AB, Topcuoglu FJW, et al. Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical, imaging, and angiographic comparison. Ann Neurol. 2016;79:882–94. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. In patients without TCH and positive angiography, neuroimaging can discriminate RCVS (no lesion) from PACNS (deep/brainstem infarcts).CrossRefPubMed
49.
Choi HA, Lee MJ, Choi H, Chung CS. Characteristics and demographics of reversible cerebral vasoconstriction syndrome: a large prospective series of Korean patients. Cephalalgia. 2018;38(4):765–75.CrossRefPubMed
50.
Singhal AB. Diagnostic challenges in RCVS, PACNS, and other cerebral arteriopathies. Cephalalgia. 2011;31(10):1067–70.CrossRefPubMed
51.
•• Singhal AB. Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome as syndromes of cerebrovascular dysregulation. Continuum (Minneap Minn). 2021;27(5, Neurocritical Care):1301–20. This article describes the causes, clinical and imaging features, management, and prognosis of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), in which the underlying pathophysiology is related to reversible dysregulation of the cerebral vasculature.PubMed
52.
• Mandell DM, Matouk CC, Farb RI, et al. Vessel wall MRI to differentiate between reversible cerebral vasoconstriction syndrome and central nervous system vasculitis: preliminary results. Stroke. 2012;43(3):860–2. Preliminary results suggest that high-resolution contrast-enhanced vessel wall MRI may enable differentiation between reversible cerebral vasoconstriction syndrome and central nervous system vasculitisCrossRefPubMed
53.
• Wagih A, Mohsen L, Rayan MM, Hasan MM, Al-Sherif AH. Posterior reversible encephalopathy syndrome (PRES): restricted diffusion does not necessarily mean irreversibility. Pol J Radiol. 2015;80:210–6. https://​doi.​org/​10.​12659/​PJR.​893460. PRES is completely reversible in the majority of patients, even with restricted diffusion. None of the variables under study could predict the reversibility of PRES lesions. It seems that this process is individual-dependentCrossRefPubMedPubMedCentral
54.
55.
Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335:2–13.CrossRefPubMedPubMedCentral
56.
Irvin W, MacDonald G, Smith JK, Kim WY. Dexamethasone- induced posterior reversible encephalopathy syndrome. J Clin Oncol. 2007;25:2484–6.CrossRefPubMed
57.
•• Kariyawasam S, Singh RR, Gadian J, Lumsden DE, Lin J-P, Siddiqui A, Hacohen Y, Absoud M, Lim M. Clinical and radiological features of recurrent demyelination following acute disseminated encephalomyelitis (ADEM), multiple sclerosis and related disorders. Mult Scler Relat Disord. 2015;4(5):451–6. https://​doi.​org/​10.​1016/​j.​msard.​2015.​06.​013. ADEM patients with infratentorial demyelination are more likely to present with a second infratentorial demyelination, although clinical and radiological features at outset could not predict the relapsing cohortCrossRefPubMed
58.
• Ergün T, Lakadamyali H, Yilmaz A. Recurrent posterior reversible encephalopathy syndrome in a hypertensive patient with end-stage renal disease. Diagn Interv Radiol. 2008;14(4):182–5. Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiologic entity characterized by headache, variable mental status, epilepsy, visual disturbances, and typical transient changes in the posterior cerebral perfusion. Recurrence of PRES is not common, but increasingly in recent years, studies demonstrate recurrence of this syndrome in populations with different diseases. In this report, we describe recurrent PRES in a hypertensive patient with end-stage renal disease, and discuss recurrence as the least-characterized feature of PRES. This condition can cause neurological sequelae such as persistent brain damage and epilepsy, arising from delays in diagnosis and therapy. To the best of our knowledge, this is the first report demonstrating recurrent PRES in a patient on hemodialysis for end-stage renal diseasePubMed
59.
Pande AR, Ando K, Ishikura R, et al. Clinicoradiological factors influencing the reversibility of posterior reversible encephalopathy syndrome: a multicenter study. Radiat Med. 2006;24:659–68.CrossRefPubMed
60.
• Prasad N, Gulati S, Gupta RK, Kumar R, Sharma K, Sharma RK. Is reversible posterior leukoencephalopathy with severe hypertension completely reversible in all patients? Pediatr Nephrol. 2003;18:1161–6. Leukoencephalopathy with severe hypertension is reversible both clinically and radiologically in the majority of children after the control of hypertension. However, a few patients may have residual damage and may need psychometric analysis and follow-up for neurodevelopmental sequelaeCrossRefPubMed
61.
Cordelli DM, Masetti R, Ricci E, Toni F, Zama D, Maffei M, Gentili A, Parmeggiani A, Pession A, Franzoni E. Life-threatening complications of posterior reversible encephalopathy syndrome in children. Eur J Paediatr Neurol. 2014;18(5):632–40.CrossRefPubMed
62.
•• Hinduja A. Posterior reversible encephalopathy syndrome: clinical features and outcome. Front Neurol. 2020;11:71. https://​doi.​org/​10.​3389/​fneur.​2020.​00071. Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome that is characterized by a spectrum neurological and radiological feature from various risk factors. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Although seizures were common, epilepsy is rare. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imagingCrossRefPubMedPubMedCentral
63.
• Sweany JM, Bartynski WS, Boardman JF. “Recurrent” posterior reversible encephalopathy syndrome. J Comput Assist Tomogr. 2007;31(1):148–56. In a retrospective review, 3 (3.8%) of 78 patients developed recurrent posterior reversible encephalopathy syndrome. Underlying clinical conditions included sickle cell disease, antibody-positive autoimmune disease, and allogeneic bone marrow transplantation. Infection (bacterial/viral) was suspected or documented in both episodes in all 3 patients. Evidence of endothelial injury (schistocyte formation and increased lactate dehydrogenase) was documented in all patients, and multiple organ dysfunction syndrome developed during the hospital course of all admissionsCrossRefPubMed
64.
Prasad N, Gulat S, Gupta RK, Kumar Sharma RK. Is reversible posterior leukoencephalopathy with severe hypertension completely reversible in all patients? Pediatr Nephrol. 18(11):1161–6.
65.
•• Trivedi S, Chakravarty A. Neurological complications of malaria. Curr Neurol Neurosci Rep. 2022;22(8):499–513. A up to date review of neurological manifestations of Malaria including thir pathophysiologyCrossRefPubMedPubMedCentral
Metadata
Title
Posterior Reversible Leucoencephalopathy Syndrome: Case Series, Comments, and Diagnostic Dilemma
Authors
Jasodhara Chaudhuri
Sagar Basu
Mrinal K Roy
Ambar Chakravarty
Publication date
28-06-2023
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 8/2023
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-023-01281-3