|Year : 2021 | Volume
| Issue : 5 | Page : 486-491
Posterior reversible encephalopathy syndrome– our experience
Sravya VV Kotaru, Pravin Naphade, Shalesh Rohatgi, Satish Nirhale, Prajwal Rao, Dhaval Dave, Akram Furqan Mohd Khan, Sahil BK Gupta
Department of Neurology, Dr DY Patil Medical College, Hospital and Research Centre, Dr DY Patil Vidyapeeth, Pune, India
|Date of Submission||17-May-2020|
|Date of Decision||15-Sep-2020|
|Date of Acceptance||21-Sep-2020|
|Date of Web Publication||14-Jul-2021|
B 104, Mahindra Royale, Nehru Nagar Road, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Posterior Reversible Encephalopathy syndrome (PRES) is an emergency medical condition with varied etiology, presentation and outcome reported in literature. The objective of this study was to determine the clinical and radiological presentations, and clinical outcomes in cases of PRES admitted over the last one year at a tertiary care hospital.
Materials and Methods: We retrospectively analysed all cases diagnosed with PRES from May 2019 to May 2020. We reviewed clinical presentations, etiological history, imaging characteristics, management and clinical outcomes.
Results: Five patients diagnosed with PRES were identified. All patients were females, with age range between 16 to 32 years. Etiological factors were eclampsia (2/5), drug (tacrolimus), massive blood transfusion and chronic kidney disease with hypertension. Headache was the most common clinical presentation. Other clinical presentations were visual symptoms, seizures, altered sensorium, vertigo and vomiting. The most common imaging characteristic was supratentorial T2/FLAIR white matter hyperintensity on MRI, predominantly in parieto-occipital region. Other areas of white matter involvement were cerebellum and brainstem. One patient had hemorrhage complicating PRES. All patients were primarily managed by elimination and treatment of the precipitating factors, along with standard anti-oedema measures and anti-epileptic drugs. There was complete recovery in all patients within one week.
Conclusion: PRES has variable clinical and radiological presentation. Early diagnosis and elimination of precipitating factors are vital for complete recovery.
Keywords: Posterior reversible encephalopathy syndrome, Vasogenic brain oedema, hypertension
|How to cite this article:|
Kotaru SV, Naphade P, Rohatgi S, Nirhale S, Rao P, Dave D, Khan AF, Gupta SB. Posterior reversible encephalopathy syndrome– our experience. Med J DY Patil Vidyapeeth 2021;14:486-91
|How to cite this URL:|
Kotaru SV, Naphade P, Rohatgi S, Nirhale S, Rao P, Dave D, Khan AF, Gupta SB. Posterior reversible encephalopathy syndrome– our experience. Med J DY Patil Vidyapeeth [serial online] 2021 [cited 2021 Oct 19];14:486-91. Available from: https://www.mjdrdypv.org/text.asp?2021/14/5/486/321652
| Introduction|| |
P osterior reversible encephalopathy syndrome (PRES), first described by Hinchey et al., refers to a clinical presentation of reversible subcortical vasogenic brain edema caused by the endothelial injury, resulting from abrupt changes in the blood pressure or direct effects of cytokines on the endothelium. This leads to vasogenic edema, the breakdown of the bloodbrain barrier, and excessive exudation into the brain parenchyma. This syndrome is manifested by neurologic symptoms: headache, nausea or vomiting, generalized seizures, visual disturbance, and altered sensorium. A variety of clinical conditions are associated with the development of PRES. Among the reported cases, the most common ones include hypertensive emergency, renal disease, preeclampsia, eclampsia, and immunosuppressive agents such as tacrolimus and cyclosporine. Other reported causes include sepsis, autoimmune diseases such as systemic lupus erythematosus, systemic sclerosis, tumor lysis syndrome, Guillain–Barre syndrome, AIDS, thrombotic thrombocytopenic purpura, massive blood transfusion, and acute intermittent porphyria. The characteristic radiological findings are T2/FLAIR hyperintensities on MRI, which are most commonly located in bilateral parieto-occipital lobe. These hyperintensities resolve within days or weeks. The presence of hemorrhage, restricted diffusion, and vasoconstriction, within these lesions, are all compatible with this diagnosis.
PRES is reversible after early appropriate treatment, which makes it important to recognize and treat the precipitating causes to prevent its progress to irreversible damage. This study demonstrates some atypical imaging manifestations of PRES as their recognition is important to avoid delay in diagnosis and early treatment with control of blood pressure and cessation of offending drug/toxin can reverse this condition and prevent progression to permanent neurological deficit. Thus, a high degree of suspicion is required so that this condition can be recognized early.
| Material And Methods|| |
We retrospectively analysed all cases of PRES diagnosed at Dr. D Y Patil Medical College, a tertiary care hospital, over one year from May 2019 to May 2020. Approval from the Institutional Ethical Committee was obtained for the study. We assessed detailed clinical history of the patients in terms of presenting complaints, vital parameters, systemic and neurological examination. Most probable etiology of PRES was documented for all patients. Results of routine blood investigations and any special blood tests, specific to each case, were reviewed. All patients had undergone 3 Tesla MRI Brain scan. The MR sequences that were reviewed were T1, T2, FLAIR, DWI and GRE. The locations of MRI signals were noted. The results of EEG findings, if performed, were documented. Management plans, and the outcomes in terms of functional recovery and neurological sequelae were noted.
| Results|| |
A 16-year-old female known case of lupus nephritis who underwent cadaveric renal transplant was on tacrolimus and mycophenolate mofetil (MMF); 15 days after the transplantation, the patient developed a diffuse headache and multiple generalized tonic–clonic seizure (GTCS). Clinically, the patient was in altered sensorium, was mute with a staring look and fixed gaze to the right, and was not following commands. Her blood pressure was within the normal range. Tacrolimus levels were maintained in a therapeutic target range of 10–12 ng/ml during this time frame. Magnetic resonance imaging (MRI) was done which showed multiple, confluent, bilaterally symmetrical T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensities in the frontal, parieto-occipital, and temporal regions [Figure 1] suggestive of PRES.
|Figure 1: Case 1: (a-c) Multiple, confluent, bilaterally symmetrical T2 and fluid-attenuated inversion recovery hyperintensities in frontal, parieto-occipital, and temporal regions. Case 1: (d-f) Magnetic resonance imaging was done after 3 months which demonstrated the resolution of all the lesions. Case 2: (a and b) Ill-defined T2-weighted and fluid-attenuated inversion recovery hyperintensities in the bilateral frontoparietal white matter with Case 2: (c) No diffusion restriction. Case 3 (a-d) Ill-defined T2-weighted and fluid-attenuated inversion recovery hyperintense lesions in cerebellar hemispheres, bilateral temporo-parieto-fronto-occipital lobes involving both gray and white matter. Case 3: (e and f) No diffusion restriction|
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Electroencephalography was normal. Tacrolimus-induced PRES was suspected. After discussion with the nephrologist, tacrolimus was stopped and the patient was continued only on MMF and antiepileptics. Cyclosporine was the alternative to tacrolimus; however, because of similar risk of PRES, it was not considered. After 1 week, the patient became fully conscious, following commands, no gaze restrictions, and no convulsions. Review MRI was done after 3 months which demonstrated the resolution of all the lesions [Figure 1].
An 18-year-old female was brought to the emergency room with a history of six episodes of GTCS, tongue bite, and altered sensorium for 4 h. The patient had a headache before the onset of seizures. A week back, the patient was admitted to a local hospital with complaints of menorrhagia. She had severe anemia with hemoglobin being 3 gm%. She was transfused four units of packed cells over a period of 5 days. There was no history of hypertension as per the records. There was no history of seizures in the past. There was no other significant history. Glasgow coma scale was 10/15. The rest neurological examination was normal. Laboratory examination revealed that hemoglobin (11.2 g/dl), erythrocyte sedimentation rate, liver function tests and renal functions, coagulation profile, antinuclear antibody (ANA), and ANA Blot were normal. The cerebrospinal fluid analysis was also normal. Ultrasound of the abdomen showed fibroid in the uterus. MRI of the brain showed ill-defined T2-weighted (T2W) and FLAIR hyperintensities in the bilateral frontoparietal white matter with no diffusion restriction, suggestive of PRES [Figure 1]. Electroencephalography was also normal.
The patient was managed with intravenous fluids, antiepileptics, and monitoring of blood pressure. The patient improved symptomatically in the form of normal sensorium and no further episodes of seizures. The patient was discharged after 7 days of admission at request. Follow-up after 1 week was uneventful. The cause was suspected to be multiple blood transfusions. Repeat MRI was not done as the patient was unwilling.
A 21-year-old female, primigravida with 33 weeks of gestation, with no history of hypertension, presented with one episode of GTCS diagnosed to have eclampsia, and emergency Lower segment Cesarian section (LSCS) was performed. Eight hours after the surgery, the patient developed severe holocranial headache associated with blurred vision. On examination, the patient was irritable but responding to verbal commands. Her blood pressure was 160/100. The fundus examination was normal. No focal neurological deficit was noted; all deep tendon reflexes were normal and the plantar response was bilaterally flexor. Parenteral magnesium sulfate (4 g over 20 min followed by 1 g hourly infusion) was continued. MRI was performed and axial T2 FLAIR MRI demonstrated ill-defined hyperintense lesions in the cerebellar hemispheres, bilateral temporo-parieto-fronto-occipital lobes involving both gray and white matter with no diffusion restriction on diffusion-weighted imaging [Figure 1] suggestive of PRES. The patient was started on antiepileptics and antihypertensives. The patient gradually improved. Her sensorium became normal in 2 days, and no further episodes of seizures were present. The patient was lost to follow-up.
A 32-year-old female patient who was a known case of chronic renal failure with hypertension on maintenance dialysis for 6 months presented with severe holocranial headache of 1-day duration associated with vertigo and vomiting. She also had complaints of blurred vision. She had one episode of GTCS. On examination, the patient was conscious and obeying commands. Her blood pressure was 190/110. The fundus examination was normal. No focal neurological deficit was noted. All deep tendon reflexes were normal and plantars were flexors. The patient was started on antihypertensives to control blood pressure. MRI of the brain was done which showed patchy areas of hyperintensity in T2 and T2 FLAIR in the bilateral frontal, occipito-parietal subcortical white matter and pons with no diffusion restriction suggestive of PRES [Figure 2]. The patient was started on antiepileptics. Blood pressure was controlled with antihypertensives. She had improved symptomatically and had no further episodes of seizures.
|Figure 2: Case 4: (a-c) Hyperintensity in the T2-weighted and T2 fluid-attenuated inversion recovery in the bilateral frontal, occipito-parietal subcortical white matter and pons. Case 4: (d and e) No diffusion restriction. Case 5: (a-c) Hyperintensities in the axial T2-weighted and T2 fluid-attenuated inversion recovery in temporoparietal and occipital white matter. Case 5: (d and e) Blooming in gradient echo sequences and thin subdural hematoma noted in the fronto-temporoparietal region|
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A 24-year-old female gravida 2 with 32 weeks of gestation presented with two episodes of GTCS with a history of eclampsia in previous pregnancy. Emergency LSCS was done. The following day, the patient developed severe holocranial headache with vision loss in both eyes. On examination, the patient was irritable and obeying commands. Her blood pressure was 160/110. Visual acuity was the only perception of light bilaterally. The pupils were normal in size reacting to light. The fundus examination was normal. The neurological examination was normal. Parenteral magnesium sulfate (4 g over 20 min followed by 1 gm hourly infusion) was continued. MRI was performed which showed ill-defined hyperintensities in axial T2 and T2 FLAIR in the temporoparietal and occipital white matter with blooming in gradient echo sequences and thin subdural hematoma noted in the fronto-temporoparietal region [Figure 2] suggestive of hemorrhagic PRES. The patient was started on antihypertensives and antiepileptics. The patient gradually improved. Her sensorium became normal in 1 day, and there were no further episodes of seizures. Vision improved gradually over a week to 6/18 both eyes.
The clinical and radiological findings in all patients are summarised in [Table 1].
|Table 1: Observations in patients with posterior reversible encephalopathy syndrome|
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| Discussion|| |
The term PRES has been used based on the characteristic imaging findings, the most common location being parieto-occipital lobe. In our study, two patients had eclampsia-induced PRES. The incidence of eclampsia-associated PRES is not known. A large prospective Indian study had found that 71% of eclamptic women developed PRES. The exact pathophysiological mechanism of PRES is still unclear. The mean baseline blood pressure, the proportional rise in blood pressure, and the rapidity with which the change takes place, leading to failure of cerebral autoregulation vasogenic edema and endothelial dysfunction with bloodbrain barrier disruption, are probably all important factors that influence the breakdown in the blood–brain barrier and failure of cerebral autoregulation.
One patient in our study had multiple blood transfusion-induced PRES. Multiple transfusions might have led to a rapid increase in total blood volume, leading to a rapid overload of cerebral blood flow that could result in the vasogenic edema responsible for PRES.
One patient had a renal failure with hypertension; the incidence of PRES associated with it is up to 55%. It is unknown to be independent risk factor unless associated with autoimmune disorder or hypertension.
One patient in our study had a renal transplant and was on tacrolimus which was the causative factor. The incidence of neurotoxicity in connection with cyclosporine or tacrolimus is 7%–9%. The immunosuppressants cause damage to the bloodbrain barrier by various means. Direct toxic effects on the vascular endothelium, leading to capillary leakage and bloodbrain barrier disruption and axonal swelling, may trigger vasogenic edema. The other mechanism described to explain the neurotoxicity of tacrolimus is vasoconstriction, which may be caused by the elaboration of endothelin, hypomagnesemia and hypocholesterolemia. Our patient had normal blood pressure and tacrolimus levels; PRES associated with immunosuppressive therapies may occur in normotensive individuals and those with normal therapeutic levels of these drugs., Even our patient had improvement after cessation of tacrolimus.
PRES usually presents with symmetrical cortical and subcortical hyperintense signal in T2 and FLAIR MRI. The most common location of white matter abnormalities in PRES is the posterior cerebral hemispheres, particularly the parieto-occipital lobes. The preferential posterior brain involvement could be due to less sympathetic innervation of the posterior fossa. Atypical locations such as the cerebellum, the brainstem, the basal ganglia, the deep white matter, or the splenium of the corpus callosum are also known. The brainstem involvement by PRES is associated with a poorer outcome. In our study, two patients had brainstem involvement and both of them did not have neurological deficits.
Restricted diffusion can be seen on MRI in 15%–30% of cases.,, The presence of restricted diffusion is generally associated with irreversible structural injury and incomplete clinical recovery. None of the patients in this study had diffusion restriction.
The incidence of intracranial hemorrhage in PRES is approximately 15%. The three distinct types of hemorrhage are small hemorrhage, sulcal subarachnoid hemorrhage, and intraparenchymal hemorrhage, pathogenesis of which is not clear. One patient in our study had hemorrhagic PRES. In the series reported by Hefzy et al., 23% of patients with PRES complicated by hemorrhage had a poor clinical outcome, with death of six of the seven patients. Severe neurological injury and fatality can be attributed to intracranial hemorrhage, but our patient had no neurological deficit.
PRES has been associated with a variety of conditions and predisposing factors. Hypertension has been recognized as a major factor in the setting of PRES. The association of preeclampsia, eclampsia, and PRES is well documented., PRES has been frequently described in allo-bone marrow transplants, stem cell, and solid organ transplantation, mostly in connection with cyclosporine or tacrolimus neurotoxicity.
There is no specific treatment for PRES, but the disorder is usually reversible when the precipitating cause is eliminated or treated.
The prognosis of PRES is usually favorable and most patients completely recover. However, the extent to which clinical and imaging findings are reversible varies in the literature. Despite its name, PRES is not always fully reversible. Severe neurological injury and fatality can be attributed to intracranial hemorrhage, posterior fossa edema with brainstem compression or acute hydrocephalus, or marked diffuse cerebral edema and increased global intracranial pressure. Persistent neurological deficits such as persistent hemiparesis, seizures, decreased visual acuity, and dizziness have been reported in 10%–20% of patients with PRES.,,
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al
. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494-500.
Chambers KA, Cain TW. Postpartum blindness: Two cases. Ann Emerg Med 2004;43:243-6.
Legriel S, Pico F, Azoulay E. Understanding Posterior Reversible Encephalopathy Syndrome. Annual Update in Intensive Care and Emergency Medicine; Springer, Berlin, Heidelberg. 2011, vol 1. p. 631-53.
Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: Clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015;14:914-25.
Verma AK, Garg RK, Pradeep Y, Malhotra HS, Rizvi I, Kumar N, et al
. Posterior encephalopathy syndrome in women with eclampsia: Predictors and outcome. Pregnancy Hypertens 2017;10:74-82.
Sudulagunta SR, Sodalagunta MB, Kumbhat M, Nataraju AS. Posterior reversible encephalopathy syndrome (PRES). Oxf Med Case Reports 2017;2017:omx011
Mueller-Mang C, Mang T, Pirker A, Klein K, Prchla C, Prayer D. Posterior reversible encephalopathy syndrome: Do predisposing risk factors make a difference in MRI appearance? Neuroradiology 2009;51:373-83.
Song T, Rao Z, Tan Q, Qiu Y, Liu J, Huang Z, Wang X, Lin T. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review. Medicine (Baltimore). 2016 Apr; 95(14):e3173.
Hammerstrom A, Howell J, Gulbis A, Rondon G, Champlin R, Popat U. Tacrolimus-associated posterior reversible encephalopathy syndrome in hematopoietic allogenic stem cell transplantation. Am J Hematol 2013;88:301-5.
Staykov D, Schwab S. Posterior reversible encephalopathy syndrome. J Intensive Care Med 2012;27:11-24.
Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: Prognostic utility of quantitative diffusion-weighted MR images. AJNR Am J Neuroradiol 2002;23:1038-48.
Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA. Posterior reversible encephalopathy syndrome: Associated clinical and radiologic findings. Mayo Clin Proc 2010;85:427-32.
Liman TG, Bohner G, Heuschmann PU, Endres M, Siebert E. The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: The retrospective Berlin PRES study. J Neurol 2012;259:155-64.
Li Y, Gor D, Walicki D, Jenny D, Jones D, Barbour P, et al
. Spectrum and potential pathogenesis of reversible posterior leukoencephalopathy syndrome. J Stroke Cerebrovasc Dis 2012;21:873-82.
Moon SN, Jeon SJ, Choi SS, Song CJ, Chung GH, Yu IK, et al
. Can clinical and MRI findings predict the prognosis of variant and classical type of posterior reversible encephalopathy syndrome (PRES)? Acta Radiol 2013;54:1182-90.
Hefzy HM, Bartynski WS, Boardman JF, Lacomis D. Hemorrhage in posterior reversible encephalopathy syndrome: Imaging and clinical features. AJNR Am J Neuroradiol 2009;30:1371-9.
Lewis LK, Hinshaw DB Jr., Will AD, Hasso AN, Thompson JR. CT and angiographic correlation of severe neurological disease in toxemia of pregnancy. Neuroradiology 1988;30:59-64.
Schwartz RB, Bravo SM, Klufas RA, Hsu L, Barnes PD, Robson CD, et al
. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am J Roentgenol 1995;165:627-31.
Grossbach AJ, Abel TJ, Hodis B, Wassef SN, Greenlee JD. Hypertensive posterior reversible encephalopathy syndrome causing posterior fossa edema and hydrocephalus. J Clin Neurosci 2014;21:207-11.
[Figure 1], [Figure 2]