Posterior reversible encephalopathy syndrome – A case report Sindrom posteriorne reverzibilne encefalopatije

Introduction. Posterior reversible encephalopathy syndrome (PRES) is characterized by the following symptoms: seizures, impaired consciousness and/or vision, vomiting, nausea, and focal neurological signs. Diagnostic imaging includes examination by magnetic resonance (MR) and computed tomography (CT), where brain edema is visualized bilaterally and symmetrically, predominantly posteriorly, parietally, and occipitally. Case report. We presented a 73-yearold patient with the years-long medical history of hipertension and renal insufficiency, who developed PRES with the symptomatology of the rear cranium. CT and MR verified changes in the white matter involving all lobes on both sides of the brain. After a two-week treatment (antihypertensive, hypolipemic and rehydration therapy) clinical improvement with no complications occurred, with complete resolution of changes in the white matter observed on CT and MR. Conclusion. PRES is a reversible syndrome in which the symptoms withdraw after several days to several weeks if early diagnosis is made and appropriate treatment started without delay.


Introduction
Posterior reversible encephalopathy syndrome (PRES) is characterized by the following symptoms: epileptic seizures, consciousness impairment, visual abnormalities, nausea, vomiting and focal neurological signs.It was first described by Hinchey et al. 1 in 1996.based on the study of 15 cases.Since then this syndrome has been also designated by reversible posterior leukoencephalopathy syndrome, reversible posterior cerebral edema syndrome and reversible occipital parietal encephalopathy [2][3][4][5] .
Studies have shown that various conditions can lead to development of PRES, hypertension, autoimmune diseases, toxic agents, sepsis, preeclampsia/eclampsia, kidney diseases being among them 1,6 .Regardless to this heterogeneity main pathophysiological mechanism which leads to development of this syndrome is cerebral vasogenic edema which occurs as a result of abnormality in blood flow through the braincerebral blood flow (CBF) 7 .
Diagnostical imaging includes magnetic resonance imaging (MR) and, less commonly, computed tomography (CT), where cerebral edema is visualized bilaterally and symetrically Correspondence to: Dejan Kostić, Institute of Radiology, Military Medical Academy, Crnotravska 17, 11 000 Belgrade, Serbia.Phone: +381 63 6969 79.E-mail: kostic_dejan@ikomline.netpredominantly in posterior parietally and occipitally, but frontal and temporal lobes can also be affected, as well as basal ganglia, brainstem and cerebellum.Also, alongside with the white matter, cortical gray matter can be affected as well 8 .
The diagnosis of PRES is complicated, since CT results are often normal or non-specific, and MR scanners not available in many centers.Standard MR sequences, which include T1-weighted images (T1W), T2-weighted images (T2W), fluid attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) map, as well as contrast T1W, are sufficient for the diagnosis.
The treatment should primarily consist of correction of the underlaying causes which led to neurological symptomatology, and then symptomatic measures should be taken.Some patients may develop severe manifestations of PRES, such as coma or status epilepticus, which require intensive care unit (ICU) admission 9,10 .
PRES is a reversible syndrome, but in a small number of patients neurological deficit is permanent.

Case report
A 73-year-old patient was complaining of headache, instability while walking and loss of balance which lasted for a few days.The patient had a history of hypertension and chronic renal insufficiency.Arterial blood pressure reached 160/90 mmHg.Clinical presentation at admittance was dominated by symptomatology of posterior fossa with discreet right faciobrachial hemiparesis.Initially, CT scanning without application of contrast was performed showing the presence of both-sided hypodensic zones, frontally more prominent on the left as well as parietally right subcortically, which resembled mostly vasogenic edema (Figure 1).

Fig. 1 -Native computed tomography (CT) scan showing hypodense zones on both sides of the frontal and parietal
lobe, more pronounced on the right.
MR spectroscopy using 2D multivoxel SE 144 and single voxel SE 144 and SE 35 sequences with positioning of the volume of interest occipitoparietally was also performed.
This scanning showed cortico-subcortical temporopolar on both sides, parieto-occipital and posterior parietal both sidedly more dominant on the right, pachy, unsharply bordered, partly confluent lesions hyperintense in T2W and FLAIR sequence with mild compressive effect on occipitial horn of the right lateral lobe, without postcontrastive enhancment of signal intensity (Figure 2).

A) B)
C) D) Fig. 2 -A There were no signs of diffusion restriction.In DWI sequence occipitoparietally on the right there were no changes in signal intensity, but on ADC map hypointensity of the signal was observed, implicating the existence of vasogenic edema.
Based on the CT and MR scanning results the patient was referred to MR spectroscopy.Using 2D multivoxel spectroscopy the obtained spectres showed normal or slightly higher values of choline for the area in question (Cho/Cr), and NAA was slightly lower.By single voxel spectroscopy spectres of low apsolute concentrations were obtained, ratio Cho/Cr did not significantly deviate from normal values for the area in question.NAA was lower.Resonance lines of lipides and lactates were not noticed.Diffusion Tensor Imaging (DTI) reveled that in the area of lesion occipitoparietally on the right fractional anizotrophy was lower.
After diagnosing the patient was regularly treated with antihypertensive, antilypemic and rehydration therapy and was discharged two weeks later with arterial tension 140/80 mmHg and normalized neurological findings.
Control MR scanning, two months after the initial one, showed complete regression of T2W and FLAIR hyperintense changes which had previously affected cortex and subcortical white matter (Figure 3).

Discussion
PRES has been reported in patients aged 4 to 90 years, although most cases occur in young to middle-aged adults.Mechanical ventilation is required in 35% to 40% of patients 12, 13 .The average hospital stay is 20 days, and the mortality rate up to 15% 12,13 .Numerous conditions may lead to the syndrome: acute hypertension, renal function disorder, immunosuppressive therapies being some of them 1 .Other possible causes are eclampsia, transplantation, chemotherapy 15 , systemic infection, shock 16 and insect bites 17,18 .
Until recently it was thought that PRES tipically affects the white matter, simetrically, predominantly in occipital and posterior parietal areas.Sporadically, changes were described in frontal and temporal lobes, basal ganglia, brain stem and cerebellum, as well as in cortical grey matter 6 .
The main pathophysiological mechanism which leads to this syndrome is cerebral vasogenic edema.Some authors think that the occurence of edema is the consequence of a disorder in cerebral autoregulation of blood flow through the brain.Other authors think that it is caused by endothelium dysfunction with cerebral hypoperfusion 7 .

Fig. 3 -Control magnetic resonance imaging (MRI) after two month. T2W axial tomogram and coronal T2W tomogram showed almost complete regression of the lesion.
CT scan is often normal or non-specific, as in our case.Topographic regions suggest the diagnosis of PRES 20 .
T2W sequence shows lesions of higher intensity signal, which indicates the existence of edema, and T1W shows low intensity signal.Changes in PRES are best seen in FLAIR sequence, as hyperintense zones cortically and/or subcortically 8 and such changes are more often frontally localized compared to the posterior presentation using this technique 21 .
Signal intensity on the DWI sequence is normal, but it is higher on ADC 22 .
Fractional isotrophy shows zones of decrease, which indicates a mild damage of brain paths which can be reversible and it is in accordance with a mild decrease of the values of N-acetylaspartate (NAA) obtained by MR spectroscopy 23,24 .
MR spectroscopy is not superior to conventional MR sequences, but it helps us to rule out other etiology of changes.Signal intensity increase after application of contrast agents is seen in about one half of cases 19 .
recent years susceptibility-weighted imaging (SWI) is used for detecting microhemorrhagies.This examination shows a higher occurrence rate of microhemorrhage in this syndrome which is associated with vasculopathy 25 .
All those characteristics of lesions were also seen in our case.
Many conditions may resemble PRES.The differential diagnosis of findings obtained by the examination of the brain using MR imaging in patients with abnormalities of cerebellar white matter includes the following 5,26 : acute disseminated encephalomyelitis (ADEM) in which, unlike the PRES, lesions in T1 can be hypo-to isointense, in DWI the signal is without changes, and on ADC map an increase of signal intensity is seen, changes being contrast uptaken 27 ; in progressive multifocal leukoencephalopathy (PML) in DWI new and active lesions show hyperintensity of signal, the old ones hypointensity, while in ADC map new and active lesions are hypointense and the old ones are hyperintense 28 ; in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in DWI and ADC sequences the restriction of diffusion always occurs, and the changes after iv application of contrast do not show signs of signal hyperintensity, changes simetrically affect basal ganglia and white matter widening the perivascular space 29 ; in acute ischemia a restriction of diffusion does exist (signal hyperintensity in DWI, signal hypointensity in ADC map) without contrast increase of signal intensity 30 ; in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like (MELAS) episodes signal hyperintensity occurs in T1 W sequence, in T1 W and T2 FLAIR it is hypointense, and in DWI iso-or hypointense.In ADC it is iso or hyperintense.The increase in signal intensity may occur post-contrastivelly 31 ; in CNS vasculitis lesions show a decrease in signal intensity in T1 W, an increase in signal intensity in T1 W and FLAIR, and in DWI and ADC.Signal hyperintensity occurs postcontrastivelly 32 ; in creutzfeldt -jakob disease the changes are isointense in T1 W, hyperintense in T2 W, T2 FLAIR and DWI, and in ADC they are hypointense 33 .

Conclusion
Posterior reversible encephalopathy syndrome has no specific clinical presentation and mortality rate is up to 15% of cases due to acute hemorrhage and ischemia.Studies show that magnetic resonance scanning is crucial for diagnosing, monitoring the course and assessing the treatment effectiveness of this syndrome.
Although the name of the syndrome implicates that posterior cerebral circulation is affected, the changes are often localized in frontal and temporal lobes, as noted in our case study, as well as in the structures of brain stem and cerebellum.
Because of the complications (hemorrhage, ischemia), as well as the lethal outcome, the acronym denoting this clinicoradiological entity has been challenged.
We consider that a suggestion to change the term into potentially reversible encephalopathy syndrome should be accepted.

R E F E R E N C E S
) T2W axial tomogram showing the zones of vasogenic edema of cortical/subcortical localization in the parietal lobes, more pronounced on the right; B) T2W axial tomogram showing the asymmetric changes frontally on the left, parietally bilaterally, more pronounced on the right; C) T2W axial tomogram showing the changes frontally on the right; D) Coronal T2W axial tomogram showing vasogenic edema bilaterally frontally, pronounced on the right.Kostić D, et al.Vojnosanit Pregl 2015; 72(8): 735-739.