Posterior reversible encephalopathy syndrome (PRES) and CT perfusion changes

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Title:
Posterior reversible encephalopathy syndrome (PRES) and CT perfusion changes
Series Title:
International Journal of Emergency Medicine
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English
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Hedna, Vishnumurthy Shushrutha
Stead, Latha Ganti
Bidari, Sharathchandra
Patel, Akhil
Gottipati, Amareshwari
Favilla, Christopher G.
Salardini, Arash
Khaku, Aunali
Mora, Diana
Pandey, Ajay
Patel, Het
Waters, Michael F.
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Abstract:
Posterior reversible encephalopathy syndrome (PRES) can present with focal neurologic deficits, mimicking a stroke and can often represent a diagnostic challenge when presenting atypically. A high degree of suspicion is required in the clinical setting in order to yield the diagnosis. Cerebral CT perfusion (CTP) is utilized in many institutions as the first line in acute stroke imaging. CTP has proved to be a very sensitive measure of cerebral blood flow dynamics, most commonly employed to delineate the infarcted tissue from penumbra (at-risk tissue) in ischemic strokes. But abnormal CTP is also seen in stroke mimics such as seizures, hypoglycemia, tumors, migraines and PRES. In this article we describe a case of PRES in an elderly bone marrow transplant recipient who presented with focal neurological deficits concerning for a cerebrovascular accident. CTP played a pivotal role in the diagnosis and initiation of appropriate management. We also briefly discuss the pathophysiology of PRES.
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Publication of this article was funded in part by the University of Florida Open-Access publishing Fund. In addition, requestors receiving funding through the UFOAP project are expected to submit a post-review, final draft of the article to UF's institutional repository, IR@UF, (www.uflib.ufl.edu/UFir) at the time of funding. The institutional Repository at the University of Florida community, with research, news, outreach, and educational materials.

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Abstract
Posterior reversible encephalopathy syndrome (PRES) can present with focal neurologic deficits, mimicking a stroke and can often represent a diagnostic challenge when presenting atypically. A high degree of suspicion is required in the clinical setting in order to yield the diagnosis. Cerebral CT perfusion (CTP) is utilized in many institutions as the first line in acute stroke imaging. CTP has proved to be a very sensitive measure of cerebral blood flow dynamics, most commonly employed to delineate the infarcted tissue from penumbra (at-risk tissue) in ischemic strokes. But abnormal CTP is also seen in stroke mimics such as seizures, hypoglycemia, tumors, migraines and PRES. In this article we describe a case of PRES in an elderly bone marrow transplant recipient who presented with focal neurological deficits concerning for a cerebrovascular accident. CTP played a pivotal role in the diagnosis and initiation of appropriate management. We also briefly discuss the pathophysiology of PRES.
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Shushrutha Hedna, Vishnumurthy
Stead, Latha Ganti
Bidari, Sharathchandra
Patel, Akihl
Gottipati, Amareshwari
Favilla, Christopher G
Salardini, Arash
Khaku, Aunali
Mora, Diana
Pandey, Ajay
Patel, Het
Waters, Michael F
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International Journal of Emergency Medicine. 2012 Feb 29;5(1):12
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au id A1 ca yes snm Hednamnm Shushruthafnm Vishnumurthyinsr iid I1 email vhedna@mail.ufl.edu
A2 SteadGantiLathaI2 lstead@ufl.edu
A3 BidariSharathchandraI3 sbidari@radiology.ufl.edu
A4 PatelAkhilakhil.ufmed@gmail.com
A5 GottipatiAmareshwaridramareshwari@ymail.com
A6 Favillami GChristophercgfavilla@gmail.com
A7 SalardiniArasha.salardini@neurology.ufl.edu
A8 KhakuAunalia.khaku@neurology.ufl.edu
A9 MoraDianadi.kmora@gmail.com
A10 PandeyAjayajay.pandey@neurology.ufl.edu
A11 PatelHethet_patel2004@yahoo.com
A12 WatersFMichaelmwaters@neurology.ufl.edu
insg
ins Department of Vascular Neurology, University of Florida, Archer Road, Gainesville, Florida, 32611, USA
Department of Emergency Medicine, University of Florida, Archer Road, Gainesville, Florida, 32611, USA
Department of Neuro-Radiology, University of Florida, Archer Road, Gainesville, Florida, 32611, USA
source International Journal of Emergency Medicine
issn 1865-1380
pubdate 2012
volume 5
issue 1
fpage 12
url http://www.intjem.com/content/5/1/12
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cpyrt 2012collab Hedna et al; licensee Springer.note This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
abs
sec
st
Abstract
Posterior reversible encephalopathy syndrome b (PRES) can present with focal neurologic deficits, mimicking a stroke and can often represent a diagnostic challenge when presenting atypically. A high degree of suspicion is required in the clinical setting in order to yield the diagnosis. Cerebral CT perfusion (CTP) is utilized in many institutions as the first line in acute stroke imaging. CTP has proved to be a very sensitive measure of cerebral blood flow dynamics, most commonly employed to delineate the infarcted tissue from penumbra (at-risk tissue) in ischemic strokes. But abnormal CTP is also seen in stroke mimics such as seizures, hypoglycemia, tumors, migraines and PRES. In this article we describe a case of PRES in an elderly bone marrow transplant recipient who presented with focal neurological deficits concerning for a cerebrovascular accident. CTP played a pivotal role in the diagnosis and initiation of appropriate management. We also briefly discuss the pathophysiology of PRES.
bdy
Background
Posterior reversible encephalopathy syndrome (PRES), as the name suggests, is a constellation of symptoms caused by reversible ischemia most commonly of the posterior cerebral vasculature, thus affecting the parietal-occipital region. Still other vascular territories can be affected in PRES (see Table tblr tid T1 1).Various terminologies have been used to describe this condition, including "reversible posterior leukoencephalopathy syndrome" and "reversible posterior cerebral edema syndrome" among others abbrgrp abbr bid B1 1. Hypertension (HTN) is the most commonly identified cause of PRES, followed by medications, eclampsia and systemic factors. The pathophysiology of HTN related PRES is due to a failure of cerebrovascular autoregulation, which in turn results in vasogenic edema. Non-hypertensive PRES may be due to an autoimmune or immune response to various stimuli B2 2. The pathology usually affects the posterior brain hemisphere (parietal-occipital region), which may be a consequence of reduced sympathetic innervation in this area. Usually it is a reversible phenomenon, as indicated by the name, but if not recognized early and treated appropriately, permanent brain injury may ensue.
tbl Table 1caption Common location of PREStblbdy cols 1
r
c left
Common location of PRES
cspan
hr
Parietal-occipital most common.
Posterior frontal
Temporal
Thalamus
Cerebellum
Brainstem
Basal ganglia
Case presentation
A 70-year-old white female presented to the emergency room with symptoms of a cerebrovascular accident. She had a history of multiple myeloma status post-autologous bone marrow transplant (BMT) with a conditioning regimen of high-dose melphalan 2 weeks prior to presentation. She woke up the morning of presentation and was found to be confused for a few minutes, followed by a gradual improvement in mental status. About an hour later, she started to experience a severe headache associated with blurry vision, and shortly thereafter she became disoriented again. Paramedics identified agitation, right-side neglect, left gaze deviation and right side weakness. On arrival in the emergency department, the patient's headache had resolved, but the patient was still agitated and disoriented. The patient's altered mental status (AMS) required that the history be obtained from the patient's husband. There was no history of recent infection, fever, weight loss or trauma. The review of systems was negative for photophobia, seizures or any other neurological issues. Pertinent past medical history was that of recent BMT with melphalan and poorly controlled hypertension. She had had thrombocytopenia since the time of BMT and chemotherapy. Her admission blood pressure was 221/114 with a mean arterial pressure (MAP) of 145 mmHg. Her admission NIH stroke scale score was 7, with problems in orientation, not following commands, not answering questions appropriately, left gaze preference, reduced blink on stimulus from the right and possible right-sided neglect. Her visual acuity was reduced to finger movements and light perception in both eyes. She was moving her extremities equally, bilaterally. Reflexes were brisk throughout with equivocal plantar response. The rest of the neurological exam was limited, as the patient was not following commands consistently. Our differential diagnosis at that time included cerebrovascular accident (CVA), PRES (due to elevated BP, recent chemotherapy and bone marrow transplant), seizures and complicated migraine. Since there was no motor deficit associated with the neglect and eye deviation, we were obligated to consider a broad differential diagnosis, including PRES. After the initial laboratory workup, we obtained a CT head and a CT angiogram of the head and neck with perfusion studies. The CTA of the head and neck failed to identify any major vessel cutoff or any acute hypo/hyper density, but the CTP demonstrated increased cerebral blood volume (CBV), cerebral blood flow (CBF) and reduced time to peak (TTP) in the posterior cerebral vascular distribution (see Figures figr fid F1 1 and F2 2). These imaging features were consistent with PRES, and we initiated intravenous anti-hypertensive medications. An MRI brain was obtained, which showed abnormal restriction in the parietal and occipital areas, confirming the diagnosis of PRES (see Figure F3 3). Reduction of the patient's systolic BP from 220 to 180 was associated with slight improvement in her visual acuity and orientation within a couple of hours. Notable laboratory data revealed a platelet count of 11,000/μl and hemoglobin of 11 g/dl. All other laboratory tests were within the normal limits. There was no evidence of thrombotic thrombocytopenic purpura (one of the causes of PRES), and she was admitted with the diagnosis of PRES. At the time of admission, PRES was considered to be secondary to malignant hypertension complicated by recent chemotherapy and BMT. Over the subsequent 48 h, she returned to baseline with improvement of her blood pressure to normal range.
fig Figure 1CTP images in our casetext
CTP images in our case.
graphic file 1865-1380-5-12-1
Figure 2MRI images in PRES
MRI images in PRES.
1865-1380-5-12-2
Figure 3Most commonly attributed theory of PRES
Most commonly attributed theory of PRES.
1865-1380-5-12-3
Discussion
PRES commonly presents with seizures (74%), altered sensorium or encephalopathy, headache and visual changes B3 3. Other neurological features such as aphasia and sensory changes are also seen. PRES can sometimes present similarly to CVA, such as in our case. In such cases, the patient may inadvertently and inappropriately receive thrombolytic therapy. We again stress the point that when a patient presents with stroke-like symptoms, but with an inconsistent neurological exam, then the stroke mimics such as PRES, seizures, migraine and tumor should be included in the differential diagnosis. The etiology of PRES can be broadly divided into five main etiological groups. In order of clinical frequency, PRES etiologies include HTN (61%), cytotoxic medications (19%), preeclampsia or eclampsia (6%) 3, autoimmune and systemic conditions, including sepsis (see Table T2 2). Currently, the pathophysiology of PRES is controversial. The most accepted theory of HTN-related PRES is that of a hyperperfusion injury model (see Figure 3). There will be a failure of cerebral autoregulation in relation to the sudden elevation of blood pressure. This sudden increase in MAP can lead to arteriolar dilation, hyperperfusion, endothelial vascular damage and disruption of the blood brain barrier. This leads to vasogenic edema and potentially reversible ischemia affecting both the grey and white matter B4 4. Another less accepted theory argues that HTN-related dysautoregulation results in vasoconstriction and hypoperfusion injury. However, the above hypothesis fails to explain non-hypertensive PRES, and so some postulate an autoimmune or immune response theory to various stimuli 2.
Table 2Etiology of PRES
Common causes of PRES
Hypertension
Eclampsia and preeclampsia
Drugs:
indent
- Recreational: Cocaine, Amphetamines, PCP, LSD
- Others: Anti-depressants (Tricyclics, MAO Inhibitors), Bronchodilators, Erythropoietin, Midodrine, Fludrocortisone, Triple H therapy, Intravenous immunoglobulins (IVIG).
Neoplastic drugs: Cyclosporine-A, Tacrolimus, Interferons, Indinavir, Cisplatin, Cytarabine, Gemcitabine.
Autoimmune and Systemic: Systemic lupus erythematosus (SLE), Scleroderma, Vasculitis like PAN, Wegener's, Thrombotic thrombocytopenic purpura (TTP), Henoch-Schönlein purpura, Hemolytic uremic syndrome (HUS), Amyloid angiopathy, Tumor lysis syndrome, Systemic inflammatory response syndrome (SIRS), Sepsis, Multiple organ Dysfunction, Electrolyte imbalance (Hypomagnesemia, hypercalcemia), Hypocholesterolemia,, GBS, Head injury, Renal failure due to any etiology.
We suggest that PRES is the result of various etiological factors that lead to blood brain barrier injury either by hyper- or hypoperfusion, endothelial dysfunction, changes in blood vessel morphology, hypocapnia or immune system activation 24B5 5. It usually affects parietal and occipital area, s but other regions can be involved as well B6 6.
In our patient we feel that elevated MAP led to regional dysautoregulation, consequently causing hyperperfusion, explaining the findings of increased CBF, CBV and reduced TTP. It is important to recognize that this patient had a recent history of bone marrow transplant with exposure to chemotherapy, which may also be a causative factor in the development of PRES, or may have independently contributed to the tissue injury.
We conclude that the mechanism of PRES is individualized in each patient and depends mainly on the causative factor identified in each case. In the setting of HTN, PRES is most likely due to the mechanism described in the previously discussed theories. In the setting of normotensive PRES, the mechanism may be based on endothelial dysfunction, immune system activation and other systemic features. Although initially edema is vasogenic in nature, a failure to reverse the disease etiology will subsequently cause cytotoxic edema and eventually brain infarction, further emphasizing the importance of early disease recognition.
A high degree of suspicion is required to make this diagnosis as the patient may present atypically. Since many patients with PRES present with inadequate history and AMS, brain imaging plays an important role in the diagnosis of PRES. Even though MRI (particularly T2-FLAIR) is the imaging of choice, CTP can play a significant role that can reveal the cerebral hemodynamics related with this condition. Since there is hyperperfusion the CBF and CBV will be elevated, and TTP will be reduced. The CTP can also have diametrically opposite findings compared to our case B7 7 (see Table T3 3). The brain MRI changes on FLAIR with no changes on diffusion weighted images (DWI) suggest vasogenic edema. Changes in both sequences (FLAIR and DWI) indicate that the cytotoxic edema has set in, which may have an unfavorable outcome. The authors imply that CTP is useful but not superior to MRI in the diagnosis of PRES.
Table 3CT perfusion changes in various brain insults5
Etiology
CBF
CBV
MTT
TTP
Infarct core




Ischemic penumbra
Varies; usually↓

Varies; usually ↑

seizure




PRES*
Usually ↑ but can be ↓
↑ or ↓
Equivocal

tblfn
CBF = cerebral blood flow; CBV = cerebral blood volume; MTT = mean transit time; TTP = time to peak.
*= CTP changes in PRES depend on whether it is a hyperperfusion or hypoperfusion mechanism of PRES.
The management of this condition depends on the etiology and should be initiated in a timely manner. The treatment of the underlying cause is typically sufficient to reverse this condition. However, a word of caution: this condition can lead to irreversible brain insult if the treatment is delayed or if there is prolonged brain insult, in which case a brain insult then becomes irreversible brain infarctions. Additionally, there may be hemorrhagic complications and raised intracranial pressure contributing further to the cerebral damage B8 8. The MAP should be reduced quickly but with caution in the cases of hypertensive PRES. In cases of non-hypertensive PRES, especially in case of neoplastic drugs, the offending agent should be withdrawn quickly to avoid further damage to the blood brain barrier. In the setting of transplant, alternative medications can be substituted to avoid organ rejections B9 9. If an autoimmune etiology is suspected, then immunosuppression has a role in the management B10 10. Seizures are managed with anti-epileptic medications.
Conclusions
Posterior reversible encephalopathy syndrome is a relatively rare syndrome that sometimes presents as a stroke mimic. As such, it is important for the emergency physician to recognize. Urgent recognition and early initiation of management of this condition are imperative as it directly impacts the neurological outcome. Brain CT perfusion can play an important role in the diagnosis.
Consent
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
All the authors were involved in the draft, graphics, grammar correction, creation of tables and figures. All authors read and approved the final manuscript.
bm
ack
Acknowledgements
Publication of this article was funded in part by the University of Florida Open-Access Publishing Fund.
refgrp Posterior reversible encephalopathy syndrome: a reviewFeskeSKSemin Neurol2011312202lpage 21510.1055/s-0031-1277990link fulltext 21590625Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edemaBartynskiWSAJNR Am J Neuroradiol20082961043104910.3174/ajnr.A092918403560Posterior reversible encephalopathy syndrome: associated clinical and radiologic findingsFugateJEClaassenDOCloftHJKallmesDFKozakOSRabinsteinAAMayo Clin Proc201085542743210.4065/mcp.2009.0590pmcid 286197120435835Cerebral circulation in acute arterial hypertension-protective effects of sympathetic nervous activityBeausang-LinderMBillAActa Physiol Scand1981111219319910.1111/j.1748-1716.1981.tb06724.x7282395Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical featuresBartynskiWSAJNR Am J Neuroradiol20082961036104210.3174/ajnr.A092818356474Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findingsMcKinneyAMShortJTruwitCLMcKinneyZJKozakOSSantaCruzKSTeksamMAJR Am J Roentgenol2007189490491210.2214/AJR.07.202417885064Posterior reversible encephalopathy syndrome on computed tomography perfusion in a patient on "Triple H" therapySanelliPCJacobsMAOugoretsIMifsudMJNeurocrit Care200531465010.1385/NCC:3:1:04616159094Hemorrhage in posterior reversible encephalopathy syndrome: imaging and clinical featuresHefzyHMBartynskiWSBoardmanJFLacomisDAJNR Am J Neuroradiol20093071371137910.3174/ajnr.A158819386731Posterior reversible encephalopathy syndrome in the Intensive Care Unit after liver transplant: a comparison of our experience with the existing literatureLunardiNSaraceniEBoccagniPSegatoMBortolatoAManaraRRossiSOriCMinerva Anestesiol2011Posterior reversible encephalopathy syndrome in systemic lupus erythematosusVaraprasadIRAgrawalSPrabuVNRajasekharLKanikannanMANarsimuluGJ Rheumatol20113881607161110.3899/jrheum.10130821572160



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CASEREPORT OpenAccessPosteriorreversibleencephalopathysyndrome (PRES)andCTperfusionchangesVishnumurthyShushruthaHedna1*,LathaGantiStead2,SharathchandraBidari3,AkhilPatel1, AmareshwariGottipati1,ChristopherGFavilla1,ArashSalardini1,AunaliKhaku1,DianaMora1,AjayPandey1, HetPatel1andMichaelFWaters1AbstractPosteriorreversibleencephalopathysyndrome ( PRES)canpresentwithfocalneurologicdeficits,mimickingastroke andcanoftenrepresentadiagnosticchallengewhenpresentingatypically.Ahighdegreeofsuspicionisrequired intheclinicalsettinginordertoyieldthediagnosis.CerebralCTperfusion(CTP)isutilizedinmanyinstitutionsas thefirstlineinacutestrokeimaging.CTPhasprovedtobeaverysensitivemeasureofcerebralbloodflow dynamics,mostcommonlyemployedtodelineatetheinfarctedtissuefrompenumbra(at-risktissue)inischemic strokes.ButabnormalCTPisalsoseeninstrokemimicssuchasseizures,hypoglycemia,tumors,migrainesand PRES.InthisarticlewedescribeacaseofPRESinanelderlybonemarrowtransplantrecipientwhopresentedwith focalneurologicaldeficitsconcerningforacerebrovascularaccident.CTPplayedapivotalroleinthediagnosisand initiationofappropriatemanagement.WealsobrieflydiscussthepathophysiologyofPRES.BackgroundPosteriorreversibleencephalopathysyndrome(PRES),as thenamesuggests,isaconstellationofsymptoms causedbyreversibleischemiamostcommonlyofthe posteriorcerebralvasculature,thusaffectingtheparietal-occipitalregion.Stillothervascularterritoriescanbe affectedinPRES(seeTable1).Variousterminologies havebeenusedtodescribethiscondition,including reversibleposteriorleukoencephalopathysyndrome and reversibleposteriorcerebraledemasyndrome amongothers[1].Hypertension(HTN)isthemost commonlyidentifiedcauseofPRES,followedbymedications,eclampsiaandsyste micfactors.ThepathophysiologyofHTNrelatedPRESisduetoafailureof cerebrovascularautoregulation,whichinturnresultsin vasogenicedema.Non-hypertensivePRESmaybedue toanautoimmuneorimmuneresponsetovariousstimuli[2].Thepathologyusuallyaffectstheposterior brainhemisphere(parietal-occipitalregion),whichmay beaconsequenceofreducedsympatheticinnervationin thisarea.Usuallyitisareversiblephenomenon,as indicatedbythename,butifnotrecognizedearlyand treatedappropriately,permanentbraininjurymay ensue.CasepresentationA70-year-oldwhitefemalepresentedtotheemergency roomwithsymptomsofacerebrovascularaccident.She hadahistoryofmultiplemyelomastatuspost-autologousbonemarrowtransplant(BMT)withaconditioningregimenofhigh-dosemelphalan2weekspriorto presentation.Shewokeupthemorningofpresentation andwasfoundtobeconfusedforafewminutes,followedbyagradualimprovementinmentalstatus. Aboutanhourlater,shestartedtoexperienceasevere headacheassociatedwithblurryvision,andshortly thereaftershebecamedisorientedagain.Paramedics identifiedagitation,right-sideneglect,leftgazedeviation andrightsideweakness.Onarrivalintheemergency department,thepatient sheadachehadresolved,butthe patientwasstillagitatedanddisoriented.Thepatient s alteredmentalstatus(AMS)requiredthatthehistorybe obtainedfromthepatient shusband.Therewasnohistoryofrecentinfection,fever,weightlossortrauma. Thereviewofsystemswasnegativeforphotophobia, seizuresoranyotherneurologicalissues.Pertinentpast *Correspondence:vhedna@mail.ufl.edu1DepartmentofVascularNeurology,UniversityofFlorida,ArcherRoad, Gainesville,Florida,32611,USA FulllistofauthorinformationisavailableattheendofthearticleHedna etal InternationalJournalofEmergencyMedicine 2012, 5 :12 http://www.intjem.com/content/5/1/12 2012Hednaetal;licenseeSpringer.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttribution License(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,andreproductioninanymedium, providedtheoriginalworkisproperlycited.

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medicalhistorywasthatofrecentBMTwithmelphalan andpoorlycontrolledhypertension.ShehadhadthrombocytopeniasincethetimeofBMTandchemotherapy. Heradmissionbloodpressurewas221/114withamean arterialpressure(MAP)of145mmHg.Heradmission NIHstrokescalescorewas7,withproblemsinorientation,notfollowingcommands,notansweringquestions appropriately,leftgazepreference,reducedblinkonstimulusfromtherightandpossibleright-sidedneglect. Hervisualacuitywasreducedtofingermovementsand lightperceptioninbotheyes.Shewasmovingherextremitiesequally,bilaterally.R eflexeswerebriskthroughoutwithequivocalplantarresponse.Therestofthe neurologicalexamwaslimited,asthepatientwasnot followingcommandsconsistently.Ourdifferentialdiagnosisatthattimeinclude dcerebrovascularaccident (CVA),PRES(duetoelevatedBP,recentchemotherapy andbonemarrowtransplant),seizuresandcomplicated migraine.Sincetherewasnomotordeficitassociated withtheneglectandeyedeviation,wewereobligatedto considerabroaddifferentialdiagnosis,includingPRES. Aftertheinitiallaboratoryworkup,weobtainedaCT headandaCTangiogramoftheheadandneckwith perfusionstudies.TheCTAoftheheadandneckfailed toidentifyanymajorvesselcutofforanyacutehypo/ hyperdensity,buttheCTPdemonstratedincreasedcerebralbloodvolume(CBV),cerebralbloodflow(CBF) andreducedtimetopeak(TTP)intheposteriorcerebralvasculardistribution(seeFigures1and2).These imagingfeatureswereconsistentwithPRES,andwe initiatedintravenousanti-h ypertensivemedications.An MRIbrainwasobtained,whichshowedabnormal restrictionintheparietalandoccipitalareas,confirming thediagnosisofPRES(seeFigure3).Reductionofthe patient ssystolicBPfrom220to180wasassociated withslightimprovementinhervisualacuityandorientationwithinacoupleofhours.Notablelaboratorydata revealedaplateletcountof11,000/ landhemoglobinof 11g/dl.Allotherlaboratorytestswerewithinthenormallimits.Therewasnoevidenceofthromboticthrombocytopenicpurpura(oneofthecausesofPRES),and shewasadmittedwiththediagnosisofPRES.Atthe timeofadmission,PRESwasconsideredtobesecondary Table1CommonlocationofPRESCommonlocationofPRES Parietal-occipital-mostcommon. Posteriorfrontal Temporal Thalamus Cerebellum Brainstem Basalganglia Figure1 CTPimagesinourcase Hedna etal InternationalJournalofEmergencyMedicine 2012, 5 :12 http://www.intjem.com/content/5/1/12 Page2of5

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tomalignanthypertensioncomplicatedbyrecentchemotherapyandBMT.Overthesubsequent48h,she returnedtobaselinewithimprovementofherblood pressuretonormalrange.DiscussionPREScommonlypresentswithseizures(74%),altered sensoriumorencephalopathy,headacheandvisual changes[3].Otherneurologicalfeaturessuchasaphasia andsensorychangesarealsoseen.PREScansometimes presentsimilarlytoCVA,suchasinourcase.Insuch cases,thepatientmayinadvertentlyandinappropriately receivethrombolytictherapy.Weagainstressthepoint thatwhenapatientpresentswithstroke-likesymptoms, butwithaninconsistentneurologicalexam,thenthe strokemimicssuchasPRES ,seizures,migraineand tumorshouldbeincludedinthedifferentialdiagnosis. TheetiologyofPREScanbebroadlydividedintofive mainetiologicalgroups.Inorderofclinicalfrequency, PRESetiologiesincludeHTN(61%),cytotoxicmedications(19%),preeclampsiaoreclampsia(6%)[3],autoimmuneandsystemicconditions,includingsepsis(see Table2).Currently,thepathophysiologyofPRESiscontroversial.ThemostacceptedtheoryofHTN-related PRESisthatofahyperperfusioninjurymodel(see Figure3).Therewillbeafailureofcerebralautoregulationinrelationtothesudde nelevationofbloodpressure.ThissuddenincreaseinMAPcanleadto arteriolardilation,hyperperfusion,endothelialvascular damageanddisruptionofthebloodbrainbarrier.This leadstovasogenicedemaandpotentiallyreversible ischemiaaffectingboththegreyandwhitematter[4]. AnotherlessacceptedtheoryarguesthatHTN-related dysautoregulationresultsin vasoconstrictionandhypoperfusioninjury.However,theabovehypothesisfailsto explainnon-hypertensivePRES,andsosomepostulate anautoimmuneorimmuneresponsetheorytovarious stimuli[2]. WesuggestthatPRESistheresultofvariousetiologicalfactorsthatleadtobloodbrainbarrierinjuryeither byhyper-orhypoperfusion, endothelialdysfunction, changesinbloodvesselmo rphology,hypocapniaor immunesystemactivation[2,4,5].Itusuallyaffectsparietalandoccipitalarea,sbutotherregionscanbe involvedaswell[6]. InourpatientwefeelthatelevatedMAPledtoregionaldysautoregulation,consequentlycausinghyperperfusion,explainingthefindingsofincreasedCBF,CBVand reducedTTP.Itisimportanttorecognizethatthis patienthadarecenthistoryofbonemarrowtransplant Figure2 MRIimagesinPRES. Figure3 MostcommonlyattributedtheoryofPRES. Hedna etal InternationalJournalofEmergencyMedicine 2012, 5 :12 http://www.intjem.com/content/5/1/12 Page3of5

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withexposuretochemotherapy,whichmayalsobea causativefactorinthedevelopmentofPRES,ormay haveindependentlycontributedtothetissueinjury. WeconcludethatthemechanismofPRESisindividualizedineachpatientanddependsmainlyonthecausativefactoridentifiedineachcase.Inthesettingof HTN,PRESismostlikelyduetothemechanism describedinthepreviously discussedtheories.Inthe settingofnormotensivePRES,themechanismmaybe basedonendothelialdysfunction,immunesystemactivationandothersystemicfeatures.Althoughinitially edemaisvasogenicinnature,afailuretoreversethe diseaseetiologywillsubsequentlycausecytotoxicedema andeventuallybraininfarction,furtheremphasizingthe importanceofearlydiseaserecognition. Ahighdegreeofsuspicionisrequiredtomakethis diagnosisasthepatientmaypresentatypically.Since manypatientswithPRESpresentwithinadequatehistory andAMS,brainimagingplaysanimportantroleinthe diagnosisofPRES.Eventhou ghMRI(particularlyT2FLAIR)istheimagingofchoice,CTPcanplayasignificantrolethatcanrevealthecerebralhemodynamics relatedwiththiscondition.Sincethereishyperperfusion theCBFandCBVwillbeelevated,andTTPwillbe reduced.TheCTPcanalsohavediametricallyopposite findingscomparedtoourcase[7](seeTable3).The brainMRIchangesonFLAIRwithnochangesondiffusionweightedimages(DWI)suggestvasogenicedema. Changesinbothsequences(FLAIRandDWI)indicate thatthecytotoxicedemahassetin,whichmayhavean unfavorableoutcome.TheauthorsimplythatCTPisusefulbutnotsuperiortoMRIinthediagnosisofPRES. Themanagementofthisconditiondependsonthe etiologyandshouldbeinitiatedinatimelymanner.The treatmentoftheunderlyingcauseistypicallysufficient toreversethiscondition.However,awordofcaution: thisconditioncanleadtoirreversiblebraininsultifthe treatmentisdelayedorifthereisprolongedbraininsult, inwhichcaseabraininsultthenbecomesirreversible braininfarctions.Additionally,theremaybehemorrhagiccomplicationsandraisedintracranialpressurecontributingfurthertothecerebraldamage[8].TheMAP shouldbereducedquicklybutwithcautioninthecases ofhypertensivePRES.Incasesofnon-hypertensive PRES,especiallyincaseofneoplasticdrugs,theoffendingagentshouldbewithdrawnquicklytoavoidfurther damagetothebloodbrainbarrier.Inthesettingof transplant,alternativemedicationscanbesubstitutedto avoidorganrejections[9].Ifanautoimmuneetiologyis suspected,thenimmunosuppressionhasaroleinthe management[10].Seizuresaremanagedwithanti-epilepticmedications.ConclusionsPosteriorreversibleencephalopathysyndromeisarelativelyraresyndromethatsometimespresentsasastroke mimic.Assuch,itisimportantfortheemergencyphysiciantorecognize.Urgentrecognitionandearlyinitiation ofmanagementofthisconditionareimperativeasit directlyimpactstheneurologicaloutcome.BrainCT perfusioncanplayanimportantroleinthediagnosis.ConsentWritteninformedconsentwasobtainedfromthepatient forpublicationofthiscasereportandany Table2EtiologyofPRESCommoncausesofPRES Hypertension Eclampsiaandpreeclampsia Drugs: -Recreational:Cocaine,Amphetamines,PCP,LSD -Others:Anti-depressants(Tricyclics,MAOInhibitors),Bronchodilators,Erythropoietin,Midodrine,Fludrocortisone,TripleHtherapy,Intravenous immunoglobulins(IVIG). N eoplasticdrugs:Cyclosporine-A,Tacrolimus,Interferons,Indinavir,Cisplatin,Cytarabine,Gemcitabine. A utoimmuneand S ystemic:Systemiclupuserythematosus(SLE),Scleroderma,VasculitislikePAN,Wegener s,Thromboticthrombocytopenicpurpura (TTP),Henoch-Schnleinpurpura,Hemolyticuremicsyndrome(HUS),Amyloidangiopathy,Tumorlysissyndrome,Systemicinflammatoryresponse syndrome(SIRS),Sepsis,MultipleorganDysfunction,Electrolyteimbalance(Hypomagnesemia,hypercalcemia),Hypocholesterolemia,,GBS,Head injury,Renalfailureduetoanyetiology. Table3CTperfusionchangesinvariousbraininsultsEtiologyCBF CBVMTTTTP Infarctcore Ischemic penumbra Varies;usually Varies;usually seizure PRES*Usually butcanbe or Equivocal CBF=cerebralbloodflow;CBV=cerebralbloodvolume;MTT=meantransit time;TTP=timetopeak. *=CTPchangesinPRESdependonwhetheritisahyperperfusionor hypoperfusionmechanismofPRES.Hedna etal InternationalJournalofEmergencyMedicine 2012, 5 :12 http://www.intjem.com/content/5/1/12 Page4of5

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accompanyingimages.Acopyofthewrittenconsentis availableforreviewbyth eEditor-in-Chiefofthis journal.Acknowledgements PublicationofthisarticlewasfundedinpartbytheUniversityofFlorida Open-AccessPublishingFund. Authordetails1DepartmentofVascularNeurology,UniversityofFlorida,ArcherRoad, Gainesville,Florida,32611,USA2DepartmentofEmergencyMedicine, UniversityofFlorida,ArcherRoad,Gainesville,Florida,32611,USA3DepartmentofNeuro-Radiology,UniversityofFlorida,ArcherRoad, Gainesville,Florida,32611,USA Authors contributions Alltheauthorswereinvolvedinthedraft,graphics,grammarcorrection, creationoftablesandfigures.Allauthorsreadandapprovedthefinal manuscript. Competinginterests Theauthorsdeclarethattheyhavenocompetinginterests. Received:7November2011Accepted:29February2012 Published:29February2012 References1.FeskeSK: Posteriorreversibleencephalopathysyndrome:areview. Semin Neurol 2011, 31(2) :202-215. 2.BartynskiWS: Posteriorreversibleencephalopathysyndrome,part2: controversiessurroundingpathophysiologyofvasogenicedema. AJNR AmJNeuroradiol 2008, 29(6) :1043-1049. 3.FugateJE,ClaassenDO,CloftHJ,KallmesDF,KozakOS,RabinsteinAA: Posteriorreversibleencephalopathysyndrome:associatedclinicaland radiologicfindings. MayoClinProc 2010, 85(5) :427-432. 4.Beausang-LinderM,BillA: Cerebralcirculationinacutearterial hypertension-protectiveeffectsofsympatheticnervousactivity. Acta PhysiolScand 1981, 111(2) :193-199. 5.BartynskiWS: Posteriorreversibleencephalopathysyndrome,part1: fundamentalimagingandclinicalfeatures. AJNRAmJNeuroradiol 2008, 29(6) :1036-1042. 6.McKinneyAM,ShortJ,TruwitCL,McKinneyZJ,KozakOS,SantaCruzKS, TeksamM: Posteriorreversibleencephalopathysyndrome:incidenceof atypicalregionsofinvolvementandimagingfindings. AJRAmJ Roentgenol 2007, 189(4) :904-912. 7.SanelliPC,JacobsMA,OugoretsI,MifsudMJ: Posteriorreversible encephalopathysyndromeoncomputedtomographyperfusionina patienton TripleH therapy. NeurocritCare 2005, 3(1) :46-50. 8.HefzyHM,BartynskiWS,BoardmanJF,LacomisD: Hemorrhageinposterior reversibleencephalopathysyndrome:imagingandclinicalfeatures. AJNR AmJNeuroradiol 2009, 30(7) :1371-1379. 9.LunardiN,SaraceniE,BoccagniP,SegatoM,BortolatoA,ManaraR,RossiS, OriC: PosteriorreversibleencephalopathysyndromeintheIntensive CareUnitafterlivertransplant:acomparisonofourexperiencewiththe existingliterature. MinervaAnestesiol 2011. 10.VaraprasadIR,AgrawalS,PrabuVN,RajasekharL,KanikannanMA, NarsimuluG: Posteriorreversibleencephalopathysyndromeinsystemic lupuserythematosus. JRheumatol 2011, 38(8) :1607-1611.doi:10.1186/1865-1380-5-12 Citethisarticleas: Hedna etal .: Posteriorreversibleencephalopathy syndrome(PRES)andCTperfusionchanges. InternationalJournalof EmergencyMedicine 2012 5 :12. Submit your manuscript to a journal and bene t from:7 Convenient online submission 7 Rigorous peer review 7 Immediate publication on acceptance 7 Open access: articles freely available online 7 High visibility within the eld 7 Retaining the copyright to your article Submit your next manuscript at 7 springeropen.com Hedna etal InternationalJournalofEmergencyMedicine 2012, 5 :12 http://www.intjem.com/content/5/1/12 Page5of5