Disorder of reversible subcortical vasogenic brain oedema in patients with acute neurological symptoms (eg, seizures, encephalopathy, headache, and visual disturbances) in the setting of renal failure, blood pressure fluctuations, cytotoxic drugs, autoimmune disorders, and pre-eclampsia or eclampsia. Also called as: Reversible posterior cerebral edema syndrome Posterior leukoencephalopathy syndrome Hyperperfusion encephalopathy Brain capillary leak syndrome PRES is caused by endothelial injury related to abrupt blood pressure changes or direct effects of cytokines on the endothelium, which leads to breakdown of the blood– brain barrier and subsequent brain edema. PRES is generally reversible, both radio graphically and clinically, and has a favourable prognosis. Cerebral blood flow can be regulated by four major mechanisms: Myogenic, Neurogenic, Metabolic, or Endothelial. These mechanisms ensure that cerebral blood flow (CBF) is maintained within a relatively normal range. NO—nitric oxide, ET1—endothelin 1

1. Dr. Vishal Gupta
Professor,
Department of General Medicine,
SMS Medical College and attached
Hospital, Jaipur

2. • Disorder of reversible subcortical vasogenic brain oedema in patients with acute
neurological symptoms (eg, seizures, encephalopathy, headache, and visual
disturbances) in the setting of renal failure, blood pressure fluctuations, cytotoxic
drugs, autoimmune disorders, and pre-eclampsia or eclampsia.
• Also called as:
• Reversible posterior cerebral edema syndrome
• Posterior leukoencephalopathy syndrome
• Hyperperfusion encephalopathy
• Brain capillary leak syndrome
INTRODUCTION

3.  PRES is caused by endothelial injury related to abrupt blood pressure changes or
direct effects of cytokines on the endothelium, which leads to breakdown of the
blood– brain barrier and subsequent brain edema.
 PRES is generally reversible, both radio graphically and clinically, and has a favourable prognosis.
Although most patients recover, PRES is not always
reversible and may be associated with considerable
morbidity and even mortality
Triplett JD, Kutlubaev MA, Kermode AG, et al Posterior reversible
encephalopathy syndrome (PRES): diagnosis and management
Practical Neurology 2022;22:183-189.

4. Cerebral blood flow autoregulation –
Cerebral circulation normally maintains a constant cerebral blood flow, despite changes in
cerebral perfusion pressure
• Blood pressure decreases - cerebral arteriolar vasodilation occurs, preserving adequate blood flow and perfusion for
neuronal and glial needs.
• Blood pressure increases – arterioles constrict as a physiological response to maintain a steady—and not increasing—cerebral blood
flow.
PHYSIOLOGYOFCEREBROVASCULAR BLOOD FLOW

5. Cerebral blood flow can be
regulated by four major
mechanisms:
1. Myogenic,
2. Neurogenic,
3. Metabolic, or
4. Endothelial.
These mechanisms ensure that
cerebral blood flow (CBF) is
maintained within a relatively
normal range. NO—nitric oxide,
ET1—endothelin 1

6. Dynamics ofCBFin patientswith chronic HTN

7. Pathophysiologyof PRES
• 1. Cerebral Hyperperfusion-
 Rapidly developing hypertension exceeds the upper limit of cerebral blood
flow autoregulation and causes hyperperfusion.
 Hyperperfusion can break down the blood–brain barrier, allowing the
interstitial extravasation of plasma and macromolecules.
 Posterior brain regions can be particularly susceptible to hyperperfusion
because little sympathetic innervation exists in posterior fossa.

8. • 2. Cerebral Hypoperfusion –
• 15–20% of patients with PRES are normotensive or hypotensive
leads to reduce cerebral perfusion.
3. Endothelial dysfunction –
From systemic toxic effects - hypertension could be a reaction to
insufficient brain perfusion.

11. Mechanisms contributing to the development of PRES

12. COMORBIDCONDITIONS/TRIGGERS
• Pregnancy-related conditions
1. Eclampsia
2. Hydatidiform mole
• Majormedical illness
3. Organ transplantation
4. Thromboticthrombocytopenic purpura
5. Henoch-Schonlein purpura
6. Autoimmune inflammatory disease: systemic lupus, scleroderma, Wegener’s, periarteritis nodosa
7. Sepsis/systemic inflammatory response syndrome/multiple organ failure
8. Alcohol and drug withdrawal
9. Hypomagnesemia, hypercalcemia, hypocholesterolemia
10. Renal failure

13. • Neurologic illness
1. Guillain-Barre’s syndrome
2. Spinal cord injury with autonomic dysreflexia
3. Head injury
• Drugs that cause endothelial dysfunction
4. Immunosuppressant agents - CyclosporineA
5. Chemotherapeutic agents, especially high-dose multidrug - Tacrolimus (FK506), Cisplatin, Gemcitabine,
Bevacizumab
6. Erythropoietin
7. Blood transfusion
8. Indinavir
9. Cytarabine
10. IVIg

15. CLINICALFEATURES
Epidemiology
 Age - 4 to 90 years, most cases occur in young to middle-aged
adults,mean age ranging across case series from 39 to 47
years
 Female predominance
 Acutely or subacutely, usually developing during several
hours or days.

16. Encephalopathy
• Severity from confusion, somnolence, and lethargy to coma
• Reported in 13 % to 90 % of cases
Seizure
• Up to 92 % of cases
• Secondary generalized seizures are common (53–62 %) , rarely focal (23 %-28
%)
• Status epilepticus - 3 % to 13 %

17. Visual abnormalities
• found in 26 % to 67 % of patients
• blurred vision (7 -18 %)
• visual neglect (4 -27 %)
• homonymous hemianopsia (4 -20 %)
• visual hallucinations (3 -5 %)
• cortical blindness (8 -33 %)
Focal neurological signs
• 3-17% cases
• hemiparesis or aphasia,
Myelopathic symptoms and signs

18. PREVALENCE OFCLINICALSYMPTOMSAND SIGNS
SYMPTOMS PREVALENCE
Encephalopathy 50–80%
Seizure 60–75%
Headache 50%
Visual disturbances 33%
Focal neurological deficit 10–15%
Status epilepticus 5–15%

19. DIAGNOSIS
• Acute and subacute neurological symptoms in the appropriate
clinical context (ie, in the presence of pronounced hypertension,
blood pressure fluctuations, immuno suppression, autoimmune
disorders, renal failure, pre-eclampsia, or eclampsia).
• Diagnosis of PRES is not mainly radiological; the
clinical context is crucial in making correct diagnosis.

20. Proposed
algorithm for
diagnosis of
PRES

22. IMAGING
• Useful to exclude alternative diagnoses
• Confirms diagnosis of PRES.
Computed tomography (CT):
Hypodensities in a suggestive
topographic distribution

23. MRI BRAIN
• T1: hypo intense in affected regions
• T1 C+ (Gd): patchy variable enhancement. It can be seen in ~35% of patients, whether
leptomeningeal or cortical pattern.
• T2: hyperintense in affected regions
• DWI: usually normal
• ADC: signal increased in affected regions due to increased diffusion
• GRE: may show hypointense signal in cases of haemorrhage
• SWI: may show microhemorrhages in up to 50%

24. RADIOLOGICALCHARACTERISTICS OFPRES
1. Holohemispheric watershed pattern (23 %)
• Watershed zone between the anterior and posterior cerebral arteries and the middle
cerebral artery
• Confluent vasogenic edema extends through the frontal, parietal, and occipital lobes

25. 2. Dominant parietal-occipital pattern (22 %)
• Previously thought to be typical of PRES
• Posterior part of the parietal and occipital lobes is predominantly
involved

26. 3. Superior frontal sulcus pattern (27 %)
• Patchy edema predominates in the frontal lobes along the mid
to posterior aspect of the superior frontal sulcus.
• Parietal and occipital lobes are variably involved

27. 4. Partial orAsymmetric Expression of the Primary Patterns (27.9%)
• Asymmetric abnormalities in the affected parietal or occipital
lobes.

28.  Advanced imaging techniques, such as MR spectroscopy or positron emission
tomography (PET) can provide additional information to determine the diagnosis.
 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

29. Multivoxel MR Spectroscopy in a PRES case shows
reduced NAA/Cr in many regions such as periventricular
white matter and around basal ganglia (A); FLAIR images
of the same case demonstrates foci of white matter
hyperintensities (B)
FLAIR images of a PRES case with white matter
hyperintensities more prominent in the right
occipital lobe (A); MR Perfusion shows
reduction in MTT in the right occipital lobe
suggestive of hyperperfusion (B).

30. Atypical MRI findings in PRES
 Edema can affect basal ganglia and
brainstem in up to a third of cases and the
cerebellum in up to half.
 Restricted diffusion can be seen on MRI in
15–30% of cases.
 Presence of restricted diffusion is
generally associated with irreversible
structural injury and incomplete clinical
recovery.
• Axial T2 fluid- attenuated inversion
recovery sequences show predominant
(A) brainstem, (B) basal ganglia, (C)
thalamus, (D) pontine involvement

31. • Enhancement is seen in about 20% of
patients with PRES
• Intracranial haemorrhage - 10–25% of
cases. Intraparenchymal hemorrhage is the
most common type and sulcal subarachnoid
haemorrhage is the second most common
type.
• About 18–30% of patients with haemorrhage
have both types

32. Radiological
Features
Hinchey 1996
(N=13)
Casey
2000
(N = 16)
Bartynski 2007
(N=136
McKinney 2007
(N=76)
Lee 2008
(N=36)
Burnett 2010
(N=79)
Bilateral 15 (100%) 11(69%) 98 (72%) NR 36(100 %) NR
Asymmetric 10 (67 %) NR 21 (15 %) 2 (3 %) NR NR
Confluent NR 2 (13 %) 31 (23 %) 44 (58 %) 2 (13 %) 12(16 %)
Gray matter 4 (27 %) NR NR 22 (29 %) 16 (44 %) NR
Posterior >
anterior
14 (93 %) 15 (94 %) 30 (22 %) NR NR NR
Occipital 14 (93 %) NR 134 (99 %) 75 (99 %) NR NR
Parietal 13 (87 %) 8 (50 %) 134 (99 %) 75 (99 %) NR 50 (67 %)
Frontal 7 (47 %) 14 (88 %) 93 (68 %) 60 (89 %) 22 (61 %) 61 (81 %)
Temporal 9 (60 %) 16 (100
%)
55 (40 %) 52 (68 %) NR 62 (83 %)
Brainstem 2 (13 %) NR 17 (13 %) 14 (18 %) 21 (58 %) NR
Cerebellum 1 (7 %) NR 41 (30 %) 26 (34 %) 21 (58 %) NR
Basal ganglia 1 (7 %) 3 (19 %) 19 (14 %) 9 (12 %) NR NR

33. RegionalinvolvementbyPRES in seriesof136 patients
AJNR 2007;28:1302-07

34. Differential diagnoses of PRES
Infectious encephalitis
• Fever
• Peripheral leucocytosis
• CSF pleocytosis
• Positive CSF Gram stain or culture
• Positive CSF microbial serology or PCR
• Can be unilateral in brain imaging
Autoimmune or paraneoplastic encephalitis
• History of malignancy or tumour
• Antigen-specific antibody in serum or CSF
• Can be unilateral in brain imaging

35. Malignancy or tumour (lymphoma, gliomatosis cerebri,
metastatic disease)
• Subacute-to-chronic clinical presentation
• History of malignant tumour
• History of unintentional weight loss
• Abnormal CSF cytology
• Absence of clinical and radiological resolution
• Can be unilateral in brain imaging
CNS vasculitis
• Often subacute clinical presentation
• CSF pleocytosis
• Cytotoxic oedema in non-PRES-like pattern

36. Progressive multifocal leukoencephalopathy
• Subacute-to-chronic clinical presentation
• Can be unilateral in brain imaging
Osmotic demyelination syndrome
• History of rapid normalisation of sodium or glucose concentrations
• Does not preferentially affect the parieto-occipital lobes
• Characteristic central pontine signal abnormality in a bat-wing shape

37. Acute demyelinating encephalomyelitis
• Usually a disorder affecting children
• Preceded by viral or bacterial infection
• Fever in 50–75% of patients
• Radiographically supratentorial lesions usually asymmetrical
Toxic leukoencephalopathy
• History of illicit drug use
• Positive drug or toxin screen
• Symptoms progress for weeks
• Magnetic resonance spectroscopy can show abnormally raised lactate and decreased N-acetyl
aspartate concentrations

38. Reversible cerebral vasoconstriction syndrome
• Thunderclap headache
• PRES quickly progresses over a few hours, complications may occur for
several days with the RCVS
• Imaging PRES- Bilateral parieto-occipital lesions on MRI, typical for PRES
• Imaging RCVS- classic pattern of ‘string of beads’ on Angiography, at least
two narrowings per artery on two different cerebral arteries at brain magnetic
resonance angiography (MRA) or at conventional angiography
• 10% of cases there seems to be overlap between this syndrome and PRES

41. TREATMENT
• General measures- aimed at maintainingABC of the patient
• Symptomatic therapy
 Antihypertensives - reduce blood pressure by 25% within first few hours.
 Anticonvulsants
• Correction/Removal of the underlying cause
 Withdrawl of offending drug
 Termination of pregnancy

42. Patient with a history of primary
myelofibrosis and bone marrow
transplant on Tacrolimus.
Axial T2-FLAIR images demonstrate
the areas of signal abnormality in the
parietal and occipital lobes, and right
frontal lobe (left images).
The Tacrolimus was stopped and the
follow up images (right images) were
obtained 6 weeks after the initial
images.

43. PROGNOSIS
• Brain lesions are reversible
• Most studies- excellent short term and long term outcome
• Symptoms usually seem to resolve in about 3–8 days (75–90%) while recovery
of the MRI abnormalities takes longer—several days to weeks
• Mortality (3–6%) - intracranial haemorrhage, posterior fossa oedema with
brainstem compression or acute hydrocephalus, or marked diffuse cerebral
oedema and increased global intracranial pressure.

44. • Persistent neurological sequelae -10–20%
• Hyperglycaemia and time to control of the causative factor have
been also reported to be independently associated with poor
outcomes
• Poor outcome may also be related to associated comorbidity
(sepsis) or intracerebral haemorrhage

45. • Recurrent PRES ~ 4% of cases
• More common in patients with uncontrolled hypertension
compared with patients who have other causes compared with
patients who have other causes (ie, immunosuppressant
therapy).
• 10–15% develop recurrent seizures in the first few years after
PRES

46. Thank you