PRES

1. POSTERIOR REVERSIBLE
ENCEPHALOPATHY
SYNDROME
DR. SUMIT KAMBLE
SENIOR RESIDENT
DM NEUROLOGY,
GMC, KOTA
MODERATOR
DR. DILIP MAHESHWARI
ASSO. PROF. NEUROLOGY

2. HISTORICAL BACKGROUND
• In 1897, Vaquez and Nobecourt pointed out the correlation of
toxemia of pregnancy and HTN
• In1928, Oppenheimer and Fishberg introduced the term
hypertensive encephalopathy
• In 1996, Hinchey and colleagues first described the clinical
condition- reversible posterior leukoencephalopathy( RPLE)
Semin Neurol 2011;31:202–215

3. INTRODUCTION
• 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.
• Reversible posterior cerebral edema syndrome
• Posterior leukoencephalopathy syndrome
• Hyperperfusion encephalopathy
• Brain capillary leak syndrome
Lancet Neurol 2015; 14: 914–25

4. • Brain imaging usually reveals vasogenic oedema predominantly
involving the bilateral parieto-occipital regions.
• 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 oedema.
• PRES is generally reversible, both radiographically and
clinically, and has a favourable prognosis.

5. PHYSIOLOGYOFCEREBROVASCULAR BLOOD FLOW
• Cerebral blood flow autoregulation - cerebral circulation
normally maintains a constant cerebral blood flow, despite
changes in cerebral perfusion pressure
• Largely driven by changes in cerebral arteriolar wall diameter,
which can be produced by several mechanisms, including
cerebrovascular pressure reactivity , chemical factors (eg,
carbon dioxide tension), and autonomic nervous system.
Lancet Neurol 2015; 14: 914–25

6. • 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.

7. • Endothelium regulates vascular tone by secreting a combination
of vasodilators (nitric oxide, prostacyclin, hydrogen sulfide, and
endothelium-derived hyperpolarising factor) and
vasoconstrictors (throm boxane A2, endothelin 1, and
angiotensin II).
• With chronic HTN, the resistance arterioles undergo
proliferation of the muscular media adapting to the chronically
high perfusion pressures
• This results in a shift of the autoregulation curve to the right

8. NORMALCEREBRALAUTOREGULATION

9. DYNAMICS OFCBFIN PTS WITH CHRONIC HTN

10. PATHOPHYSIOLOGYOF PRES
• 1. Cerebral Hyperperfusion- Rapidly developing hypertension
exceeds the upper limit of cerebral blood flow autoregulation
and causes hyperperfusion.
• When the pressure rise is rapid and severe, the autoregulatory
response might be insufficient, hyperperfusion can occur, and
the blood–brain barrier breaks down, 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.
J Stroke Cerebrovasc Dis 2012; 21: 873–82.

11. • Important factors that influence breakdown in the blood–brain
barrier
1. Patient’s mean baseline blood pressure,
2. Proportional rise in blood pressure,
3. Rapidity with which the change takes place

12. • 2. Cerebral Hypoperfusion - 15–20% of patients with PRES
are normotensive or hypotensive and that, even among patients
who are hypertensive, less than 50% have a documented mean
arterial pressure above the usually quoted upper limit of
cerebral blood flow autoregulation (≥140–150 mm Hg).
• Endothelial dysfunction - from systemic toxic effects -
hypertension could be a reaction to insufficient brain perfusion

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

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

16. 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.

17. 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 %

18. 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 (Am J Neuroradiol 2012; 33: 896–903.)

19. 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%
J Stroke Cerebrovasc Dis 2012; 21: 873–82.

20. DISTRIBUTIONOFCLINICALFEATURESINCOHORTSTUDIESOFPRES
Clinical Features Hinchey
1996
(N=13)
Bartynski
2007(N=13
6)
McKinney
2007(N=76)
Lee
2008(N=36)
Burnett
2010(N=79)
Encephalopathy 10 (67 %) 39 (26 %) 10 (13 %) 34 (94 %) 76 (90 %)
Seizure 11 (73 %) 97 (71 %) 58 (76 %) 33 (92 %) 56 (70 %)
Headaches 8 (53 %) 39 (26 %) 3 (4 %) 19 (53 %) 26 (31 %)
Visual abnormalities 10 (67 %) 39 (26 %) 3 (4 %) 13 (36 %) 24 (29 %)
Nausea/vomiting 8 (53 %) 39 (26 %) NR NR NR
Focal neurological
signs
NR NR 2 (3 %) 1 (3 %) 14 (17 %)
Acute hypertension 12 (80 %) 91 (67 %) NR NR 62 (78 %)
Annual Update in Intensive Care and Emergency Medicine 2011

21. 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.

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

24. 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%

25. 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

26. 2. Dominant parietal-occipital pattern (22 %)
• previously thought to be typical of PRES
• posterior part of the parietal and occipital lobes is
predominantly involved
Am J Neuroradiol 2012; 33: 896–903.)

27. 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

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

29. ATYPICALMRI FINDINGS IN POSTERIOR
REVERSIBLE ENCEPHALOPATHYSYNDROME
• 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.
Am J Neuroradiol 2012; 33: 896–903

30. • 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

31. DIFFERENTTYPESOF INTRACRANIALHAEMORRHAGEINPOSTERIOR
REVERSIBLEENCEPHALOPATHYSYNDROME

32. ATYPICALMRI FINDINGS IN POSTERIOR
REVERSIBLE ENCEPHALOPATHYSYNDROME
• Axial T2 fluid-
attenuated inversion
recovery sequences
show predominant
• (A) brainstem
• (B) basal ganglia
• (C) thalamus
• (D) pontine
involvement

33. 23 yr-old-male cocaine-induced malignant hypertension, presenting
with headaches, confusion and spinal cord syndrome

34. 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=7
9)
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

35. REGIONALINVOLVEMENTBYPRES IN SERIES OF136
PATIENTS
AJNR 2007;28:1302-07

36. DIFFERENTIALDIAGNOSES OFPOSTERIOR REVERSIBLE
ENCEPHALOPATHYSYNDROME (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
Lancet Neurol 2015; 14: 914–25

37. 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

38. 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

39. 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

40. 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 maintaining ABC 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

44. 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.

45. • 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

46. • 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

47. PAEDIATRIC POSTERIOR REVERSIBLE
ENCEPHALOPATHYSYNDROME
• Incidence - 0.4%
• Common causes- haematological disorders, kidney disease, or
those taking cytotoxic drugs after organ transplantation,
Glomerulonephritis, acute leukaemia, Henoch- Schonlein
purpura, and haemolytic uraemic syndrome
• Clinical and radiological presentation appears to be similar to
that in adults
• Mean blood pressure at presentation -140/85 mm Hg

48. AREAS OF UNCERTAINTYAND CONTROVERSY
• Opposing pathophysiological hypothesis – hypoperfusion /
hyperprfusion
• Co-occurrence of neuromyelitis optica spectrum disorders and
PRES - role of aquaporin-4 channelopathy in its pathogenesis ?
• Myelopathy or brainstem dysfunction
• PRES can be also be diagnosed in the presence of normal brain
imaging ?

49. THANK YOU

50. REFERENCES
• Posterior reversible encephalopathy syndrome: clinical and
radiological manifestations, pathophysiology, and outstanding
questions Lancet Neurol 2015; 14: 914–25
• Semin Neurol 2011;31:202–215
• Understanding Posterior Reversible Encephalopathy Syndrome
S. Legriel, F. Pico, and E. Azoulay. Annual Update in
Intensive Care and Emergency Medicine 2011
• Posterior Reversible Encephalopathy Syndrome, Fundamental
Imaging and Clinical Features Am J Neuroradiol 2012; 33:
896–903