Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a neurotoxic state that occurs secondary to the inability of the posterior circulation to autoregulate in response to acute changes in blood pressure. Hyperperfusion with resultant disruption of the blood-brain barrier results in vasogenic edema, usually without infarction, most commonly in the parieto-occipital regions.
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Terminology
The term posterior reversible encephalopathy syndrome may be a misnomer as the syndrome can involve or extend beyond the posterior cerebrum. Furthermore, although most cases involve a resolution of changes with the treatment of the precipitating cause and clinical recovery, some patients can progress to develop permanent cerebral injury and be left with residual neurological defects.
It should not be confused with chronic hypertensive encephalopathy, also known as hypertensive microangiopathy, which results in microhemorrhages in the basal ganglia, pons, and cerebellum.
Clinical presentation
Common presenting clinical features include 16,19:
headache
seizures
encephalopathy (acute confusion or altered mental state or decreased level of consciousness)
visual disturbance, including reversible cortical blindness 20
However, the presentation can be quite varied, and may include other neurological symptoms such as ataxia, focal neurological deficits, vertigo, or tinnitus 19.
Pathology
Although posterior reversible encephalopathy syndrome is most commonly thought of occurring as secondary to marked hypertension, this does not appear to be a necessary or sufficient explanation, given the very large and heterogeneous clinical scenarios that precipitate the development of posterior reversible encephalopathy syndrome and the fact that hypertension is not present or does not reach the upper limits of self-regulation (140-160 mmHg) in 25% of patients.
The underlying mechanisms involved are not well understood but is thought to culminate in altered integrity of the blood-brain barrier. Three main precipitant theories have been proposed, that are not mutually exclusive 19:
high blood pressure (breakthrough theory) leads to loss of self-regulation, hyperperfusion with endothelial damage and vasogenic edema
vasospasm theory results in local ischemia and hypoperfusion
endothelial dysfunction secondary to circulating endogenous or exogenous toxins
Etiology
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severe hypertension
postpartum
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drug toxicity
cisplatin
cyclophosphamide 10
interferon
erythropoietin
tacrolimus
cyclosporine
azathioprine
L-asparaginase
filgrastim 15
ustekinumab 17,18
bone marrow or stem cell transplantation
solid organ transplantation
Microscopic appearance
during the acute course of PRES: vasogenic edema, without inflammation, ischemia, or neuronal damage 3
during the late course of PRES: demyelination and myelin pallor along with evidence of ischemia, anoxic neuronal damage, laminar necrosis, or older hemorrhage in the white matter and cortex 3
Radiographic features
Typical posterior reversible encephalopathy syndrome manifests as bilateral vasogenic edema within the occipital and parietal regions (70-90% of cases), perhaps relating to the posterior cerebral artery supply. Despite its name, however, posterior reversible encephalopathy syndrome can be found in a non-posterior distribution, mainly in watershed areas, including within the frontal, inferior temporal, cerebellar, and brainstem regions 2,19. Both cortical and subcortical locations are affected.
Uncommon patterns of posterior reversible encephalopathy syndrome in <5% include:
purely unilateral
central ("central PRES"): brainstem or basal ganglia involvement without cortical or subcortical white matter involvement
spinal cord involvement ("PRES-SCI")
Parenchymal infarctions and hemorrhages are associated with posterior reversible encephalopathy syndrome in 10-25% and 15% of cases respectively. The presence of contrast enhancement, no matter the pattern or how avid, does not portend the clinical outcome.
CT
The affected regions, as outlined above, are hypoattenuating.
Angiography (DSA)
There may be signs of vasospasm or arteritis 3:
diffuse vasoconstriction
focal vasoconstriction
vasodilatation
string-of-beads appearance
MRI
Signal characteristics of affected areas usually reflect vasogenic edema, with some exceptions.
T1: hypointense in affected regions
T1 C+ (Gd): patchy variable enhancement can be seen in ~35% of patients, in either a leptomeningeal or cortical pattern
T2: hyperintense in affected regions
DWI: usually normal, sometimes hyperintense due to edema (T2 shine-through) or true restricted diffusion
ADC: usually increased signal due to increased diffusion, but restricted diffusion is present in a quarter of cases 5
GRE/SWI: may show hemorrhages (including microhemorrhages) in 9-50% 5
MRA: may show patterns of vasculopathy with vessel irregularity consistent with focal vasoconstrictions/vasodilatation and diffuse vasoconstriction 3
MRV: tends to be normal 3
Treatment and prognosis
Management is supportive, with discontinuation of any offending medication, gradual lowering of blood pressure, and antiseizure medications if appropriate 20.
History and etymology
Posterior reversible encephalopathy syndrome was described for the first time as a distinct entity in 1996 by an American neurologist Judy Hinchey et al. 13. Although others had previously described similar reversible CT and MRI findings in hypertension back to the 1980s 14.
Differential diagnosis
General imaging differential considerations include:
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inflammatory cerebral amyloid angiopathy
edema usually centered on microhemorrhages
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progressive multifocal leukoencephalopathy (PML)
periventricular and subcortical involvement, sparing the cortex
little or no mass effect or enhancement
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occipital and cerebellar involvement
acute infarct demonstrates restricted diffusion; PRES typically does not restrict
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hypertensive brainstem encephalopathy
absence of parieto-occipital involvement
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more asymmetric
