DEFINITION
Posterior reversible encephalopathy syndrome (PRES) have always been described as a neurological syndrome due to neurotoxicity recognized in a variety of ethiological conditions (hypertension,
eclampsia,
sepsis,
immunosuppresion…),
characterised by a variety of symptoms,
and with the classic imaging finding being vasogenic edema in the subcortical white matter of the posterior territories (parietal and occipital lobe). Fig. 2
In fact,
its real definition is complex,
because there are no specific findings that allow the diagnosis,
which is a combination of clinical and radiological findings.
Although the true physiopathology remains unknown,
ongoing research show that it’s not always reversible,
does not always have a posterior localization and its imaging findings are not always vasogenic edema,
leading to a change of the old paradigm of physiopathology to the new one while more information about ethiological causes and imaging findings is available.
CLINICAL PRESENTATION Fig. 3
Clinical features include headache (the most important and more frequently present),
seizures (common,
even leading to coma),
visual disturbance,
altered mental state,
paresis,
hemianopsia and nausea.
Symptoms may develop acute or over some days.
In 70-80% of the patients,
moderate to severe hypertension is also observed.
PHYSIOPATHOLOGY Fig. 4
Whilst the current theories define hypertension as the etiologic agent,
earlier original theories stablished that the main factor is endothelial dysfunction from diverse origins,
causing vasoconstriction and hypoperfusion; both hypotheses are commonly cited,
but the real mechanism is controversial.
CLASSIC HYPOTHESIS Fig. 5
Classic hypothesis suggests that severe hypertension leads to failed autoregulation and injury in the capilary bed,
leading to hyperperfusion.
The posterior location predominance is postulated to be due to the minor adrenergic inervation,
being more sensitive to autoregulation loss.
Autoregulation is an intrinsec mechanism performed by brain vasculature to mantain blood flow stable over fluctuating blood pressure,
by contracting or relaxing endothelial muscular tone in small arteries,
arterioles and capillary bed,
in order to keep pressure between 50-150 mmHg.
When cerebral blood pressure gets over 150 mmHg,
there’s passive arteriolar dilatacion and injury to the capillary bed (that may become permanent if CBP gets over 200 mm Hg),
with vasogenic edema and vessel injury,
leading to hyperperfusion.
Problems regarding the classic hypertension theory:
- PRES is commonly seen with normal blood pressure or with only minor hypertension,
that does not tipically reach the limits of failed autoregulation.
- Hyperperfusion is only documented in several isolated early case reports,
whilst a moderate number of recent series demonstrate hypoperfusion.
- Extent of brain edema does not seem to correlate with the severity of the hypertension.
Moreover,
the extent of brain edema was in some studies stadistically lower in patients with severe hypertension.
This is the opposite of what is expected if severe hypertension were the cause of vasogenic edema.
EARLY ORIGINAL THEORY Fig. 6
Latter findings and new evidence suggests another hypothesis in the development of PRES,
where a neurotoxicity state is developed following the activation of the immune system from diverse etiologies (“triggers”),
in which details vary according to each causal agent.
The general mechanism is:
- Activation of the immune system from diverse origins,
varying from T-cell activation (eg.
Organ transplantation) to cytokine release (eg.
Eclampsia).
- Diffuse endothelial activation produces endothelial injury due to endothelial cell swelling,
increased surface markers (selectin,
VCAM-ICAM…).
- Systemic vasoconstriction leads to vascular instability,
due to abnormal response to vasopressors and endothelial damage.
That results in platelet adhesion,
hemolysis,
protein and fluid leakage and systemic edema.
In some cases endotoxines are produced.
- All of the above leads to systemic/organ hypoperfusion and is manifested as vasogenic edema in imaging studies.
There are many evidences supporting the hypoperfusion theory:
- Image findings: there is evidence of vasculopathy demostrated in PRES,
with vasoconstriction/vasodilatation and reduced perfusion demonstrated with cerebral angiography and angio-CT/MRI.
- Vasogenic edema can be explained by sustained hypoperfusion,
because hypoxia activate endothelial cells and stimulates angiogenesis and increased endothelial permeability.
- Recent evidence suggests that vasogenic edema is reduced,
and not increased,
in patients with severe hypertension,
suggesting that hypertension may have the role of a modulator in PRES,
designed to increase perfusion and reverse brain hypoxemia.
- Hypomagnesemia might be associated with PRES.
and it’s been observed that magnesium administration reverses cerebral vasoconstriction in preeclamptics.
TRIGGERS Fig. 7
There are multiple agents involved in the activation of immune system: (pre)eclampsia,
severe infections (sepsis-shock),
chemotherapy and drugs,
transplantation (BMT or solid organ),
etc.
Some of them are even related,
such as transplants-immunosuppresion,
tumors-chemotherapy,
organ failure-infection/shock…
Besides we don’t know real etiology,
common point from both theories is the production of vasogenic edema.
This suggests damage locates on brain-blood barrier,
aside from the mechanism of production (this explains PRES without arterial hypertension).
That’s why vasogenic edema is the most common image finding in this patients.