Posterior Leukoencephalopathy Syndrome

Synonym: posterior reversible encephalopathy syndrome (PRES)

Reversible posterior leukoencephalopathy syndrome presents with rapid onset of symptoms including headache, seizures, altered consciousness and visual disturbance. It is often but not always associated with acute hypertension. If promptly recognised and treated, the clinical syndrome usually resolves within a week and the changes seen in magnetic resonance imaging (MRI) resolve over days to weeks.^[1]

The underlying pathogenesis is not fully understood.^[2] The pathological mechanism is thought to relate either to hypertension and hyperperfusion or to vasculopathy with resulting hypoperfusion.^[3]

Epidemiology

It is rare. However, with increasing awareness and increasing use of MRI, the diagnosis may be made more frequently in the future.^[4]

Most of the literature is single or a few cases. It usually presents in adults but has been reported in children.^[5]

Aetiology

Chronic kidney disease and acute kidney injury are both often present and there is a strong association with conditions that co-exist in patients with renal disease, such as hypertension, vascular and autoimmune diseases, exposure to immunosuppressive drugs, and organ transplantation.^[1] Underlying risk factors/precipitants may include the following:

• Severe hypertension, pre-eclampsia or renal disease, leading to failed auto-regulation, hyperperfusion and endothelial injury/vasogenic oedema. Rapidly developing, fluctuating or intermittent hypertension is a particular risk. Vasoconstriction and hypoperfusion leads to brain ischaemia and subsequent vasogenic oedema. Recent evidence suggests that the latter is more likely.
• A wide range of drugs but most commonly with immunosuppressants and chemotherapy.^[6]
• Infection with sepsis and shock, which are being recognised more often as other aetiological factors.^[7]
• Autoimmune disease has also been seen.^[8]
• It can also occur after carotid endarterectomy when the carotid baroreceptors fail.
• In one series of seven patients, six were found to have an underlying bleeding diathesis or coagulopathy.^[9]

Despite the name 'leukoencephalopathy', lesions can occur in both white and grey areas. It is also increasingly recognised that it can affect the anterior cerebrum, as well as the anterior and posterior cortex, brainstem, cerebellum or even the spinal cord.^[10]

Presentation

Clinical signs and symptoms are nonspecific and may be acute or subacute:

• Headaches.
• Altered mental state, lethargy and somnolence, possibly progressing to confusion and coma.
• Convulsions - status epilepticus has been reported.^[11]
• Blurred vision, hemianopia, visual neglect, hallucinations, cortical visual impairment.
• Fundoscopy often shows papilloedema, haemorrhages and exudates.
• Blood pressure is usually high.

The clinical symptoms are not enough to establish the diagnosis but MRI is often characteristic and essential to the diagnosis.

Imaging^[1]

In the acute setting, CT imaging allows for rapid assessment. It can also exclude major cerebral haemorrhage and space-occupying lesions. Although not 100% sensitive, CT may also demonstrate venous sinus thrombosis or arterial ischaemia or thrombosis. However, CT imaging may be normal and should not necessarily provide reassurance.

Typical MRI findings are bilateral white-matter abnormalities in vascular watershed areas in the posterior regions of both cerebral hemispheres, affecting mostly the occipital and parietal lobes. Using standard MRI, it may not be easy to differentiate from other acute vascular diseases but venous sinus thrombosis can be rapidly diagnosed by CT or MR venography.

Angiography can identify vessel thrombosis, dissection, or vasculitis. Electroencephalography  (EEG) can be used to identify subclinical seizures and can point to other causes of encephalopathy. Lumbar puncture can diagnose infection or subarachnoid haemorrhage but may be normal early in the illness or after antibiotic treatment.

Differential diagnosis

The presentation is often nonspecific and it can easily be mistaken for other conditions.^[1]Possible differential diagnoses include:

• Cerebrovascular event
• Sinus thrombosis
• Demyelination
• Vasculitis
• Encephalitis

Associated diseases^[10]

• Hypertensive encephalopathy.
• Eclampsia or severe pre-eclampsia.
• Use of stimulant drugs that can raise blood pressure, including phenylephrine, pseudoephedrine and even caffeine.
• Abuse of cocaine and amfetamines.
• Phaeochromocytoma.^[5]
• Haemolytic uraemic syndrome.
• Blood transfusion.
• Infection.
• Autoimmune disease - eg, systemic lupus erythematosus.

This list is far from exhaustive but high blood pressure is a common theme.

The following drugs are just some that have been implicated:

• Ciclosporin A
• Vincristine
• Tacrolimus
• Cisplatin
• Interferon alfa
• Antiretroviral therapy
• Erythropoietin

Management^[1]

Rapid withdrawal of the trigger speeds recovery and reduces the risk of complications - eg, aggressive blood pressure control, withdrawal of the offending drug, or delivery in eclampsia. Antiepileptic drugs should be used to treat seizures; anaesthesia and ventilation should be used for generalised status epilepticus and to protect the airway in comatose patients.

Prognosis^[4]

• If it is caught in time it is reversible but, if infarction has occurred, there will be irreversible damage.
• There are case reports of patients experiencing brain herniation and death.
• Delay in diagnosis gives a worse prognosis.
• Recurrence can occur but is unusual.