Published: 2 March 2017

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Posterior Reversible (Leuko) Encephalopathy Syndrome (PRES) – Increasingly Linked to Medicines

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Prescriber Update 38(1):  5-6
March 2017

Key Messages

  • Posterior reversible (leuko) encephalopathy syndrome (PRES) describes a disorder of acute onset neurological symptoms due to reversible subcortical vasogenic brain oedema.
  • The most common symptoms are seizure and headache. The majority of patients have hypertension or an acute increase in blood pressure.
  • PRES is usually reversible on prompt diagnosis and treatment of underlying conditions.
  • Medicines linked to PRES are generally used in transplant and cancer patients and include ciclosporin, tacrolimus, sunitinib, immunoglobulin and interferon alpha.


Posterior reversible (leuko) encephalopathy syndrome (PRES) is a clinico-radiological syndrome that is increasingly being recognised as a side effect of medicines1,2. The syndrome refers to a disorder of reversible subcortical vasogenic brain oedema in patients with acute neurological symptoms.

PRES was first described in the 1990s3. The incidence is generally unknown. For patients undergoing organ or stem cell transplant the reported incidence ranges from 1% to 10% in both adults and children4. PRES is slightly more common in women1.

PRES is often associated with conditions such as hypertension (53% of reported cases), kidney disease (45%), malignancy (32%), dialysis dependency (21%), transplantation (24%), autoimmune disorders (11%) and eclampsia (11%)1.

PRES is also associated with the use of several medicines, particularly immunosuppressants and cancer chemotherapy1. Medicines implicated in PRES include (this is not an exhaustive list)2,4,5,6:

  • tacrolimus (rarely sirolimus)
  • ciclosporin
  • bevacizumab
  • sunitinib
  • sorafenib
  • interferon alpha
  • intravenous immunoglobulins
  • cisplatin
  • cytarabine
  • fludarabine
  • rituximab
  • infliximab
  • alemtuzumab
  • corticosteroids
  • bortezomib

The time between starting a medicine and the onset of PRES has not been well described. For medicines used in solid organ transplant, onset times may be over a year and may be associated with episodes of graft versus host disease or infection4.

The pathophysiology of PRES is unclear but is thought to be partially due to increased blood pressure2.

The most common clinical signs and symptoms are1:

  • seizures (occur in around 85% of cases)
  • headache (around 50%)
  • amaurosis/hemianopsia (blindness in nearly 50%)
  • altered mental status/coma (around 40%)
  • nausea and vomiting (around 30%)
  • transient motor defects (around 10%).

The onset of symptoms is usually rapid, reaching a peak in 12 to 48 hours4.

Diagnosis is difficult, and clinical context and clinical judgement are essential. Differential diagnoses include encephalitis, malignancy, reversible cerebral vasoconstriction syndrome, stroke, progressive multifocal leukoencephalopathy and vasculitis. Although the clinical picture is not specific, an early MRI is usually diagnostic1,3. Brain imaging usually reveals vasogenic oedema in the parieto-occipital regions of both cerebral hemispheres3.

There is no specific treatment, but the disorder usually resolves when the underlying cause is removed2. Seizures should be treated in the normal manner1,2, however, the length of treatment is debated2. The general consensus is that blood pressure (BP) should be lowered in patients with hypertension. Experts recommend that BP is reduced by 25% in the first few hours1,2,4. Pronounced fluctuations in BP should be avoided and therefore intravenous (IV) infusion of nitroprusside or nicardapine has generally been used1,2,4. Any medicines suspected of causing PRES should be discontinued2.

In most cases of PRES, symptoms typically improve within one week. Neuroimaging resolution normally takes longer4.

However, cerebral haemorrhage or ischaemia can occur. Irreversible neurological defects have been reported in 10% to 20% of cases and death in 3% to 6% of cases1,2. PRES may recur in 5% to 10% of cases, more commonly in patients with uncontrolled hypertension.

The Centre for Adverse Reactions Monitoring (CARM) has received three reports of PRES.

  • Reported in 2009 in association with ciclosporin, the patient was changed to sirolimus and was recovering7.
  • Reported in 2011 in association with R-CHOP therapy, the patient was successfully treated with IV labetalol followed with oral felodipine8.
  • Reported in 2015 in association with ciclosporin, improved with antihypertensive treatment9.

Please continue to report any adverse reactions to CARM. Reports can be submitted on paper or electronically (https://nzphvc.otago.ac.nz/).

References
  1. Granata G, Greco A, Iannella G, et al. 2015. Posterior reversible encephalopathy syndrome – insight into pathogenesis, clinical variants and treatment approaches. Autoimmunity Reviews 14(9): 830-6
  2. Fugate J, Rabinstein A. 2015. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurology 14(9): 914-25
  3. Hinchey J, Chaves C, Appignani B, et al. 1996. A reversible posterior leukoencephalopathy syndrome. The New England Journal of Medicine 334: 494-500
  4. Masetti R, Cordelli D, Zama D, et al. 2015. PRES in children undergoing hematopoietic stem cell or solid organ transplantation. Pediatrics 135(5): 890-901.
  5. Garg R. 2001. Posterior leukoencephalopathy syndrome. Postgraduate Medical Journal 77(903): 24-28.
  6. Oshikawa G, Kojima A, Doki N, et al. 2013. Bortezomib-induced posterior reversible encephalopathy syndrome in a patient with newly diagnosed multiple myeloma. Internal Medicine 52(1): 111-4
  7. CARM case ID 85779. URL: medsafe.govt.nz/Projects/B1/adrsearch.asp
  8. CARM case ID 98013. URL: medsafe.govt.nz/Projects/B1/adrsearch.asp
  9. CARM case ID 115521. URL: medsafe.govt.nz/Projects/B1/adrsearch.asp
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