A 65 year old chronic hypertensive man underwent a bone marrow transplant for acute myeloid leukaemia. He was subsequently treated for neutropaenic sepsis. He developed acute confusion and a subsequent drop in GCS requiring intubation. CT head and CSF investigation was normal. EEG was non-diagnostic. He was persistently hypertensive on the ICU. Review of notes showed that his anti-hypertensive medications had been omitted since admission, and that his ward blood pressures had been persistently elevated. Antihypertensives were established and the blood pressure improved. The neurological features improved with the blood pressure. A subsequent MRI confirmed the diagnosis.
What are the clinical features of Reversible Posterior Leukoencephalopathy Syndrome (RPLS)?
Reversible posterior leukoencephalopathy is classically precipitated by hypertension. Neurological deterioration can be exacerbated by certain comorbidities, including sepsis and immunosuppressive drugs. It typically presents with altered mental status, headaches, seizures and visual changes in the setting of hypertension. It is quite a rare disorder, and was first defined as a single name syndrome in a 1996 case series (1). It has been described at a blood pressure as low as 160/100, but is more commonly found in patients whose antihypertensive therapy has been stopped with a blood pressure in the region of 220/120.
The pathophysiology relates to disruption of the autoregulatory mechanisms of the central nervous system vasculature, leading to areas of vasoconstriction and vasodilatation. There are two aetiological theories. The first theory states that vasodilatation leads to hyperperfusion, endothelial injury and vasogenic oedema. The second theory is that vasoconstriction leads to hypoperfusion with subsequent brain ischaemia and subsequent vasogenic oedema. Typical findings on a T2 weighted MRI image typically show areas of increased signal density in the parieto-occipital regions of the brain representing vasogenic oedema. These changes partially or completely resolve on follow up scanning, suggesting that infarction is not involved. One of the largest reported case series showed an association with the extent of anatomical MRI findings with outcome (2). The pathophysiology of immunosuppressive therapy and sepsis is unclear but may be related to direct toxic effects on vascular endothelial cells with both direct damage, and release of inflammatory mediators. The syndrome has a predilection for the parieto-occipital lobes for reasons which remain unclear, but it can also affect the frontal lobe (explaining the perseveration seen in this patient), brainstem and cerebellum.
A meta-analysis study of 25 patients showed that resolution of neurological signs usually takes place within 3 to 15 days of blood pressure correction (3). Case reports do suggest that a delay in diagnosis and treatment is associated with a worse prognosis (4). For patients who do not have malignant hypertension, there are no specific guidelines for correction of blood pressure, but a downward titration in 10 to 25 percent increments using clinical symptoms and knowledge of baseline blood pressure as a guide seems to be advocated as a reasonable approach.
Early diagnosis of hypertensive reversible posterior leukoencephalopathy is essential as prompt treatment usually leads to complete resolution of the syndrome with no neurological sequelae, as seen in this patient. Current data suggests that a delay in diagnosis and treatment is associated with a worse prognosis.
1 Hinchey J, Chaves C, Appignani B, et al; A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996 Feb 22;334(8):494-500
2 Covarrubias, DJ, Luetmer, PH, Campeau, NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. AJNR Am J Neuroradiol 2002; 23:1038
3 Pavlakis SG, Frank Y, Chusid R: Hypertensive encephalopathy, reversible occipitoparietal encephalopathy, or reversible posterior leukoencephalopathy: Three names for an old syndrome. J Child Neurol 1999;14:277-281
4 Striano P, Striano S, Tortora F, et al; Clinical spectrum and critical care management of Posterior Reversible Encephalopathy Syndrome (PRES). Med Sci Monit 2005 Nov;11(11):549-53
5 Arora et al. Reversible posterior leukoencephalopathy syndrome: a report of 2 cases. Neurol India 2001;49:311-313
6 Kwon S, Koo J, Lee S: Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Pediatr Neurol 2001;24:361-364