Reversible Posterior Leukoencephalopathy (RPLS): A Syndrome of Diverse Etiologies
Abstract & Commentary
By Alan Z. Segal, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College, Attending Neurologist, NewYork- Presbyterian Hospital Dr. Segal reports no financial relationships relevant to this field of study.
Synopsis: RPLS occurs in a variety of clinical settings that cause an acute elevation of blood pressure, or cause damage to the endothelial cell junctions in brain blood vessels.
Source: Lee VH, et al. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol 2008; 65:205-210.
Reversible posterior leukoencephalopathy (RPLS) typically presents with encephalopathy, seizures, headache, and visual disturbance. It is characterized by reversible, predominantly posterior, vasogenic subcortical edema without infarction. RPLS shows a predilection for the posterior circulation; it is postulated that this vasculature has a relative lack of sympathetic innervation and, therefore, a more easily disrupted autoregulation. RPLS may be precipitated by acute increases in blood pressure (hypertensive encephalopathy) but also may occur with normal blood pressure. Often blood pressures in the borderline range (e.g., 140/90) may be pathogenic, especially in young patients with low baseline blood pressures.
RPLS has been directly associated with eclampsia in pregnant women, but may occur throughout the puerperium. RPLS has been closely associated with renal failure, collagen vascular diseases, and treatment with immunosuppressant drugs, particularly the calcineurins (tacrolimus and cyclosporin), which may be directly toxic to endothelial cells. Notably, the anti-angiogenic chemotherapeutic agent, bevacizumab also has been recently shown to cause RPLS. Although RPLS can be appreciated on CT scan, it is more readily diagnosed on MRI showing vasogenic edema, with increased signal on T2 weighted sequences and normal to slightly increased apparent diffusion coefficient (ADC). This is distinguished from cytotoxic edema, seen in ischemic stroke, for which ADC values are low.
Lee and her colleagues present a series of 38 episodes of RPLS, drawn from the Mayo Clinic records between 1999 and 2006. Patients presented with seizures or encephalopathy (87% and 92%, respectively) much more commonly than headache or visual disturbance (53% and 39%, respectively). There was a high incidence of comorbid medical conditions such as renal disease (45%), dialysis dependency (21%), and malignancy (32%). More than one-half of the patients (53%) carried a diagnosis of hypertension and nearly a quarter (24%) were transplant patients. Six patients (16%) were alcoholics. Surprisingly, only 4 patients were pregnant or post-partum, perhaps a reflection of the referral population at the Mayo Clinic.
Neuroimaging findings of RPLS are well documented in this series and highlight multiple atypical features not classically associated with this syndrome. More than one-half of the patients (58%) showed frontal involvement and an equal proportion showed brainstem or cerebellar lesions. The majority of patients showed full resolution, but 26% did have small residual abnormalities on MRI. As the authors note, a subset of RPLS lesions may be slow to clear and might show resolution at more delayed imaging, two weeks or more post-onset.
The series by Lee et al includes additional atypical cases, such as two with unilateral involvement, two with a component of hemorrhage, and five that showed gadolinium-enhancing lesions. Also, two patients had recurrence of RPLS; one of these was a C5 quadriplegic, who interestingly had normal blood pressure (BP) on his initial presentation (BP=107/66) but had significant hypertension upon RPLS recurrence (BP=170/100).
Commentary
Finding an appropriate nomenclature for RPLS has been a source of some controversy, since it so commonly presents with atypical features. As this series clearly shows, it is not always reversible, not consistently posterior, and often not purely a leukoencephalopathy. In the radiological literature, RPLS is more commonly referred to as posterior reversible encephalopathy syndrome (PRES), perhaps appropriately avoiding a specific reference to white matter predominance. As Hinchey (who originally reported this syndrome in the New England Journal of Medicine in 1996) observes in the editorial attached to Lee's report, the exact name of this disorder is less important than immediate recognition and prompt treatment.1 Following removal of any offending agents, BP control is the mainstay of treatment for RPLS. Importantly, for a subset of patients with particularly low blood pressures at baseline such as young pregnant women BP levels may require even more aggressive control into "subnormal" ranges.
Reference
1. Hinchey JA. Reversible posterior leukoencephalopathy syndrome: what have we learned in the last 10 years? Arch Neurol 2008;65:175-176.
RPLS occurs in a variety of clinical settings that cause an acute elevation of blood pressure, or cause damage to the endothelial cell junctions in brain blood vessels.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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