Communication • DOI: 10.2478/v10134-010-0016-9 • Translational Neuroscience • 1(2) •2010 •115–123
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Dimitri Renard and Pierre LabaugeDepartment of Neurology CHU Nîmes, Hôpital CaremeauPlace Pr Debre,30029 Nîmes, France
Department of Neurology Universitair Ziekenhuis GasthuisbergHerestraat 49,3000 Leuven, Belgium
Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by subacute onset of headache,decreased alertness, vomiting, seizures, visuoperceptual disturbances, together with bilateral white matterlesions in posterior brain regions on brain imaging. The most frequently associated conditions related to RPLSare arterial hypertension and the use of immunosuppressive or cytotoxic treatment. T2-, Fluid AttenuationInversion Recovery (FLAIR), and Apparent Diusion Coecient (ADC)- weighted magnetic resonance imaging(MRI) reveal hyperintensities in parietooccipital white matter but grey matter and other regions including frontaland temporal lobes, brainstem, cerebellum, basal ganglia, or even spinal cord may also be involved. According toADC ndings, the underlying pathophysiologic mechanism is probably one of vasogenic (rather than cytotoxic)oedema. These MRI ndings help in dierentiating RPLS from ischaemic events and other diseases resemblingRPLS. Failure of cerebral autoregulation, endothelial dysfunction, disrupted blood-brain barrier, vasospasm, anddirect toxic drug eects may all play a role in the pathophysiology of RPLS. Treatment consists of discontinuationof the causal drug, treatment of high blood pressure, and antiepileptic therapy. Clinical recovery and regression of radiological abnormalities are typically seen after early treatment. However, delay in diagnosis and treatment canresult in irreversible brain damage, often in association with complicating cerebral infarction or haemorrhage.
Received 19 May 2010accepted 15 June 2010
Drug-induced • Hypertensive • White matter • Cyclosporine • MRI • Brain • Immunosuppression
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Reversible posterior leukoencephalopathysyndrome (RPLS) was rst described byHinchey et al in 1996 who reported 15 patientswith a wide variety of diseases presentingwith headache, decreased alertness, vomiting,seizures, and visuoperceptual disturbances
]. Of these 15 patients, 7 had previouslyreceived immunosuppressive treatment, 1was on interferon treatment, 3 had eclampsia,and 4 suered from acute hypertensiveencephalopathy related to renal disease. In 12 of these patients, arterial hypertension was noted.Brain imaging showed bilateral extensive whitematter abnormalities suggestive of oedema inthe posterior cerebral regions. In all 15 patients,neurological abnormalities resolved afterantihypertensive treatment and withdrawalor dose reduction of immunosuppressivetherapy. Prior to this initial description, severalpatients with similar clinical ndings andradiological abnormalities had been described(e.g. associated with malign hypertension,eclampsia, or cyclosporine use) [2-4]. Most
RPLS patients are adults. However, RPLS canalso occur in children and is the most commonabnormality leading to seizures in children withleukaemia[
].Most of the literature concerning RPLS is basedon reports of single or multiple cases rather thanconsecutive series of at-risk populations. To thebest of our knowledge no reliable estimates of incidence of RPLS are available. Furthermore,the condition may be underdiagnosed: theclinical syndrome of RPLS is often incomplete,magnetic resonancy imaging (MRI) is not alwaysperformed, and symptoms may be reversible(e.g. after correction of hypertension, change orwithdrawal of immunosuppressive or cytotoxictreatment) even when the diagnosis of RPLS wasoverlooked. It is generally considered a relativelyuncommon disorder. The two most frequentlyassociated conditions related to RPLS are arterialhypertension and the use of immunosuppressiveor cytotoxic treatment. The distinction betweendrug-related RPLS and hypertension-inducedRPLS may be dicult since elevated bloodpressure often complicates RPLS associated withimmunosuppressive and cytotoxic treatment.In principle, RPLS should be distinguished frommore diuse toxic leukoencephalopathiesthat lack any posterior predilection and bydenition aect periventricular white matterand the centrum semiovale relatively evenly [6
(see below).Post-mortem studies of RPLS reveal relativelyaspecic changes, such as oedema, reactiveastrocytosis, neuronal loss, demyelination,ischaemic infarction, and haemorrhage.
Drugs associated with RPLS are often - but notlimited to - immunosuppressive and cytotoxicagents (
). The exact oending drug is sometimesdicult to identify since oncological patientsundergoing chemotherapy or transplantpatients on immunosuppressive medicationtypically receive multiple drugs that couldcontribute to the development of RPLS. TheRPLS risk associated with specic drugs is hardto quantify since most of the literature consistsof case reports rather than prevalence studiesin at-risk populations. RPLS symptom onset isoften related to the introduction of new drugs,dose increase, or increased blood pressure butcan also occur in patients on stable doses of