Reversible posterior leukoencephalopathy syndrome

Abstract

A 40-year-old woman presented with headache, lethargy,dysarthria, diplopia and altered mental status. Her pastmedical history was significant for cystic fibrosis for whichshe underwent bilateral lung transplantation 3 years priorto admission. Her medications included tacrolimus andprednisone. On physical examination, she was afebrile andnormotensive without neck stiffness; she was intubated andon mechanical ventilation. Her MRI brain with intravenousgadolinium showed symmetric hyperdense signals withinthe white matter involving parietal (Fig. 1a), occipital(Fig. 1b) and cerebellar regions (Fig. 1c), without intrace-rebral space-occupying lesions. Cerebrospinal fluid (CSF)studies revealed clear and colorless fluid with normalopening pressure, cell counts, glucose and protein. Evalu-ation for infections, including routine blood cultures, CSFGram’s stain and cultures, VDRL, cryptococcal antigen,cytomegalovirus (CMV) polymerase chain reaction (PCR)assay, Epstein–Barr virus (EBV) PCR, human herpes virus-6 (HHV-6) PCR and JC virus PCR, was, however, unre-vealing. Serum tacrolimus drug level was 5 ng/ml (normal5–20 ng/ml). The clinical diagnosis of tacrolimus-associ-ated reversible posterior leukoencephalopathy syndrome(RPLS) was entertained given the negative infectious dis-eases workup. Tacrolimus was cautiously tapered off overa week, and her neurological condition slowly improved.Repeat MRI brain imaging a week after complete discon-tinuation of the tacrolimus showed the resolution of thehyperintense lesions (Fig. 1d, e).RPLS, also known as posterior reversible encephalopa-thy syndrome (PRES), is a clinical syndrome of varyingetiologies, but with similar neuroimaging findings. Char-acteristic clinical manifestations include non-localizedheadache unresponsive to analgesics, altered mental status,visual disturbances and seizures [1, 2]. RPLS is frequentlyassociated with acute hypertension, preeclampsia oreclampsia, sepsis, renal failure, thrombotic thrombocyto-penic purpura, hypercalcemia, hypomagnesium, autoim-mune diseases, cytotoxic therapies andimmunosuppressants [2]. Because of widespread use ofcalcineurin inhibitors (cyclosporine and tacrolimus) inpatients with solid organ transplantation (SOT) to preventorgan rejection, neurotoxicity of these agents has beenincreasingly reported, although the incidence of RPLSamong patients with SOT is low (0.5 %) [3]. The under-lying pathophysiology of RPL is poorly defined. Hypoth-eses include cerebral ischemia from vasospasm, disorderedcerebral autoregulation and endothelial dysfunction [1, 2].RPLS associated with calcineurin is thought to result fromdirect toxic injury to vascular endothelium, leading toproduction of inflammatory cytokines and capillary leak-age, which triggers vasogenic cerebral edema [1, 3, 4].Hypertension and high serum tacrolimus level are com-monly associated with RPLS but there are reported RPLScases with normal blood pressure and normal serum ta-crolimus drug concentrations [5]. Brain MRI, particularlyfluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences, is the imagingmodality of choice of diagnosing RPLS. Typical MRIfindings are symmetrical white matter changes primarily