Quiz Page January 2008:
Altered Mental Status in a Kidney Transplant Recipient Receiving Tacrolimus
Article Outline
Clinical Presentation
A 51-year-old white woman with a history of end-stage renal disease secondary to focal segmental glomerulonephritis underwent a live donor renal transplantation almost 4 years before her presentation with mental status changes. Allograft function was stable, with a serum creatinine level of 1.5 mg/dL (133 μmol/L) corresponding to an estimated glomerular filtration rate of 39 mL/min/1.73 m2 (0.65 mL/s/1.73 m2) using the Modification of Diet in Renal Disease Study equation. She was on maintenance immunosuppression therapy with methylprednisolone, mycophenolate, and tacrolimus. Before presentation, trough tacrolimus levels were maintained between 5 and 10 ng/dL. She did not have a history of proteinuria. Her initial presentation was right lower-extremity weakness that rapidly deteriorated to severe confusion, disorientation, generalized tonic-clonic seizure, and unconsciousness. There was no history of trauma, fever, recent travel, or changes in her medications. Systemic examination findings were normal except for the change in mental status. Blood pressure on admission was 114/75 mm Hg. Cerebrospinal fluid analysis showed no increase in white blood cell count or protein, and all other investigation results for bacterial, viral, or fungal infections were negative. Immunosuppressive medications were discontinued at initial presentation, and she was intubated for airway protection. The patient made a spontaneous recovery during a 2-week period without specific therapy. She was discharged on an immunosuppressive regimen that included sirolimus in place of a calcineurin inhibitor.
■What diagnosis best explains the radiological features present in Fig 1?
Figure 1.
Magnetic resonance imaging of the brain performed at the time of admission.
Discussion
What diagnosis best explains the radiological features present in Fig 1?
Neuroimaging of this patient shows the typical findings of symmetrical subcortical white matter edema in the posterior cerebral hemispheres, particularly in the parieto-occipital regions in the T2-fluid-attenuated inversion recovery images of the brain (Fig 1). The clinical recovery in addition to near-total resolution of these neuroimaging findings within 2 weeks after discontinuation of immunosuppression (tacrolimus) without any other specific therapy suggest the diagnosis of posterior reversible (leuko) encephalopathy syndrome (PRES or PRLS syndrome; Fig 2).
Figure 2.
Magnetic resonance imaging performed 2 weeks after admission when the patient showed almost complete recovery of mental status.
PRES is a clinicoradiological syndrome of heterogeneous causes with similar neuroimaging findings as described. This descriptive diagnostic term was first used after a case series in 1996.1 This syndrome usually is of insidious onset, with headache, confusion, decreased level of consciousness, visual changes, and seizure disorder associated with the typical neuroimaging findings. This syndrome was described in many medical conditions, including hypertensive encephalopathy, eclampsia, and administration of immunosuppressive or cytotoxic medications. The pathogenesis is unclear, but it appears to be caused by vasogenic edema, mostly in the posterior circulation, secondary to endothelial dysfunction and altered cerebral autoregulation.1, 2 This clinical disorder should be in the differential diagnosis in renal transplant recipients presenting with insidious onset of neurological illness because calcineurin inhibitors are implicated in this condition.3, 4, 5 Early diagnosis in such patients is very important because discontinuation of calcineurin inhibitors may avoid permanent neurological deficits. Our patient recovered completely and was maintained on corticosteroid and rapamycin therapy.
Final Diagnosis
PRES secondary to calcineurin inhibitor (tacrolimus) therapy.
References
- A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334:494–500
- . Posterior reversible encephalopathy syndrome: Prognostic utility of quantitative diffusion-weighted MR images. AJNR Am J Neuroradiol. 2002;23:1038–1048
- Tacrolimus-associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2003;122:128–134
- Evaluation of neurologic complications by brain MRI in kidney and liver transplant recipients. Transplant Proc. 2006;38:611–618
- Posterior reversible encephalopathy syndrome in children: Its high prevalence and more extensive imaging findings. Am J Kidney Dis. 2006;48:231–238
Case provided and authored by Vivek Soi, MD, Vanji Karthikeyan, MD, and Ravi Parasuraman, MD, Department of Nephrology, Henry Ford Hospital, Detroit, MI.
Support: None.
Financial Disclosure: None.
PII: S0272-6386(07)01356-X
doi:10.1053/j.ajkd.2007.10.004
© 2007 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved.
