Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation

Abstract

-Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.KEY WORDS: neurological complications, cyclosporine A, bone marrow transplantation.Leucoencefalopatia posterior reversível associada a transplante de medula óssea RESUMO -A síndrome de leucoencefalopatia posterior reversível (SLPR) tem sido descrita em pacientes com insuficiência renal, eclâmpsia, encefalopatia hipertensiva e em pacientes que recebem terapia imunossupressora. O mecanismo pelo qual os agentes imunossupressores podem causar a síndrome ainda não são conhecidos, porém estão provavelmente relacionados aos efeitos citotóxicos destes agentes no endotélio vascular. Relatamos oito pacientes que receberam ciclosporina A (CSA) após transplante de medula óssea alogênico ou para tratamento de anemia aplástica severa e que desenvolveram a SLPR. Os sinais e sintomas mais comuns foram convulsões e cefaléia. A disfunção neurológica ocorreu simultaneamente ou precedida por elevação da pressão arterial sistêmica e disfunção renal aguda em seis pacientes. O exame de tomografia computadorizada do crânio demonstrou a presença de áreas de baixos valores de atenuação na distribuição da substância branca, envolvendo áreas posteriores de ambos os hemisférios cerebrais. O quadro clínico e as anormalidades tomográficas foram reversíveis; a melhora ocorreu em todos os pacientes em que as doses de CSA foram reduzidas ou quando a droga foi retirada. A SLPR pode ser considerada uma expressão de neurotoxicidade da CSA.PALAVRAS-CHAVE: complicações neurológicas, ciclosporina A, transplante de medula óssea.Serviço

Posterior reversible encephalopathy in a child with Langerhans cell histiocytosis following allogeneic PBSCT treatment with cyclosporine

“…Under most circumstances, the neurological symptoms and signs associated with cyclosporine use are reversible when the drug's administered dosage is decreased or it is withdrawn altogether, but symptoms may recur when the drug is reintroduced. Although neurotoxicity would appear to be more frequent when blood cyclosporine levels are substantially elevated, neurotoxicity may also occur when the drug is administered within the normal therapeutic range [4,10]. In our patient's case, his blood cyclosporine level during therapy (437 ng/ml) was only marginally above the recommended normal range (200-400 ng/ml) [10].…”

“…Regions of vasodilatation and vasoconstriction tend to develop for individuals afflicted with PRES, especially in arterial boundary zones, this leading to some breakdown of the blood-brain barrier with focal transudation of fluid and petechial hemorrhages [4]. An alternative mechanism of PRES also implicates endothelial dysfunction, such a notion underpinning the treatment of affected individuals with immunosuppressive therapy, mainly cyclosporine [4,10]. It would seem likely that PRES acts by way of imparting direct toxicity on to the vascular endothelium, vasoconstriction being caused by elaboration of endothelin, similar to the appearance of microthrombosis, as in the hemolytic-uremic syndrome [4].…”

Fatal Leukoencephalopathy after Reduced-Intensity Allogeneic Stem Cell Transplantation

“…This patient had clinical findings and white matter alterations as reported in CSA-associated central neurotoxicity [2][3][4]. However, MRI revealed extensive leukoencephalopathy without restriction to the parieto-occipital brain areas and thus did not match the definition of a posterior leukoencephalopathy syndrome, a radiographically defined variant of leukoencephalopathy which is considered reversible after withdrawal or dose reduction of CSA [5]. This case is remarkable with respect to its refractoriness to dose reduction and withdrawal of CSA and its rapid clinical course with subsequent fatal outcome.…”

Reversible posterior leukoencephalopathy associated with chronic graft-versus-host disease: A case report

“…Teive et al (14) reported eight cases of RPLS associated with bone marrow transplantation. The patients were treated with cyclosporine A following an allogeneic bone marrow transplantation or to treat severe aplastic anemia.…”