Final Diagnosis -- Posterior leukoencephalopathy


  1. Posterior leukoencephalopathy
  2. Thrombotic microangiopathy related to thrombotic thrombocytopenic purpura (TTP).


This report details the neuropathology of the 'reversible posterior leukoencephalopathy syndrome' (6). A previous brain biopsy found 'edematous white matter' (8). The pathology of these cases is rarely examined, because the syndrome is usually transient and non-fatal. In this case, the patient died of intracerebral hemorrhage, a complication of hypertension, while posterior leukoencephalopathy was present, and therefore came to autopsy.

The reversible posterior leukoencephalopathy syndrome (PLS) was initially described in 15 cases, 12 with acute hypertension; 7 on immunosuppressants. Imaging showed bilateral posterior white matter changes suggesting edema. In all cases, drugs were withdrawn or hypertension treated, resulting in reversal of clinical and imaging abnormalities (6). In a minority of cases, PLS is not associated with hypertension (3), and the imaging changes can become permanent (2,3). Cyclosporin itself can play a role in the syndrome by contributing to hypertension through TTP/HUS leading to renal microangiopathy, as was seen in this case (4). Other reports suggest that cyclosporin is a direct cause of the syndrome, both in the absence of hypertension (5), and when co-administered with chemotherapy (9).

The pathology supports the notion that PLS reflects cerebral edema. The generalized pallor of white matter on stains for axons and myelin, and the formation of cystic spaces (parenchymal and perivascular) suggest increased fluid with separation of myelinated axons. Acute hemorrhages were seen, in keeping with acute hypertension, which can disrupt the blood-brain barrier and so generate vasogenic cerebral edema (7). The overlying lesions of TTP may have contributed to the pathogenesis of PLS through altered vascular dynamics or ischemia. They have been described as consisting of petechial hemorrhages, microthrombus formation and cortical microinfarcts (1). These were conspicuously confined to the occipital lobes. Why this should be the case is unknown, but it may account for the association between TTP and PLS in this case. This would imply that cerebral TTP is a predisposing factor for PLS that requires the superimposed effect of acute hypertension.


  1. Adams RD, Cammermeyer J, Fitzgerald PJ (1948) Neuropathological aspects of thrombocytic acroangiothrombosis; clinico-anatomical study of generalized platelet thrombosis. J Neurol Neurosurg Psychiat 11:27-43.
  2. Antunes NL, Small TN, George D, Boulad F, Lis E (1999) Posterior leukoencephalopathy syndrome may not be reversible. Pediatr Neurol 20:241-243.
  3. Ay H, Buonanno FS, Schaefer PW, Le DA, Wang B, Gonzalez RG, Koroshetz WJ (1998) Posterior leukoencephalopathy without severe hypertension: utility of diffusion weighted MRI. Neurology 51:1369-1376.
  4. Bonser AS, Adu D, Franklin I, McMaster P (1984) Cyclosporin induced haemolytic uremic syndrome in liver allograft recipient. Lancet ii:1337.
  5. Gijtenbeek JM, van den Bent MJ, Vecht CJ (1999) Cyclosporine neurotoxicity: a review. J Neurol 246:339-346.
  6. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR (1996) A reversible posterior leukoencephalopathy syndrome. N Eng J Med 334:494-500.
  7. Johansson BB (1980) The blood-brain barrier in acute and chronic hypertension. Adv Exp Med Biol 131:211-226.
  8. Lanzino G, Cloft H, Hemstreet MK, West K, Alston S, Ishitani M (1997) Reversible posterior leukoencephalopathy following organ transplantation. Description of two cases. Clin Neurol Neurosurg 99:222-226.
  9. Tweedle DA, Windebank KP, Campbell Hewson Q, Yule SM (1999) Cyclosporin neurotoxicity after chemotherapy. BMJ 318:1113.

Contributed by Alexander Easton, MBBS, PhD

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