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 In all cases, drugs were withdrawn or hypertension treated, resulting in reversal of clinical and imaging abnormalities (6).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.
Contributed by Alexander Easton, MBBS, PhD