In 1996, Hinchey et al coined the term "reversible posterior leukoencephalopathy" to describe a syndrome of headaches, confusion, and visual disturbances associated with transient, predominantly posterior lesions in the cerebral white matter on neuroimages (1). Reversible posterior leukoencephalopathy syndrome (RPLS) is often associated with an abrupt increase in blood pressure and is seen in patients with eclampsia, renal disease, and hypertensive encephalopathy. It is also seen in the patients treated with cytotoxic and immunosuppressive drugs such as cyclosporin and tacrolimus. Thus, early recognition of this condition is of paramount importance because prompt control of blood pressure or withdrawal of immunosuppressive agents will cause reversal of the syndrome. Delay in the diagnosis and treatment can result in permanent damage to affected brain tissues.

A wide variety of diseases may develop RPLS and various acute neurological conditions such as stroke, cerebral venous thrombosis, encephalitis, demyelinating disorders, and collagen diseases in the brain should be distinguished from RPLS (1, 2). Malignant disease such as Hodgkin's disease or acute lymphoblastic leukemia (ALL) is a possible disease developing RPLS (1–6). Although the underlying pathophysiology of PRLS has been controversial, disturbed permeability of cerebral vessels may be one candidate. The permeability of cerebral vessels may be disturbed in many pathologic conditions including angiitis, hypertensive encephalopathy (3, 7) that may develop low density lesions in cerebral CT, prolonged T2 lesions in cerebral MRI, and hyperperfusion (8, 9) in single photon emission computed tomography (SPECT) images. Some patients with RPLS showed hypoperfusion in SPECT (10), but hyperperfusion can be also observed in these patients at least in their acute phases.

Diffusion-weighted MR imaging (DWI) provides information about the reversibility of RPLS. Covarrubias et al investigated 22 patients with RPLS and concluded that high DWI signal intensity and pseudonormalized ADC values are associated with cerebral infarction and may represent the earliest sign of nonreversibility as severe vasogenic edema progresses to cytotoxic edema, and that the extent of combined T2 and DWI signal abnormalities correlate with patient outcome (11). Considering reversible but symptomatic abnormal findings in neuroimages, we find similarity with those of mitochondrial encephalomyopathy such as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events (MELAS) (12, 13). The underlying pathophysiology of abnormal findings in neuroimages of MELAS has also been unclear. Yoneda (12) observed in a patient with MELAS that DWI demonstrated a higher apparent diffusion coefficient in the lesion than in the control region during the acute stage of stroke. Summarizing this and other observations concerning neuroimages of MELAS, we believe that vasogenic edema is present in stroke-like episodes in MELAS and shows reversible lesions in neuroimages (13, 14). Then, we should also raise MELAS into candidate diseases developing condition of RPLS, although in MELAS abnormal findings are primarily in the gray matter not in the white matter.

As discussed above, RPLS includes a wide variety of diseases and is a syndrome with characterized findings in neuroimages, the existence of RPLS itself may be not directly reflected in clinical diagnosis of the underlying pathognomonic disese. However, the existence of RPLS may suggest possible vasogenic edema in the brain that may be originated from malignant diseases or other fatal pathologic conditions and that it has the possibility to develop fatal intracranial high pressure (3). Thus, we should accumulate further evidence concerning RPLS and make a critical path towards diagnosis and therapeutic methods for underlying diseases.