Posterior reversible encephalopathy syndrome associated with use of anlotinib to treat squamous cell carcinoma of the cervix: case report and literature review

In some patients who are hospitalized for acute illness, we have noted a reversible syndrome of headache, altered mental functioning, seizures, and loss of vision associated with findings indicating predominantly posterior leukoencephalopathy on imaging studies. To elucidate this syndrome, we searched the log books listing computed tomographic (CT) and magnetic resonance imaging (MRI) studies performed at the New England Medical Center in Boston and Hôpital Sainte Anne in Paris; we found 15 such patients who were evaluated from 1988 through 1994. Of the 15 patients, 7 were receiving immunosuppressive therapy after transplantation or as treatment for aplastic anemia, 1 was receiving interferon for melanoma, 3 had eclampsia, and 4 had acute hypertensive encephalopathy associated with renal disease (2 with lupus nephritis, 1 with acute glomerulonephritis, and 1 with acetaminophen-induced hepatorenal failure). Altogether, 12 patients had abrupt increases in blood pressure, and 8 had some impairment of renal function. The clinical findings included headaches, vomiting, confusion, seizures, cortical blindness and other visual abnormalities, and motor signs. CT and MRI studies showed extensive bilateral white-matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres, but the changes often involved other cerebral areas, the brain stem, or the cerebellum. The patients were treated with antihypertensive medications, and immunosuppressive therapy was withdrawn or the dose was reduced. In all 15 patients, the neurologic deficits resolved within two weeks. Reversible, predominantly posterior leukoencephalopathy may develop in patients who have renal insufficiency or hypertension or who are immunosuppressed. The findings on neuroimaging are characteristic of subcortical edema without infarction.

Almost two decades have elapsed since posterior reversible encephalopathy syndrome (PRES) was described in an influential case series. This usually reversible clinical syndrome is becoming increasingly recognised, in large part because of improved and more readily available brain imaging. Although the pathophysiological changes underlying PRES are not fully understood, endothelial dysfunction is a key factor. A diagnosis of PRES should be considered in the setting of acute neurological symptoms in patients with renal failure, blood pressure fluctuations, use of cytotoxic drugs, autoimmune disorders, or eclampsia. Characteristic radiographic findings include bilateral regions of subcortical vasogenic oedema that resolve within days or weeks. The presence of haemorrhage, restricted diffusion, contrast enhancement, and vasoconstriction are all compatible with a diagnosis. In most cases, PRES resolves spontaneously and patients show both clinical and radiological improvements. The range of symptoms that can comprise the syndrome might be broader than usually thought. In its mild form, this disorder might cause only one clinical symptom (headache or seizure) and radiographically might show few areas of vasogenic oedema or even normal brain imaging in some rare cases. In severe forms, PRES might cause substantial morbidity and even mortality, most often as a result of acute haemorrhage or massive posterior fossa oedema causing obstructive hydrocephalus or brainstem compression.