From the FDA Drug Label
Encephalopathy, including Posterior Reversible Encephalopathy Syndrome (PRES), has been described both in post-marketing reports and in the literature Manifestations include impaired consciousness, convulsions, visual disturbances (including blindness), loss of motor function, movement disorders and psychiatric disturbances. The changes in most cases have been reversible upon discontinuation of cyclosporine, and in some cases improvement was noted after reduction of dose
The risk of Reversible Posterior Leukoencephalopathy Syndrome (RPLS), also known as Posterior Reversible Encephalopathy Syndrome (PRES), in patients undergoing immunosuppressive therapy with calcineurin inhibitors such as cyclosporine is a concern.
- Predisposing factors for RPLS include hypertension, hypomagnesemia, hypocholesterolemia, high-dose corticosteroids, high cyclosporine blood concentrations, and graft-versus-host disease.
- Manifestations of RPLS include impaired consciousness, convulsions, visual disturbances, loss of motor function, movement disorders, and psychiatric disturbances.
- In most cases, the changes associated with RPLS are reversible upon discontinuation of cyclosporine or reduction of dose 1.
From the Research
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) is a significant risk for patients on calcineurin inhibitors like cyclosporine and tacrolimus during immunosuppressive therapy, with a dose-dependent risk and higher incidence in patients with hypertension, renal dysfunction, or those on high-dose therapy. Patients typically present with headaches, altered mental status, visual disturbances, seizures, and hypertension. The risk can occur within days to weeks of starting therapy. Management involves prompt recognition, reducing or discontinuing the calcineurin inhibitor, controlling blood pressure, and providing supportive care. Blood pressure should be maintained below 140/90 mmHg, and neuroimaging (preferably MRI) should be obtained to confirm diagnosis, as seen in cases described by 2.
Key Considerations
- The syndrome develops because calcineurin inhibitors disrupt the blood-brain barrier and impair cerebral autoregulation, leading to vasogenic edema primarily in posterior brain regions.
- Regular monitoring of drug levels, blood pressure, and neurological symptoms is essential for early detection and management of this potentially reversible condition, as highlighted by 3 and 2.
- Most cases resolve within days to weeks after drug discontinuation, though permanent neurological damage can occur if not addressed promptly.
Diagnosis and Treatment
- Neuroimaging, preferably MRI, is crucial for diagnosis, as it shows the edema primarily in the cortex and subcortical white matter of the posterior brain regions, as noted in 2.
- Interruption of calcineurin inhibitors is essential for the treatment of patients with RPLS, and in some cases, substitution with another immunosuppressive agent may be considered, as demonstrated by 3.
- Controlling blood pressure and providing supportive care are also vital components of management, as emphasized by 4 and 2.
Patient Monitoring
- Regular monitoring of patients on calcineurin inhibitors for signs of RPLS, including headaches, seizures, and visual disturbances, is critical for early detection and prevention of permanent neurological damage, as suggested by 5 and 6.
- Blood pressure control and monitoring of drug levels are also important aspects of patient care to minimize the risk of RPLS, as indicated by 4 and 2.