The most accepted theory of PRES is a loss of autoregulation in cerebral blood flow induced by hypertension with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes, producing vasogenic edema with petechial hemorrhage [1, 2]. A histologic evaluation of PRES is uncommon and is often obtained late in the course of complex systemic disease. Activated reactive astrocytes, scattered macrophages and lymphocytes have often been noted without inflammation, ischemia or neuronal damage. Three hemispheric pattern variants may be encountered with similar frequency: holohemispheric, superior frontal sulcal and primary parietal-occipital .
PRES has been less commonly described in the setting of autoimmune disease, and the distinctive role of SLE in the pathophysiology of PRES is often clouded by concurrent hypertension and renal disease . To date, there have been two types of "PRES-SLE" syndromes described: "hypertensive PRES," which is reversible with conventional antihypertensive and anticonvulsive treatments concomitant with inactive SLE, and "immunological PRES," which requires immunosuppressive therapy and is considered a neurological manifestation of active SLE . Our patient likely had the former type of PRES-SLE, given the fact that markers of lupus activity were normal and her clinical findings were not consistent with cerebral vasculitis or a systemic disease process.
In infection-associated PRES, a clinical pattern consistent with systemic inflammatory response syndrome develops with evidence of multiple organ dysfunction syndrome . A case of an association between influenza A virus and PRES with documentation of cerebral vasculopathy has been reported . Influenza infection can precipitate encephalopathy, or encephalitis with the development of cerebral edema, which might confuse the initial clinical picture. The case of our patient is unique in that parainfluenza virus infection has not been reported in the literature in association with the development of PRES. Parainfluenza infections are a common cause of respiratory infection in infants and children; however, immunocompromised adults can also be affected . Parainfluenza virus type 3 usually presents with lower respiratory features (bronchiolitis and pneumonia), which might have been related to this patient's history of flu-like symptoms that triggered the discontinuation of clonidine, likely representing the incubation period of the virus, which can extend up to seven days. No rash has been reported to be associated with parainfluenza virus . In a study of hematopoietic cell transplant recipients by Peck et al., asymptomatic parainfluenza virus infection was detected in 17.9% of recipients .
PRES in our patient was likely precipitated by multiple factors, including uncontrolled hypertension, immunosuppression due to a history of autoimmune disease and ESRD, and acute parainfluenza virus infection.
In addition to viral infection and SLE, PRES has also been associated with high-dose methylprednisolone therapy, uremic encephalopathy, pheochromocytoma, Henoch-Schönlein purpura, acute hepatic failure, sickle cell disease, thrombotic thrombocytopenic purpura, organ transplantation, HIV infection and gemcitabine therapy [3, 6].
There are no specific guidelines for the management of hypertension in PRES; however, the general recommendation is to treat all PRES patients presenting with malignant hypertension with parenteral agents for a goal reduction in diastolic blood pressure to 100 to 105 mmHg within two to six hours while not exceeding a decline in mean arterial pressure by more than 25% to avoid cerebral hypoperfusion and stroke. Those patients who present with lesser degrees of hypertension should be managed with smaller incremental changes in blood pressure decline as per ischemic stroke guidelines . Treatment of PRES generally includes antihypertensive and/or anticonvulsant therapies and the withdrawal of a suspected drug if applicable . When seven-day therapy for hypertension and convulsion does not reverse the manifestation, immunosuppressive treatments are recommended to reverse PRES . Recurrence of atypical PRES in a hypertensive child with ESRD on peritoneal dialysis was reported by Girişgen et al., and they noted infection and sudden increases in blood pressure as causes for recurrence . In the case series reported by Varaprasad et al., the duration of hospital stay ranged from five to 26 days (median of 14 days) and the time to recovery from PRES was two to 10 days (median of three and a half days) . Most case reports have described excellent outcomes; however, one report by Covarrubias et al. reported mortality of more than 25% with significant residual neurologic morbidity in survivors as well .