Case Presentation: A 63-year-old woman woman presented after multiple episodes of seizure. She had no prior history of seizures or alcoholism. The patient had a deceased donor renal transplant 6 months prior complicated by persistent right perinephric fluid collection treated with long term piperacillin-tazobactam therapy. Attempts to obtain microbiology were unsuccessful and patient was started on linezolid 7 days before admission. Her transplantation has been otherwise without complication and she was given prednisone, tacrolimus and mycophenolate. On the day of admission she experienced nausea, vomiting and diarrhea. In the Emergency Department, IV midazolam and intubation led to a cessation of seizure activity. The patient was afebrile with initial blood pressure of 189/100, heart rate 85 and oxygen saturation 100% while intubated. The neurologic evaluation was limited by sedation, although pupils were equal and reactive with no evidence of focal deficits. Labs were significant for normocytic, normochromic anemia, thrombocytopenia, BUN and creatinine of 42 and 2.32 mg/dl. A CT of the head without contrast did not exhibit hemorrhage, masses or areas of infarction. CT abdomen confirmed stranding around the right transplanted kidney. An MRI of the brain revealed symmetric subcortical areas of abnormal hyperintense T2/FLAIR involving mainly occipital lobes, and frontal lobes with minimal focal area of susceptibility . These findings favors a posterior reversible encephalopathy syndrome (P R E S). Tacrolimus was held and levels checked. Antibiotic therapy was adjusted. The patient remained seizure-free, afebrile, and normotensive. She was extubated on the third hospital day.
Discussion: The clinical picture of PRES is characterized by an acute or subacute encephalopathy with headache, vomiting, focal neurological deficits, altered mental status, visual impairment and seizure. 75 % of patients have moderate to severe hypertension at presentation, however it may also occur in normotensive patients. MRI is the gold standard for diagnosing this syndrome. Typically, the lesions of PRES are described as symmetric and bilateral in the cortical and subcortical regions of the parietal and occipital lobes. FLAIR is the most sensitive sequence for recognition of the vasogenic edema in those areas. The pathogenesis of PRES remains unclear, but it appears to be related to a disordered in cerebral autoregulation and endothelial dysfunction. Different mechanisms seem to be important in different clinical situations. Concern about pharmacotoxic side effects of antibiotics has been raised. Neurotoxic effect by mitochondrial protein synthesis inhibition has been described with linezolid. PRES can also be a consequence of cytotoxic therapy. Incidence of tacrolimus induced PRES has been reported after solid organ transplant to be between 0.49% and 1.6%.Awareness of the vague early clinical signs together with MRI findings is likely to elicit an early diagnosis and management and may prevent permanent damage in this otherwise typically reversible condition.
Conclusions: PRES is a rare neurological condition that requires early diagnosis to avoid permanent neurological deficits. Our case is the second reported case of PRES presenting after a short course of linezolid use. However, the contribution of chronic cytotoxic therapy with tacrolimus is worth mentioning.The clinician should consider linezolid as a contributing factor in the development of tacrolimus associated PRES.