Profound neurological injury in a patient with atypical hemolytic uremic syndrome.

Dear Editor, Atypical HUS (aHUS) is a thrombotic microangiopathy (TMA) characterized by complement-mediated end-organ injury. While patients with aHUS may present similarly to patients with thrombotic thrombocytopenic purpura (TTP), they have different underlying pathophysiologies, and this may explain differing responses to plasma-based therapy. It can be challenging to differentiate aHUS from TTP. It had been presumed in the past that profound renal injury is due to aHUS, while neurologic injury was felt to be more consistent with TTP. Although kidney injury may be the overriding feature in aHUS, it has been recognized that multiple end organs may be affected including the brain, heart, lung, and GI tract [1, 2]. We report a patient with aHUS and profound neurological symptoms that recovered following eculizumab therapy. An otherwise healthy 66-year-old female was admitted to the medical ICU after presenting with nausea, crampy abdominal pain, and intermittent bloody diarrhea following consumption of a salad at a local restaurant 9 days prior. A Shiga toxin assay was negative. Although not thrombocytopenic on admission, over the 36 h of hospitalization, platelet count decreased to 100×10/μL platelet, and on peripheral blood smear, she was noted to have 3+ schistocytes per high power field. She quickly became anuric and developed mental status changes. Given her deteriorating condition, she was transferred to our institution. On admission, she was intubated for airway protection. Laboratory studies showed findings consistent with a microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. ADAMTS13 activity level was 68 %. On day 3 of plasma exchange, she experienced a generalized tonic– clonic seizure. Following the seizure, despite being off all sedating medications, she remained unresponsive but maintained gag and corneal reflexes. CT of head was unremarkable and an MRI demonstrated only a focal 3×3-mm area of increased FLAIR signal abnormality in the left superior temporal gyrus cortex. EEG was suggestive of a moderate, nonspecific encephalopathy. Lumbar puncture was unremarkable. Despite an extensive neurological evaluation, no etiology of her mental status changes other than her TMA was identified. On day 4, therapy with eculizumab was initiated. Eculizumab is a humanized monoclonal antibody against CS that blocks terminal compliment activity. Therapy consisted of induction infusion administered at 900 mg iv weekly for 4 weeks followed by maintenance therapy at 1,200 mg biweekly. Following her third weekly infusion, she became independent of hemodialysis, though still unresponsive with a tracheostomy for airway protection. On week 7 of therapy, she rather abruptly awoke and became verbal. She gradually improved neurologically and has been making tremendous strides in her rehabilitation. She is currently continuing biweekly eculizumab therapy and is now functionally independent, approaching her pre-illness state. Results of her mutation studies demonstrated the presence of a heterozygous mutation G. Salem (*) Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Starling Loving Hall, Room 365, 320 West 10th Avenue, Columbus 43210, USA e-mail: Galena.Salem@osumc.edu