New-onset seizures in two adults with hemophagocytic lymphohistiocytosis.

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal hematologic disease marked by an exaggerated immune response with prolonged, excessive production of cytokines [1]. While seizures and other neurological manifestations are well described in children with HLH, reports of central nervous system (CNS) involvement in adults with HLH are exceptionally rare [2–5]. We report two such cases at Columbia University Medical Center. A 63-year-old man with rheumatoid arthritis presented with fevers, new-onset focal motor seizures, left hemiparesis, deteriorating mental status, and pancytopenia. MRI brain is shown in Fig. 1a. The patient’s course was complicated by persistent fevers, hepatic failure, and respiratory failure. Liver biopsy on hospital day 14 revealed lobular disarray, confluent hepatocyte necrosis, and macrophage aggregates with hemophagocytosis. Bone marrow biopsy on hospital day 18 (Fig. 1b) and laboratory testing were consistent with HLH deemed secondary to rheumatoid arthritis (Table 1). The patient was treated with dexamethasone, cyclosporine, etanercept, and plasmapheresis. His condition improved and he was eventually discharged to a long-term acute care facility on hospital day 90. A previously healthy 27-year-old man presented with fevers, diffuse myalgias, a normal neurological exam, and pancytopenia. He subsequently developed new-onset refractory status epilepticus. Electroencephalography demonstrated secondarily generalized seizures with independent left and right temporal onsets. MRI brain is shown in Fig. 1c. Extensive testing for infectious, autoimmune, and neoplastic etiologies was negative. The course was complicated by persistent electrographic seizures, renal failure requiring hemodialysis, acute respiratory distress syndrome, heart failure, and fungemia. Bone marrow biopsy on hospital day 14 was consistent with HLH (Fig. 1d). Subsequent laboratory studies confirmed this diagnosis (Table 1). No cause of HLH was identified. He was treated with systemic etoposide, corticosteroids, and intrathecal methotrexate [1]. Brain death was declared on hospital day 24 secondary to diffuse cerebral edema. Postmortem examination of the brain revealed a diffuse increase in activated macrophages without definite hemophagocytosis. There were no focal abnormalities within the temporal lobes to account for the epileptic foci. HLH may present as either a primary autosomal recessive form or an acquired form that develops in response to viral infection, rheumatologic disease, or hematologic malignancy [6]. The cause of acquired HLH is not always identifiable [6]. HLH may be diagnosed when a molecular diagnosis consistent with HLH is present or when five of eight diagnostic criteria are met (Table 1) [1]. In a nationwide survey, the combined annual incidence of familial and acquired HLH in Japan was 1 in 800,000, with C. A. Gold (&) S. J. Sheth S. Agarwal J. Claassen B. Foreman Department of Neurology, Neurological Institute of New York, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA e-mail: cag2181@cumc.columbia.edu