Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection

Ann Med. 2010 Jul;42(5):344-51. doi: 10.3109/07853890.2010.480979.


Background: Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS) also called nephropathia epidemica (NE). Recent case reports and retrospective studies suggest that NE may damage the pituitary gland. Based on these observations, our goal was to explore the nature of this complication prospectively.

Methods: A total of 58 hospitalized patients with acute NE volunteered to participate. Central nervous system (CNS) symptoms were recorded, cerebrospinal fluid (CSF) samples were collected, human leukocyte antigen (HLA) haplotype was analyzed, brain magnetic resonance imaging (MRI) was acquired, and electroencephalography (EEG) was recorded. Patients with abnormal pituitary MRI finding were examined by an endocrinologist.

Results: Most patients experienced CNS symptoms, and half of the CSF samples were positive for PUUV IgM, elevated protein level, or leukocyte count. CSF of patients negative for DR15(2)-DQ6 haplotype was less frequently affected. MRI revealed pituitary hemorrhage in two patients; these two patients suffered sudden loss of vision associated with headache, and they both developed hypopituitarism. Only one patient required long-term hormonal replacement therapy.

Conclusion: CNS-related symptoms and inflammation in the CSF are common in acute NE. Genetic properties of the host may predispose to CNS involvement. It does seem that pituitary injury and subsequent hormonal insufficiency may complicate the recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / virology
  • Central Nervous System Diseases / genetics
  • Central Nervous System Diseases / virology*
  • Cerebrospinal Fluid / virology
  • Electroencephalography
  • Female
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • Haplotypes
  • Hemorrhagic Fever with Renal Syndrome / complications*
  • Hemorrhagic Fever with Renal Syndrome / genetics
  • Humans
  • Immunoglobulin M / cerebrospinal fluid
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Prospective Studies
  • Puumala virus / isolation & purification*


  • HLA Antigens
  • Immunoglobulin M