title: Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Oulu University Hospital, Oulu, Finland. timo.hautala@oulu.fi
authors.forename: Timo
authors.initials: T
authors.lastname: Hautala
authors.forename: Saara-Mari
authors.initials: SM
authors.lastname: Mähönen
authors.forename: Tarja
authors.initials: T
authors.lastname: Sironen
authors.forename: Nina
authors.initials: N
authors.lastname: Hautala
authors.forename: Eija
authors.initials: E
authors.lastname: Pääkkö
authors.forename: Ari
authors.initials: A
authors.lastname: Karttunen
authors.forename: Pasi I
authors.initials: PI
authors.lastname: Salmela
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Olli
authors.initials: O
authors.lastname: Vainio
authors.forename: Virpi
authors.initials: V
authors.lastname: Glumoff
authors.forename: Seppo
authors.initials: S
authors.lastname: Rytky
authors.forename: Alexander
authors.initials: A
authors.lastname: Plyusnin
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.forename: Olli
authors.initials: O
authors.lastname: Vapalahti
authors.forename: Heikki
authors.initials: H
authors.lastname: Kauma
mesh_terms: D000328:Adult; D001921:Brain / Q000821:virology; D002493:Central Nervous System Diseases / Q000235:genetics / Q000821:virology*; D002555:Cerebrospinal Fluid / Q000821:virology; D004569:Electroencephalography; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006480:Hemorrhagic Fever with Renal Syndrome / Q000150:complications* / Q000235:genetics; D006801:Humans; D007075:Immunoglobulin M / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029262:Puumala virus / Q000302:isolation & purification*
chemical_list: D006680:HLA Antigens; D007075:Immunoglobulin M