title: Impairment of small somatic and autonomic nerve fibres in intensive care unit patients with severe sepsis and critical illness polyneuropathy--a single center controlled observational study.
abstract: BACKGROUND
  Axonal damage in large myelinated nerve fibres occurs in about 70% of patients with severe sepsis, known as critical illness polyneuropathy and contributes significantly to an increased short- and long-term morbidity and mortality in this population. Among other pathophysiological mechanisms, autonomic dysregulation, characterized by high concentrations of circulating catecholamines in the presence of impaired sympathetic modulation of heart and vessels have been discussed. We hypothesize that autonomic small fibre neuropathy play an important role in autonomic failure.
  
  
  METHODS
  Single center, non-randomized, controlled, observational study. Skin biopsies of patients with severe sepsis and/or septic shock are compared with those of age-matched controls. In order to assess impairment of small nerve fibres, skin biopsies are taken at onset of severe sepsis, and two and 16 weeks later. Intraepidermal nerve fibre densities are histologically analyzed using anti protein gene product (PGP) 9.5 immunostaining. In addition, standardized clinical examinations, as Medical Research Council (MRC) scores of muscle strength, Rankin scores, and standardized nerve conduction studies of the right median nerve, the right tibial nerve, the left fibular nerve, and both sural nerves are performed, to identify critical illness polyneuropathy and to neurophysiologically quantify the damage of large nerve fibres.
  
  
  CONCLUSIONS
  The study will allow to describe the frequency of small fibre neuropathy in patients with severe sepsis up to four months after onset of severe sepsis and to evaluate its relationship to critical illness polyneuropathy.
  
  
  BACKGROUND
  The trial has been registered to the German Clinical Trials Register. The trial registration number is DRKS-ID: DRKS00000642.
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07747 Jena, Germany. hubertus.axer@med.uni-jena.de.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Axer
authors.forename: Alexander
authors.initials: A
authors.lastname: Grimm
authors.forename: Christine
authors.initials: C
authors.lastname: Porzelius
authors.forename: Ulrike
authors.initials: U
authors.lastname: Teschner
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schumacher
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
authors.forename: Frank M
authors.initials: FM
authors.lastname: Brunkhorst
mesh_terms: D006801:Humans; D017776:Autonomic Pathways / Q000473:pathology / Q000503:physiopathology; D007362:Intensive Care Units / Q000639:trends; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009431:Neural Conduction; D011115:Polyneuropathies / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D018805:Sepsis / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology