Asymptomatic loss of intraepidermal nerve fibers with preserved thermal detection thresholds after repeated exposure to severe cold

Thomas Krøigård*, Martin Wirenfeldt, Toke K. Svendsen, Søren H. Sindrup

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Background: Cold-induced peripheral neuropathy has been described in individuals exposed to severe cold resulting in pain, hypersensitivity to cold, hyperhidrosis, numbness, and skin changes. Nerve conduction studies and thermal detection thresholds are abnormal in symptomatic patients, and intraepidermal nerve fiber density (IENFD) in skin biopsies is reduced. Case presentation: A 41-year-old male was included as a healthy subject in a study of the spontaneous variability of quantitative sensory testing (QST), nerve conduction studies (NCS), and IENFD. Unexpectedly, IENFD was significantly reduced, whereas the rest of the examination was normal except for reduced vibration detection threshold. The results were confirmed at follow-up examination. The subject had been repeatedly exposed to severe cold resulting in short lasting numbness and paresthesia while living in the eastern part of Greenland and the northern part of Norway. Conclusion: Loss of intraepidermal nerve fibers caused by exposure to severe cold may be asymptomatic, and their function assessed by thermal detection thresholds may be preserved. This case illustrates that QST and IENFD are complementary tests and that subclinical cold-induced peripheral neuropathy may be prevalent in subjects living in or near polar regions which could have implications for the recruitment of healthy subjects.

Original languageEnglish
Article numbere009147
JournalBrain and Behavior
Issue number3
Pages (from-to)e009147
Number of pages4
Publication statusPublished - Mar 2018


  • Adult
  • Cold Temperature/adverse effects
  • Greenland
  • Humans
  • Male
  • Nerve Fibers/physiology
  • Neurologic Examination/methods
  • Norway
  • Pain Threshold/physiology
  • Peripheral Nervous System Diseases/diagnosis
  • Skin/innervation


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