title: Evaluation of clinical tools and their diagnostic use in distal symmetric polyneuropathy.
abstract: OBJECTIVE
  To compare the diagnostic usefulness of tuning fork, monofilament, biothesiometer and skin biopsies in peripheral neuropathy in individuals with varying glucose metabolism.
  
  
  METHODS
  Normoglycaemic, impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) individuals were recruited. Nerve conduction studies (NCS) and thermal threshold tests were performed. Vibrotactile sense was tested with a biothesiometer and a 128-Hz tuning fork. Touch/pressure perception was examined with a 10-g monofilament. Skin biopsies were performed and intraepidermal nerve fibres were quantified. Distal symmetric polyneuropathy (DSPN) was defined as neuropathy disability score ≥2 and abnormal NCS. Thermal threshold tests were used to define small nerve fibre neuropathy (sDSPN) in cases where NCS (large nerve fibres) were normal.
  
  
  RESULTS
  The prevalence of DSPN and sDSPN in the whole group (n=119) was 18% and 23%, respectively. For the biothesiometer, a cut-off of ≥24.5V had a sensitivity of 82% and specificity of 70% (AUC=0.81, 95% CI 0.71-0.91) when evaluating DSPN. An intraepidermal nerve fibre density cut-off of ≤3.39fibres/mm showed a sensitivity of 74% and specificity of 70% in the detection of sDSPN, whereas the sensitivity of the tuning fork and the biothesiometer were relatively low, 46% and 67%, respectively. When combining skin biopsies with the tuning fork, 10 more sDSPN cases were identified. Adding skin biopsy to the combination of the tuning fork and biothesiometer increased the sensitivity of finding sDSPN cases, but not DSPN, from 81% to 93%.
  
  
  CONCLUSIONS
  Using a biothesiometer in clinical routine might be a sensitive method to detect large nerve fibre dysfunction in the lower extremity, whereas skin biopsies in combination with methods measuring vibrotactile sense could increase the diagnostic sensitivity of detecting peripheral neuropathy at an early stage.
authors.affiliation: Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden. Electronic address: kaveh.pourhamidi@fammed.umu.se.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Pourhamidi
authors.affiliation: Department of Clinical Sciences, Hand Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Lars B
authors.initials: LB
authors.lastname: Dahlin
authors.affiliation: Department of Pathology, Division of Neuropathology, Lund University, Lund, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Englund
authors.affiliation: Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Rolandsson
mesh_terms: D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D011237:Predictive Value of Tests; D011312:Pressure; D015995:Prevalence; D012684:Sensory Thresholds; D012867:Skin / Q000294:innervation*; D013548:Sweden / Q000453:epidemiology; D013696:Temperature; D014110:Touch; D014732:Vibration
chemical_list: D015415:Biomarkers; D001786:Blood Glucose
keywords: Biothesiometer; Diabetes mellitus; Nerve fibres; Neuropathy; Skin biopsy