title: Sensory neuron death after upper limb nerve injury and protective effect of repair: clinical evaluation using volumetric magnetic resonance imaging of dorsal root Ganglia.
abstract: BACKGROUND
  Extensive death of sensory neurons after nerve trauma depletes the number of regenerating neurons, contributing to inadequate cutaneous innervation density and poor sensory recovery. Experimentally proven neuroprotective neoadjuvant drugs require noninvasive in vivo measures of neuron death to permit clinical trials. In animal models of nerve transection, magnetic resonance imaging (MRI) proved a valid tool for quantifying sensory neuron loss within dorsal root ganglia (DRG) by measuring consequent proportional shrinkage of respective ganglia.
  
  
  OBJECTIVE
  This system is investigated for clinical application after upper limb nerve injury and microsurgical nerve repair.
  
  
  METHODS
  A 3-T clinical magnet was used to image and measure volume (Cavalieri principle) of C7-T1 DRG in uninjured volunteers (controls, n = 14), hand amputees (unrepaired nerve injury, n = 5), and early nerve repair patients (median and ulnar nerves transected, microsurgical nerve repair within 24 hours, n = 4).
  
  
  RESULTS
  MRI was well tolerated. Volumetric analysis was feasible in 74% of patients. A mean 14% volume reduction was found in amputees' C7 and C8 DRG (P < .001 vs controls). Volume loss was lower in median and ulnar nerve repair patients (mean 3% volume loss, P < .01 vs amputees), and varied among patients. T1 DRG volume remained unaffected.
  
  
  CONCLUSIONS
  MRI provides noninvasive in vivo assessment of DRG volume as a proxy clinical measure of sensory neuron death. The significant decrease found after unrepaired nerve injury provides indirect clinical evidence of axotomy-induced neuronal death. This loss was less after nerve repair, indicating a neuroprotective benefit of early repair. Volumetric MRI has potential diagnostic applications and is a quantitative tool for clinical trials of neuroprotective therapies.
authors.affiliation: †Department of Integrative Medical Biology, Section for Anatomy, Umea University, Umea, Sweden; ‡Department of Surgical and Perioperative Science, Section for Hand & Plastic Surgery, University Hospital, Umea, Sweden; §Plastic Surgery Research, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; ¶Canniesburn Plastic Surgery Unit, Scottish National Brachial Plexus Service, Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Christian Alexander
authors.initials: CA
authors.lastname: West
authors.forename: Christina
authors.initials: C
authors.lastname: Ljungberg
authors.forename: Mikael
authors.initials: M
authors.lastname: Wiberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Hart
mesh_terms: D000328:Adult; D000674:Amputees; D016923:Cell Death; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology; D011984:Sensory Receptor Cells / Q000473:pathology*; D055815:Young Adult