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Sensory Neuron Death After Upper Limb Nerve Injury and Protective Effect of Repair: Clinical Evaluation Using Volumetric Magnetic Resonance Imaging of Dorsal Root Ganglia

West, Christian Alexander MD†,‡; Ljungberg, Christina PhD†,‡; Wiberg, Mikael PhD†,‡; Hart, Andrew PhD‡,§,¶

doi: 10.1227/NEU.0000000000000066
Research-Human-Clinical Studies

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.

CONCLUSION: 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.

ABBREVIATIONS: ANOVA, analysis of variance

DRG, dorsal root ganglia

SD, standard deviation

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

Correspondence: Christian Alexander West, MD, Department of Integrative Medical Biology, Section for Anatomy, Umea University, Umea, Sweden. E-mail:

Received November 16, 2012

Accepted June 20, 2013

Copyright © by the Congress of Neurological Surgeons