Clinical trial NCT02960516: MRI Diffusion Tensor Tractography to Monitor Peripheral Nerve Recovery After Severe Crush or Cut/Repair Nerve Injury
Official title: MRI Diffusion Tensor Tractography to Track and Monitor Peripheral Nerve Recovery After Severe Crush or Cut/Repair Nerve Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Nerve Injury
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2016-11-09
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: subjects between ages of 18 and 64 year of age diagnosed with a Sunderland Class V traumatic neuropathy (transection injury) of the upper extremity nerves that require immediate operative repair of this injury

Brief summary: It is estimated that up to 5% of all admissions to level one trauma centers have a peripheral nerve injury. These peripheral nerve injuries may have devastating impacts on quality of life and require months or years to regain function. Neurotmesis, or peripheral nerve transection, is a common injury, with singly cut nerve lacerations accounting for over 60% of the peripheral nerve surgical interventions in civilian studies. For recovery to occur in these patients, axons must grow from the site of repair to the target tissues, a length of up to a meter in humans. By that time, revisional surgery may not be a viable option due to the onset of irreversible muscle atrophy - a transected nerve is estimated to induce a loss of achievable function of approximately 1% for every 6 days of delay. The scenario is even worse for more proximal nerve injuries, such as those that occur in the brachial plexus.

The investigators aim is to longitudinally assess diffusion tensor tractography (DTI) in order to optimize, validate, and translate the ability of DTI to monitor and, more importantly, predict nerve regrowth following trauma and surgical repair. The overall objective of this study is to evaluate the ability of (DTI) to monitor and, more importantly, predict nerve regrowth following crush or cut with surgical repair. The investigators hypothesize that the additional information available via DTI will improve our ability to monitor and predict nerve regrowth following surgical repair or severe crush injury, guiding clinical management either toward or away from surgical intervention.

Detailed description: Although nerve transfers can reduce the length of axonal growth required, failures still occur and revisions are rarely an option due to the aforementioned delays in detection. Current neurodiagnostics \[e.g., electromyography (EMG), nerve conduction studies (NCS)\] are of limited utility in severely damaged nerves, providing an incomplete picture of nerve microstructural features until target reinnervation occurs. Thus, physicians are limited to a "wait and watch" approach based on qualitative measures obtained from patient history and/or physical exam. This leads to a suboptimal management of peripheral nerve injuries, which in turn can lead to increased instances of irreversible muscle atrophy, paralysis, and/or formation of painful traumatic neuroma.

In terms of the military, extremity injuries accounted for 54% of combat wounds in Operation Iraqi Freedom and Operation Enduring Freedom and recent review of service member injuries during Operation Enduring Freedom noted significant increases in brachial plexus, ulnar, and radial nerve injuries attributable to modern warfare. In addition, symptomatic neuroma occurs in 13% to 32% of amputees, causing pain and limiting or preventing the use of prosthetic devices. Take the example of a wounded warrior with a shrapnel injury to his/her elbow, resulting in the loss of an ulnar nerve segment. Even if nerve grafting is performed, true recovery (motor and/or sensory innervation of the hand) could take up to a year under typical circumstances. If the repair fails, which occurs in up to 40% of patients the failure is typically not truly recognized until that year expires using current management protocols. By that time, revisional surgery is typically not a viable option due to the aforementioned onset of irreversible muscle atrophy. In additional to an inability to effectively monitor nerve recovery after repair, diagnosis of peripheral nerve injuries is difficult using the currently available methods. For example, neurotmesis is a common, but difficult to distinguish, diagnosis following traumatic or iatrogenic extremity injury. Current electrodiagnostic and clinical examinations are invasive, time consuming, and painful. In addition, they cannot perfectly discriminate a severe axonotmetic laceration from a self-resolving neurapraxic injury in the acute setting. This is particularly important in penetrating injuries, or after iatrogenic nerve injuries resulting from nerve blocks, or from intraoperative positioning or external compression, because the degree of axonal injury is unknown.

Eligibility criteria: Inclusion Criteria:

subjects between ages of 18 and 64 year of age diagnosed with a Sunderland Class V traumatic neuropathy (transection injury) of the upper extremity nerves that require repair

* Candidates for immediate operative repair of this injury and do not have significant medical comorbidities precluding immediate operative intervention
* willing to comply with all aspects of the treatment (post-operative visits, occupational therapy) and evaluation schedule over the following 12 months
* have peripheral nerve injuries complicated by significant vascular or orthopedic damage

Exclusion Criteria:

* Injuries exhibit gross contamination
* soft tissue coverage is inadequate
* planned staged repair
* have diabetes
* have a neuromuscular disease
* undergoing chemotherapy, radiation therapy or other treatments known to affect the growth of the neural and vascular system
* unlikely to complete occupational therapy
* pregnant or breast-feeding
* subject with any ferromagnetic objects that cannot be removed (cardiac pacemakers, aneurysm clips etc).
* history of claustrophobia

Primary outcomes:
measure: Michigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery
timeFrame: 1, 3, 4, 6, and 9 months post surgery
measure: Grip Strength in Subjects With TPNI Post Surgery
timeFrame: 1, 3, 4, and 6 months post surgery
measure: 9 Hole Peg Test in Subjects With TPNI
timeFrame: 1, 3, 4, and 6 months post surgery
measure: Diffusion Tensor Imaging (DTI) Diffusivity Metrics Post Surgery
timeFrame: Subjects with TPNI underwent imaging at time points falling between 1 and 9 months post surgery. Subjects with CTS underwent imaging at time points falling between 1 and 24 months post surgery.
measure: Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Metric Post Surgery
timeFrame: Subjects with TPNI underwent imaging at time points falling between 1 and 9 months post surgery. Subjects with CTS underwent imaging at time points falling between 1 and 24 months post surgery.
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Wesley Thayer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Noble J, Munro CA, Prasad VS, Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma. 1998 Jul;45(1):116-22. doi: 10.1097/00005373-199807000-00025.