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MRI Diffusion Tensor Tractography to Monitor Peripheral Nerve Recovery After Severe Crush or Cut/Repair Nerve Injury

MRI Diffusion Tensor Tractography to Track and Monitor Peripheral Nerve Recovery After Severe Crush or Cut/Repair Nerve Injury

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT02960516
Enrollment
19
Registered
2016-11-09
Start date
2016-10-31
Completion date
2021-07-29
Last updated
2023-03-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nerve 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.

Interventions

DEVICEMRI of 3.0T

Diffusion Tensor Testing for peripheral nerve monitoring

Sponsors

United States Department of Defense
CollaboratorFED
Vanderbilt University
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Michigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery1, 3, 4, 6, and 9 months post surgeryMichigan Hand Questionnaire assesses hand function and well being of patients with hand injuries. It is divided into 6 scales: Overall hand function, scored in a range of 5-25; Activities of daily living, scored in a range of 5-25; Work, scored in a range of 5-25; Pain, scored in a range of 5-25; Aesthetics, scored in a range of 4-16; Satisfaction, scored in a range of 6-30. For the pain scale, higher scores indicate more pain. For the other 5 scales, higher scores indicate better hand performance. These raw scores are then converted to a range of 0-100 based on the following equations: Overall hand function: -(raw score-25)/20*100; Activities of daily living: -(raw score-25) 20*100; Work: (raw score-5)/20*100; Pain: If question 1=5, then pain score =0; if question 1≠5,then -(raw score-25)/20*100; Aesthetics:(raw score-4)/16*100; Satisfaction: -(raw score-30)/24*100. For every patient, an overall MHQ score is obtained by summing the scores for all 6 scales and dividing by 6.
Grip Strength in Subjects With TPNI Post Surgery1, 3, 4, and 6 months post surgeryThe grip strength test is performed by having the participant squeeze as hard as possible on a tool known as dynamometer. Grip strength findings were compared between injured and uninjured hands in subjects with TPNI at 3,4, and 6 months post surgery. However not all participants were assessed at all time points.
9 Hole Peg Test in Subjects With TPNI1, 3, 4, and 6 months post surgeryThe Nine Hole Peg Test is used to evaluate patients' fine hand control or dexterity. The total time required to insert nine pegs into nine holes is recorded. The lower the number, the faster the time, the better the performance. 9HPT findings were compared between injured and uninjured hand at 3,4, and 6 months post surgery in subjects with TPNI. However not all participants were assessed at all time points.
Diffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgerySubjects 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.Subjects underwent DTI at different time points post surgery; and the metrics analyzed were: Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD). Imaging was done to the healthy median nerve in controls, injured and healthy (median or ulnar) nerves in patients with TPNI, and compressed median nerve in patients with Carpal Tunnel Syndrome (CTS). Imaging was done at multiple timepoints post surgery. 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. The values were then averaged for each group, as presented below.
Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Metric Post SurgerySubjects 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.Subjects underwent DTI at different time points post surgery and the metric Fractional anisotropy (FA) was analyzed. FA is a scalar value between 0-1 that describe anisotropy of a diffusion process. A value of zero means that diffusion is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. Imaging was done to the healthy median nerve in controls, injured and healthy (median or ulnar) nerves in patients with TPNI, and compressed median nerve in patients with Carpal Tunnel Syndrome (CTS). Imaging was done at multiple timepoints post surgery.

Countries

United States

Participant flow

Participants by arm

ArmCount
TPNI Group
Subjects who had traumatic peripheral nerve injury (TPNI)
3
CTS Group
Participants who had carpal tunnel syndrome (CTS)
8
Controls
Healthy control subjects
8
Total19

Baseline characteristics

CharacteristicTPNI GroupCTS GroupControlsTotal
Age, Customized
Age
33.3 years53.3 years32.4 years39.6 years
BMI23.7 kg/m^230.5 kg/m^225.7 kg/m^226.5 kg/m^2
Race and Ethnicity Not Collected0 Participants
Sex: Female, Male
Female
1 Participants5 Participants7 Participants13 Participants
Sex: Female, Male
Male
2 Participants3 Participants1 Participants6 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 30 / 80 / 8
other
Total, other adverse events
0 / 30 / 80 / 8
serious
Total, serious adverse events
0 / 30 / 80 / 8

Outcome results

Primary

9 Hole Peg Test in Subjects With TPNI

The Nine Hole Peg Test is used to evaluate patients' fine hand control or dexterity. The total time required to insert nine pegs into nine holes is recorded. The lower the number, the faster the time, the better the performance. 9HPT findings were compared between injured and uninjured hand at 3,4, and 6 months post surgery in subjects with TPNI. However not all participants were assessed at all time points.

Time frame: 1, 3, 4, and 6 months post surgery

Population: The overall number of participants was 2; however at each of the time points, only 1 participant was assessed, as presented below.

ArmMeasureGroupValue (NUMBER)
Injured Hand in TPNI9 Hole Peg Test in Subjects With TPNI1 month post surgeryNA seconds
Injured Hand in TPNI9 Hole Peg Test in Subjects With TPNI3 months post surgery43 seconds
Injured Hand in TPNI9 Hole Peg Test in Subjects With TPNI4 months post surgery100 seconds
Injured Hand in TPNI9 Hole Peg Test in Subjects With TPNI6 months post surgery51 seconds
Healthy Hand in TPNI9 Hole Peg Test in Subjects With TPNI6 months post surgery26 seconds
Healthy Hand in TPNI9 Hole Peg Test in Subjects With TPNI1 month post surgery23 seconds
Healthy Hand in TPNI9 Hole Peg Test in Subjects With TPNI4 months post surgery27 seconds
Healthy Hand in TPNI9 Hole Peg Test in Subjects With TPNI3 months post surgery27 seconds
Primary

Diffusion Tensor Imaging (DTI) Diffusivity Metrics Post Surgery

Subjects underwent DTI at different time points post surgery; and the metrics analyzed were: Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD). Imaging was done to the healthy median nerve in controls, injured and healthy (median or ulnar) nerves in patients with TPNI, and compressed median nerve in patients with Carpal Tunnel Syndrome (CTS). Imaging was done at multiple timepoints post surgery. 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. The values were then averaged for each group, as presented below.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Injured Hand in TPNIDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryMean Diffusivity (MD)1.41 μm^2/msStandard Deviation 0.15
Injured Hand in TPNIDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryRadial Diffusivity (RD)1.16 μm^2/msStandard Deviation 0.15
Injured Hand in TPNIDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryAxial Diffusivity (AD)1.91 μm^2/msStandard Deviation 0.19
Healthy Hand in TPNIDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryMean Diffusivity (MD)1.13 μm^2/msStandard Deviation 0.28
Healthy Hand in TPNIDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryRadial Diffusivity (RD)0.78 μm^2/msStandard Deviation 0.25
Healthy Hand in TPNIDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryAxial Diffusivity (AD)1.82 μm^2/msStandard Deviation 0.42
Carpal Tunnel Syndrome (CTS)Diffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryAxial Diffusivity (AD)1.90 μm^2/msStandard Deviation 0.06
Carpal Tunnel Syndrome (CTS)Diffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryMean Diffusivity (MD)1.27 μm^2/msStandard Deviation 0.06
Carpal Tunnel Syndrome (CTS)Diffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryRadial Diffusivity (RD)1.01 μm^2/msStandard Deviation 0.06
ControlsDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryMean Diffusivity (MD)1.09 μm^2/msStandard Deviation 0.05
ControlsDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryRadial Diffusivity (RD)0.67 μm^2/msStandard Deviation 0.05
ControlsDiffusion Tensor Imaging (DTI) Diffusivity Metrics Post SurgeryAxial Diffusivity (AD)1.92 μm^2/msStandard Deviation 0.05
Primary

Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Metric Post Surgery

Subjects underwent DTI at different time points post surgery and the metric Fractional anisotropy (FA) was analyzed. FA is a scalar value between 0-1 that describe anisotropy of a diffusion process. A value of zero means that diffusion is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. Imaging was done to the healthy median nerve in controls, injured and healthy (median or ulnar) nerves in patients with TPNI, and compressed median nerve in patients with Carpal Tunnel Syndrome (CTS). Imaging was done at multiple timepoints post surgery.

Time frame: 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.

ArmMeasureValue (MEAN)Dispersion
Injured Hand in TPNIDiffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Metric Post Surgery0.32 score on a scaleStandard Deviation 0.06
Healthy Hand in TPNIDiffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Metric Post Surgery0.48 score on a scaleStandard Deviation 0.14
Carpal Tunnel Syndrome (CTS)Diffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Metric Post Surgery0.43 score on a scaleStandard Deviation 0.03
ControlsDiffusion Tensor Imaging (DTI) Fractional Anisotropy (FA) Metric Post Surgery0.59 score on a scaleStandard Deviation 0.03
Primary

Grip Strength in Subjects With TPNI Post Surgery

The grip strength test is performed by having the participant squeeze as hard as possible on a tool known as dynamometer. Grip strength findings were compared between injured and uninjured hands in subjects with TPNI at 3,4, and 6 months post surgery. However not all participants were assessed at all time points.

Time frame: 1, 3, 4, and 6 months post surgery

Population: The overall number of participants was 2; however at each of the time points, only 1 participant was assessed, as presented below.

ArmMeasureGroupValue (NUMBER)
Injured Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery1 month post surgeryNA pounds
Injured Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery3 months post surgery30 pounds
Injured Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery4 months post injury40 pounds
Injured Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery6 months post surgery18 pounds
Healthy Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery6 months post surgery74 pounds
Healthy Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery1 month post surgery92 pounds
Healthy Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery4 months post injury100 pounds
Healthy Hand in TPNIGrip Strength in Subjects With TPNI Post Surgery3 months post surgery75 pounds
Primary

Michigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery

Michigan Hand Questionnaire assesses hand function and well being of patients with hand injuries. It is divided into 6 scales: Overall hand function, scored in a range of 5-25; Activities of daily living, scored in a range of 5-25; Work, scored in a range of 5-25; Pain, scored in a range of 5-25; Aesthetics, scored in a range of 4-16; Satisfaction, scored in a range of 6-30. For the pain scale, higher scores indicate more pain. For the other 5 scales, higher scores indicate better hand performance. These raw scores are then converted to a range of 0-100 based on the following equations: Overall hand function: -(raw score-25)/20*100; Activities of daily living: -(raw score-25) 20*100; Work: (raw score-5)/20*100; Pain: If question 1=5, then pain score =0; if question 1≠5,then -(raw score-25)/20*100; Aesthetics:(raw score-4)/16*100; Satisfaction: -(raw score-30)/24*100. For every patient, an overall MHQ score is obtained by summing the scores for all 6 scales and dividing by 6.

Time frame: 1, 3, 4, 6, and 9 months post surgery

Population: At each time point only 1 participant was assessed

ArmMeasureGroupValue (NUMBER)
Injured Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery3 months post surgery5 score on a scale
Injured Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery6 months post surgery0.8 score on a scale
Injured Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery4 months post surgery69 score on a scale
Injured Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery9 months post surgery6.8 score on a scale
Injured Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery1 month post surgery33 score on a scale
Healthy Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery9 months post surgery81 score on a scale
Healthy Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery1 month post surgery83 score on a scale
Healthy Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery3 months post surgery75 score on a scale
Healthy Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery4 months post surgery83 score on a scale
Healthy Hand in TPNIMichigan Hand Questionnaire (MHQ) in TPNI Subjects Post Surgery6 months post surgery81 score on a scale

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026