DETERMINANTS OF NERVE CONDUCTION RECOVERY AFTER NERVE INJURIES: COMPRESSION DURATION AND NERVE FIBER TYPES TO-JUNG TSENG, PhD,1 TIN-HSIN HSIAO, PhD,2 SUNG-TSANG HSIEH, MD, PhD,3 and YU-LIN HSIEH, PhD2 1 Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung, Taiwan 2 Department of Anatomy, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan 3 Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan Accepted 29 October 2014 ABSTRACT: Introduction: The aims of this study were to determine the influences of: (1) timing of nerve decompression; and (2) nerve fiber types on the patterns of nerve conduction studies (NCS) after nerve injury. Methods: Nerve conduction studies (NCS) were performed on 3 models of nerve injury: (1) crush injury due to transient nerve compression (crush group); (2) chronic constriction injury (CCI), or permanent compression (CCI group); and (3) CCI with removal of ligatures, or delayed nerve decompression (De-CCI group). Results: There were distinct patterns of NCS recovery. The crush and De-CCI groups achieved similar motor nerve recovery, better than that of the CCI group. In contrast, recovery of sensory nerves was limited in the CCI and De-CCI groups and was lower than in the crush group. Conclusions: Immediate relief of compression resulted in the best recovery of motor and sensory nerve conduction. In contrast, delayed decompression restored only motor nerve conduction. Muscle Nerve 52: 107–112, 2015
Reconstruction of functional connections after nerve injury is essential for restoration of nerve function. Clinically, nerve degeneration induced by compression leads to failure of nerve conduction and neural functions, including block of motor nerve1,2 and sensory nerve conduction.2,3 The timing of elimination of nerve compression injury appears to affect the degree of functional recovery.4–6 Decompression is a standard surgical procedure in clinic practice for relieving nerve dysfunction and damage.7–10 The degree of recovery of motor and sensory function, however, is variable.11 There is a paucity of data demonstrating successful restoration of nerve function after decompression, particularly with respect to differences in recovery between sensory and motor nerve fibers. Pathologic examination of injured and repaired nerves is the “gold standard” for understanding factors important for clinical decision-making to promote nerve regeneration. It is, however, impractical to perform nerve biopsies in every nerve of every patient. Nerve conduction studies Abbreviations: CCI, chronic constriction injury; CMAP, compound muscle action potential; NCS, nerve conduction study; SNAP, sensory nerve action potential Key words: chronic constriction injury; compound muscle action potential; crush injury; nerve decompression; sensory nerve action potential Correspondence to: Y.-L. Hsieh; e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Published online 31 October 2014 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.24501
Neurophysiology of Nerve Injury and Repair
(NCS) are convenient to assess pathologic counterparts of peripheral nerve function.12 NCS parameters reliably reflect pathologic characteristics of peripheral nerves, including amplitudes of compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs). In our previous work we used NCS to examine neurophysiologic functions of motor and sensory nerves in various models of peripheral neuropathy,13 nerve crush injury,14 and autologous nerve repair.15 These observations formed the basis for applying NCS to assess the restoration of functional nerve conduction during nerve regeneration in experimental animal models. The aim of this study was to determine whether the timing of nerve decompression influenced the neurophysiologic recovery of motor and sensory nerves by comparing NCS parameters in different models of nerve injury and nerve decompression, including acute crush compression,14 chronic constriction injury (CCI), and decompression after constriction.6 Specifically, we sought to determine whether: (1) the interval between nerve injury and nerve decompression affected the restoration of nerve conduction; and (2) the degrees of nerve conduction recovery differed between motor and sensory nerve fibers. METHODS Animal Surgery and Experimental Design. The nerve compression experiments were conducted on 8week-old, adult, male Sprague-Dawley rats assigned randomly to 3 groups: (1) a crush compression (crush) group; (2) a CCI group; and (3) a decompression group, with removal of ligatures (De-CCI group). All 3 experimental procedures were performed proximal to the sciatic nerve trifurcation in the hindlimb. The distances between the site of nerve compression and the distal point at which the NCS were performed was the same in all 3 groups. The other hindlimb was left intact for comparison to normalize individual variations of different animals. Crush Compression. The protocol for crush compression has been described elsewhere.14 Briefly, a skin incision was made at the mid-thigh level of the hindlimb, the gluteus and biceps femoris muscles were separated carefully to expose the MUSCLE & NERVE
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sciatic nerves, and the nerve was crushed with a #5 forceps (Regine, Morbio Inferiore, Switzerland) for 30 s and then released. The crush compression induced complete nerve degeneration distal to the crush site.14 After nerve crush, muscles and skin were sutured, and the animals were permitted to recover undisturbed. CCI. CCI was performed using a previously established protocol.6 Briefly, the sciatic nerve was exposed at the mid-thigh level, and 4 ligatures (4/0 chromic gut; Ethicon, Cincinnati, Ohio) were tied loosely around the nerve at 1-mm intervals and left in place.16 De-CCI. In a third group, the ligatures were removed carefully under a dissecting microscope at postoperative month 1 (POM1) after CCI (De-CCI group). Five animals were observed at each time-point and in each group. All experimental procedures were performed under anesthesia with 4% chloral hydrate in accordance with ethical guidelines for laboratory animals.17 The protocol was approved by Kaohsiung Medical University and National Taiwan University. Animals were housed in plastic cages on a 12-h light/12-h dark cycle after surgery for recovery and had access to water and food ad libitum. All efforts were made to minimize the suffering of the animals. Neurophysiologic Studies. To evaluate neurophysiologic function, CMAP and SNAP amplitudes were recorded with a Nicolet Viking Quest System (Nicolet Biomedical, Madison, Wisconsin)13 at postoperative months (POMs) 1, 3, and 6. Briefly, a monopolar stimulating needle electrode was placed at the sciatic notch, and 2 surface recording electrodes were placed on the plantar muscle for recording CMAP. Stimuli were applied with an intensity of 100 V and a duration of 0.1 ms. The filters were set at 2–10,000 HZ. For SNAP recordings, orthodromic stimulation was performed on the sural nerves. The stimulating electrodes were placed on the lateral side of the ankle, and the recording electrodes were placed on the sural nerves. Stimulus intensity was 10 mA, stimulus duration was 0.1 ms, and the rate was 0.7 HZ. The filters were set at 20–3000 HZ. A monopolar electrode was inserted into the tail for grounding. To eliminate interrater bias, the same investigator, blinded to the study group, performed all neurophysiologic studies. The CMAP and SNAP amplitudes were measured as baseline-to-peak values of the recorded waveforms. To normalize individual variations, the amplitude on the surgical side was divided by that on the unoperated side and expressed as the CMAP or SNAP ratio. Histopathological Studies of Sciatic Nerves. We performed morphometric studies on sciatic nerves according to our established protocols.13,14 Briefly, 108
Neurophysiology of Nerve Injury and Repair
the distal stump of the sciatic nerve was dissected after intracardiac perfusion with 5% glutaraldehyde and further fixed for another 2 days in the same fixative. After rinsing in phosphate buffer (PB), tissues were postfixed in 2% osmium tetraoxide for 2 h, dehydrated through a graded ethanol series, and embedded in Epon 812 resin (Polysciences, Inc., Warrington, Pennsylvania). Semithin sections were cut on an ultramicrotome (Reichert Ultracut E; Leica, Wetzlar, Germany) and stained with toluidine blue. For morphometric analyses, photographs were taken at a magnification of 4003 under an Axiophot microscope (Carl Zeiss, Oberkochen, Germany) and the following analyses were performed: (1) nerve fiber density; and (2) histogram of the fiber diameter. The nerve fiber density was defined as the total number of nerve fibers divided by the area of the sciatic nerves on cross-section. The fiber diameter and crosssectional area of each nerve fascicle were measured with Image-Pro Plus software (Media Cybernetics, Bethesda, Maryland). Statistical Analysis. All data are expressed as mean 6 standard deviation (SD), and t-tests were performed for data with a Gaussian distribution. For data that did not follow a Gaussian distribution, a nonparametric Mann-Whitney U-test was conducted. P < 0.05 was considered statistically significant. We performed multiple regression analysis to evaluate the determinants of: (1) CMAP and SNAP amplitude recovery; and (2) physiologic recovery after nerve decompression. In the determinants of CMAP and SNAP recovery, the independent variables were: (1) duration of recovery; and (2) decompression surgery. For the determinants of physiologic recovery, independent variables were: (1) nerve fiber type; (2) duration of recovery; and (3) decompression surgery. RESULTS Decrease in Amplitudes of CMAPs and SNAPs after CCI and Crush Injury. At POM1, both CMAP and SNAP waveforms completely disappeared in the CCI and crush group, and these data provided the foundation for further evaluation of the neurophysiologic recovery of the effects of relieving nerve compression. Patterns of CMAP Recovery in CCI, De-CCI, and Crush Injury Groups. At POM3, CMAP waveforms on the operated side reappeared in all groups (Fig. 1A). At POM6, animals in the De-CCI and crush groups had better CMAP recovery than those in the CCI group (Fig. 1B). The relative degree of CMAP recovery in each group was quantified by comparing CMAP amplitudes. These findings were similar in the De-CCI and crush groups (4.8 6 0.5 vs. MUSCLE & NERVE
July 2015
FIGURE 1. Recovery of motor nerve conduction after decompression. (A, B) Graphs show the recovery profiles of compound muscle action potential (CMAP) at postoperative month 3 (POM3) (A) and POM6 (B) for the chronic constriction injury group (CCI, upper panels), the decompression after CCI group (De-CCI, middle panels), and the crush group (lower panels). (C) The graph shows the differences in CMAP amplitudes at POM3 (open bars) and POM6 (filled bars) for the CCI, De-CCI, and crush groups, according to (A) and (B). Horizontal bar (latency) 5 1 ms; vertical bar (amplitude) 5 5 mV. *P < 0.05; **P < 0.01.
4.9 6 0.9 mV), and higher than in the CCI group (3.6 6 1.2 mV; Fig. 1C). Taken together, the data indicate that CMAP recovery was promoted by nerve decompression surgery. Patterns of SNAP Recovery in CCI, De-CCI, and Crush
The amplitudes of SNAP waveforms on the operated side at POM3 in each group were similar (Fig. 2A). In contrast, at POM6, the SNAP amplitude in the crush group was higher than those in the CCI and De-CCI groups (Fig. 2B); that is, in the crush group, there was an increase in SNAP amplitude from POM3 to POM6 (168.0 6 59.2 vs. 530.5 6 38.6 mV). This pattern, however, was not observed in the CCI and De-CCI groups (Fig. 2C).
Injury Groups.
Differences in CMAP and SNAP Recovery after Nerve Decompression. For motor nerve recovery, there
was an increase in the CMAP ratio from POM3 to POM6 in each group, but to a different degree. CMAP ratios were similar in the De-CCI and crush groups (0.85 6 0.07 vs. 0.81 6 0.12), and both were higher than the CMAP ratio in the CCI group (0.54 6 0.14; Fig. 3A). For sensory nerve recovery, only the SNAP ratio in the crush group (0.90 6 0.08) at POM6 was higher than SNAP ratios of the CCI (0.48 6 0.10) and De-CCI (0.62 6 0.15) groups (Fig. 3B). These findings were confirmed by multiple linear regression analysis with CMAP and SNAP ratios as the dependent variables, respectively. Both duration of recovery and decompression status were
FIGURE 2. Recovery of sensory nerve conduction after decompression. (A, B) Graphs show the recovery profiles of sensory nerve action potentials (SNAP) at postoperative month 3 (POM3) (A) and POM6 (B) for the chronic constriction injury group (CCI, upper panels), the decompression after CCI group (De-CCI, middle panels), and the crush group (lower panels). (C) The graph shows the changes in SNAP amplitudes at POM3 (open bar) and POM6 (filled bar) of the CCI, De-CCI, and crush groups, according to (A) and (B). Horizontal bar (latency) 5 2 ms; vertical bar (amplitude) 5 500 mV. *P < 0.05. Neurophysiology of Nerve Injury and Repair
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FIGURE 3. Comparison of recovery in motor and sensory nerve conduction. The amplitudes of compound muscle action potentials (CMAP) and sensory nerve action potentials (SNAP), are normalized as CMAP ratio and SNAP ratio. The graphs compare the differences in CMAP ratio (A) and SNAP ratio (B) of the chronic constriction injury group (CCI), the group that underwent decompression after CCI (De-CCI), and the crush group at postoperative month 3 (POM3, open bar) and POM6 (filled bar). The crush and De-CCI groups had better CMAP recovery. In contrast, only the crush group had better SNAP recovery. *P < 0.05; **P < 0.01; ***P < 0.0001; N.S., no significant difference.
associated independently with CMAP and SNAP ratios (Table 1). Using amplitude ratio as the dependent variable (Table 2), all 3 parameters (nerve fiber type, duration of recovery, and decompression status) were independent determinants of amplitude recovery. This confirmed that CMAP recovery was much better than SNAP recovery even after long-duration nerve decompression. Morphometric Studies of Nerve Regeneration after Nerve Decompression. On cross-sections, the sciatic nerve on the contralateral side was composed of large- and small-diameter nerve fibers (Fig. 4A). There were distinct patterns of nerve fiber profiles at POM6; that is, both the De-CCI and crush groups had large myelinated nerve fibers, which were absent in the CCI group (Fig. 4B-D). These observations were confirmed by morphometric
analyses of nerve fibers. For example, the histogram of nerve fiber diameters was bimodal on the contralateral side, and the spectrum in the CCI group was left-shifted (25th275th percentile 2.41– 4.46 mm) compared with the De-CCI (3.41–7.29 mm) and crush (3.73–6.79 mm) groups (Fig. 4E-H). However, nerve fiber densities were similar among all groups (P 5 0.41). In summary, the morphometric findings were consistent with the neurophysiologic observations after nerve decompression, indicating that neurophysiologic examinations reliably reflected the neuropathology. DISCUSSION Acute and Chronic Nerve Compression Blocks Nerve Conduction. The differences in neurophysiologic
recovery may be due to acute vs. chronic nerve injury and duration of nerve injury. The recovery
Table 1. Factors associated with recovery of CMAP and SNAP amplitude after decompression surgery. CMAP amplitude 2
Model (R 5 77.62, P < 0.0001) Duration of recovery Decompression surgery
Standardized coefficient
Standard error
95% CI
T ratio
P-value
0.105 20.201
0.012 0.040
0.080 to 0.134 20.282 to 20.119
8.468 5.013
Reconstruction of functional connections after nerve injury is essential for restoration of nerve function. Clinically, nerve degeneration induced by compression leads to failure of nerve conduction and neural functions, including block of motor nerve1,2 and sensory nerve conduction.2,3 The timing of elimination of nerve compression injury appears to affect the degree of functional recovery.4–6 Decompression is a standard surgical procedure in clinic practice for relieving nerve dysfunction and damage.7–10 The degree of recovery of motor and sensory function, however, is variable.11 There is a paucity of data demonstrating successful restoration of nerve function after decompression, particularly with respect to differences in recovery between sensory and motor nerve fibers. Pathologic examination of injured and repaired nerves is the “gold standard” for understanding factors important for clinical decision-making to promote nerve regeneration. It is, however, impractical to perform nerve biopsies in every nerve of every patient. Nerve conduction studies Abbreviations: CCI, chronic constriction injury; CMAP, compound muscle action potential; NCS, nerve conduction study; SNAP, sensory nerve action potential Key words: chronic constriction injury; compound muscle action potential; crush injury; nerve decompression; sensory nerve action potential Correspondence to: Y.-L. Hsieh; e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Published online 31 October 2014 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.24501
Neurophysiology of Nerve Injury and Repair
(NCS) are convenient to assess pathologic counterparts of peripheral nerve function.12 NCS parameters reliably reflect pathologic characteristics of peripheral nerves, including amplitudes of compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs). In our previous work we used NCS to examine neurophysiologic functions of motor and sensory nerves in various models of peripheral neuropathy,13 nerve crush injury,14 and autologous nerve repair.15 These observations formed the basis for applying NCS to assess the restoration of functional nerve conduction during nerve regeneration in experimental animal models. The aim of this study was to determine whether the timing of nerve decompression influenced the neurophysiologic recovery of motor and sensory nerves by comparing NCS parameters in different models of nerve injury and nerve decompression, including acute crush compression,14 chronic constriction injury (CCI), and decompression after constriction.6 Specifically, we sought to determine whether: (1) the interval between nerve injury and nerve decompression affected the restoration of nerve conduction; and (2) the degrees of nerve conduction recovery differed between motor and sensory nerve fibers. METHODS Animal Surgery and Experimental Design. The nerve compression experiments were conducted on 8week-old, adult, male Sprague-Dawley rats assigned randomly to 3 groups: (1) a crush compression (crush) group; (2) a CCI group; and (3) a decompression group, with removal of ligatures (De-CCI group). All 3 experimental procedures were performed proximal to the sciatic nerve trifurcation in the hindlimb. The distances between the site of nerve compression and the distal point at which the NCS were performed was the same in all 3 groups. The other hindlimb was left intact for comparison to normalize individual variations of different animals. Crush Compression. The protocol for crush compression has been described elsewhere.14 Briefly, a skin incision was made at the mid-thigh level of the hindlimb, the gluteus and biceps femoris muscles were separated carefully to expose the MUSCLE & NERVE
July 2015
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sciatic nerves, and the nerve was crushed with a #5 forceps (Regine, Morbio Inferiore, Switzerland) for 30 s and then released. The crush compression induced complete nerve degeneration distal to the crush site.14 After nerve crush, muscles and skin were sutured, and the animals were permitted to recover undisturbed. CCI. CCI was performed using a previously established protocol.6 Briefly, the sciatic nerve was exposed at the mid-thigh level, and 4 ligatures (4/0 chromic gut; Ethicon, Cincinnati, Ohio) were tied loosely around the nerve at 1-mm intervals and left in place.16 De-CCI. In a third group, the ligatures were removed carefully under a dissecting microscope at postoperative month 1 (POM1) after CCI (De-CCI group). Five animals were observed at each time-point and in each group. All experimental procedures were performed under anesthesia with 4% chloral hydrate in accordance with ethical guidelines for laboratory animals.17 The protocol was approved by Kaohsiung Medical University and National Taiwan University. Animals were housed in plastic cages on a 12-h light/12-h dark cycle after surgery for recovery and had access to water and food ad libitum. All efforts were made to minimize the suffering of the animals. Neurophysiologic Studies. To evaluate neurophysiologic function, CMAP and SNAP amplitudes were recorded with a Nicolet Viking Quest System (Nicolet Biomedical, Madison, Wisconsin)13 at postoperative months (POMs) 1, 3, and 6. Briefly, a monopolar stimulating needle electrode was placed at the sciatic notch, and 2 surface recording electrodes were placed on the plantar muscle for recording CMAP. Stimuli were applied with an intensity of 100 V and a duration of 0.1 ms. The filters were set at 2–10,000 HZ. For SNAP recordings, orthodromic stimulation was performed on the sural nerves. The stimulating electrodes were placed on the lateral side of the ankle, and the recording electrodes were placed on the sural nerves. Stimulus intensity was 10 mA, stimulus duration was 0.1 ms, and the rate was 0.7 HZ. The filters were set at 20–3000 HZ. A monopolar electrode was inserted into the tail for grounding. To eliminate interrater bias, the same investigator, blinded to the study group, performed all neurophysiologic studies. The CMAP and SNAP amplitudes were measured as baseline-to-peak values of the recorded waveforms. To normalize individual variations, the amplitude on the surgical side was divided by that on the unoperated side and expressed as the CMAP or SNAP ratio. Histopathological Studies of Sciatic Nerves. We performed morphometric studies on sciatic nerves according to our established protocols.13,14 Briefly, 108
Neurophysiology of Nerve Injury and Repair
the distal stump of the sciatic nerve was dissected after intracardiac perfusion with 5% glutaraldehyde and further fixed for another 2 days in the same fixative. After rinsing in phosphate buffer (PB), tissues were postfixed in 2% osmium tetraoxide for 2 h, dehydrated through a graded ethanol series, and embedded in Epon 812 resin (Polysciences, Inc., Warrington, Pennsylvania). Semithin sections were cut on an ultramicrotome (Reichert Ultracut E; Leica, Wetzlar, Germany) and stained with toluidine blue. For morphometric analyses, photographs were taken at a magnification of 4003 under an Axiophot microscope (Carl Zeiss, Oberkochen, Germany) and the following analyses were performed: (1) nerve fiber density; and (2) histogram of the fiber diameter. The nerve fiber density was defined as the total number of nerve fibers divided by the area of the sciatic nerves on cross-section. The fiber diameter and crosssectional area of each nerve fascicle were measured with Image-Pro Plus software (Media Cybernetics, Bethesda, Maryland). Statistical Analysis. All data are expressed as mean 6 standard deviation (SD), and t-tests were performed for data with a Gaussian distribution. For data that did not follow a Gaussian distribution, a nonparametric Mann-Whitney U-test was conducted. P < 0.05 was considered statistically significant. We performed multiple regression analysis to evaluate the determinants of: (1) CMAP and SNAP amplitude recovery; and (2) physiologic recovery after nerve decompression. In the determinants of CMAP and SNAP recovery, the independent variables were: (1) duration of recovery; and (2) decompression surgery. For the determinants of physiologic recovery, independent variables were: (1) nerve fiber type; (2) duration of recovery; and (3) decompression surgery. RESULTS Decrease in Amplitudes of CMAPs and SNAPs after CCI and Crush Injury. At POM1, both CMAP and SNAP waveforms completely disappeared in the CCI and crush group, and these data provided the foundation for further evaluation of the neurophysiologic recovery of the effects of relieving nerve compression. Patterns of CMAP Recovery in CCI, De-CCI, and Crush Injury Groups. At POM3, CMAP waveforms on the operated side reappeared in all groups (Fig. 1A). At POM6, animals in the De-CCI and crush groups had better CMAP recovery than those in the CCI group (Fig. 1B). The relative degree of CMAP recovery in each group was quantified by comparing CMAP amplitudes. These findings were similar in the De-CCI and crush groups (4.8 6 0.5 vs. MUSCLE & NERVE
July 2015
FIGURE 1. Recovery of motor nerve conduction after decompression. (A, B) Graphs show the recovery profiles of compound muscle action potential (CMAP) at postoperative month 3 (POM3) (A) and POM6 (B) for the chronic constriction injury group (CCI, upper panels), the decompression after CCI group (De-CCI, middle panels), and the crush group (lower panels). (C) The graph shows the differences in CMAP amplitudes at POM3 (open bars) and POM6 (filled bars) for the CCI, De-CCI, and crush groups, according to (A) and (B). Horizontal bar (latency) 5 1 ms; vertical bar (amplitude) 5 5 mV. *P < 0.05; **P < 0.01.
4.9 6 0.9 mV), and higher than in the CCI group (3.6 6 1.2 mV; Fig. 1C). Taken together, the data indicate that CMAP recovery was promoted by nerve decompression surgery. Patterns of SNAP Recovery in CCI, De-CCI, and Crush
The amplitudes of SNAP waveforms on the operated side at POM3 in each group were similar (Fig. 2A). In contrast, at POM6, the SNAP amplitude in the crush group was higher than those in the CCI and De-CCI groups (Fig. 2B); that is, in the crush group, there was an increase in SNAP amplitude from POM3 to POM6 (168.0 6 59.2 vs. 530.5 6 38.6 mV). This pattern, however, was not observed in the CCI and De-CCI groups (Fig. 2C).
Injury Groups.
Differences in CMAP and SNAP Recovery after Nerve Decompression. For motor nerve recovery, there
was an increase in the CMAP ratio from POM3 to POM6 in each group, but to a different degree. CMAP ratios were similar in the De-CCI and crush groups (0.85 6 0.07 vs. 0.81 6 0.12), and both were higher than the CMAP ratio in the CCI group (0.54 6 0.14; Fig. 3A). For sensory nerve recovery, only the SNAP ratio in the crush group (0.90 6 0.08) at POM6 was higher than SNAP ratios of the CCI (0.48 6 0.10) and De-CCI (0.62 6 0.15) groups (Fig. 3B). These findings were confirmed by multiple linear regression analysis with CMAP and SNAP ratios as the dependent variables, respectively. Both duration of recovery and decompression status were
FIGURE 2. Recovery of sensory nerve conduction after decompression. (A, B) Graphs show the recovery profiles of sensory nerve action potentials (SNAP) at postoperative month 3 (POM3) (A) and POM6 (B) for the chronic constriction injury group (CCI, upper panels), the decompression after CCI group (De-CCI, middle panels), and the crush group (lower panels). (C) The graph shows the changes in SNAP amplitudes at POM3 (open bar) and POM6 (filled bar) of the CCI, De-CCI, and crush groups, according to (A) and (B). Horizontal bar (latency) 5 2 ms; vertical bar (amplitude) 5 500 mV. *P < 0.05. Neurophysiology of Nerve Injury and Repair
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FIGURE 3. Comparison of recovery in motor and sensory nerve conduction. The amplitudes of compound muscle action potentials (CMAP) and sensory nerve action potentials (SNAP), are normalized as CMAP ratio and SNAP ratio. The graphs compare the differences in CMAP ratio (A) and SNAP ratio (B) of the chronic constriction injury group (CCI), the group that underwent decompression after CCI (De-CCI), and the crush group at postoperative month 3 (POM3, open bar) and POM6 (filled bar). The crush and De-CCI groups had better CMAP recovery. In contrast, only the crush group had better SNAP recovery. *P < 0.05; **P < 0.01; ***P < 0.0001; N.S., no significant difference.
associated independently with CMAP and SNAP ratios (Table 1). Using amplitude ratio as the dependent variable (Table 2), all 3 parameters (nerve fiber type, duration of recovery, and decompression status) were independent determinants of amplitude recovery. This confirmed that CMAP recovery was much better than SNAP recovery even after long-duration nerve decompression. Morphometric Studies of Nerve Regeneration after Nerve Decompression. On cross-sections, the sciatic nerve on the contralateral side was composed of large- and small-diameter nerve fibers (Fig. 4A). There were distinct patterns of nerve fiber profiles at POM6; that is, both the De-CCI and crush groups had large myelinated nerve fibers, which were absent in the CCI group (Fig. 4B-D). These observations were confirmed by morphometric
analyses of nerve fibers. For example, the histogram of nerve fiber diameters was bimodal on the contralateral side, and the spectrum in the CCI group was left-shifted (25th275th percentile 2.41– 4.46 mm) compared with the De-CCI (3.41–7.29 mm) and crush (3.73–6.79 mm) groups (Fig. 4E-H). However, nerve fiber densities were similar among all groups (P 5 0.41). In summary, the morphometric findings were consistent with the neurophysiologic observations after nerve decompression, indicating that neurophysiologic examinations reliably reflected the neuropathology. DISCUSSION Acute and Chronic Nerve Compression Blocks Nerve Conduction. The differences in neurophysiologic
recovery may be due to acute vs. chronic nerve injury and duration of nerve injury. The recovery
Table 1. Factors associated with recovery of CMAP and SNAP amplitude after decompression surgery. CMAP amplitude 2
Model (R 5 77.62, P < 0.0001) Duration of recovery Decompression surgery
Standardized coefficient
Standard error
95% CI
T ratio
P-value
0.105 20.201
0.012 0.040
0.080 to 0.134 20.282 to 20.119
8.468 5.013
