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Poor electroneurography but excellent hand function 31 years after nerve repair in childhood

Chemnitz, Anette; Andersson, Gert; Rosén, Birgitta; Dahlin, Lars B.; Björkman, Anders

doi: 10.1097/WNR.0b013e32835b6efd
NEUROPHYSIOLOGY, BASIC AND CLINICAL
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SDC

Children, in contrast to adults, show an excellent clinical recovery after a peripheral nerve injury, which may be explained by better peripheral nerve regeneration and a superior plasticity in the young brain. Our aim was to study the long-term electrophysiological outcome after nerve repair in children and young adults and to compare it with the clinical outcome. Forty-four patients, injured at an age younger than 21 years, were assessed by electrophysiology (amplitude, conduction velocity and distal motor latency) at a median of 31 years after a complete median or ulnar nerve injury at the level of the forearm. Electrophysiological evaluation showed pathology in all parameters and in all patients, irrespective of age at injury. No significant differences were observed in the electrophysiological results between those injured in childhood, that is, before the age of 12 years, and those injured in adolescence, that is, between 12 and 20 years of age. In contrast, the clinical nerve function was significantly better for those injured in childhood (87% of complete recovery, P=0.002) compared with those injured in adolescence. We conclude that the mechanism behind the superior clinical outcome in children is not located at the periphery, but is explained by cerebral plasticity.

Department of Hand Surgery and Neurophysiology, Skåne University Hospital, Malmö, Sweden

Correspondence to Anette Chemnitz, MD, Department of Hand Surgery, Skåne University Hospital, S-205 02 Malmö, Sweden Tel: +46 40 331678; fax: +46 40 928855; e-mail: anette.chemnitz@med.lu.se

Received October 8, 2012

Accepted October 12, 2012

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Introduction

Most patients operated on for a median or an ulnar nerve injury improve over time. Hand function often becomes excellent following nerve repair in those injured in childhood, whereas those injured as adults frequently show a poor clinical outcome 1–3. The mechanisms behind these differences are not completely understood. It has been suggested that children have a better capacity for regeneration in the peripheral nervous system following an injury 4, whereas others believe that a better cerebral adaptability in the young brain is the reason for the better clinical recovery 5,6. Few studies have addressed this neurobiological issue. Better knowledge is crucial for the design of new treatment strategies after nerve injuries.

Following a peripheral nerve injury, electrophysiological investigations can be used to localize the injury, analyze the pathophysiology of the injury, assess the severity of dysfunction, and to evaluate the progress of reinnervation 7. However, there is limited knowledge about the value of electrophysiological studies in the long-term perspective. Previous studies, notably with a shorter follow-up, in animals 8, human adults 9,10, and children 11 have shown a poor correlation between electrophysiological results and clinical outcome after nerve repair.

Our aim was to evaluate long-term electrophysiological results following median and ulnar nerve injuries repaired or reconstructed at a young age and relate them to the clinical outcome.

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Methods

Patients younger than 21 years of age operated on at our hospital for complete median or ulnar nerve injuries in the forearm during the period 1970–1989 were identified and asked to participate in the study. Forty-four of 45 available patients were examined by electrophysiology, 36 males and eight females. The median age at injury was 14 years (minimum 1–maximum 20 years) and the median follow-up was 31 years (minimum 21–maximum 41 years). A difference in the short-term clinical outcome following median nerve repair in children and young adults has been shown 5, where those injured before the age of 12 years had a better clinical outcome compared with those injured between the ages of 12 and 20. Thus, we divided our study group into two subgroups. Fourteen patients (10 males and four females) were aged below 12 years at injury (i.e. childhood injuries) and 30 patients (26 males and four females) were aged 12–20 years (i.e. adolescent injuries). Of the 44 patients, 24 had a median nerve injury, 10 had an ulnar nerve injury, and 10 had injury of both nerves, where at least one of the nerve injuries was complete. Eight patients (all >12 years of age) underwent reconstruction of their nerve injury by sural nerve grafts.

Orthodromic sensory nerve conduction studies were carried out by stimulating the thumb, the index, and the long finger for the median nerve and the little finger for the ulnar nerve. Ring electrodes were placed at the proximal interphalangeal and distal interphalangeal joints for the index, long and little fingers, and just proximal and distal to the interphalangeal joint for the thumb. Recording electrodes were placed over the respective nerve at the proximal wrist crease and 3 cm more proximally. For motor conduction studies, responses from the abductor pollicis brevis muscle (median nerve) and abductor digiti minimi muscle (ulnar nerve) were recorded on stimulation at wrist and elbow levels. The patients’ skin temperature was above 30°C during the electrophysiological examination. Amplitudes, conduction velocities, and distal motor latencies were measured. The electrophysiological results of the injured side were expressed as the percentage of those of the uninjured side (controls).

Clinical assessment was carried out using the total (Rosen) score and its subdomains, which is a diagnosis-specific instrument to assess outcome after nerve injuries in the upper extremity 12. Patients included in this study have recently been included in a study focusing on epidemiology and clinical outcome after nerve injuries in childhood and adolescence (accepted for publishing in J Bone Joint Surg Am, Chemnitz et al., in preparation).

At the time of follow-up, two patients had been diagnosed with diabetes (type 1 and type 2) and one with a cervical disc herniation (level C5–6). Patients were specifically asked about any clinical signs of nerve compression or neuropathy on the healthy uninjured side. Two patients had clinical signs of a carpal tunnel syndrome on the uninjured hand and another four patients had no clinical signs of carpal tunnel syndrome, but showed mild pathological electrophysiological values indicating a slight compression of the median nerve in the uninjured hand. In two of these six patients, there were no sensory responses in the injured hand. In the other four patients, the comparison between the injured and the uninjured hands was affected by the median nerve disorder in the uninjured hand. However, as the pathology in the uninjured hand was very moderate, the values in the tables are not significantly affected.

A nonparametric statistical analysis was carried out and the results are presented as median (minimum–maximum). A P-value of less than 0.05 was considered statistically significant. Comparisons were made between injuries sustained in childhood (<12 years) and in adolescence (>12 years), between isolated median and ulnar nerve injury (no nerve grafts), and finally, between nerve injuries without a nerve graft and those with nerve grafts in adolescence. Correlations (Spearman’s ρ) were performed to calculate any significant correlations between age at nerve injury and the different electrophysiological parameters, and a significant correlation was estimated (ρ≥0.35, P<0.05).

The study was carried out according to the Helsinki Declaration and the local ethics committee approved the study design (Dnr 2009/728). All participants provided their written, informed consent.

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Results

The electrophysiological results of the injured side, expressed as a percentage of those of the uninjured side, are presented in Tables 1 and 2. All patients, irrespective of age at nerve injury, showed reduced motor and sensory amplitudes, reduced sensory and conduction velocities as well as increased distal motor latencies. No statistically significant differences were found in the different parameters when the results of those injured in childhood and in adolescence were compared (Table 1). Patients with a median nerve injury had significantly lower sensory amplitudes and lower motor conduction velocity compared with patients with an ulnar nerve injury. A significant correlation was only observed between age at nerve injury and the motor amplitude ratio (ρ=−0.53, P<0.001), but not with the other variables.

Table 1

Table 1

Table 2

Table 2

Patients who had undergone direct nerve repair showed significantly higher sensory amplitudes than those who had undergone a reconstruction procedure with sural nerve grafts (Table 2). A similar pattern was observed for sensory conduction velocities. However, with respect to the motor components of the electrophysiology, a significant difference between the two groups was only found in the motor conduction velocity.

The results from the clinical outcome score (total score) and its domains are presented as the percentage ratio of the maximum score in Table 1. Data from the eight patients operated on with a sural nerve graft to reconstruct the median nerve (n=5), the ulnar nerve (n=2), or both nerves (n=1) are presented separately in Table 2.

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Discussion

Here, we show that patients with a median and/or an ulnar nerve repair, irrespective of the age at injury and repair/reconstruction, showed pathological changes in all electrophysiological parameters studied after a median follow-up time of 31 years. Apart from the motor amplitude, which correlated with age, no correlations were found between the different electrophysiological parameters and age at nerve injury. Those injured in childhood, in contrast to those injured in adolescence, had an excellent clinical outcome. As the peripheral nerves show pathology to the same extent irrespective of age at injury, the most likely explanation for the difference is a better cerebral plasticity in those injured in childhood. Interestingly, those injured in adolescence show results similar to those injured as adults 13, which suggests that the capacity of the central nervous system to adapt to changed somatosensory information decreases already around the age of 12 years.

Patients who received sural nerve grafts showed very poor results, which may be explained by the fact the injury may have been more severe. Furthermore, a delay in nerve repair is known to influence the outgrowth of nerve fibers 14 and the outcome after nerve repair 15. Experimental studies have shown that more nerve cells may die and the regrowth of nerve fibers, as well as their remyelination, may be poor following delayed nerve repair 16. In addition, the sural nerve is a sensory nerve that is used as grafts for both sensory and motor function. Differences in the myelin sheath 17, with less myelination in the sural nerve, together with an impaired axonal outgrowth through sural nerve grafts are possible explanations for the poorer electrophysiological results in grafted patients.

Following a peripheral nerve injury and repair, the patients often gradually recover both sensory and motor functions over time 13,18. Interestingly, previous studies have shown that the sensory recovery may continue for a longer period of time than the motor recovery 13. In addition, mechanisms related to regeneration, such as the presence of transcription factors (e.g. ATF 3) in the neurons, last longer in sensory neurons than in motor neurons 19. However, when considering the long follow-up in the present study, the nerve regeneration process is most likely finished. The present findings imply that there could be different mechanisms behind sensory and motor recovery after a nerve injury, which is further supported by the fact that the motor amplitudes were less reduced than the sensory amplitudes.

Two interesting questions arise in this context. Why is clinical motor recovery superior to clinical sensory recovery and why is sensory recovery significantly better in those injured in childhood? One neurobiological explanation for the superior clinical motor recovery could be the ability of each regenerating axon to reinnervate as many as four to five times the normal number of muscle fibers 20, thereby compensating for the reduced number of axons that succeed in reaching the denervated muscle. However, the significantly better clinical motor and sensory recovery seen in those injured in childhood cannot be explained by electrophysiological detectable differences in the peripheral nerve. Instead, this suggests that the mechanism behind the better results could be changes in the central nervous system. It is likely that the misdirection of the outgrowing nerve observed at the repair site 21 is similar in all age groups and that the altered signal pattern from the periphery along the sensory axons to the central nervous system is similar. Using different neuroimaging techniques, considerable changes with a destroyed finger somatotopy in the hand area of the primary somatosensory cortex have been shown in adults following peripheral nerve injuries in the upper extremity 22,23. It is well known that the young brain has a superior adaptability to change 24, and this superior plasticity can allow the young brain to adapt to the change in afferent nerve signals as well as interpret the new signal pattern in a way not possible for the older brain.

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Conclusion

Thirty-one years after nerve repair, when the nerve regeneration process is completed, electrophysiological results are still poor, irrespective of age. Thus, changes in the peripheral nervous system cannot explain the superior clinical outcome in patients injured in childhood.

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Acknowledgements

Supported by grants from the Swedish Research Council (Medicine), the Swedish Society for Medicine, Zoega’s Fund, HKH Kronprinsessan Lovisa’s Fund, Lundgren’s Fund, Region Skåne, and Funds from Malmö University Hospital. The authors thank technician Lena Goldberg for all the help.

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Conflicts of interest

There are no conflicts of interest.

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Keywords:

age; electrophysiology; long term; median; nerve injury; outcome; ulnar

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