[Comparative studies of morphometric and functional results following reconstruction of motor nerves]. / Vergleichende Untersuchungen morphometrischer und funktioneller Ergebnisse nach Rekonstruktion motorischer Nerven.

In order to determine the value of a reconstructive procedure in the peripheral nerve, experimental studies often evaluate the number and the diameter of myelinated nerve fibers as a parameter for the quality of regeneration. This study addresses the correlation between the number of fibers in a peripheral motor nerve after microsurgical reconstruction and the functional result, expressed as the force of the reinnervated muscle. In a total number of 24 sheep, the motor branch to the rectus femoris muscle was severed. The muscle was reinnervated either by direct neurorrhaphy or by nerve grafting, performed in three different ways (free grafting to the ipsilateral muscle, free grafting to the contralateral muscle, vascularized grafting to the ipsilateral muscle). In the final experiments, the muscle force in the reinnervated muscle was determined by supramaximal electrical stimulation. Number and diameter of myelinated nerve fibers were evaluated by computer-assisted morphometric analysis. Regression analysis of morphometric data and the muscle forces was calculated. No correlation was found between fiber numbers in the nerve graft and the maximal force. However, a positive correlation between the number of myelinated fibers in the motor branch distal to the site of coaptation and the functional result was observed in some cases. The diameter of myelinated fibers had no influence on the functional outcome.

Role of a muscle target organ on the regeneration of motor nerve fibres in long nerve grafts: a synopsis of experimental and clinical data.

The importance of the muscle target organ as a promoting factor for nerve fibre regeneration in nerve grafts is still a subject of controversial discussion. In the last few years we published uniform results of experimental series in sheep and rabbits in which we investigated the biology of nerve fibre regeneration in long nerve autografts without connection to a target organ. Surprisingly, we found excellent regeneration of myelinated nerve fibres without the influence of a target organ through the whole length of the nerve graft, with an increase in the number of nerve fibres up to fourfold at the distal end. In the sheep series the additional contact with a muscle target organ for 6 months had a variable effect on the fibre population in the distal end of the nerve graft. The results of our planimetric analyses of nerve biopsies in patients with facial paralysis, who were treated by cross-face nerve grafting and free muscle transplantation, are extremely divergent from the results of our experimental series. Instead of an increase, we found a decrease in number of regenerating nerve fibres arriving at the distal end of the cross-face nerve graft down to 20%. Species-specific differences in the biology of nerve regeneration are discussed, together with their implications for the complex clinical situation of nerve grafting with or without the influence of a target organ.

Effect of the CO2 milliwatt laser on neuroma formation in rats.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine whether the milliwatt laser can suppress neuroma formation at the end of a divided nerve. STUDY DESIGN/MATERIALS AND METHODS: The peripheral nerves of eight rats were transected with microscissors and the cross-sectional area of their proximal ends was irradiated using the CO2 milliwatt laser. The power ranges used were similar to those applied to weld neural tissue. RESULTS: None of the eight irradiated nerve ends formed a neuromatous bulb and only one of them regenerated into the surrounding tissues. Histologically, these nerve ends did not show the disorganized picture of classic neuromas. On morphometric measurements, they contained less connective tissue than the control nerve ends (P < 0.001) and their nerve fibers were larger in diameter (P < 0.001) and better myelinated (P < 0.001). CONCLUSION: These findings in rats show that the CO2 milliwatt laser has the ability to suppress neuroma formation at the end of a divided nerve.

Regenerative potential of abdominal vagal nerves in rats.

After truncal vagotomy, impaired gastric emptying may represent a serious complication. This led us to study the feasibility of a reinnervation of the antrum by microsurgical vagorrhaphy and vagoplasty. Sixty-four rats were randomly assigned to undergo either 1) no operation (control), 2) laparotomy and vagal dissection (sham operation), 3) truncal abdominal vagotomy with nerve segment resection, 4) truncal vagotomy followed by vagorrhaphy, or 5) vagal resection extending to the nerve of Latarjet followed by grafting of the gap using the resected vagal segment (vagoplasty). Six months after surgery, vagal regeneration was assessed by morphometry of the anterior vagus and the antral wall and by recording the gastric emptying of a radiolabeled meal, the contractile response to electrical stimulation of the cervical vagi, and basal and insulin-stimulated acid secretion. After truncal vagotomy, there was a marked degeneration of vagal fibers and no evidence of spontaneous reinnervation. After vagorrhaphy, a recovery of gastric secretory and motor functions as well as morphological data indicated vagal regeneration. After vagoplasty, a partial recovery of gastric motor functions and the morphological appearance suggested a partial vagal reinnervation.

[Relations between donor nerve size and degree of neurotization in the nerve transplant--an experimental study]. / Die Beziehung zwischen Spendernervgrösse und Neurotisationsgrad im Nerventransplantat--Eine experimentelle Studie.

The present study was undertaken to investigate whether the number of myelinated fibers in a sensory nerve used as an autograft influences the result of nerve fiber regeneration in the graft. In 30 rabbits, the left saphenous nerve was used as an autograft. It was coapted to the motor branch to the rectus femoris muscle. Biopsies from both ends of the graft were taken. Animals were separated into four investigation groups, which were reexamined 3, 6, 9 and 12 months after the grafting procedure. Biopsies for histological and morphometric examination were again taken from the proximal and the distal part of the grafts. Thus, the number of myelinated nerve fibers in the different specimens could be obtained by computer-assisted image analysis. At the proximal end of the original saphenous nerve, the number of fibers varied between 1032 and 3100 (mean 2145). Corresponding data obtained from the distal end ranged from 1044 to 3084 myelinated nerve fibers (mean 1724). Fiber numbers in the proximal and distal parts of the grafts before and after regeneration were correlated to each other. In the whole population of specimens (correlation coefficient +/-0) as well as in the experimental subgroups, the quantitative success of neurotization in the grafts did not depend to a high degree upon the fiber numbers in the original saphenous nerve. The correlation coefficient for the proximal part of the graft exceeded 0.5 to only three and twelve months after grafting, but did not reach a level of statistical significance. In the distal part of the graft, the coefficient for a linear correlation was always less than 0.45.

Occurrence of Andermann syndrome out of French Canada--agenesis of the corpus callosum with neuronopathy.

We report on two siblings, a boy and a girl, with agenesis of corpus callosum and neuronopathy. The children show diffuse hypotonia, delayed motor and mental development. Neurophysiological examinations revealed reduction of the motor nerve conduction velocity, absence of sensory nerve action potentials, abnormal somatosensory and visual evoked potentials. Nerve biopsies showed reduced density of myelinated and unmyelinated fibres in both children. We also found signs of hypomyelination and suggest this is secondary to degeneration of peripheral sensory and motor neurons. Our findings are consistent with the diagnosis of Andermann syndrome. This is the first report of the occurrence of Andermann syndrome out of French Canada.

Fiber regeneration in nerve grafts without connection to a target muscle: an experimental study in rabbits.

In 30 rabbits, both saphenous nerves were harvested as autografts and coapted to the branch for the rectus femoris muscle without connection to any distal target muscle. The graft from the right thigh was led to the contralateral extremity (crossover grafting). The graft on the left side remained on the same extremity (ipsilateral grafting). Animals were separated into four groups and were sacrificed 3, 6, 9, and 12 months after grafting. Specimens of the grafts and the donor motor branches were harvested for histomorphometric examination. The number of myelinated nerve fibers in the distal end of the nerve grafts was significantly increasing from 3 to 6 months after grafting and remained on a relatively constant level in the long-term groups. Three months after the first operation, greater numbers of myelinated nerve fibers were counted after ipsilateral grafting than after crossover grafting. In the long-term groups, this difference could not be observed.

Time course of histomorphometric alterations in nerve grafts without connection to a muscle target organ: an experimental study in sheep.

In 15 adult sheep, the saphenous nerve (28 +/- 1.8 cm) was used for ipsilateral or for cross-nerve grafting and was sutured to the proximal stump of the cut, motor-nerve branch of the vastus muscle. The distal end of the nerve graft was left without a target organ. Semi-thin cross sections of normal vastus nerves and saphenous grafts and of the distal ends of the grafts were analyzed by computer-assisted planimetry, 3, 6, 9, 12, and 18 months after the nerve-grafting procedure. Electronmicroscopy was also performed on specimens from the distal ends of the nerve grafts. Comparing the total number of myelinated nerve fibers in the distal end of the graft, the ipsilateral group showed an increase with time elapsed since nerve grafting, while the cross-over group showed a maximum after 3 and 6 months, and fewer fibers after longer periods of regeneration. Independent of the time passed since nerve grafting, the diameters of the myelinated nerve fibers were homogeneously thin in both experimental groups. Most interesting, the cross-nerve grafts did more poorly than the ipsilateral ones, even before they were influenced by the target muscle. With ultrastructural investigation, the ends of the grafts containing only a few myelinated fibers also showed a low number of unmyelinated fibers, but an increase of collagen fibers. The results have consequences for the clinical application of cross-nerve grafting.

Long-term results of nervous tissue alterations caused by epineurial electrode application: an experimental study in rat sciatic nerve.

In order to evaluate the long-term effects of epineurial electrode application for functional electrical stimulation (FES) the left sciatic nerve of seven rats was exposed. Four ring-shaped stainless steel wire electrodes were sutured to the epineurium of each nerve in the same manner as performed clinically for carrousel stimulation in man. The nerves were reexposed 1 year after implantation and the stimulation threshold to obtain a tetanic contraction in the lower limb was determined for each electrode. Afterwards the animals were sacrificed. The electrodes were excised and cross sections of the sciatic nerve directly at site of the electrodes, 2-mm proximal and 2-mm distal to them were harvested for histologic and planimetric assessment of nerve lesions. The area of damaged neural tissue was expressed as a percentage of the total cross-sectional area within the perineural sheath. The sciatic nerves of the right side served as controls. The values for the stimulation thresholds ranged between 0.1 and 1.0 mA (mean 0.43 mA). By morphometric examination five of seven nerves were seen altered, the altered areas captured between 1% and 4.8% of the total cross-sectional area of the nerves within the perineural sheath. Besides two specimens, all altered nerve segments exhibited distinct signs of nerve fiber regeneration. The clinical implications of the results for long-term electrical stimulation, such as phrenic pacing, are discussed.

Histological assessment of nerve lesions caused by epineurial electrode application in rat sciatic nerve.

The left sciatic nerve of 36 rats was exposed and four ring-shaped stainless steel wire electrodes were sutured to the epineurium of each nerve in the same manner as performed clinically for "carousel stimulation" in man. The rats were sacrificed 10 days (Group 1), 3 weeks (Group 2), or 3 months (Group 3) after implantation. The electrodes were excised, the nerves were embedded in Epon, and semithin sections were obtained for histological and planimetric assessment of lesions caused by the epineurially sutured electrodes. The right sciatic nerves served as controls. The total area of neural tissue within the perineurium was determined at three levels: at the site of the electrodes, 8 mm proximal, and 8 mm distal. The area of neural tissue damaged by the surgical procedure was expressed as a percentage of the total area. In Group 1, nine of 12 nerves showed lesions ranging from 0.39% to 25.39% of the total area of neural tissue, in Group 2 eight of 11 sciatic nerves showed lesions ranging from 0.24% to 13.03% of the total area, and in Group 3 five of 12 nerves showed lesions ranging from 0.21% to 4.96% of the total area. The pathologically altered areas in Groups 2 and 3 exhibited distinct signs of nerve fiber regeneration. The reasons for the decrease in damage from Group 1 to Group 3 and the clinical implications of the results for long-term electrical stimulation are discussed.