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PubMed1991

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Use of vein grafts in emergency in peripheral nerve defect.

Peripheral nerve defects represent a frequent lesion in emergency. The vein graft is the alternative to nerve graft in cases where the nerve defect does not allow a direct approximation. Our experience on the use of venous graft has brought about excellent functional results that, together with a simple execution of the methodology, are at the bottom of our study. During the last 6 months we have treated 3 cases of peripheral nerve defect with nerve gap >2 cm; 1 lesion of ulnar nerve, 1 lesion of median nerve treated with vein graft and in 1 case an association of the median and ulnar nerve treated with reversed vein graft. An immediate resolution of the pain was observed in all patients already during the first 36/48 hrs. The clinical and electrophysiological evaluations at 3 and 6 months have demonstrated encouraging data regarding functional reparation and re-innervation. Even in consideration of the limited number of cases, comparison with data related to the autologous nerve graft shows a slightly slower recovery, but certainly overlapping to the classical methodology; moreover, excellent clinical results appear from the use of reversed vein graft. The advantage of vein grafts are multiple. There is an overlapping of the functional recovery, that represents the condition sine qua non of each new surgical experimental procedure. The simplicity of the technical execution and the possibility to cover missing nerves without sensory damage is advantageous both for the patient and for the structure, reducing operating time and related costs.

Humans↗
PubMed1995

Contribution of the proximal and distal nerve stumps to peripheral nerve regeneration in silicone chambers.

The specific contribution of the proximal and distal nerve stumps across an 8 mm gap within silicone chamber regeneration models was studied. For this, proximal and distal (Group A), distal and distal (Group B) and proximal and proximal (Group C) nerve stumps were placed in opposite ends of silicone chambers. In all the groups, a tissue cable forms between the nerve stumps, demonstrating that, without distinction, proximal or distal stumps can stimulate the growth of other proximal or distal stumps. Furthermore, in Group B, the newly formed pseudo-nerve, in the absence of regenerating axons, contains a number of Schwann cells significantly similar to Group A, which confirms that proliferation and migration of Schwann cells do not require axonal presence or contact. Likewise, the findings demonstrate that, with the exception of the axons, the distal stump contributes to the peripheral nerve regeneration in the same way as the proximal stump. Finally, when proximal stumps are placed in both the opposite ends of the silicone chamber, Schwann cells and regenerating axons grow into the chamber gap from both inserts, and myelination also proceeds from both ends to the centre of the chambers.

Animals↗
PubMedDate not supplied

Malignant peripheral nerve sheath tumor arising in association with the sural nerve.

Malignant peripheral nerve sheath tumor is a rare sarcoma of peripheral nerves found most often in deep soft tissue. This aggressive tumor is difficult to diagnose clinically and must be surgically excised for therapy. An incisional biopsy will allow for testing and in most cases, diagnosis. The authors present a case of a 39-year-old African American woman with malignant peripheral nerve sheath tumor in association with the sural nerve. The tumor was surgically removed and sent for pathologic studies. The patient reported to her first postoperative appointment and was referred to an oncologist for follow-up. Despite multiple attempts at contacting the patient and explaining the prognosis of the diagnosis, the patient refused further follow-up care including referral to an oncologist.

Adult↗
PubMed1977

Incorporation of glycoproteins into peripheral nerve myelin.

Peripheral nerve myelin contains a dominant low molecular weight glycoprotein called Po. To study the metabolism of this glycoprotein, tritiated fucose was injected into the peripheral nerves of adult mice and developing rats, and the temporal distribution of label was examined by autoradiography and gel electrophoresis. Mice and rat pups, injected with fucose, were sacrificed from 1 h to 98 days later. Series of autoradiographs were prepared. At the shortest labeling periods, newly formed product was confined to juxtanuclear Schwann cell cytoplasm, in association with regions rich in Golgi apparatus. After longer labeling periods, silver grain levels in Schwann cell cytoplasm decreased; concomitantly, there was an increase of silver grains associated with myelin. In adult animals, label associated with myelin was concentrated over outer layers of thickly myelinated fibers. Even at the longest time intervals examined (72 and 98 days), this distribution of label was largely retained. In contrast, in developing animals, label became associated with inner layers of the thicker sheaths. At no time was label observed over axons. Gel electrophoresis revealed that tritiated fucose was a suitable precursor for the faster migrating peripheral nerve glycoprotein(s). At all times examined, there was a single major peak of radioactivity that co-migrated on sodium dodecyl sulfate (SDS) acrylamide gels with the Po protein. Sometimes, a faster migrating shoulder of radioactivity was noted. With increased labeling periods, there was an enrichment of radioactivity associated with Po, indicative of a relatively slow turnover rate.

Animals↗
PubMed1985

A method for in vitro enzymatic dissociation of nerve roots and peripheral nerves from adult mammals.

Preparations yielding a high percentage of undamaged axons from fresh peripheral nerve or nerve root were made using an enzymatic dissociation regimen. The nerve was placed in a temperature-controlled chamber mounted over an inverted phase-contrast microscope. An oxygenated solution (Brimijoins) or modified Hank's solution was pumped through the chamber, first in a calcium-free form and then containing enzymes. The enzymes for dissociation were collagenase and trypsin, alternated. Enzymatic dissociation of the epineurium, perineurium and extracellular matrix was achieved. We supplemented the gentle agitation of a 10-roller peristaltic pump by periodically raising and lowering the fluid level in the chamber to provide a controlled mechanical agitation that promoted dissociation. A large percentage of the axons can be dissociated from the nerve, varying from approximately one-quarter to occasional complete dissociation. Action potentials were still conducted through dissociated axons, and axon transport was also still present, as documented by direct visualization using an AVEC-DIC type of microscope system. The axons had a better morphological appearance and displayed better transport than comparison preparations prepared by the usual mechanical teasing method, in our hands. The enzymatic method allows study of axons in an adult or developing mammal with regard to their electrical conduction and axon transport mechanisms. It should help to avoid a selection process for more hardy axons which may be imposed by traditional mechanical teasing methods. Mechanical stress was observed to cause widened Schmidt-Lanterman clefts, widened nodes, myelin bubbles, and other abnormal morphology as evidence of damage.

Animals↗
PubMed2003

Nerve stimulators used for peripheral nerve blocks vary in their electrical characteristics.

BACKGROUND: Nerve stimulation with a low-intensity electrical current has become a vital part of the performance of peripheral nerve blockade. The purpose of this study was to compare the accuracy and characteristics of peripheral nerve stimulators used in clinical practice in the United States. METHODS: Fifteen peripheral nerve stimulators were fitted with fresh batteries and set to deliver currents ranging from 0.1 to 4.0 mA into a series of high-tolerance resistance loads ranging from 1 to 100 komega. The current output, stimulus duration, morphology, frequency, and maximum voltage output were studied using a factory-calibrated oscilloscope. RESULTS: All peripheral nerve stimulators performed uniformly well when set to deliver currents of 1.0 mA or more into a standard resistance load of 1 or 2 komega. However, at lower currents, the median error (%) increased from 2.4 (-5-144%) at 0.5 mA to 10.4 (-24-180%) at 0.1 mA into a 1 komega load. The morphology of the stimulus was characterized by a regular monophasic square pulse at current outputs of up to 1 mA and at a resistance of 1 komega. The stimulus waveform became particularly distorted as the impedance load was increased. The duration of the default stimulus set by the manufacturer varied from 34.8 to 460 micros among the peripheral nerve stimulators tested. The maximum voltage output ranged from 7.4 to 336 Volts. CONCLUSIONS: Nerve stimulators used for regional anesthesia vary greatly in accuracy of current output and in manufacturer-selected electrical characteristics (e.g., current duration, stimulating frequency, maximum voltage output).

Electric Stimulation↗
PubMed1978

Recent developments in peripheral nerve surgery. Management of open traumatic peripheral nerve lesions.

The modern technique of operative repair of traumatic nerve interruption is discussed. The results of microsurgical repair have proved to be superior to those of conventional methods. Besides the anatomy and the operative technique, the indications and timing for surgical intervention are discussed. Reference to the literature and the authors' own experience show that delayed primary repair is the method of choice.

Humans↗
PubMed2005

Structural parameters of collagen nerve grafts influence peripheral nerve regeneration.

Large nerve defects require nerve grafts to allow regeneration. To avoid donor nerve problems the concept of tissue engineering was introduced into nerve surgery. However, non-neuronal grafts support axonal regeneration only to a certain extent. They lack viable Schwann cells which provide neurotrophic and neurotopic factors and guide the sprouting nerve. This experimental study used the rat sciatic nerve to bridge 2 cm nerve gaps with collagen (type I/III) tubes. The tubes were different in their physical structure (hollow versus inner collagen skeleton, different inner diameters). To improve regeneration Schwann cells were implanted. After 8 weeks the regeneration process was monitored clinically, histologically and morphometrically. Autologous nerve grafts and collagen tubes without Schwann cells served as control. In all parameters autologous nerve grafts showed best regeneration. Nerve regeneration in a noteworthy quality was also seen with hollow collagen tubes and tubes with reduced lumen, both filled with Schwann cells. The inner skeleton, however, impaired nerve regeneration independent of whether Schwann cells were added or not. This indicates that not only viable Schwann cells are an imperative prerequisite but also structural parameters determine peripheral nerve regeneration.

Animals↗
PubMed1991

Postnatal change in lipid composition and nerve conduction of peripheral nerves of young rhesus monkeys.

Body weight, motor and sensory nerve conduction velocities of fore and hind limbs, and lipid composition were measured sequentially in peripheral nerves of 15 rhesus monkeys. Initially measurements were made with monkeys six to eight months of age. There were significant increases in body weight, motor, and sensory nerve conduction and myelin marker lipids over a five months period, but no change was observed in free fatty acids, triglycerides, and esterified cholesterol. These results indicate that myelination continues at least for 11 to 13 months of postnatal age in rhesus monkeys.

Aging↗
PubMed1998

Recommendations for the examination of peripheral nerve biopsies.

Peripheral nerve biopsy is now an established, valuable investigative procedure, but as it can give rise to significant residual symptoms it should only be undertaken after careful consideration of the indications and with informed consent from the patient. Nerve biopsies should only be processed and evaluated in a laboratory with the relevant particular expertise. It is generally recommended that a sural nerve biopsy be performed in combination with a muscle biopsy but not vice versa (muscle biopsies together with a nerve biopsy). Nerve biopsy is not the only means of sampling peripheral nerve tissue to study the peripheral nervous system. Examination of the innervation of the skin may be informative. The same is likely to be true for motor point muscle biopsy. Nerve biopsy is mainly used for morphology although molecular genetic techniques using fresh or archival nerve biopsies are increasingly available. Chemical analysis is undertaken mainly for research purposes.

Biopsy↗
PubMed1997

Growth-associated protein 43 immunoreactivity in the superficial dorsal horn of the rat spinal cord is localized in atrophic C-fiber, and not in sprouted A-fiber, central terminals after peripheral nerve injury.

Peripheral nerve injury induces the up-regulation in dorsal root ganglion cells of growth-associated protein 43 (GAP-43) and its transport to the superficial laminae of the dorsal horn of the spinal cord, where it is located primarily in unmyelinated axons and growth-cone like structures. Peripheral nerve injury also induces the central terminals of axotomized myelinated axons to sprout and form novel synaptic contacts in lamina II of the dorsal horn. To investigate whether the sprouting of A-fiber central terminals into lamina II is the consequence of GAP-43 incorporation into their terminal membranes, we have used an ultrastructural analysis with double labelling to identify the localization of GAP-43 immunoreactivity. Transganglionic transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to identify C-fiber terminals. Transganglionic transport of the B fragment of cholera toxin conjugated to horseradish peroxidase (B-HRP) was used to label A-fiber sciatic nerve central terminals in combination with GAP-43 immunocytochemistry. GAP-43 was found to colocalize only with WGA-HRP- and not with B-HRP-labelled synapses or axons. In addition, many single-labelled GAP-43 synapses were observed. Many of the WGA-HRP-labelled terminals that were characterized by degenerative changes were GAP-43 immunoreactive. Our results indicate that peripheral nerve injury induces novel synapse formation of A fibers in lamina II but that up-regulated levels of GAP-43 are present mainly in other axon projections to the superficial dorsal horn.

Animals↗
PubMed2005

HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor.

Histological separation of synovial sarcomas from malignant peripheral nerve sheath tumors can be difficult and available immunohistochemical markers sometimes give rise to overlapping staining patterns. Additional markers are needed to better define the two entities in the routine surgical pathology practice. To this end, we explored diagnostic applications of HMGA (HMGA1 and HMGA2) protein immunohistochemistry in comparable groups of synovial sarcoma and malignant peripheral nerve sheath tumors. The histological diagnosis of these cases was confirmed by the presence or absence of synovial sarcoma specific SYT-SSX fusion transcript analyzed by real-time reverse transcription polymerase chain reaction. In all, 13 malignant peripheral nerve sheath tumors and 15 synovial sarcomas were included in this study. Immunohistochemically, most malignant peripheral nerve sheath tumors expressed both HMGA1 and HMGA2 protein (12/13 and 12/13 cases, respectively) with moderate to strong nuclear staining patterns. Most cases of synovial sarcomas demonstrated variable expression of HMGA1. However, significant immunoreactivity for HMGA2 was present in the glandular component of a biphasic tumor (1/1) and rarely detected in monophasic synovial sarcomas (1/14). In summary, expression of HMGA2 is a feature of MPNST but not of synovial sarcoma and immunohistochemical staining of HMGA2 may be a useful marker to separate malignant peripheral nerve sheath tumor from synovial sarcoma.

Adult↗
PubMed1979

Subperineurial space of the sural nerve in various peripheral nerve diseases.

The size of the subperineurial space of the sural nerve has been evaluated quantitatively in 69 cases of various peripheral nerve diseases and in controls. A significant increase was found in beriberi neuropathy (6 cases) and idiopathic polyradiculoneuropathy (9 cases) as compared with the control (8 cases). On electron microscopy a few macrophages, fibroblast processes, collagen fibrils with a diameter of 50 nm, microfibrils with a diameter of 8 nm, and amorphous material were observed in both the enlarged subperineural space and the endoneurial intercellular space. They were less frequently observed in controls. No significant correlation was found between the size of subperineurial space and the density of myelinated fibers.

Adolescent↗
PubMed2006

Effect of oblique nerve grafting on peripheral nerve regeneration in rats.

Current methods of peripheral nerve repair are to rejoin cut nerve stumps directly or to bridge large gaps with autologous nerve grafts. In both cases the surface of nerve stump endings is typically cut perpendicularly to the long axis of the nerve. The outcome of such operations, however, is still not satisfactory. In this study, we examine the effect of oblique nerve cutting and grafting on morphological as well as functional features of regeneration. In adult rats, sciatic nerve was cut and rejoined either directly or using an autologous graft, at 90 degrees or 30 degrees angle. Functional regeneration was assessed by walking track analysis during 12-week follow-up. Afterwards muscle weight was measured and histological studies were performed. The latter included nerve fibers and Schwann cells counting, as well as visualization of scar formation and epineural fibrosis. Nerves cut obliquely and rejoined showed better functional recovery than perpendicularly transected. Similar effect was observed after oblique grafting when compared to perpendicular one. Numbers of nerve fibers growing into the distal stump of the nerve as well as the number of Schwann cells were significantly higher in obliquely than in perpendicularly operated nerves. Moreover, growing axons were arranged more regularly following oblique treatment. These data indicate that joining or grafting the nerve stumps at acute angle is a more profitable method of nerve repair than the standard procedure performed at right angle.

Animals↗
PubMed1991

Treatment of traumatic peripheral nerve injury.

Peripheral nerve injuries are caused by traction, laceration and missile injury. Primary surgical repair is recommended for clean, sharp injuries that cause transection of a nerve. In compressed, stretched or contused nerves, surgical repair at three months is indicated if functional recovery has not occurred. Electromyography and nerve conduction studies are helpful in deciding which patients need secondary repair. Recovery is possible for 18 months following injury. Since nerve regeneration occurs at a rate of one inch per month, the distance from the nerve injury to the innervated muscle must be less than 18 inches. Therefore, the outcome is generally better in distal lesions than in proximal ones.

Action Potentials↗
PubMed2005

Distribution of sodium channels during nerve elongation in rat peripheral nerve.

A number of studies have investigated electrophysiological and morphological changes of peripheral nerves during gradual elongation. There has been, however, no report on the distribution of sodium channels at Ranvier's nodes during peripheral nerve elongation. We investigated peripheral nerve injury after the gradual elongation of rat sciatic nerves. Indirect nerve elongation was induced by leg lengthening at a rate of 3 mm/day by 15 or 30 mm. At 7 days after the leg lengthening, the electrophysiological properties of sciatic nerves, the ultrastructures of the Ranvier's nodes and axons, and the distribution of voltage-dependent sodium channels were examined. In the control nerves, most sodium channels were localized at Ranvier's nodes in myelinated axons, providing the physiological basis of saltatory conduction. In the elongated nerves, both the amplitude and conduction velocity of compound nerve action potential decreased following leg lengthening. The elongated nerves also showed paranodal demyelination in Ranvier's nodes longer than those in the control group. In addition, the distribution of sodium channels became diffuse or disappeared at Ranvier's nodes of elongated nerves. The diffuse distribution and/or disappearance of sodium channels may underlie the electrophysiological changes in compound nerve action potential induced by nerve elongation.

Animals↗