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Biomedical subjects

J K Terzis

Publications and source records attributed to J K Terzis.

At least 19 recordsLinked to original sources
PubMed2001

IGF-I and end-to-side nerve repair: a dose-response study.

End-to-side nerve repair allows for target-muscle reinnervation, with simultaneous preservation of donor-nerve function. Local administration of insulin-like growth factor-I (IGF-I) has been shown to increase the rate of axon regeneration in crush-injured and freeze-injured rat sciatic nerve. The purpose of the current project was to determine the effects of IGF-I in a rat model of end-to-side nerve repair. The left musculocutaneous nerve of 18 adult male Sprague-Dawley rats was fully transected to induce biceps-muscle paralysis. The distal stump of the musculocutaneous nerve was then coapted by end-to-side neurorrhaphy through a perineurial window to the ipsilateral median nerve. All animals were randomly assigned to three groups: Group A received 100 microg/ml IGF-I; Group B received 50 microg/ml IGF-I; and control Group C received 10 mM acetic acid vehicle solution. Infusions were regulated by the Alzet model 2004 mini-osmotic pump, with an attached catheter directed at the coaptation site. Weekly postoperative behavioral evaluations revealed significantly increased functional return over control in both experimental groups as early as 3 weeks. After 28 days, histology evaluations revealed statistically significantly higher musculocutaneous nerve axon counts and myelin thickness/axon diameter ratios in both experimental groups vs. controls. The three groups were not significantly different in motor endplate counts of the biceps muscle. Groups A and B were not significantly different in all parameters tested. This study suggests that local infusion of IGF-I may expedite the functional recovery of a paralyzed muscle, by increasing the rate of axon regeneration through an end-to-side nerve graft.

Anastomosis, Surgical↗
PubMed2001

Enhanced reinnervation of the paralyzed orbicularis oculi muscle after insulin-like growth factor-I (IGF-I) delivery to a nerve graft.

Facial paralysis (FP) remains today one of the most disturbing cranial nerve disorders. The present study utilized the rat model of FP and examined a dual approach of combining the current microsurgical treatment of cross-facial nerve graft (CFNG) with local administration of insulin-like growth factor-I (IGF-I). The efficacy of this combined treatment approach was assessed by motor end-plate analysis of the reinnervated orbicularis oculi muscle (OOM). Local administration of IGF-I (50 microg/ml) to the CFNG demonstrated a 61 percent increase in the number of end-plates in the reinnervated OOMs, compared to the OOMs reinnervated with CFNG plus vehicle. These results indicate that the local therapeutic augmentation of IGF-I levels at the coaptation site(s) of the CFNG may, in fact, enhance reinnervation of muscle and recovery of function in general.

Animals↗
PubMed2000

Ultrastructure of early axonal regeneration in an end-to-side neurorrhaphy model.

The ultrastructure of the early regenerative response in an end-to-side neurorrhaphy rat model was studied using transmission electron microscopy. The ipsilateral saphenous nerve was grafted to the sciatic nerve under the following conditions: Group 1, the epineurium and perineurium of the sciatic nerve remained intact; Group 2, an epineurial and perineurial window was created at the site of the lateral neurorrhaphy; Group 3, the same as in Group 2 and, in addition, the sciatic nerve sustained a partial neurectomy. Rats were perfused through the heart with fixative containing 2 percent paraformaldehyde and 2.5 percent glutaraldehyde in 0.1 M cacodylate buffer (pH 7.4) at 4, 8, 12, 24 and 48 hr after surgery. In Group 1, no regenerating axons were observed and the myelin sheath in the donor nerve did not demonstrate any degenerative changes through 48 hr. In Group 2, an increased diameter of the unmyelinated axons and growth cones was observed in the donor nerve proximal to the coaptation site after 12 hr. Degenerative changes in the myelin sheath were observed after 12 hr within the several layers under the coaptation site. In Group 3, many growth cone-like structures were observed in the area proximal to the coaptation site after 12 hr. After 24 hr, proximal regenerating axons elongated to the coaptation site and, at 48 hr, many regenerating nerves grew inside the Schwann cell basement membrane of the graft nerve. These results indicate that the perineurial window and nerve graft are the critical conditions for inciting nerve regeneration in the donor nerve.

Animals↗
PubMed2000

Efficacy of the "baby-sitter" procedure after prolonged denervation.

This study was undertaken to evaluate whether 40 percent of the hypoglossal nerve, which showed optimal efficacy in restoring orbicularis oculi muscle (OOM) function after different percentages of partial neurectomy in a previous study would be effective after prolonged denervation time. Twenty Sprague-Dawley rats were divided into four groups. In first-stage surgery the left facial nerve of all animals was transected at the level of the stylomastoid foramen and main zygomatic branch. Group A (controls) consisted of animals with only left facial nerves transected (no repair). In Groups B, C, and D the facial nerve was transected and the facial musculature was denervated for a period of 4, 8, and 12 weeks respectively. During a second-stage procedure, a 40 percent neurectomy was performed on the hypoglossal nerve. Subsequently, a nerve transfer was performed by coaptations of a saphenous nerve graft to the neurectomized hypoglossal nerve and the main zygomatic branch of the facial nerve that innervated the OOM. Behavioral analysis of blink reflex, electrophysiology, and axon and motor end-plate counts in Groups B, C, and D showed superior results compared to Group A. There was no statistically significant difference observed among Groups B, C, and D (p > 0.05). Despite the diminished number of axons in the zygomatic branch and motor end-plates in the orbicularis oculi muscle after 12 weeks of denervation, there was still sufficient muscle target recovery to effect some eye closure in all groups except the controls. This study demonstrated in this model that the 40 percent partial neurectomy of the XII to VII component of the "baby-sitter" procedure was effective even after prolonged denervation.

Animals↗
PubMed2000

Effects of testosterone on a cross-facial nerve graft model.

A cross-facial nerve graft (CFNG) can be used to restore the blink reflex following facial paralysis. However, the efficacy of a CFNG depends on the ability of regenerating axons to breach two nerve coaptations and reinnervate endplates in denervated muscle. The neurons involved, facial motor neurons, are androgen-dependent. Testosterone enhances facial-nerve regeneration and accelerates blink-reflex recovery following nerve crush. The current study tested the hypothesis that testosterone administered to castrated or normal adult male rats would enhance axonal regeneration through a CFNG, and thereby enhance recovery of the blink reflex. To test this hypothesis, 20 adult male rats were randomly assigned to four groups, (1) normal, intact; (2) castrated; (3) castrated with testosterone proprionate (TP) administration; and (4) normal, intact with TP Each rat underwent transection of the left facial nerve, and a CFNG using the saphenous nerve as an interpositional graft, with coaptations to the ipsilateral and contralateral zygomatic branches, was carried out. Assessments included return of blink reflex, electrophysiology, quantification of motor endplates, and axonal numbers. The data from the blink reflex evaluation, the electrophysiologic assessment, and the endplate quantification suggested that TP may have an effect on regeneration through a CFNG, but that the differences between groups were not statistically significant. In contrast, exogenously administered TP significantly enhanced the number of axons that entered the nerve graft. These data suggest that pharmacologic doses of testosterone may enhance recovery following a CFNG.

Analysis of Variance↗
PubMed2000

Efficacy of intervention strategies in a brachial plexus global avulsion model in the rat.

The treatment of brachial plexus avulsion lesions invariably involves the use of neurotization procedures. Although some of these therapeutic strategies have been used for the past 20 years to restore selective function to the injured extremity, the individual efficacy of these nerve transfers has not been measured objectively, thereby rendering the prognostication of outcomes for these techniques a major problem. Using a true global avulsion model, the present study compares outcomes of the various neurotization procedures for the first time. The strength of this experimental model is that each nerve transfer tested leads to a common terminal pathway involving a single target-namely, the biceps muscle. Thus, quantitative measurements of biceps restoration will provide strong clues to the power of axonal regrowth of that particular motor pool. This study also introduces the Terzis grooming test, a modified behavioral test that can be quantified and that can provide an overall functional scale in the assessment of outcome. Thirty-five Sprague-Dawley rats were divided into seven groups, with each group testing a different motor donor for biceps reinnervation. The ipsilateral brachial plexus was globally avulsed in all animals, with the exception of the ipsilateral C7 group, and the respective motor donor coapted in an end-to-end fashion to the musculocutaneous nerve. Functional outcomes were measured by the Terzis grooming test, electromyography, biceps muscle force measurements, motor end plate counts, and quantitative axonal morphometry. The values of the different parameters were expressed as a standard score on a common scale. The relative standings of each group on each parameter were compared. Superior outcome was observed in the phrenic, the hypoglossal, and the ipsilateral C7 groups.

Animals↗
PubMed2000

The surgical treatment of brachial plexus injuries in adults.

Posttraumatic brachial plexus palsy is a severe injury primarily affecting young individuals at the prime of their life. The devastating neurological dysfunction inflicted in those patients is usually lifelong and creates significant socioeconomic issues. During the past 30 years, the surgical repair of these injuries has become increasingly feasible. At many centers around the world, leading surgeons have introduced new microsurgical techniques and reported a variety of different philosophies for the reconstruction of the plexus. Microneurolysis, nerve grafting, recruitment of intraplexus and extraplexus donors, and local and free-muscle transfers are used to achieve optimal outcomes. However, there is yet no consensus on the priorities and final goals of reconstruction among the various centers.

Adolescent↗
PubMed1999

Optimal time for distraction osteogenesis in limbs with nerve repairs: experimental study in the rat.

The optimal period of time between peripheral-nerve repair and initiation of limb lengthening procedures has never been precisely determined. In the clinical setting, the surgeon must decide how long the repaired nerves should be allowed to heal before subjecting them to the forces created by the limb-lengthening process. The authors designed a study to quantify and qualify the effects of different recovery periods between initial nerve repair and subsequent limb-lengthening via distraction osteogenesis. Forty-two Sprague-Dawley male rats were randomized in two different categories of nerve repair: end-to-end and nerve grafts. At 4, 8 and 12 weeks after nerve reconstruction, the femur was submitted to limb-lengthening at a rate of 1 mm/day (0.25 mm every 6 hr). Sciatic Function Index (SFI) evaluation indicated that the impact of distraction was detrimental in the grafted nerves, although they maintained their electrical and morphologic properties at comparable levels to the non-distracted nerves. Nerves with direct coaptation presented an overall superior regeneration pattern. The findings in end-to-end repairs distracted at 8 weeks and those of grafted nerves at 12 weeks were comparable to those in distracted normal nerves. The morphology of the distracted nerves appeared to be more organized than that observed in the non-distracted nerves.

Animals↗
PubMed1999

Effects of IGF-II in a new end-to-side model.

Insulin-like growth factor-II (IGF-II) has been shown to increase the rate of axon regeneration in a number of models involving the rat sciatic nerve. This project studied the effects of IGF-II on an end-to-side nerve repair. In this study, the musculocutaneous nerve of a Sprague-Dawley rat was transected and coapted by end-to-side neurorrhaphy to the median nerve. Experimental animals received a local infusion of IGF-II at the repair site, while control animals received a local infusion of placebo solution. This new model allowed for the assessment of functional outcome through the Terzis grooming test. The use of an end-to-side repair minimized potential damage to the motor nerve donor (median nerve) and encouraged lateral axon sprouting into the severed nerve (musculocutaneous nerve). Histologic results showed that the IGF-II treated group had higher axon counts and greater myelin thickness in the reinnervated musculocutaneous nerve. IGF-II-treated animals also had significantly greater motor-end-plate counts in the biceps muscle. Furthermore, the IGF-II group scored consistently higher in the grooming test, compared to the control group.

Animals↗
PubMed1999

End-to-side neurorrhaphy: evaluation of axonal response and upregulation of IGF-I and IGF-II in a non-injury model.

This research group has introduced a model of end-to-side neurorrhaphy, in which reinnervation occurs without frank damage to donor axons. The current study used in situ hybridization to test the hypothesis that insulin-like growth factor (IGF-I and IGF-II) mRNA levels increase at the coaptation site and grafted nerve following end-to-side repair, and that this increase is associated with axonal sprouting and growth. One week after end-to-side coaptation, IGF-I mRNA was localized predominantly on the epineurial side of the graft perineurium, while IGF-II was seen mainly on the endoneurial side. IGF-I hybridization was greatest at this time and declined by 2 weeks post-procedure. No changes in IGF mRNA levels occurred in the distal donor nerve. The increase in IGF-I mRNA at 1 week preceded the appearance of myelinated axons. The presence of myelinated axons within the graft 2 weeks after end-to-side coaptation was associated with a decline in IGF-I mRNA. These data are the first to demonstrate increased IGF mRNA levels associated with axonal sprouting and growth following end-to-side neurorrhaphy. Moreover, the findings support those of earlier studies by others implicating IGFs in axonal regeneration. The increase in IGF mRNA during sprouting and axonal growth into an end-to-side coaptation indicates that the local therapeutic augmentation of endogenous IGF levels at the coaptation site may enhance axonal sprouting from a minimally injured donor nerve, and thereby increase the number of axons that reinnervate the graft.

Anastomosis, Surgical↗
PubMed1999

Outcomes of brachial plexus reconstruction in 204 patients with devastating paralysis.

Thus far, devastating injuries of the adult brachial plexus have had a poor prognosis. This article presents the possible outcomes of aggressive microsurgical reconstruction in the largest series of patients in North America to date. It should change the pessimistic outlook that has surrounded these lesions. In this study, the outcomes of surgery were analyzed in relation to the type and level of injury, the age of the patient, and the denervation time; stronger donors for neurotization in relation to the various targets were delineated. The results were analyzed in 204 patients with adequate follow-up from a total of 263 patients who were operated on between 1978 and 1996. The mean age of the patients was 25.9 years, and the injuries were caused by high-velocity motor accidents involving avulsion in 55 percent of the patients. Nerve reconstruction included 577 nerve repairs (140 direct neurotizations and 437 cases of nerve grafting). Microneurolysis was performed in 89 cases. Vascularized nerve grafts were used in 120 repairs. Muscle transfers (29 pedicled and 78 free) were used to enhance function. The results were good or excellent in 75 percent of suprascapular nerve reconstructions, 40 percent of deltoid reconstructions, 48 percent of biceps reconstructions, 30 percent of triceps reconstructions, 35 percent of finger-flexion reconstructions, and 15 percent of finger-extension reconstructions. The majority of the patients had protective sensation and pain relief postoperatively.

Adolescent↗
PubMed1999

Management of obstetric brachial plexus palsy.

OBPP is a disease with deleterious medical, psychological, and socioeconomic sequelae for the patient and his or her family. The majority of patients show acceptable spontaneous recovery with nonoperative management, which includes aggressive physical rehabilitation and electrical stimulation. There are patients with guarded prognosis, however, who have no chance of recovery unless they undergo early aggressive surgical reconstruction of the injured brachial plexus. It is of great importance to diagnose the injury type as early as possible, especially if there is minimal recovery in the early weeks of follow-up. This allows timely reconstruction to take place, earlier than 3 months for global palsy cases and at 3 months in Erb's type lesions, for best functional results.

Brachial Plexus Neuropathies↗
PubMed1998

Ultrastructure and cellular biology of nerve regeneration.

Hippocrates provided the first written description of the peripheral nervous system (PNS), as early as the 4th century B.C., and later Herophilus identified nerves as such, distinguished them from tendons; he also traced nerves to the spinal cord. The traditional Hippocratic teaching of the time, however, doubted that nerve healing occurred. Through the subsequent centuries, several papers were written about the PNS but, without sufficient understanding of anatomy, physiology, and the regenerative capacity of the PNS, it is not difficult to comprehend the frustration that might have been encountered by surgeons in dealing with nerve injuries and their subsequent repair. This was probably the reason why nerve repair was rarely actually undertaken prior to the 19th century. A plethora of studies on the PNS and its regeneration has been reported over the last 150 years and has provided us with current knowledge. It is important, before describing the most recent developments in the area of peripheral nerve regeneration, to briefly outline the major advances over the last century. Currently, the therapeutic approaches taken toward the patient with peripheral nerve injury change continuously. Sophisticated advances in technology, cellular and molecular neurobiology, and electron microscopy will doubtless optimize reconstructive strategies in treating nerve injury. A greater awareness and understanding of the nerve ultrastructure, as well as the underlying mechanisms of the regenerative process and those factors detrimental to nerve regeneration, will assist in the successful repair of nerve injury. This paper reviews the cellular, biochemical, and ultrastructural elements of nerve injury and repair, and the rationale for current reconstructive strategies and techniques.

Animals↗
PubMed1998

Gains and losses of the XII-VII component of the "baby-sitter" procedure: a morphometric analysis.

The classic hypoglossal transfer to the facial nerve is invariably followed by complications caused by tongue atrophy. In 1984, Terzis introduced the "baby-sitter" procedure which involved a formal cross-facial procedure, in addition to partial neurectomy of the hypoglossal nerve, and an end-to-side coaptation with the ipsilateral facial nerve. This reported study provides, for the first time, quantification of the number of hypoglossal motor fibers needed to successfully restore eye sphincter function, using an end-to-side coaptation with preservation of the tongue. Thirty adult Sprague-Dawley rats were divided into six groups: control, denervated, perineurial window, 20 percent partial neurectomy (PN), 40 percent PN, and 80 percent PN. The procedure involves interposing a nerve graft (saphenous) between the partially severed XII nerve and the upper zygomatic branch of the facial nerve. Evaluation of the behavioral data (blink reflex) revealed good-to-superb return of the blinking mechanism in the 40 percent group, without significant tongue atrophy. Electrophysiologic data in the 40 percent neurectomy group demonstrated superiority to the other groups. Quantitative axonal morphometry of the coaptation sites and graft, as well as motor end-plates of the orbicularis oculi muscle and tongue showed the 40 percent partial neurectomy group to be the optimal group.

Animals↗
PubMed1998

Effect of distraction osteogenesis on the peripheral nerve: experimental study in the rat.

Distraction osteogenesis is the current method of choice for bone lengthening. Despite the gain in experience, various complications are reported, among them, adverse effects on peripheral-nerve function. In order to thoroughly investigate the effect of distraction on neural tissue, a distraction osteogenesis model in the rat was established, using the femur of 30 Sprague-Dawley rats. The animals were randomized in three groups, following different rates of distraction (0.5 mm, 1.0 mm, and 1.5 mm/day) for 50, 25, and 16 days, respectively, so that the final length of distraction was the same in all groups. The mean sciatic function index ranged near normal in all groups. All groups demonstrated decrease of conduction velocity and the area under the curve of the compound action potential, while morphologic alterations consisted of decrease in the number of axons and evidence of active degeneration. Animals in Groups 1 (0.5 mm/day) and 2 (1 mm/day) displayed comparable changes, while in Group 3 animals (1.5 mm/day), changes were significantly more adversely dramatic. The safest and fastest rate of distraction in this rat model was determined to be 1 mm/day.

Action Potentials↗
PubMed1997

End-to-side neurorrhaphy: a histologic and morphometric study of axonal sprouting into an end-to-side nerve graft.

This study investigated axonal regeneration in a denervated nerve graft sutured end-to-side with a main peripheral nerve trunk. To demonstrate morphologic changes, the peroneal nerve was severed in a rat and coapted end-to-side to the posterior tibial nerve. The integrity of the epineurial and perineurial sheath was altered in four different groups. Histologic evaluation 30 days after operation showed axonal regeneration in the nerve graft in all groups. Morphometric analysis of cross sections of the grafted nerve elucidated the importance of severance of the perineurium in end-to-side neurorrhaphy.

Anastomosis, Surgical↗