Acute intermittent hypoxia enhances regeneration of surgically repaired peripheral nerves in a manner akin to electrical stimulation.

The intrinsic repair response of injured peripheral neurons is enhanced by brief electrical stimulation (ES) at time of surgical repair, resulting in improved regeneration in rodents and humans. However, ES is invasive. Acute intermittent hypoxia (AIH) - breathing alternate cycles of regular air and air with ~50% normal oxygen levels (11% O2), considered mild hypoxia, is an emerging, promising non-invasive therapy that promotes motor function in spinal cord injured rats and humans. AIH can increase neural activity and under moderately severe hypoxic conditions improves repair of peripherally crushed nerves in mice. Thus, we posited an AIH paradigm similar to that used clinically for spinal cord injury, will improve surgically repaired peripheral nerves akin to ES, including an impact on regeneration-associated gene (RAG) expression-a predictor of growth states. Alterations in early RAG expression were examined in adult male Lewis rats that underwent tibial nerve coaptation repair with either 2 days AIH or normoxia control treatment begun on day 2 post-repair, or 1 h ES treatment (20 Hz) at time of repair. Three days post-repair, AIH or ES treatments effected significant and parallel elevated RAG expression relative to normoxia control at the level of injured sensory and motor neuron cell bodies and proximal axon front. These parallel impacts on RAG expression were coupled with significant improvements in later indices of regeneration, namely enhanced myelination and increased numbers of newly myelinated fibers detected 20 mm distal to the tibial nerve repair site or sensory and motor neurons retrogradely labeled 28 mm distal to the repair site, both at 25 days post nerve repair; and improved return of toe spread function 5-10 weeks post-repair. Collectively, AIH mirrors many beneficial effects of ES on peripheral nerve repair outcomes. This highlights its potential for clinical translation as a non-invasive means to effect improved regeneration of injured peripheral nerves.

Transcutaneous tibial nerve home stimulation for overactive bladder in women with Parkinson's disease: A randomized clinical trial.

AIMS: This study aims to investigate the efficacy of transcutaneous tibial nerve home stimulation for overactive bladder (OAB) in women with Parkinson's disease (PD). METHODS: The current study is a prospective, randomized, double-blind, sham-controlled trial. Home intervention was carried out and assessments were conducted at a tertiary hospital in South Brazil. Women with PD and OAB symptoms were included in the study. Patients were randomly divided into two groups: (1) stimulation and (2) sham. Both groups underwent intervention at home for 12 weeks. Patients were evaluated at baseline and at 12 weeks (end of intervention), 30- and 90-day follow-up. The primary outcome was the mean reduction in the number of urgency incontinence episodes, and secondary outcomes included daytime and nighttime urinary frequency, urinary urgency episodes, use of pad (reported in a 24-h bladder diary), OAB-V8 and King's Health Questionnaire scores, and maintenance of symptom relief after discontinuation of the intervention. RESULTS: In total, 30 consecutive patients completed the study (15/group). The stimulation group showed a reduction in nighttime urinary frequency (0.9 ± 0.6), urinary urgency (1.0 ± 1.2), urgency incontinence episodes (0.5 ± 0.6), use of pads (1.3 ± 1.2), and OAB-V8 (1.3 ± 1.2) and King's Health Questionnaire scores. In a 30-day and 90-day follow-up, 8 (53.3%) and 5 (33.3%) stimulation patients, respectively, reported full maintenance of symptom relief after discontinuation of the intervention. Stimulation patients presented a statistically significant improvement of symptoms as compared with sham patients (p = .001). CONCLUSIONS: Transcutaneous tibial nerve home stimulation can be used in clinical practice as an effective nonpharmacological resource for the reduction of OAB symptoms in women with PD, and the resulting relief seems to persist in the follow-up (30 and 90 days).

Where Are We Headed with Neuromodulation for Overactive Bladder?

Overactive bladder (OAB) affects millions of people around the world and decreases quality of life for those affected. Over the past two decades, significant advances in treatment have transformed the lives of those with OAB. Sacral neuromodulation (SNM), posterior tibial nerve stimulation (PTNS), and dorsal genital nerve stimulation are the most effective contemporary treatment modalities. New techniques and bio-sensing schemes offer promise to advance therapy beyond what is currently available. Current neuromodulation techniques do not use real-time data from the body or input from the patient. Incorporating this is the goal of those pursuing a neuroprosthesis to enhance bladder function for these patients. Dorsal genital nerve, pudendal nerve, S3 afferent nerve roots, and S1 and S2 ganglia have all been used as targets for stimulation. Some of these have also been used as sources of afferent nerve information to detect significant bladder events and even to estimate the fullness of the bladder. As technology improves, an intelligent neuroprosthesis with the ability to sense significant bladder events may revolutionize treatment of OAB.

Effects of intraperitoneally administered folic acid on the healing of repaired tibial nerves in rats.

BACKGROUND: Complete nerve regeneration and clinical healing remain a challenge despite considerable advances in the treatment of peripheral nerve injuries. To improve nerve regeneration, several experimental molecular procedures have been attempted. This study aimed to investigate the effects of folic acid on peripheral nerve healing after transection and end-to-end suture repair of the tibial nerve in rats. METHODS: In this study, 20 adult male Wistar Albino rats weighing 225 to 250 g were used. The right tibial nerves of 20 rats were explored, transected, and sutured using the end-to-end technique. The rats were randomly allocated to either the intraperitoneally administered folic acid group (test group) or the control group. Preoperative and 6-week postoperative neurophysiological studies were performed by the same researcher. Myelin-sheathed axons were counted. RESULTS: The results demonstrated that the folic acid-treated group exhibited improved electromyographic results compared with the control group. Histological evaluation revealed that the axons were well preserved and that the axon quantity and density were increased in the test group compared with the control group. Quantitative results also increased in the test group compared with the control group (p = 0.001). CONCLUSION: In this study, 6-week intraperitoneal administration of 80 µg/kg of folic acid significantly improved peripheral nerve healing. Histological analysis of the group that received folic acid revealed increased axon myelination with little granular tissue or fibrosis. We propose that folic acid supplementation may be an effective component of peripheral nerve injury treatment.

Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

OBJECTIVE: This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. MATERIALS AND METHODS: TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. RESULTS: TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. CONCLUSIONS: Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.

The influence of spatial pulsed magnetic field application on neuropathic pain after tibial nerve transection in rat.

The purpose of the study was to examine the influence of the spatial variable magnetic field (induction: 150-300 µT, 80-150 µT, 20-80 µT; frequency 40 Hz) on neuropathic pain after tibial nerve transection. The experiments were carried out on 64 male Wistar C rats. The exposure of animals to magnetic field was performed 1 d/20 min., 5 d/week, for 28 d. Behavioural tests assessing the intensity of allodynia and sensitivity to mechanical and thermal stimuli were conducted 1 d prior to surgery and 3, 7, 14, 21 and 28 d after the surgery. The extent of autotomy was examined. Histological and immunohistochemical analysis was performed. The use of extremely low-frequency magnetic fields of minimal induction values (20-80 µT/40 Hz) decreased pain in rats after nerve transection. The nociceptive sensitivity of healthy rats was not changed following the exposition to the spatial magnetic field of the low frequency. The results of histological and immunohistochemical investigations confirm those findings. Our results indicate that extremely low-frequency magnetic field may be useful in the neuropathic pain therapy.

Stimulation of the medial plantar nerve for complex regional pain syndrome.

We describe a 47-year old male with complex regional pain syndrome II in the distribution of the medial plantar nerve following metatarsal fracture, which was treated with peripheral nerve stimulation. Using a new technique of nerve stimulation with a percutaneous-type electrode, the patient experienced sustained relief at 12 months follow-up. To our knowledge, this is the first report of peripheral neurostimulation effectively managing pain for the medial plantar nerve.

End-to-side nerve repair using fibrin glue in rats / Anastomose nervosa término-lateral usando cola de fibrina em ratos

Purpose: To evaluate axonal regeneration after end-to-side nerve repair with fibrin glue in rats. Methods: Forty-five Wistar rats were divided into three groups: group A (n=15), were not submitted to surgery (control group); group B (n=15) were submitted to fibular transection without repair; and group C (n=15), were submitted to fibular transection with end-to-side nerve anastomosis using fibrin glue, in the lateral surface of an intact tibial nerve. The three groups were submitted to walking track (30 and 90 days) and posterior morphometrical analysis (90 days). Results: The functional tests demonstrated that there was no difference in the walking track during the study in group A (p>0.05). The group B had walking pattern impairment in the two tests (p>0.05). The group C had walking pattern impairment in the first test, with important recovery in the second test (p<0.05). The morphometrical assessment revealed significantly higher number of regenerated mielinates axons in group C, compared to group B (p<0.05). Conclusion: The end-to-side nerve repair with fibrin glue shows axonal recovery, demonstrated through functional and morphometrical ways in rats.

Objetivo: Avaliar a regeneração axonal após anastomose nervosa término-lateral (ATL) usando cola de fibrina em ratos. Métodos: Quarenta e cinco ratos Wistar distribuídos em três grupos: os animais do grupo A (n=15) não foram submetidos à secção nervosa (grupo controle); os animais do grupo B (n=15) foram submetidos apenas à secção do nervo fibular, sem posterior anastomose; e os animais do grupo C (n=15) foram submetidos à secção do nervo fibular e à ATL com cola de fibrina no nervo tibial. Posteriormente, os animais foram submetidos a dois testes de marcha (30 e 90 dias) e à análise morfométrica (90 dias). Resultados: A análise estatística dos testes de marcha demonstrou que o grupo A não apresentou alteração no padrão de caminhada durante o estudo (p>0,05). O grupo B apresentou prejuízo motor no primeiro e no segundo teste (p>0,05). O grupo C apresentou um padrão de atrofia no primeiro teste, com recuperação da marcha no segundo teste (p<0,05). Na análise morfométrica, o grupo C apresentou regeneração axonal significativamente superior ao grupo B (p<0,05). Conclusão: A ATL realizada com cola de fibrina resultou em regeneração axonal no rato, demonstrada tanto histologicamente quanto funcionalmente.

End-to-side nerve repair using fibrin glue in rats.

PURPOSE: To evaluate axonal regeneration after end-to-side nerve repair with fibrin glue in rats. METHODS: Forty-five Wistar rats were divided into three groups: group A (n=15), were not submitted to surgery (control group); group B (n=15) were submitted to fibular transection without repair; and group C (n=15), were submitted to fibular transection with end-to-side nerve anastomosis using fibrin glue, in the lateral surface of an intact tibial nerve. The three groups were submitted to walking track (30 and 90 days) and posterior morphometrical analysis (90 days). RESULTS: The functional tests demonstrated that there was no difference in the walking track during the study in group A (p>0.05). The group B had walking pattern impairment in the two tests (p>0.05). The group C had walking pattern impairment in the first test, with important recovery in the second test (p<0.05). The morphometrical assessment revealed significantly higher number of regenerated mielinates axons in group C, compared to group B (p<0.05). CONCLUSION: The end-to-side nerve repair with fibrin glue shows axonal recovery, demonstrated through functional and morphometrical ways in rats.

Resection of the sciatic, peroneal, or tibial nerves: assessment of functional status.

BACKGROUND: Lower-extremity tumors are often treated by amputation rather than limb-sparing excision that sacrifices the sciatic nerve or a branch. This study assessed the functional outcome of major nerve sacrifice during limb-sparing resections for lower-extremity soft tissue sarcoma. METHODS: Patients who underwent division of the sciatic, tibial, or peroneal nerve(s) during limb-sparing sarcoma surgery (January 1982 through June 2000) were identified. Eleven surviving patients evaluated their pre- and postoperative functional status by self-administered questionnaire (six sciatic, two tibial, and three peroneal nerve divisions). RESULTS: Eighteen patients (10 male, 8 female; 14-84 years old) had nine primary and nine locally recurrent tumors. Tumors were high (16) or low grade (two). Five patients died of disease and two died of other causes. Median overall survival was 50 months. One of 11 reported increased pain. Eight had new phantom sensations with a median intensity of 4.5 (1 = least; 10 = most). All patients used an ankle brace to walk after a sciatic (four) or peroneal (one) division. Walking ability and distance after surgery was unchanged (nine), improved (one), and worsened (one). Standing improved in 7 of 11 patients. Proprioception in the affected extremity was retained in six. The median postoperative leg functional score was 8 (1 = worst; 10 = best). No patient developed foot ulcers. One patient underwent amputation for recurrence. All patients preferred their status over having an amputation. CONCLUSIONS: Objectively and subjectively, division of the major lower-extremity nerves causes acceptable functional deficits in most patients. Resection of affected sciatic nerve (branches) during limb-sparing tumor surgery is an excellent alternative to amputation.

[Structure of skeletal muscles in combined conditions of denervation, physical load and laser acupuncture]. / Struktura skeletnykh myshts v usloviiakh sochetaniia denervatsii, fizicheskoi nagruzki i lazeropunktury.

An experimental investigation of the skeletal muscles denervation with a subsequent histological, electron microscopical and morphometrical study of their structural state has been carried out on 77 Wistar male rats. Structure of the muscles in the animals, subjected to laseropuncture and also to its combination with physical load after denervation, is disturbed to an essentially less degree than after denervation only. Combination of laseropuncture and physical load ensures activation of regeneration and reinnervation processes of the skeletal muscles.

Selective neurotomy of the tibial nerve for treatment of the spastic foot.

One of the most frequent neurological sequelae seen by the specialist in rehabilitation is the spastic foot. Spasticity in the foot may be responsible for abnormal posture and painful or trophic disturbances impairing standing and walking. This disability can be corrected by a simple neurosurgical procedure, the selective tibial neurotomy. In this procedure, one sections the tibial nerve branches to the muscles sustaining spasticity, i.e., the soleus and/or the gastrocnemius nerves for equinus and ankle clonus or the posterior tibialis branch for varus and the flexor fascicles for tonic flexion of the toes. After microsurgical dissection of each tibial nerve branch at the lower part of the popliteal region and their identification with bipolar electrostimulation, the selected branches are partially sectioned under the operating microscope. The present series consists of 62 operations performed in 53 patients, 9 bilaterally and 44 unilaterally. Operation obtained complete suppression of the disabling spasticity that had been present for 2 to 17 years (4 on average), total pain relief, and consequently improvement of the residual voluntary movements (by achieving a better balance between agonist and antagonist muscles) in 51 of the 62 spastic feet (i.e., 82% of the cases). For all of these patients, the beneficial effects were long-lasting over the 1- to 10-year follow-up (3 years on average). Selective neurotomy of the tibial nerve should be considered only after failure of intensive prolonged kinestherapy and of all available medical treatment. It must take place, however, before the onset of irreversible articular disturbances and musculotendinous retractions, which require complementary orthopedic corrections.

Microsurgical procedures in the peripheral nerves and the dorsal root entry zone for the treatment of spasticity.

When spasticity becomes severe and harmful, in spite of physical and medical therapy, neurosurgery can give functional improvement. This paper deals with the long term results of Selective Peripheral Neurotomies of the Tibial Nerve and Selective Posterior Rhizotomies in the Dorsal Root Entry Zone, in 123 patients with spastic disorders localized to the limbs. The micro-techniques and intra-operative electro-stimulation for identification of the nervous structures responsible for the spastic components, can give a substantial reduction of the harmful spasticity, without suppressing the useful muscle tone and impairing the residual motor and sensory functions. The results were effective, with a 1 to 13 year follow-up (5 on average), in 89% of 47 Selective Peripheral Neurotomies of the tibial nerve for spastic foot, in 92% of 53 Selective Posterior Rhizotomies for paraplegia and in 87% of 23 Selective Posterior Rhizotomies for hemiplegia. In the most severe situations ("comfort" indications), correction of the abnormal postures and relief of pain facilitated nursing and physiotherapy. Sometimes there was reappearance of some useful voluntary movements. In the less affected patients ("functional" indications), the suppression of the harmful spastic components made the persistant capacities more effective.

Microsurgical selective procedures in peripheral nerves and the posterior root-spinal cord junction for spasticity.

This review deals with the long-term results of selective peripheral neurotomy (SPN) of the tibial nerve and selective posterior rhizotomy (SPR) in 123 cases of severe spastic syndromes in the limbs. The microtechniques and preoperative electrostimulation for identification of the nervous structures responsible for the spastic components give to these methods an advantage of a substantial reduction of the harmful spasticity, without suppressing the useful muscle tone and impairing the residual motor and sensory functions. The results were effective, with a 1- to 13-year follow-up, in 89% of 47 SPN of the tibial nerve for spastic foot, in 92% of 53 SPR for paraplegia and in 87% of 23 SPR for hemiplegia.

[Treatment of spastic foot by selective neurotomy of the tibial nerve. Results of a series of 31 cases]. / Traitement du pied spastique par la neurotomie sélective du nerf tibial. Résultats sur une série de 31 cas.

A large number of patients suffering from various neurological diseases remain disabled because of spastic disorders in their foot. These disorders--which are responsible for abnormal postures and painful disturbances for walking and standing--can be corrected by an effective procedure: the so-called Selective Neurotomy of the Tibial Nerve (T.N.), developed in its modern form by Gros in 1972. The procedure aims at sectioning the T.N. branches corresponding to the muscles, the spasticity of which is considered harmful, i.e. the soleus (and/or gastrocnemius) nerves for equinus and ankle clonus, the posterior tibialis branch for varus, and the flexor fascicles for tonic flexion of the toes. After dissection of each T.N. branches at the lower part of the popliteal region and their identification with bipolar electro-stimulation, the selected nerves are sectioned partially (about two-third of their caliber) under the operative microscope. The present series consists of 37 operations--performed 25 times unilaterally and 6 bilaterally--in 31 patients, 17 to 68 year old (39 on average). In 11 patients spasticity was from spinal cord origin and in the 20 others from vascular or traumatic cerebral damages. The spastic disorders--installed for 2 to 17 years (4 on average)--were due to one, several or all the following components: equinus, ankle clonus, varus, flexion of the toes. Surgery obtained complete suppression of the disabling spastic components, total pain relief and consequently improvement of the residual voluntary movements by achieving balance between agonist and antagonist muscles, in 33 out of the 37 cases, i.e. in 91% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)