Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

PubMed Central

Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

2011-01-01

The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MDC1A. We found that, compared with wild-type, sciatic nerves of Lama2−/− mice had a significant increase in both proliferating (Ki67+) cells and premyelinating (Oct6+) Schwann cells, but also had a significant decrease in both immature/non-myelinating [glial fibrillary acidic protein (GFAP)+] and myelinating (Krox20+) Schwann cells. To extend our previous work in which we found that doxycycline, which has multiple effects on mammalian cells, improves motor behavior and more than doubles the median life-span of Lama2−/− mice, we also determined how nerve pathology was affected by doxycycline treatment. We found that myelinating (Krox20+) Schwann cells were significantly increased in doxycycline-treated compared with untreated sciatic nerves. In addition, doxycycline-treated peripheral nerves had significantly less pathology as measured by assays such as amount of unmyelinated or disorganized axons. This study thus identified aberrant proliferation and differentiation of Schwann cells as key components of pathogenesis in peripheral nerves and provided proof-of-concept that pharmaceutical therapy can be of potential benefit for peripheral nerve dysfunction in MDC1A. PMID:21505075

Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy

PubMed Central

Nicotra, Alessia; Newman, Claus; Johnson, Martin; Eremin, Oleg; Friede, Tim; Malik, Omar; Nicholas, Richard

2016-01-01

Background Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life. Methods Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment. Results Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)). Conclusions We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation. PMID:27100829

Intraoperative Sedation With Dexmedetomidine is Superior to Propofol for Elderly Patients Undergoing Hip Arthroplasty: A Prospective Randomized Controlled Study.

PubMed

Mei, Bin; Meng, Gaige; Xu, Guanghong; Cheng, Xinqi; Chen, Shishou; Zhang, Ye; Zhang, Ming; Liu, Xuesheng; Gu, Erwei

2018-03-09

Peripheral nerve block is a preferable method for elderly patients receiving hip arthroplasty. Sedation with dexmedetomidine may reduce postoperative delirium. The aim of this study was to investigate whether intraoperative sedation with dexmedetomidine, as a supplementary to peripheral nerve block for elderly patients receiving total hip arthroplasty, can decrease the prevalence of postoperative delirium. A prospective, randomized controlled study was conducted with patients 65 years of age or older who underwent total hip arthroplasty between June 2016 and June 2017. The patients were randomly assigned to receive a lumbosacral plexus plus T12 paravertebral block supplemented with propofol or dexmedetomidine for sedation. Incidence of postoperative delirium was the primary endpoint and was determined with the Confusion Assessment Method, and incidence of postoperative cognitive dysfunction was assessed with the Mini-Mental State Examination. The time of ambulation, discharge time, and complications over a 30-day post-surgery period were also recorded. 296 patients were randomly assigned to two groups. The patients sedated with dexmedetomidine had lower incidences of postoperative delirium and postoperative cognitive dysfunction and were out of bed and discharged sooner than the patients sedated with propofol. There was no difference in complications between the two groups. As a supplementary to peripheral nerve block, intraoperative sedation with dexmedetomidine could be associated with a lower incidence of POD, which may have benefits on reducing the incidence of early postoperative cognitive dysfunction and offering a better short-term recovery for elderly patients receiving hip arthroplasty.

Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

PubMed

Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

2008-12-15

A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

Rare encounter of unilateral facial nerve palsy in an adolescent with Guillain-Barré syndrome

PubMed Central

Iqbal, Mehtab; Sharma, Parnika; Charadva, Creana; Prasad, Manish

2016-01-01

Unilateral facial nerve palsy is rarely encountered in Guillain-Barré syndrome (GBS). We report a case of an adolescent girl who presented with peripheral ascending weakness, preceded by Campylobacter jejuni infection. After treatment with intravenous immunoglobulin, the peripheral weakness improved. Electro-diagnostic testing confirmed axonal dysfunction and the patient was positive for antiganglioside antibodies. However, the patient developed unilateral left-sided facial weakness. She was managed with further intravenous immunoglobulin and intensive physiotherapy. The outcome for facial palsy was very good, with almost complete resolution after 2 weeks. PMID:26823357

Pathological features of polyneuropathy in three dogs.

PubMed

Tsuboi, Masaya; Uchida, Kazuyuki; Ide, Tetsuya; Ogawa, Mizue; Inagaki, Takehiko; Tamura, Shinji; Saito, Miyoko; Chambers, James K; Nakayama, Hiroyuki

2013-01-01

Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested.

Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

PubMed

Patzkowski, Michael S

2016-03-01

Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted. Published by Elsevier Inc.

Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice.

PubMed

Toyama, Satoshi; Shimoyama, Naohito; Szeto, Hazel H; Schiller, Peter W; Shimoyama, Megumi

2018-04-18

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.

[Neurofibromatosis type 2 in childhood: a clinical characterization].

PubMed

Hinojosa-Mateo, C M; Reche-Sainz, J A; Hernandez-Nunez, A; Ramos-Lopez, M; Arpa-Fernandez, A; Natera-de Benito, D

2017-02-01

Neurofibromatosis type 2 (NF2) is a dominantly inherited neuroectodermal syndrome that predispose to the development of tumors of the central and peripheral nervous system. Additional features include eye and skin abnormalities. A 12-year old male with diagnosis of MF2 according to Baser et al and presentation in childhood was included. A comprehensive bibliographic review of evolution of the diagnostic criteria for NF2 in children was performed. The pattern of presentation of NF2 in childhood differs from adulthood in many aspects. Ophthalmologic and skin manifestations, and not an auditory dysfunction, are the most common initial symptoms in prepuberal-onset NF2. The most frequent symptoms and signs at presentation are posterior subcapsular cataract, skin manifestations as NF2 plaques and/or peripheral nerve tumors, and neurological dysfunction related to isolated or multiple cranial nerve deficits (other than nerve VIII), brainstem masses or spinal masses. As sensitivity of diagnostic criteria in children is low, those prepuberal patients with congenital or early-onset cataracts and typical skin manifestations of NF2 should be systematically assessed.

The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus.

PubMed

Ishibashi, Fukashi; Kojima, Rie; Taniguchi, Miki; Kosaka, Aiko; Uetake, Harumi; Tavakoli, Mitra

2016-01-01

This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia-induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients.

Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression.

PubMed

Zhang, Lei; Yang, Wen; Tao, Kaixiong; Song, Yu; Xie, Hongjian; Wang, Jian; Li, Xiaolin; Shuai, Xiaoming; Gao, Jinbo; Chang, Panpan; Wang, Guobin; Wang, Zheng; Wang, Lin

2017-02-01

Chronic nerve compression (CNC), a common form of peripheral nerve injury, always leads to chronic peripheral nerve pain and dysfunction. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability toward restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated. This scaffold combines the advantages of both chitosan and sericin, such as high porosity, adjustable mechanical properties and swelling ratios, the ability of supporting Schwann cells growth, and improving nerve regeneration. The degradation products of the composite scaffold upregulate the mRNA levels of the genes important for facilitating nerve function recovery, including glial-derived neurotrophic factor (GDNF), early growth response 2 (EGR2), and neural cell adhesion molecule (NCAM) in Schwann cells, while down-regulating two inflammatory genes' mRNA levels in macrophages, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). Importantly, our tissue-engineered strategy achieves significant nerve functional recovery in a preclinical CNC animal model by decreasing neuralgia, improving nerve conduction velocity (NCV), accelerating microstructure restoration, and attenuating gastrocnemius muscles dystrophy. Together, this work suggests a promising clinical alternative for treating chronic peripheral nerve compression injury.

Characterization of nerve and microvessel damage and recovery in type 1 diabetic mice after permanent femoral artery ligation.

PubMed

Lozeron, Pierre; Mantsounga, Chris S; Broqueres-You, Dong; Dohan, Anthony; Polivka, Marc; Deroide, Nicolas; Silvestre, Jean-Sébastien; Kubis, Nathalie; Lévy, Bernard I

2015-09-01

Neuropathy is the most common complication of the peripheral nervous system during the progression of diabetes. The pathophysiology is unclear but may involve microangiopathy, reduced endoneurial blood flow, and tissue ischemia. We used a mouse model of type 1 diabetes to study parallel alterations of nerves and microvessels following tissue ischemia. We designed an easily reproducible model of ischemic neuropathy induced by irreversible ligation of the femoral artery. We studied the evolution of behavioral function, epineurial and endoneurial vessel impairment, and large nerve myelinated fiber as well as small cutaneous unmyelinated fiber impairment for 1 month following the onset of ischemia. We observed a more severe hindlimb dysfunction and delayed recovery in diabetic animals. This was associated with reduced density of large arteries in the hindlimb and reduced sciatic nerve epineurial blood flow. A reduction in sciatic nerve endoneurial capillary density was also observed, associated with a reduction in small unmyelinated epidermal fiber number and large myelinated sciatic nerve fiber dysfunction. Moreover, vascular recovery was delayed, and nerve dysfunction was still present in diabetic animals at day 28. This easily reproducible model provides clear insight into the evolution over time of the impact of ischemia on nerve and microvessel homeostasis in the setting of diabetes. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury.

PubMed

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A

2016-02-24

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury.

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury

PubMed Central

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A.

2016-01-01

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID:26906090

Multifocal Neuropathy: Expanding the Scope of Double Crush Syndrome.

PubMed

Cohen, Brian H; Gaspar, Michael P; Daniels, Alan H; Akelman, Edward; Kane, Patrick M

2016-12-01

Double crush syndrome (DCS), as it is classically defined, is a clinical condition composed of neurological dysfunction due to compressive pathology at multiple sites along a single peripheral nerve. The traditional definition of DCS is narrow in scope because many systemic pathologic processes, such as diabetes mellitus, drug-induced neuropathy, vascular disease and autoimmune neuronal damage, can have deleterious effects on nerve function. Multifocal neuropathy is a more appropriate term describing the multiple etiologies (including compressive lesions) that may synergistically contribute to nerve dysfunction and clinical symptoms. This paper examines the history of DCS and multifocal neuropathy, including the epidemiology and pathophysiology in addition to principles of evaluation and management. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

PubMed Central

Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

2010-01-01

After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

Schwann cell glycogen selectively supports myelinated axon function.

PubMed

Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

2012-09-01

Interruption of energy supply to peripheral axons is a cause of axon loss. We determined whether glycogen was present in mammalian peripheral nerve, and whether it supported axon conduction during aglycemia. We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Glycogen was present in sciatic nerve, its concentration varying directly with ambient glucose. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm, and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time course of glycogen loss. Latency to compound action potential (CAP) failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small-diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large-diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. . Copyright © 2012 American Neurological Association.

Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

PubMed Central

Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

2012-01-01

Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

Low Median Nerve Palsy as Initial Manifestation of Churg-Strauss Syndrome.

PubMed

Roh, Young Hak; Koh, Young Do; Noh, Jung Ho; Gong, Hyun Sik; Baek, Goo Hyun

2017-06-01

Anterior interosseous nerve (AIN) syndrome is typically characterized by forearm pain and partial or complete dysfunction of the AIN-innervated muscles. Although the exact etiology and pathophysiology of the disorder remain unclear, AIN syndrome is increasingly thought to be an inflammatory condition of the nerve rather than a compressive neuropathy because the symptoms often resolve spontaneously following prolonged observation. However, peripheral neuropathy can be 1 of the first symptoms of systemic vasculitis that needs early systemic immunotherapy to prevent extensive nerve damage. Churg-Strauss syndrome (CSS; eosinophilic granulomatosis with polyangiitis) is 1 type of primary systemic vasculitis that frequently damages the peripheral nervous system. CSS-associated neuropathy usually involves nerves of the lower limb, and few studies have reported on the involvement of the upper limb alone. We report on a rare case of low median nerve palsy as the initial manifestation of CSS. The patient recovered well with early steroid treatment for primary systemic vasculitis. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Nerve transfers for restoration of upper extremity motor function in a child with upper extremity motor deficits due to transverse myelitis: case report.

PubMed

Dorsi, Michael J; Belzberg, Allan J

2012-01-01

Transverse myelitis (TM) may result in permanent neurologic dysfunction. Nerve transfers have been developed to restore function after peripheral nerve injury. Here, we present a case report of a child with permanent right upper extremity weakness due to TM that underwent nerve transfers. The following procedures were performed: double fascicle transfer from median nerve and ulnar nerve to the brachialis and biceps branches of the musculocutaneous nerve, spinal accessory to suprascapular nerve, and medial cord to axillary nerve end-to-side neurorraphy. At 22 months, the patient demonstrated excellent recovery of elbow flexion with minimal improvement in shoulder abduction. We propose that the treatment of permanent deficits from TM represents a novel indication for nerve transfers in a subset of patients. Copyright © 2011 Wiley Periodicals, Inc.

Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies.

PubMed

Arnold, Ria; Kwai, Natalie C G; Krishnan, Arun V

2013-11-01

The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Raman spectroscopy of non-penetrating peripheral nerve damage in swine: a tool for spectral pathology of nerves

NASA Astrophysics Data System (ADS)

Cilwa, Katherine E.; Slaughter, Tiffani; Elster, Eric A.; Forsberg, Jonathan A.; Crane, Nicole J.

2015-03-01

Over 30% of combat injuries involve peripheral nerve injury compared to only 3% in civilian trauma. In fact, nerve dysfunction is the second leading cause of long-term disability in injured service members and is present in 37% of upper limb injuries with disability. Identification and assessment of non-penetrating nerve injury in trauma patients could improve outcome and aid in therapeutic monitoring. We report the use of Raman spectroscopy as a noninvasive, non-destructive method for detection of nerve degeneration in intact nerves due to non-penetrating trauma. Nerve trauma was induced via compression and ischemia/reperfusion injury using a combat relevant swine tourniquet model (>3 hours ischemia). Control animals did not undergo compression/ischemia. Seven days post-operatively, sciatic and femoral nerves were harvested and fixed in formalin. Raman spectra of intact, peripheral nerves were collected using a fiber-optic probe with 3 mm diameter spot size and 785 nm excitation. Data was preprocessed, including fluorescence background subtraction, and Raman spectroscopic metrics were determined using custom peak fitting MATLAB scripts. The abilities of bivariate and multivariate analysis methods to predict tissue state based on Raman spectroscopic metrics are compared. Injured nerves exhibited changes in Raman metrics indicative of 45% decreased myelin content and structural damage (p<<0.01). Axonal and myelin degeneration, cell death and digestion, and inflammation of nerve tissue samples were confirmed via histology. This study demonstrates the non-invasive ability of Raman spectroscopy to detect nerve degeneration associated with non-penetrating injury, relevant to neurapraxic and axonotmetic injuries; future experiments will further explore the clinical utility of Raman spectroscopy to recognize neural injury.

Relevance of nerve conduction velocity in the assessment of balance performance in older adults with diabetes mellitus.

PubMed

Wang, Ting-Yun; Chen, Shih-Ching; Peng, Chih-Wei; Kang, Chun-Wei; Chen, Yu-Luen; Chen, Chun-Lung; Chou, Yi-Lin; Lai, Chien-Hung

2017-03-01

Purpose This study investigated the relationship between peripheral nerve conduction velocity (NCV) and balance performance in older adults with diabetes. Methods Twenty older adults with diabetes were recruited to evaluate the NCV of their lower limbs and balance performance. The balance assessments comprised the timed up and go (TUG) test, Berg balance scale (BBS), unipedal stance test (UST), multidirectional reach test (MDRT), maximum step length (MSL) test and quiet standing with eyes open and closed. The relationship between NCV and balance performance was evaluated by Pearson's correlation coefficients, and the balance performances of the diabetic patients with and without peripheral neuropathy were compared by using Mann-Whitney U tests. Results The NCV in the lower limbs exhibited a moderate to strong correlation with most of the balance tests including the TUG (r = -0.435 to -0.520, p < 0.05), BBS (r = 0.406-0.554, p < 0.05), UST (r = 0.409-0.647, p < 0.05) and MSL (r = 0.399-0.585, P < 0.05). In addition, patients with diabetic peripheral neuropathy had a poorer TUG (p < 0.05), BBS (p < 0.01), UST (p < 0.05) and MSL performance (p < 0.05) compared with those without peripheral neuropathy (p < 0.05). Conclusion Our findings revealed that a decline in peripheral nerve conduction in the lower limb is not only an indication of nerve dysfunction, but may also be related to the impairment of balance performance in patients with diabetes. Implications for Rehabilitation Nerve conduction velocity in the lower limbs of diabetic older adults showed moderate to strong correlations with most of the results of balance tests, which are commonly used in clinics. Decline in nerve conduction velocity of the lower limbs may be related to the impairment of balance control in patients with diabetes. Diabetic older adults with peripheral neuropathy exhibited greater postural instability than those without peripheral neuropathy.

Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

PubMed

Vucic, Steve; Kiernan, Matthew C

2008-03-01

Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

Neurologic complications in common wrist and hand surgical procedures

PubMed Central

Verdecchia, Nicole; Johnson, Julie; Baratz, Mark; Orebaugh, Steven

2018-01-01

Nerve dysfunction after upper extremity orthopedic surgery is a recognized complication, and may result from a variety of different causes. Hand and wrist surgery require incisions and retraction that necessarily border on small peripheral nerves, which may be difficult to identify and protect with absolute certainty. This article reviews the rates and ranges of reported nerve dysfunction with respect to common surgical interventions for the distal upper extremity, including wrist arthroplasty, wrist arthrodesis, wrist arthroscopy, distal radius open reduction and internal fixation, carpal tunnel release, and thumb carpometacarpal surgery. A relatively large range of neurologic complications is reported, however many of the studies cited involve relatively small numbers of patients, and only rarely are neurologic complications included as primary outcome measures. Knowledge of these neurologic outcomes should help the surgeon to better counsel patients with regard to perioperative risk, as well as provide insight into workup and management of any adverse neurologic outcomes that may arise.

Peripheral neuropathy: an often-overlooked cause of falls in the elderly.

PubMed

Richardson, J K; Ashton-Miller, J A

1996-06-01

Peripheral neuropathy is common in the elderly and results in impairments in distal proprioception and strength that hinder balance and predispose them to falls. The loss of heel reflexes, decreased vibratory sense that improves proximally, impaired position sense at the great toe, and inability to maintain unipedal stance for 10 seconds in three attempts all suggest functionally significant peripheral neuropathy. Physicians can help their patients with peripheral neuropathy to prevent falls by teaching them and their families about peripheral nerve dysfunction and its effects on balance and by advising patients to substitute vision for the lost somatosensory function, correctly use a cane, wear proper shoes and orthotics, and perform balance and upper extremity strengthening exercises.

The Association Between the Levels of Thyroid Hormones and Peripheral Nerve Conduction in Patients with Type 2 Diabetes Mellitus.

PubMed

Zhu, Fan-Fan; Yang, Li-Zhen

2018-06-26

Type 2 diabetes has an underlying pathology with thyroid dysfunction. However, few studies have investigated the association between thyroid hormones and diabetic peripheral neuropathy. Our aim was to evaluate the relationship between thyroid hormones and electrophysiological properties of peripheral nerves in type 2 diabetes. The medical records of 308 patients with type 2 diabetes were enrolled in this study. Subjects stratified by sex were divided into subgroups based on the diagnosis of nerve conduction study. The nerve conduction parameters were separately described with the spectrum of thyroid hormones. Multivariate regression models to analyze the potential links between thyroid hormones and nerve conduction parameters. The serum free triiodine thyronine levels between normal and abnormal nerve conduction groups were statistically different in total (4.55±0.65 vs 4.37±0.63, P<0.05) and female diabetic patients (4.46±0.50 vs 4.14±0.57, P<0.01). Moreover, the summed amplitude and velocity Z score of female and male increased with free triiodine thyronine levels (P<0.05). Sex-specific binary logistic regression models showed that free triiodine thyronine levels were associated with decreased odds of abnormal nerve conduction diagnosis (odds ratio [95%CI]=0.151[0.047-0.186]) and low tertile of summed amplitude Z score (odds ratio [95%CI]=0.283[0.099-0.809]) in female. In total patients, free triiodine thyronine level was negatively associated with odds of abnormal nerve conduction (odds ratio [95%CI]=0.436 [0.226-0.842]), low tertile of summed velocity (odds ratio [95%CI]=0.44[0.226-0.858]) and amplitude (odds ratio [95%CI]=0.436[0.227-0.838) Z score. Serum free triiodine thyronine level is associated with nerve conduction in diabetes. Low free triiodine thyronine may be a potential risk for diabetic peripheral neuropathy. © Georg Thieme Verlag KG Stuttgart · New York.

Peripheral nervous system neuroimmunology seen by a neuro-pathologist.

PubMed

Vallat, J-M

2014-10-01

In most dysimmune neuropathies, historically the microscopical lesions were described prior to immunological studies. The latter along with neuropathological studies have found some immune, albeit incomplete, explanations of the mechanisms of these lesions which we will describe in two main syndromes: the primitive auto-immune inflammatory peripheral polyneuropathies (GBS and CIDP) and polyneuropathies induced by a monoclonal dysglobulinemia. In some patients who have to be discussed case by case pathology (nerve biopsy) will confirm the diagnosis, may help to delineate the molecular anomalies and identify lesional mechanisms. We will review the high variability of nerve lesions which is characteristic of dysimmune neuropathies. Pathological studies confirm that both humoral and cellular immune reactions against Schwann cell and/or axonal antigens are implicated in primitive dysimmune neuropathies due to a dysfunction or failure of immune tolerance mechanisms. In case of a polyneuropathy associated to a monoclonal dysglobulinemia, pathological and immunological studies have shown that in many patients, the dysglobulinemia did harm the peripheral nerve; knowledge of the pathological lesions and their mechanisms is of major interest for orienting specific treatments. Copyright © 2014. Published by Elsevier Masson SAS.

Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

PubMed Central

2011-01-01

Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate. PMID:21619592

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.

PubMed

Hinder, Lucy M; Park, Meeyoung; Rumora, Amy E; Hur, Junguk; Eichinger, Felix; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

2017-09-01

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Sympathetically maintained pain presenting first as temporomandibular disorder, then as parotid dysfunction.

PubMed

Giri, Subha; Nixdorf, Donald

2007-08-01

Complex regional pain syndrome (CRPS) is a chronic condition that usually affects extremities, such as the arms or legs. It is characterized by intense pain, swelling, redness, hypersensitivity in a region not defined by a single peripheral nerve and additional sudomotor effects, such as excessive sweating. The clinical criteria for the diagnosis of sympathetically maintained pain as outlined by the International Association for the Study of Pain include: Onset following an initiating noxious event (CRPS-type I) or nerve injury (CRPS-type II). Spontaneous allodynia that is not limited to peripheral nerve distribution and is not proportionate to the inciting event; abnormal sudomotor activity, skin blood flow abnormality, edema, other autonomic symptoms; and exclusion of other conditions that may otherwise contribute to the extent of the symptoms. Only 13 cases of CRPS involving sympathetically maintained pain in the head and neck region have been described, and all reported trauma as the identifiable etiologic factor. The case presented here is another occurrence of sympathetically maintained pain in the head and neck region, but without nerve injury as a clear initiating factor.

Sacral neuromodulation for women with Fowler's syndrome.

PubMed

Swinn, M J; Kitchen, N D; Goodwin, R J; Fowler, C J

2000-10-01

Neuromodulation of the sacral nerves has been found to be an effective therapy for a variety of lower urinary tract dysfunctions. The reported success rate for the period of trial stimulation (peripheral nerve evaluation test) prior to permanent implantation of a sacral nerve stimulator is variable, but generally reported to be in the region of 30-50%. We present here the results of the peripheral nerve evaluation test in 38 patients with urinary retention. 34 of the 38 had been found to have an abnormality of their striated urethral sphincter on electromyography using a concentric needle electrode, i.e., they had the disorder which was described by Fowler and coworkers in 1988. The overall success rate in this group was 68%. We believe that our relatively high success rate is due to sacral neuromodulation working via a mechanism which involves the urethral sphincter, an abnormality which had been demonstrated in 89% of these patients. Twelve of the patients subsequently underwent permanent implantation of a sacral nerve stimulator, and all of them have experienced a return of voiding. However, in 2 patients, there is a persisting need for self-catheterization. There is, however, a high reoperation rate.

Electroneurographic findings in patients with solvent induced central nervous system dysfunction.

PubMed Central

Orbaek, P; Rosén, I; Svensson, K

1988-01-01

The function of the peripheral nervous system was examined in a group of 32 men aged 30-65 (mean 49) with diagnosed solvent induced chronic toxic encephalopathy. The subjects were examined at the time of diagnosis and 26 were re-examined after a follow up period of 22-72 months (mean 40) and compared with a group of 50 unexposed male workers aged 27-64 (mean 42) with appropriate adjustment for age. All subjects were carefully scrutinised for alcohol abuse and other neurological diseases. The results of motor fibre neurography disclosed no difference between the groups. Nevertheless, a significant decrease in motor conduction velocity was found in the patients at follow up. Sensory fibre neurography showed signs of slight axonal degeneration with significantly decreased sensory nerve action potential amplitudes in the median and sural nerves; these amplitudes increased during follow up. The duration of sensory nerve action potentials was longer in the exposed group for the median and the sural nerves. The percentage of late components was significantly higher in the median nerve. The warm-cold sensitivity in the exposed group also indicated a slight sensory dysfunction with statistically significant wider detection limits. PMID:2840109

Peripheral Nerve Injury Leads to Working Memory Deficits and Dysfunction of the Hippocampus by Upregulation of TNF-α in Rodents

PubMed Central

Ren, Wen-Jie; Liu, Yong; Zhou, Li-Jun; Li, Wei; Zhong, Yi; Pang, Rui-Ping; Xin, Wen-Jun; Wei, Xu-Hong; Wang, Jun; Zhu, He-Quan; Wu, Chang-You; Qin, Zhi-Hai; Liu, Guosong; Liu, Xian-Guo

2011-01-01

Patients with chronic pain usually suffer from working memory deficits, which may decrease their intellectual ability significantly. Despite intensive clinical studies, the mechanism underlying this form of memory impairment remains elusive. In this study, we investigated this issue in the spared nerve injury (SNI) model of neuropathic pain, a most common form of chronic pain. We found that SNI impaired working memory and short-term memory in rats and mice. To explore the potential mechanisms, we studied synaptic transmission/plasticity in hippocampus, a brain region critically involved in memory function. We found that frequency facilitation, a presynaptic form of short-term plasticity, and long-term potentiation at CA3–CA1 synapses were impaired after SNI. Structurally, density of presynaptic boutons in hippocampal CA1 synapses was reduced significantly. At the molecular level, we found that tumor necrosis factor-α (TNF-α) increased in cerebrospinal fluid, in hippocampal tissue and in plasma after SNI. Intracerebroventricular or intrahippocampal injection of recombinant rat TNF mimicked the effects of SNI in naive rats, whereas inhibition of TNF-α or genetic deletion of TNF receptor 1 prevented both memory deficits and synaptic dysfunction induced by SNI. As TNF-α is critical for development of neuropathic pain, we suggested that the over-production of TNF-α following peripheral nerve injury might lead to neuropathic pain and memory deficits, simultaneously. PMID:21289602

Peripheral neuropathy in the twitcher mouse: accumulation of extracellular matrix in the endoneurium and aberrant expression of ion channels.

PubMed

Kagitani-Shimono, Kuriko; Mohri, Ikuko; Yagi, Takashi; Taniike, Masako; Suzuki, Kinuko

2008-05-01

Globoid cell leukodystrophy (GLD; Krabbe's disease), caused by a genetic galactosylceramidase deficiency, affects both the central and peripheral nervous systems (CNS and PNS). Allogenic hematopoietic stem-cell transplantation (HSCT) has been beneficial for clinical improvement of this disease. However, recent reports by Siddiqi et al. suggested that none of their transplanted patients achieved complete normalization of their peripheral nerve function, despite the well-documented remyelination of the CNS and PNS in the treated patients. We hypothesized that the PNS dysfunction in GLD is due to altered Schwann cell-axon interactions, resulting in structural abnormalities of the node of Ranvier and aberrant expression of ion channels caused by demyelination and that the persistence of this altered interaction is responsible for the dysfunction of the PNS after HSCT. Since there has not been any investigation of the Schwann cell-axonal relationship in twitcher mice, an authentic model of GLD, we first investigated structural abnormalities, focusing on the node of Ranvier in untreated twitcher mice, and compared the results with those obtained after receiving bone marrow transplantation (BMT). As expected, we found numerous supernumerary Schwann cells that formed structurally abnormal nodes of Ranvier. Similar findings, though at somewhat variable extent, were detected in mice treated with BMT. Activated supernumerary Schwann cells expressed GFAP immunoreactivity and generated Alcian blue-positive extracellular matrix (ECM) in the endoneurial space. The processes of these supernumerary Schwann cells often covered and obliterated the nodal regions. Furthermore, the distribution of Na(+) channel immunoreactivity was diffuse without the concentration at the nodes of Ranvier as seen in wild-type mice. Neither K(+) channels nor Neurexin IV/ Caspr/ Paranoidin (NCP-1) were detected in the twi/twi sciatic nerve. The results of our study suggest the importance of normalization of the Schwann cell-axon relationship for the functional recovery of peripheral nerves, when one considers therapeutic strategies for PNS pathology in GLD.

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

NASA Astrophysics Data System (ADS)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction.

PubMed

Dimova, Rumyana; Tankova, Tsvetalina; Chakarova, Nevena

2017-09-01

Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Accumulating data indicate the presence of peripheral nerve injury at these early stages of dysglycemia and its multifactorial pathogenesis. Prediabetes is associated with vitamin D insufficiency. Vitamin D is proposed to prevent the progression of glucose intolerance. The putative underlying mechanisms include maintenance of the intracellular calcium concentration, direct stimulation of insulin receptor expression, and enhancement of the insulin response to glucose transporters. Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the demyelination process and inducing axonal regeneration. The effects of vitamin D supplementation on glucose tolerance and related autonomic nerve dysfunction have been a recent focus of scientific interest. Although well-designed observational studies are available, the causative relation between vitamin D deficiency, glucose intolerance, and CAN is still debatable. One reason might be that interventional studies are unpersuasive with regard to the beneficial clinical effects of vitamin D supplementation. Because of its favorable side effect profile, vitamin D supplementation might represent an attractive therapeutic option for treating the pandemic prevalence of prediabetes and vitamin D deficiency. Vitamin D supplementation can improve glucose tolerance and cardiovascular autonomic function and can thus reduce cardiovascular mortality among subjects with different stages of glucose intolerance and autonomic dysfunction. However, more patient-centered trials on the use of vitamin D supplementation in different conditions are needed. © 2017 American Society for Nutrition.

Bell's Palsy as a Possible Complication of Hepatitis B Vaccination in A Child

PubMed Central

Tan, Hüseyin; Orbak, Zerrin

2009-01-01

Bell's Palsy is the sudden onset of unilateral temporary paralysis of facial muscles resulting from seventh cranial nerve dysfunction. Presented here is a two-year old female patient with right peripheral facial palsy following hepatitis B vaccination. Readers’ attention is drawn to an uncommon cause of Bell's Palsy, as a rare complication of hepatitis B vaccination. PMID:19902808

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

PubMed Central

Smith, Darrell R.; Frizzi, Katie; Sabbir, Mohammad Golam; Chowdhury, Subir K. Roy; Mixcoatl-Zecuatl, Teresa; Saleh, Ali; Muttalib, Nabeel; Van der Ploeg, Randy; Ochoa, Joseline; Gopaul, Allison; Tessler, Lori; Wess, Jürgen; Jolivalt, Corinne G.

2017-01-01

Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor–dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity. M1R-deficient mice made diabetic with streptozotocin were protected from physiological and structural indices of sensory neuropathy. Pharmacological blockade of M1R using specific or selective antagonists, pirenzepine, VU0255035, or muscarinic toxin 7 (MT7) activated AMPK and overcame diabetes-induced mitochondrial dysfunction in vitro and in vivo. These antimuscarinic drugs prevented or reversed indices of peripheral neuropathy, such as depletion of sensory nerve terminals, thermal hypoalgesia, and nerve conduction slowing in diverse rodent models of diabetes. Pirenzepine and MT7 also prevented peripheral neuropathy induced by the chemotherapeutic agents dichloroacetate and paclitaxel or HIV envelope protein gp120. As a variety of antimuscarinic drugs are approved for clinical use against other conditions, prompt translation of this therapeutic approach to clinical trials is feasible. PMID:28094765

[Importance of electromiographic examination in diagnostification and monitoring of chronic inflammatory demyelinating polyneuropathy].

PubMed

Damjan, Igor; Cvijanović, Milan; Erak, Marko

2010-01-01

Polyneuropathies or peripheral neuropathies present a dysfunction or disease of larger number of peripheral nerves or their dysfunction. Considering their morbidity - mortality characteristics they present an important aspect in daily clinical practice. One particular polyneuropathy that deserves special review is chronic inflammatory demyelinating polyneuropathy, which, due to its clinical-laboratory presentation, does not include the group of "simple" neuropathies, thus requiring further examinations. Neurophysiological testing should be performed using the protocol for neuropathy examinations. Neurophysiological examination, during the electroneurographic examination, shows neurographic parameters referring to polyneuropatic demyelinating type of lesion, while the electromyographic finding records the presence of neuropathic lesions (denervation activity, great action potentials with a reduced sample). A 54-year-old patient was diagnosed to have a "complicated" demyelinating polyneuropathy according to the clinical-laboratory findings and electromyographic examination. Exclusion criteria, targeted diagnostic examinations, considering the mentioned peripheral neuropathies, pointed to acute inflammatory demyelinating polyneuropathy. However, the chronic inflammatory demyelinating polyneuropathy was finally differentiated during the clinical and electromyographic monitoring.

Diabetes, peripheral neuropathy, and lower-extremity function.

PubMed

Chiles, Nancy S; Phillips, Caroline L; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M; Patel, Kushang V

2014-01-01

Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β=-0.99; p<0.01), decreased walking speed (β=-0.1m/s; p<0.01), decreased nerve conduction velocity (β=-1.7m/s; p<0.01), and increased neuropathy (β=0.25; p<0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. © 2014.

Diabetes, Peripheral Neuropathy, and Lower Extremity Function

PubMed Central

Chiles, Nancy S.; Phillips, Caroline L.; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M.; Patel, Kushang V.

2014-01-01

Objective Diabetes among older adults causes many complications, including decreased lower extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. Research Design and Methods This study included 983 participants, age 65 and older from the InCHIANTI Study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0-12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cut-points of PNF tests were used to create a neuropathy score from 0-5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. Results and Conclusion 12.8% (n=126) of participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β= −0.99; p< 0.01), decreased walking speed (β= −0.1m/s; p< 0.01), decreased nerve conduction velocity (β= −1.7m/s; p< 0.01), and increased neuropathy (β= 0.25; p< 0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. PMID:24120281

Peripheral neuropathy as a complication of diabetic ketoacidosis in a child with newly diagnosed diabetes type 1 - case report.

PubMed

Baszyńska-Wilk, Marta; Wysocka-Mincewicz, Marta; Świercz, Anna; Świderska, Jolanta; Marszał, Magdalena; Szalecki, Mieczysław

2017-12-08

Neurological complications of diabetic ketoacidosis are considered to be very serious clinical problem. The most common complication is cerebral edema. However this group includes also less common syndromes such as ischemic or hemorrhagic stroke, cerebral venous and sinus thrombosis or very rare peripheral neuropathy. We present a case of 9-year old girl with new onset type 1 diabetes, diabetic ketoacidosis, cerebral edema, multifocal vasogenic brain lesions and lower limbs peripheral paresis. The patient developed polydipsia and polyuria one week before admission to the hospital. In laboratory tests initial blood glucose level 1136 mg/dl and acidosis (pH 7.1; BE-25.9) were noted. She was admitted to the hospital in a critical condition and required treatment in intensive care unit. Computed tomography scan showed brain edema and hipodense lesion in the left temporal region. Brain MRI revealed more advanced multifocal brain lesions Nerve conduction studies demonstrated damage of the motor neuron in both lower extremities with dysfunction in both peroneal nerves and the right tibial nerve. As a result of diabetological, neurological treatment and physiotherapy patient's health state gradually improved. Acute neuropathy after ketoacidosis is rare complication and its pathomechanism is not clear. Patients with DKA require careful monitoring of neurological functions even after normalization of glycemic parameters.

21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted peripheral nerve stimulator for pain....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral nerve...

Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice.

PubMed

Anderson, Nicholas J; King, Matthew R; Delbruck, Lina; Jolivalt, Corinne G

2014-06-01

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype. © 2014. Published by The Company of Biologists Ltd.

Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

PubMed

Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B

2017-10-01

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ultrasound-Guided Treatment of Peripheral Nerve Pathology.

PubMed

Dettori, Nathan; Choudur, Hema; Chhabra, Avneesh

2018-07-01

High-resolution ultrasound serves as a fast, accessible, reliable, and radiation-free tool for anatomical and dynamic evaluation of various peripheral nerves. It can be used not only to identify and diagnose peripheral nerve and perineural pathology accurately but also to guide various nerve and perineural interventions. We describe the normal and pathologic appearances of peripheral nerves, the pathologies commonly affecting the individual peripheral nerves, and the current ultrasound-guided peripheral nerve interventions and techniques. Future directions are also highlighted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia

PubMed Central

Peh, Wendy Yen Xian; Mogan, Roshini; Thow, Xin Yuan; Chua, Soo Min; Rusly, Astrid; Thakor, Nitish V.; Yen, Shih-Cheng

2018-01-01

The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential peripheral targets for stimulation to treat dysfunctional bladders, but typical electrical stimulation of pelvic nerves activates both the parasympathetic efferent pathway to excite the bladder, as well as the sensory afferent pathway that causes unwanted sphincter contractions. Thus, a novel pelvic nerve stimulation paradigm is required. In anesthetized female rats, we combined a low frequency (10 Hz) stimulation to evoke bladder contraction, and a more proximal 20 kHz stimulation of the pelvic nerve to block afferent activation, in order to produce micturition with reduced bladder-sphincter dyssynergia. Increasing the phase width of low frequency stimulation from 150 to 300 μs alone was able to improve voiding outcome significantly. However, low frequency stimulation of pelvic nerves alone evoked short latency (19.9–20.5 ms) dyssynergic EUS responses, which were abolished with a non-reversible proximal central pelvic nerve cut. We demonstrated that a proximal 20 kHz stimulation of pelvic nerves generated brief onset effects at lower current amplitudes, and was able to either partially or fully block the short latency EUS responses depending on the ratio of the blocking to stimulation current. Our results indicate that ratios >10 increased the efficacy of blocking EUS contractions. Importantly, we also demonstrated for the first time that this combined low and high frequency stimulation approach produced graded control of the bladder, while reversibly blocking afferent signals that elicited dyssynergic EUS contractions, thus improving voiding by 40.5 ± 12.3%. Our findings support advancing pelvic nerves as a suitable neuromodulation target for treating bladder dysfunction, and demonstrate the feasibility of an alternative method to non-reversible nerve transection and sub-optimal intermittent stimulation methods to reduce dyssynergia. PMID:29618971

Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

PubMed

Telleman, Johan A; Stellingwerff, Menno D; Brekelmans, Geert J; Visser, Leo H

2018-02-01

Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018. © 2017 Wiley Periodicals, Inc.

Study of Autophagy and Microangiopathy in Sural Nerves of Patients with Chronic Idiopathic Axonal Polyneuropathy

PubMed Central

Samuelsson, Kristin; Osman, Ayman A. M.; Angeria, Maria; Risling, Mårten; Mohseni, Simin; Press, Rayomand

2016-01-01

Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy. PMID:27662650

Pyridostigmine prevents peripheral vascular endothelial dysfunction in rats with myocardial infarction.

PubMed

Qin, Fangfang; Lu, Yi; He, Xi; Zhao, Ming; Bi, Xueyuan; Yu, Xiaojiang; Liu, Jinjun; Zang, Weijin

2014-03-01

1. Myocardial infarction (MI) is characterized by the withdrawal of vagal activity and increased sympathetic activity. We have shown previously that pyridostigmine (PYR), an acetylcholinesterase inhibitor, was able to improve vagal activity and ameliorate cardiac dysfunction following MI. However, the effect of PYR on endothelial dysfunction in peripheral arteries after MI remains unclear. 2. In the present study, MI was induced by coronary artery ligation in adult Sprague-Dawley rats. Rats were treated intragastrically with saline or PYR (approximately 31 mg/kg per day) for 2 weeks, at which time haemodynamic and parasympathetic parameters and the vascular reactivity of isolated mesenteric arteries were measured and the ultrastructure of the endothelium evaluated. 3. Compared with the MI group, PYR not only improved cardiac function, vagal nerve activity and endothelial impairment, but also reduced intravascular superoxide anion and malondialdehyde. In addition, in the PYR-treated MI group, nitric oxide (NO) bioavailability was increased and attenuated endothelium-dependent relaxations were improved, whereas restored vasodilator responses were inhibited by N(G)-nitro-L-arginine methyl ester. 4. Based on our results, PYR is able to attenuate the impairment of peripheral endothelial function and maintain endothelial ultrastructural integrity in MI rats by inhibiting reactive oxygen species production, enhancing NO bioavailability and improving vagal activity. © 2014 Wiley Publishing Asia Pty Ltd.

Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb.

PubMed

Kowalska, Berta; Sudoł-Szopińska, Iwona

2012-06-01

The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the "elevator technique". All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the "Journal of Ultrasonography".

Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb

PubMed Central

Sudoł-Szopińska, Iwona

2012-01-01

The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the “elevator technique”. All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the “Journal of Ultrasonography”. PMID:26674560

Nerve compression injuries due to traumatic false aneurysm.

PubMed Central

Robbs, J V; Naidoo, K S

1984-01-01

Experience with 17 patients with delayed onset of compression neuropraxia due to hemorrhage following nonoperative treatment of penetrating arterial injuries is presented. Fifteen cases involved the arteries of the neck shoulder girdle and upper extremity and two the gluteal vessels. This resulted in dysfunction of components of the brachial plexus, median ulnar, and sciatic nerves. Follow-up extended from 3 to 18 months. Of 10 brachial plexus lesions two recovered fully, five partially, and three not at all. Of seven peripheral nerve injuries, full recovery occurred in two patients and none in five. Adverse prognostic factors for neurological recovery are sepsis, involvement of intrinsic hand innervation and the sciatic nerve. An improved prognosis may be expected for upper trunk lesions of the brachial plexus and radial nerve lesions. The complication is essentially avoidable and a careful appraisal of the circulatory status must be made in all patients with penetrating trauma in the neck and shoulder girdle and buttock. PMID:6732331

Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

PubMed

Krajnak, Kristine; Miller, G R; Waugh, Stacey

2018-01-01

Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

Intraoperative Ultrasound for Peripheral Nerve Applications.

PubMed

Willsey, Matthew; Wilson, Thomas J; Henning, Phillip Troy; Yang, Lynda J-S

2017-10-01

Offering real-time, high-resolution images via intraoperative ultrasound is advantageous for a variety of peripheral nerve applications. To highlight the advantages of ultrasound, its extraoperative uses are reviewed. The current intraoperative uses, including nerve localization, real-time evaluation of peripheral nerve tumors, and implantation of leads for peripheral nerve stimulation, are reviewed. Although intraoperative peripheral nerve localization has been performed previously using guide wires and surgical dyes, the authors' approach using ultrasound-guided instrument clamps helps guide surgical dissection to the target nerve, which could lead to more timely operations and shorter incisions. Copyright © 2017 Elsevier Inc. All rights reserved.

21 CFR 868.2775 - Electrical peripheral nerve stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve stimulator. (a) Identification. An electrical peripheral nerve stimulator (neuromuscular blockade monitor) is...

21 CFR 868.2775 - Electrical peripheral nerve stimulator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve stimulator. (a) Identification. An electrical peripheral nerve stimulator (neuromuscular blockade monitor) is...

21 CFR 868.2775 - Electrical peripheral nerve stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve stimulator. (a) Identification. An electrical peripheral nerve stimulator (neuromuscular blockade monitor) is...

Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

PubMed

Puhakka, A; Forssell, H; Soinila, S; Virtanen, A; Röyttä, M; Laine, M; Tenovuo, O; Teerijoki-Oksa, T; Jääskeläinen, S K

2016-05-01

The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Extraneural findings during peripheral nerve ultrasound: Prevalence and further assessment.

PubMed

Bignotti, Bianca; Zaottini, Federico; Airaldi, Sonia; Martinoli, Carlo; Tagliafico, Alberto

2018-01-01

In this study we evaluated the frequency and further assessment of extraneural findings encountered during peripheral nerve ultrasound (US). Our retrospective review identified 278 peripheral nerve US examinations of 229 patients performed between December 2014 and December 2015. Reports were reviewed to assess the number of studies without peripheral nerve abnormalities and the frequency and further assessment of extraneural findings. A total of 107 peripheral nerve US examinations of 90 patients (49 men and 41 women, mean age 55 ± 16 years) did not report peripheral nerve abnormalities. Extraneural findings were observed in 24 of 107 (22.4%) studies. Fifteen of the 278 [5.4% (95% confidence interval 2.7%-8.1%)] studies led to a recommendation for additional imaging or clinical evaluation of an extraneural finding. At least 5.4% (15 of 278) of peripheral nerve US studies led to additional clinical or imaging assessment. Muscle Nerve 57: 65-69, 2018. © 2017 Wiley Periodicals, Inc.

Hyposensitivity of C-fiber Afferents at the Distal Extremities as an Indicator of Early Stages Diabetic Bladder Dysfunction in Type 2 Diabetic Women

PubMed Central

Lee, Wei-Chia; Wu, Han-Ching; Huang, Kuo-How; Wu, Huey-Peir; Yu, Hong-Jeng; Wu, Chia-Ching

2014-01-01

Purpose To investigate the relationship between distal symmetric peripheral neuropathy and early stages of autonomic bladder dysfunction in type 2 diabetic women. Materials and Methods A total of 137 diabetic women with minimal coexisting confounders of voiding dysfunction followed at a diabetes clinic were subject to the following evaluations: current perception threshold (CPT) tests on myelinated and unmyelinated nerves at the big toe for peroneal nerve and middle finger for median nerve, uroflowmetry, post-void residual urine volume, and overactive bladder (OAB) symptom score questionnaire. Patients presenting with voiding difficulty also underwent urodynamic studies and intravesical CPT tests. Results Based on the OAB symptom score and urodynamic studies, 19% of diabetic women had the OAB syndrome while 24.8% had unrecognized urodynamic bladder dysfunction (UBD). The OAB group had a significantly greater mean 5 Hz CPT test value at the big toe by comparison to those without OAB. When compared to diabetic women without UBD, those with UBD showed greater mean 5 Hz CPT test values at the middle finger and big toe. The diabetic women categorized as C-fiber hyposensitivity at the middle finger or big toe by using CPT test also had higher odds ratios of UBD. Among diabetic women with UBD, the 5 Hz CPT test values at the big toe and middle finger were significantly associated with intravesical 5 Hz CPT test values. Conclusions Using electrophysiological evidence, our study revealed that hyposensitivity of unmyelinated C fiber afferents at the distal extremities is an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women. The C fiber dysfunction at the distal extremities seems concurrent with vesical C-fiber neuropathy and may be a sentinel for developing early diabetic bladder dysfunction among female patients. PMID:24466107

Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system functions after developmental exposure to ethanol vapors.

PubMed

Boyes, William K; Degn, Laura L; Martin, Sheppard A; Lyke, Danielle F; Hamm, Charles W; Herr, David W

2014-01-01

Ethanol-blended gasoline entered the market in response to demand for domestic renewable energy sources, and may result in increased inhalation of ethanol vapors in combination with other volatile gasoline constituents. It is important to understand potential risks of inhalation of ethanol vapors by themselves, and also as a baseline for evaluating the risks of ethanol combined with a complex mixture of hydrocarbon vapors. Because sensory dysfunction has been reported after developmental exposure to ethanol, we evaluated the effects of developmental exposure to ethanol vapors on neurophysiological measures of sensory function as a component of a larger project evaluating developmental ethanol toxicity. Pregnant Long-Evans rats were exposed to target concentrations 0, 5000, 10,000, or 21,000 ppm ethanol vapors for 6.5h/day over GD9-GD20. Sensory evaluations of male offspring began between PND106 and PND128. Peripheral nerve function (compound action potentials, nerve conduction velocity (NCV)), somatosensory (cortical and cerebellar evoked potentials), auditory (brainstem auditory evoked responses), and visual evoked responses were assessed. Visual function assessment included pattern elicited visual evoked potentials (VEPs), VEP contrast sensitivity, and electroretinograms recorded from dark-adapted (scotopic), light-adapted (photopic) flashes, and UV flicker and green flicker. No consistent concentration-related changes were observed for any of the physiological measures. The results show that gestational exposure to ethanol vapor did not result in detectable changes in peripheral nerve, somatosensory, auditory, or visual function when the offspring were assessed as adults. Published by Elsevier Inc.

[Regeneration and repair of peripheral nerves: clinical implications in facial paralysis surgery].

PubMed

Hontanilla, B; Vidal, A

2000-01-01

Peripheral nerve lesions are one of the most frequent causes of chronic incapacity. Upper or lower limb palsies due to brachial or lumbar plexus injuries, facial paralysis and nerve lesions caused by systemic diseases are one of the major goals of plastic and reconstructive surgery. However, the poor results obtained in repaired peripheral nerves during the Second World War lead to a pessimist vision of peripheral nerve repair. Nevertheless, a well understanding of microsurgical principles in reconstruction and molecular biology of nerve regeneration have improved the clinical results. Thus, although the results obtained are quite far from perfect, these procedures give to patients a hope in the recuperation of their lesions and then on function. Technical aspects in nerve repair are well established; the next step is to manipulate the biology. In this article we will comment the biological processes which appear in peripheral nerve regeneration, we will establish the main concepts on peripheral nerve repair applied in facial paralysis cases and, finally, we will proportionate some ideas about how clinical practice could be affected by manipulation of the peripheral nerve biology.

Recovery of Peripheral Nerve with Massive Loss Defect by Tissue Engineered Guiding Regenerative Gel

PubMed Central

Nevo, Zvi

2014-01-01

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated. Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect. The proposed technology is a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats. Preclinical study on rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment. PMID:25105121

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection

PubMed Central

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration. PMID:29085283

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.

PubMed

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration.

Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

2018-02-01

Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.

PubMed

Chan, Isaac; Brown, Anthony R; Park, Kenneth; Winfree, Christopher J

2010-09-01

Peripheral nerve stimulation is a form of neuromodulation that applies electric current to peripheral nerves to induce stimulation paresthesias within the painful areas. To report a method of ultrasound-guided, percutaneous peripheral nerve stimulation. This technique utilizes real-time imaging to avoid injury to adjacent vascular structures during minimally invasive placement of peripheral nerve stimulator electrodes. We describe a patient that presented with chronic, bilateral foot pain following multiple foot surgeries, for whom a comprehensive, pain management treatment strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve stimulation at a thigh level to provide durable pain relief on the right side, and open peripheral nerve stimulation on the left. The patient experienced appropriate stimulation paresthesias and excellent pain relief on the plantar aspect of the right foot with the percutaneous electrode. On the left side, we were unable to direct the stimulation paresthesias to the sole of the foot, despite multiple electrode repositionings. A subsequent, open placement of a left tibial nerve stimulator was performed. This revealed that the correct electrode position against the tibial nerve was immediately adjacent to the popliteal artery, and was thus not appropriate for percutaneous placement. We describe a method of ultrasound-guided peripheral nerve stimulation that avoids the invasiveness of electrode placement via an open procedure while providing excellent pain relief. We further describe limitations of the percutaneous approach when navigating close to large blood vessels, a situation more appropriately managed with open peripheral nerve stimulator placement. Ultrasound-guided placement may be considered for patients receiving peripheral nerve stimulators placed within the deep tissues, and not easily placed in a blind fashion.

Cranial nerve vascular compression syndromes of the trigeminal, facial and vago-glossopharyngeal nerves: comparative anatomical study of the central myelin portion and transitional zone; correlations with incidences of corresponding hyperactive dysfunctional syndromes.

PubMed

Guclu, Bulent; Sindou, Marc; Meyronet, David; Streichenberger, Nathalie; Simon, Emile; Mertens, Patrick

2011-12-01

The aim of this study was to evaluate the anatomy of the central myelin portion and the central myelin-peripheral myelin transitional zone of the trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The aim was also to investigate the relationship between the length and volume of the central myelin portion of these nerves with the incidences of the corresponding cranial dysfunctional syndromes caused by their compression to provide some more insights for a better understanding of mechanisms. The trigeminal, facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined. The length of these nerves from the brainstem to the foramen that they exit were measured. Longitudinal sections were stained and photographed to make measurements. The diameters of the nerves where they exit/enter from/to brainstem, the diameters where the transitional zone begins, the distances to the most distal part of transitional zone from brainstem and depths of the transitional zones were measured. Most importantly, the volume of the central myelin portion of the nerves was calculated. Correlation between length and volume of the central myelin portion of these nerves and the incidences of the corresponding hyperactive dysfunctional syndromes as reported in the literature were studied. The distance of the most distal part of the transitional zone from the brainstem was 4.19  ±  0.81 mm for the trigeminal nerve, 2.86  ±  1.19 mm for the facial nerve, 1.51  ±  0.39 mm for the glossopharyngeal nerve, and 1.63  ±  1.15 mm for the vagus nerve. The volume of central myelin portion was 24.54  ±  9.82 mm(3) in trigeminal nerve; 4.43  ±  2.55 mm(3) in facial nerve; 1.55  ±  1.08 mm(3) in glossopharyngeal nerve; 2.56  ±  1.32 mm(3) in vagus nerve. Correlations (p  < 0.001) have been found between the length or volume of central myelin portions of the trigeminal, facial, glossopharyngeal and vagus nerves and incidences of the corresponding diseases. At present it is rather well-established that primary trigeminal neuralgia, hemifacial spasm and vago-glossopharyngeal neuralgia have as one of the main causes a vascular compression. The strong correlations found between the lengths and volumes of the central myelin portions of the nerves and the incidences of the corresponding diseases is a plea for the role played by this anatomical region in the mechanism of these diseases.

3D printing strategies for peripheral nerve regeneration.

PubMed

Petcu, Eugen B; Midha, Rajiv; McColl, Erin; Popa-Wagner, Aurel; Chirila, Traian V; Dalton, Paul D

2018-03-23

After many decades of biomaterials research for peripheral nerve regeneration, a clinical product (the nerve guide), is emerging as a proven alternative for relatively short injury gaps. This review identifies aspects where 3D printing can assist in improving long-distance nerve guide regeneration strategies. These include (1) 3D printing of the customizable nerve guides, (2) fabrication of scaffolds that fill nerve guides, (3) 3D bioprinting of cells within a matrix/bioink into the nerve guide lumen and the (4) establishment of growth factor gradients along the length a nerve guide. The improving resolution of 3D printing technologies will be an important factor for peripheral nerve regeneration, as fascicular-like guiding structures provide one path to improved nerve guidance. The capability of 3D printing to manufacture complex structures from patient data based on existing medical imaging technologies is an exciting aspect that could eventually be applied to treating peripheral nerve injury. Ultimately, the goal of 3D printing in peripheral nerve regeneration is the automated fabrication, potentially customized for the patient, of structures within the nerve guide that significantly outperform the nerve autograft over large gap injuries.

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

PubMed

Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of pediatric upper extremity peripheral nerve injuries.

PubMed

Ho, Emily S

2015-01-01

The evaluation of motor and sensory function of the upper extremity after a peripheral nerve injury is critical to diagnose the location and extent of nerve injury as well as document functional recovery in children. The purpose of this paper is to describe an approach to the evaluation of the pediatric upper extremity peripheral nerve injuries through a critical review of currently used tests of sensory and motor function. Outcome studies on pediatric upper extremity peripheral nerve injuries in the Medline database were reviewed. The evaluation of the outcome in children less than 10 years of age with an upper extremity peripheral nerve injury includes careful observation of preferred prehension patterns, examination of muscle atrophy and sudomotor function, provocative tests, manual muscle testing and tests of sensory threshold and tactile gnosis. The evaluation of outcome in children with upper extremity peripheral nerve injuries warrants a unique approach. Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Ultrasound-guided percutaneous injection of methylene blue to identify nerve pathology and guide surgery.

PubMed

Osorio, Joseph A; Breshears, Jonathan D; Arnaout, Omar; Simon, Neil G; Hastings-Robinson, Ashley M; Aleshi, Pedram; Kliot, Michel

2015-09-01

OBJECT The objective of this study was to provide a technique that could be used in the preoperative period to facilitate the surgical exploration of peripheral nerve pathology. METHODS The authors describe a technique in which 1) ultrasonography is used in the immediate preoperative period to identify target peripheral nerves, 2) an ultrasound-guided needle electrode is used to stimulate peripheral nerves to confirm their position, and then 3) a methylene blue (MB) injection is performed to mark the peripheral nerve pathology to facilitate surgical exploration. RESULTS A cohort of 13 patients with varying indications for peripheral nerve surgery is presented in which ultrasound guidance, stimulation, and MB were used to localize and create a road map for surgeries. CONCLUSIONS Preoperative ultrasound-guided MB administration is a promising technique that peripheral nerve surgeons could use to plan and execute surgery.

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

PubMed Central

Ayala-Caminero, Radamés; Pinzón-Herrera, Luis; Martinez, Carol A. Rivera; Almodovar, Jorge

2018-01-01

Understanding peripheral nerve repair requires the evaluation of 3D structures that serve as platforms for 3D cell culture. Multiple platforms for 3D cell culture have been developed, mimicking peripheral nerve growth and function, in order to study tissue repair or diseases. To recreate an appropriate 3D environment for peripheral nerve cells, key factors are to be considered including: selection of cells, polymeric biomaterials to be used, and fabrication techniques to shape and form the 3D scaffolds for cellular culture. This review focuses on polymeric 3D platforms used for the development of 3D peripheral nerve cell cultures. PMID:29515936

Biology of eating behavior in obesity.

PubMed

Schwartz, Gary J

2004-11-01

Understanding normal and dysfunctional energy regulation and body weight regulation requires neural evaluation of the signals involved in the control of food intake within a meal, as well as signals related to the availability of stored fuels. Work from our laboratory has focused on peripheral and central nervous system studies of behavior and physiology designed to improve our understanding of the role of gut-brain communication in the control of food intake and energy homeostasis. Gastrointestinal administration of nutrients reduces subsequent meal size, suggesting a potent role for peripheral nutrient sensing in the negative feedback control of ingestion. Vagal afferent nerves supply gastrointestinal sites stimulated during food intake, and these nerves are responsive to mechanical and nutrient chemical properties of ingested food. In addition, the presence of nutrients in these gastrointestinal sites stimulates the release of peptides that affect energy intake. These gut peptides also modulate the activity of peripheral gastrointestinal sensory nerves in ways that may contribute to their effects on food intake. In the central nervous system, adiposity hormones and their downstream mediators have been shown to work at both hindbrain and forebrain sites to affect food intake and metabolism. Importantly, recent data has shown that adiposity hormones acting in the brain increase the behavioral and neural potency of feeding inhibitory gastrointestinal stimuli. These data support the suggestion that insensitivity to adiposity hormones in obesity may be characterized by alterations in their ability to modulate the neural processing of food signals important in determining how much food is consumed during a meal.

Regenerative peripheral nerve interface viability and signal transduction with an implanted electrode.

PubMed

Kung, Theodore A; Langhals, Nicholas B; Martin, David C; Johnson, Philip J; Cederna, Paul S; Urbanchek, Melanie G

2014-06-01

The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual peripheral nerve. Adding a conductive polymer coating on electrodes improves electrode conductivity. This study examines regenerative peripheral nerve interface tissue viability and signal fidelity in the presence of an implanted electrode coated or uncoated with a conductive polymer. In a rat model, the extensor digitorum longus muscle was moved as a nonvascularized free tissue transfer and neurotized by the divided peroneal nerve. Either a stainless steel pad electrode (n = 8) or a pad electrode coated with poly(3,4-ethylenedioxythiophene) conductive polymer (PEDOT) (n = 8) was implanted on the muscle transfer and secured with an encircling acellular extracellular matrix. The contralateral muscle served as the control. The free muscle transfers were successfully revascularized and over time reinnervated as evidenced by serial insertional needle electromyography. Compound muscle action potentials were successfully transduced through the regenerative peripheral nerve interface. The conductive polymer coating on the implanted electrode resulted in increased recorded signal amplitude that was observed throughout the course of the study. Histologic examination confirmed axonal sprouting, elongation, and synaptogenesis within regenerative peripheral nerve interface regardless of electrode type. The regenerative peripheral nerve interface remains viable over seven months in the presence of an implanted electrode. Electrodes with and without conductive polymer reliably transduced signals from the regenerative peripheral nerve interface. Electrodes with a conductive polymer coating resulted in recording more of the regenerative peripheral nerve interface signal.

Inhibition of miR-25 aggravates diabetic peripheral neuropathy.

PubMed

Zhang, Yanzhuo; Song, Chunyu; Liu, Jing; Bi, Yonghong; Li, Hao

2018-06-05

The hyperglycemia-induced enhanced oxidative stress is a key factor of diabetic peripheral neuropathy implicated in the pathogenesis of diabetic neuropathy, and microRNA may be involved, playing promotion or protection roles. In this study, we aimed to investigate the function of miR-25 during the development of oxidative/nitrative stress and in subsequent neurological problems. We detected the oxidative stress effects and expression of miR-25 on sciatic nerves from db/db diabetic model mice and analyzed the expression of related genes by qPCR and Western blotting. Interestingly, we observed increased reactive oxygen species (ROS) and Nox4 expression in db/db mice accompanied with reduced miR-25. MiR-25 inhibitor treatment increased nicotinamide adenine dinucleotide phosphate activity in Schwann cells, whereas miR-25 precursor overexpression led to opposite results. MiR-25 precursor reduced the activation of protein kinase C and decreased Nox4 expression at both mRNA and protein levels. Advanced glycation endproducts (AGEs) and the receptor for advanced glycation endproducts (RAGE) were increased in the serum and in the peripheral nerves obtained from diabetic mice, and miR-25 inhibitor treatment in Schwann cells from wt mice led to the same effect. However, miR-25 precursor transfection reduced AGEs and RAGE, and further reduced inflammatory factors that contribute to the pathological process of peripheral nerves. These findings, for the first time, indicate that miR-25 acts as a protection factor in diabetic neuropathy by downregulating AGE-RAGE and reducing nicotinamide adenine dinucleotide phosphate oxidase. miR-25 reduced protein kinase C-α phosphorylation to produce less reactive oxygen species in diabetic peripheral nerves, and therefore it played an important role in the regulation of oxidative/nitrative stress and in consequent neurological dysfunction.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function.

PubMed

Jayaraman, Anusha; Lent-Schochet, Daniella; Pike, Christian J

2014-09-16

Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices in the central and peripheral nervous systems. Male C57B6/J mice were maintained on normal or high-fat diet under varying testosterone conditions for a four-month treatment period, after which metabolic indices were measured and RNA isolated from cerebral cortex and sciatic nerve. Cortices were used to generate mixed glial cultures, upon which embryonic cerebrocortical neurons were co-cultured for assessment of neuron survival and neurite outgrowth. Peripheral nerve damage was determined using paw-withdrawal assay, myelin sheath protein expression levels, and Na+,K+-ATPase activity levels. Our results demonstrate that detrimental effects on both metabolic (blood glucose, insulin sensitivity) and proinflammatory (cytokine expression) responses caused by diet-induced obesity are exacerbated by testosterone depletion. Mixed glial cultures generated from obese mice retain elevated cytokine expression, although low testosterone effects do not persist ex vivo. Primary neurons co-cultured with glial cultures generated from high-fat fed animals exhibit reduced survival and poorer neurite outgrowth. In addition, low testosterone and diet-induced obesity combine to increase inflammation and evidence of nerve damage in the peripheral nervous system. Testosterone and diet-induced obesity independently and cooperatively regulate neuroinflammation in central and peripheral nervous systems, which may contribute to observed impairments in neural health. Together, our findings suggest that low testosterone and obesity are interactive regulators of neuroinflammation that, in combination with adipose-derived inflammatory pathways and other factors, increase the risk of downstream disorders including type 2 diabetes and Alzheimer's disease.

Peripheral Glial Cells in the Development of Diabetic Neuropathy.

PubMed

Gonçalves, Nádia Pereira; Vægter, Christian Bjerggaard; Pallesen, Lone Tjener

2018-01-01

The global prevalence of diabetes is rapidly increasing, affecting more than half a billion individuals within the next few years. As diabetes negatively affects several physiological systems, this dramatic increase represents not only impaired quality of life on the individual level but also a huge socioeconomic challenge. One of the physiological consequences affecting up to half of diabetic patients is the progressive deterioration of the peripheral nervous system, resulting in spontaneous pain and eventually loss of sensory function, motor weakness, and organ dysfunctions. Despite intense research on the consequences of hyperglycemia on nerve functions, the biological mechanisms underlying diabetic neuropathy are still largely unknown, and treatment options lacking. Research has mainly focused directly on the neuronal component, presumably from the perspective that this is the functional signal-transmitting unit of the nerve. However, it is noteworthy that each single peripheral sensory neuron is intimately associated with numerous glial cells; the neuronal soma is completely enclosed by satellite glial cells and the length of the longest axons covered by at least 1,000 Schwann cells. The glial cells are vital for the neuron, but very little is still known about these cells in general and especially how they respond to diabetes in terms of altered neuronal support. We will discuss current knowledge of peripheral glial cells and argue that increased research in these cells is imperative for a better understanding of the mechanisms underlying diabetic neuropathy.

Peripheral Glial Cells in the Development of Diabetic Neuropathy

PubMed Central

Gonçalves, Nádia Pereira; Vægter, Christian Bjerggaard; Pallesen, Lone Tjener

2018-01-01

The global prevalence of diabetes is rapidly increasing, affecting more than half a billion individuals within the next few years. As diabetes negatively affects several physiological systems, this dramatic increase represents not only impaired quality of life on the individual level but also a huge socioeconomic challenge. One of the physiological consequences affecting up to half of diabetic patients is the progressive deterioration of the peripheral nervous system, resulting in spontaneous pain and eventually loss of sensory function, motor weakness, and organ dysfunctions. Despite intense research on the consequences of hyperglycemia on nerve functions, the biological mechanisms underlying diabetic neuropathy are still largely unknown, and treatment options lacking. Research has mainly focused directly on the neuronal component, presumably from the perspective that this is the functional signal-transmitting unit of the nerve. However, it is noteworthy that each single peripheral sensory neuron is intimately associated with numerous glial cells; the neuronal soma is completely enclosed by satellite glial cells and the length of the longest axons covered by at least 1,000 Schwann cells. The glial cells are vital for the neuron, but very little is still known about these cells in general and especially how they respond to diabetes in terms of altered neuronal support. We will discuss current knowledge of peripheral glial cells and argue that increased research in these cells is imperative for a better understanding of the mechanisms underlying diabetic neuropathy. PMID:29770116

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve...of Decellularized Nerve Allograft with 5a. CONTRACT NUMBER Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve 5b. GRANT NUMBER W81XWH...commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with autologous bone marrow

Estimation of ultrasound reference values for the lower limb peripheral nerves in adults: A cross-sectional study.

PubMed

Bedewi, Mohamed Abdelmohsen; Abodonya, Ahmed; Kotb, Mamdouh; Kamal, Sanaa; Mahmoud, Gehan; Aldossari, Khaled; Alqabbani, Abdullah; Swify, Sherine

2018-03-01

The objective of this study is to estimate the reference values for the lower limb peripheral nerves in adults.The demographics and physical characteristics of 69 adult healthy volunteers were evaluated and recorded. The estimated reference values and their correlations with the age, weight, height, body mass index (BMI) were evaluated.The cross sectional area reference values were obtained at 5 predetermined sites for 3 important lower limb peripheral nerves. Our CSA values correlated significantly with age, weight, and BMI. The normal reference values for each nerve were as follows: Tibial nerve at the popliteal fossa 19 mm ± 6.9, tibial nerve at the level of the medial malleolus 12.7 mm ± 4.5, common peroneal nerve at the popliteal fossa 9.5 mm ± 4, common peroneal nerve fibular head 8.9 mm ± 3.2, sural nerve 3.5 mm ± 1.4.The reference values for the lower limb peripheral nerves were identified. These values could be used for future management of peripheral nerve disorders.

[RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM].

PubMed

Shen, Jie; Song, Diyu; Wang, Xiaoyu; Wang, Changjiang; Zhang, Shuming

2016-02-01

To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three-dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini-invasive approach. The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed.

Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

PubMed

Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin

2017-10-01

Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Label-free photoacoustic microscopy of peripheral nerves

NASA Astrophysics Data System (ADS)

Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

2014-01-01

Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.

PubMed

Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

2017-12-01

High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm 2 ) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score ( p < 0.001). The diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm 2 ) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm 2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

[Involvement of the peripheral nervous system in systemic connective tissue diseases: report on clinical cases].

PubMed

Kujawska-Danecka, Hanna; Masiak, Anna; Smoleńska, Zaneta; Zdrojewski, Zbigniew

2011-01-01

The peripheral nervous system is usually involved in the majority of systemic connective tissue diseases, particularly in systemic lupus erythematosus, Sjögren's syndrome, vasculitis and systemic sclerosis. The pathogenesis of lesions in the peripheral nervous system associated with the autoimmune process is complex and it appears that two mechanisms, immunological and ischemic, are of greatest importance. Structures of the nervous system may be damaged by several autoantibodies (e.g. antineuronal, anti-nerve growth factor, anti-neurotrophins), by cytotoxic effects ofproinflammatory cytokines and by activated cells of the immune system. Local ischemia and hypoxia of neurons caused by inflammation of vasa nervosum represents the second significant mechanism leading to damage of nerve fibres in the peripheral nervous system. We present 3 cases with involvement of the peripheral nervous system as a dominant feature in the clinical picture of systemic connective tissue diseases. Clinical conditions in which the peripheral nervous system is involved include peripheral sensory and sensorimotor polyneuropathy, mononeuropathies, cranial neuropathies, acute inflammatory demyelinating polyneuropathy (Guillian-Barré syndrome), chronic inflammatory demyelinating polyneuropathy, plexopathy, myasthenia gravis, and dysfunctions of the autonomic nervous system. The diagnosis is based on clinical symptoms reported by the patient and disclosed during neurologic examination. The importance of electrophysiologic tests is advocated. Selection of treatment depends on the patient's clinical condition, as well as on the clinical form and type of disease. Treatment relies principally on glucocorticosteroids, intravenous immunoglobulins, cyclophosphamide, and other immunosuppressive drugs. Plasmapheresis and rituximab are administered in severe cases. Rehabilitation of the patient appears to be an important element of therapy. Cases with neurologic symptoms as the first and often the sole manifestation of systemic connective tissue disease are particularly problematic requiring a multidimensional approach; their process of diagnosis and treatment is usually long.

Roles of neural stem cells in the repair of peripheral nerve injury.

PubMed

Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

2017-12-01

Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

Mitochondrial dysfunction precedes depression of AMPK/AKT signaling in insulin resistance induced by high glucose in primary cortical neurons.

PubMed

Peng, Yunhua; Liu, Jing; Shi, Le; Tang, Ying; Gao, Dan; Long, Jiangang; Liu, Jiankang

2016-06-01

Recent studies have demonstrated brain insulin signaling impairment and mitochondrial dysfunction in diabetes. Hyperinsulinemia and hyperlipidemia arising from diabetes have been linked to neuronal insulin resistance, and hyperglycemia induces peripheral sensory neuronal impairment and mitochondrial dysfunction. However, how brain glucose at diabetic conditions elicits cortical neuronal insulin signaling impairment and mitochondrial dysfunction remains unknown. In the present study, we cultured primary cortical neurons with high glucose levels and investigated the neuronal mitochondrial function and insulin response. We found that mitochondrial function was declined in presence of 10 mmol/L glucose, prior to the depression of AKT signaling in primary cortical neurons. We further demonstrated that the cerebral cortex of db/db mice exhibited both insulin resistance and loss of mitochondrial complex components. Moreover, we found that adenosine monophosphate-activated protein kinase (AMPK) inactivation is involved in high glucose-induced mitochondrial dysfunction and insulin resistance in primary cortical neurons and neuroblastoma cells, as well as in cerebral cortex of db/db mice, and all these impairments can be rescued by mitochondrial activator, resveratrol. Taken together, our results extend the finding that high glucose (≥10 mmol/L) comparable to diabetic brain extracellular glucose level leads to neuronal mitochondrial dysfunction and resultant insulin resistance, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. We found that high glucose (≥10 mmol/L), comparable to diabetic brain extracellular glucose level, leads to neuronal mitochondrial dysfunction and resultant insulin resistance in an AMPK-dependent manner, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. © 2016 International Society for Neurochemistry.

Ultrasound assessment of peripheral nerve pathology in neurofibromatosis type 1 and 2.

PubMed

Winter, Natalie; Rattay, Tim W; Axer, Hubertus; Schäffer, Eva; Décard, Bernhard F; Gugel, Isabel; Schuhmann, Martin; Grimm, Alexander

2017-05-01

The neurofibromatoses (NF) type 1 and 2 are hereditary tumor predisposition syndromes caused by germline mutations in the NF1 and NF2 tumor suppressor genes. In NF1 and 2, peripheral nerve tumors occur regularly. For further characterizing nerve ultrasound was performed in patients with NF1 and 2. Patients with established diagnosis of NF1 (n=27) and NF2 (n=10) were included. Ultrasound of peripheral nerves and cervical roots was performed during routine follow-up visits. Healthy volunteers were studied for comparison. In patients with NF1, median cross-sectional area (CSA) of most nerves was significantly increased compared to controls and to NF2 due to generalized plexiform tumors, which arose out of multiple fascicles in 23 of 27 patients (85%). These were often accompanied by cutaneous or subcutaneous neurofibromas. In NF2, the overall aspect of peripheral nerves consisted of localized schwannomas (80%) and, apart from that, normal nerve segments. Nerve ultrasound is able to visualize different nerve pathologies in NF1 and NF2. It is a precise and inexpensive screening method for peripheral nerve manifestation in neurofibromatosis and should be considered as the first choice screening imaging modality for all peripheral nerves within reach of non-invasive ultrasound techniques. Ultrasound patterns of peripheral nerve pathologies are described for the first time in a large cohort of patients with NF1 and NF2. It is a suitable screening tool and enables targeted MRI analysis. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Hyperglycemia and diabetes mellitus are related to vestibular organs dysfunction: truth or suggestion? A literature review.

PubMed

Gioacchini, Federico Maria; Albera, Roberto; Re, Massimo; Scarpa, Alfonso; Cassandro, Claudia; Cassandro, Ettore

2018-06-23

Diabetes mellitus is an independent risk factor for falling, particularly in the elderly. Due to chronic hyperglycemia and hyperinsulinemia patients with diabetes mellitus may have neurological deficits as peripheral neuropathy that is a debilitating micro-vascular complication affecting the proximal and distal peripheral sensory and motor nerves. Sensory neuropathy is prominent and represents the chief contributor to postural instability in diabetic subjects. Diabetic retinopathy is another complication consequent to a breakdown of the inner blood-retinal barrier with accumulation of extracellular fluids in the macula and growth of new vessels causing retinal detachment. Together peripheral neuropathy and retinopathy contribute to increase the risk of falls in diabetic patients, but a certain vestibular organs impairment should not be underestimated. Nevertheless, the exact mechanism and localization of peripheral vestibular damage consequent to chronic hyperglycemia and hyperinsulinemia are currently not still understood. Moreover it is not defined the possible role of these two blood conditions in worsening the prognosis of typical vestibular pathologies like "benign paroxysmal positional vertigo" and "Meniere disease". The aim of this review was to retrieve all studies investigating about the balance system alterations in patients suffering of diabetes. A search thorough Ovid MEDLINE was performed to enroll all eligible articles. Fourteen studies comprising a total of 1364 patients were included and analyzed in detail. On the basis of data reported in our review it appears plausible to hypothesize a direct connection among chronic hyperglycemic/hyperinsulinemic damage and peripheral vestibular organ dysfunction.

Tissue engineered constructs for peripheral nerve surgery

PubMed Central

Johnson, P. J.; Wood, M. D.; Moore, A. M.; Mackinnon, S. E.

2013-01-01

Summary Background Tissue engineering has been defined as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ”. Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. Methods A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. Results Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. Conclusions The field of tissue engineering should consider its challenge to not only meet the autograft “gold standard” but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft. PMID:24385980

Novel technique for repair of severed peripheral nerves in rats using polyurea crosslinked silica aerogel scaffold.

PubMed

Sabri, Firouzeh; Gerth, David; Tamula, George-Rudolph M; Phung, Thien-Chuong N; Lynch, Kyle J; Boughter, John D

2014-10-01

To design, synthesize, and test in vivo an aerogel-based top-open peripheral nerve scaffold to simultaneously support and guide multiple completely severed peripheral nerves in a rat model. Also, to explore options for immobilizing severed nerves on the aerogel material without the use of sutures resulting in reduced surgical time. A novel material and approach was developed for the reattachment of severed peripheral nerves. Nerve confinement and alignment in this case relies on the surface properties of a lightweight, highly porous, polyurea crosslinked silica aerogel scaffold. The distal and proximal ends of completely transected nerve terminals were positioned inside prefabricated "top-open" corrugated channels that cradled approximately two thirds of the circumference of the nerve trunk and connectivity of the severed nerves was evaluated using sciatic function index (SFI) technique for five months post-surgery on 10 female Sprague-Dawley rats then compared with the gold standard for peripheral nerve repair. The interaction of nerves with the surface of the scaffold was investigated also. Multichannel aerogel-based nerve support scaffold showed similar SFI recovery trend as the case suture repair technique. Usage of an adhesion-promoting coating reduced the friction between the nerve and the scaffold leading to slippage and lack of attachment between nerve and surface. The aerogel scaffold used in this study did not collapse under pressure during the incubation period and allowed for a rapid and non-invasive peripheral nerve repair approach without the demands of microsurgery on both time and surgical expertise. This technique may allow for simultaneous repair and reconnection of multiple severed nerves particularly relevant to nerve branching sites.

Expression patterns and role of PTEN in rat peripheral nerve development and injury.

PubMed

Chen, Hui; Xiang, Jianping; Wu, Junxia; He, Bo; Lin, Tao; Zhu, Qingtang; Liu, Xiaolin; Zheng, Canbin

2018-05-29

Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of nerve conduits for peripheral nerve injury repair: A Web of Science-based literature analysis.

PubMed

Nan, Jinniang; Hu, Xuguang; Li, Hongxiu; Zhang, Xiaonong; Piao, Renjing

2012-12-15

To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.

Side Effects: Nerve Problems (Peripheral Neuropathy)

Cancer.gov

Nerve problems, such as peripheral neuropathy, can be caused by cancer treatment. Learn about signs and symptoms of nerve changes. Find out how to prevent or manage nerve problems during cancer treatment.

Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An Experimental Rat Model.

PubMed

Nicolas, Nicolas; Kobaiter-Maarrawi, Sandra; Georges, Samuel; Abadjian, Gerard; Maarrawi, Joseph

2018-06-01

Immediate microsurgical nerve suture remains the gold standard after peripheral nerve injuries. However, functional recovery is delayed, and it is satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation proximal to the lesion enhances nerve regeneration and muscle reinnervation. This study aims to evaluate the effects of the motor cortex electrical stimulation on peripheral nerve regeneration after injury. Eighty rats underwent right sciatic nerve section, followed by immediate microsurgical epineural sutures. Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15 minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed over the course of two weeks after nerve suture (MCSc). Assessment included electrophysiology and motor functional score at day 0 (baseline value before nerve section), and at weeks 4, 8, and 12. Rats were euthanized for histological study at week 12. Our results showed that MCS enhances functional recovery, nerve regeneration, and muscle reinnervation starting week 4 compared with the control group (P < 0.05). The MCS induces higher reinnervation rates even compared with peripheral stimulation, with better results in the MCSa group (P < 0.05), especially in terms of functional recovery. MCS seems to have a beneficial effect after peripheral nerve injury and repair in terms of nerve regeneration and muscle reinnervation, especially when acute mode is used. Copyright © 2018 Elsevier Inc. All rights reserved.

Airway complications in the head injured.

PubMed

Woo, P; Kelly, G; Kirshner, P

1989-07-01

Fifty head-injured patients who had tracheostomy were followed during rehabilitation by video fiberoptic laryngoscopy examination. Complications of aspiration (23/50), airway stenosis (13/50), and phonation dysfunction (16/24) were followed. Spontaneous resolution of aspiration may require a prolonged course. A majority of patients (37/50) had improvement and could be decannulated. Prognostic factors correlated to eventual decannulation included age, level on the Glasgow Coma Outcome Scale, and type of head injury. Those with poor neurologic improvement and glottic incompetence (13/50) are poor candidates for decannulation. Significant airway stenosis can involve both laryngeal and tracheal sites. Neurologic dysfunction may complicate the decannulation process after airway anatomy has been restored by surgery. Dysphonia resulting from intubation, peripheral laryngeal and nerve injury, or central laryngeal movement dysfunction are common. Preventive maintenance with ongoing evaluation can avoid airway crises such as aspiration pneumonia, hemoptysis, and innominate artery.

A 63-year-old man with peripheral facial nerve paralysis and a pulmonary lesion.

PubMed

Yserbyt, J; Wilms, G; Lievens, Y; Nackaerts, K

2009-01-01

Occasionally, malignant neoplasms may cause peripheral facial nerve paralysis as a presenting symptom. A 63-year-old man was referred to the Emergency Department because of a peripheral facial nerve paralysis, lasting for 10 days. Initial diagnostic examinations revealed no apparent cause for this facial nerve paralysis. Chest X-ray, however, showed a suspicious tumoural mass, located in the right hilar region, as confirmed by CAT scan. The diagnosis of an advanced stage lung adenocarcinoma was finally confirmed by bronchial biopsy. MRI scanning showed diffuse brain metastases and revealed a pontine lesion as the most probable underlying cause of this case of peripheral facial nerve paralysis. Platin-based palliative chemotherapy was given, after an initial pancranial irradiation. According to the MRI findings, the pontine lesion was responsible for the peripheral facial nerve paralysis, as an initial presenting symptom in this case of lung adenocarcinoma. This clinical case of a peripheral facial nerve paralysis was caused by a pontine brain metastasis and illustrates a rather rare presenting symptom of metastatic lung cancer.

Peripheral Nerve Block as a Supplement to Light or Deep General Anesthesia in Elderly Patients Receiving Total Hip Arthroplasty: A Prospective Randomized Study.

PubMed

Mei, Bin; Zha, Hanning; Lu, Xiaolong; Cheng, Xinqi; Chen, Shishou; Liu, Xuesheng; Li, Yuanhai; Gu, Erwei

2017-12-01

Peripheral nerve block combined with general anesthesia is a preferable anesthesia method for elderly patients receiving hip arthroplasty. The depth of sedation may influence patient recovery. Therefore, we investigated the influence of peripheral nerve blockade and different intraoperative sedation levels on the short-term recovery of elderly patients receiving total hip arthroplasty. Patients aged 65 years and older undergoing total hip arthroplasty were randomized into 3 groups: a general anesthesia without lumbosacral plexus block group, and 2 general anesthesia plus lumbosacral plexus block groups, each with a different level of sedation (light or deep). The extubation time and intraoperative consumption of propofol, sufentanil, and vasoactive agent were recorded. Postoperative delirium and early postoperative cognitive dysfunction were assessed using the Confusion Assessment Method and Mini-Mental State Examination, respectively. Postoperative analgesia was assessed by the consumption of patient-controlled analgesics and visual analog scale scores. Discharge time and complications over a 30-day period were also recorded. Lumbosacral plexus block reduced opioid intake. With lumbosacral plexus block, intraoperative deep sedation was associated with greater intake of propofol and vasoactive agent. In contrast, patients with lumbosacral plexus block and intraoperative light sedation had lower incidences of postoperative delirium and postoperative cognitive decline, and earlier discharge readiness times. The 3 groups showed no difference in complications within 30 days of surgery. Lumbosacral plexus block reduced the need for opioids and offered satisfactory postoperative analgesia. It led to better postoperative outcomes in combination with intraoperative light sedation (high bispectral index).

Composite pheochromocytoma with a malignant peripheral nerve sheath tumor: Case report and review of the literature.

PubMed

Namekawa, Takeshi; Utsumi, Takanobu; Imamoto, Takashi; Kawamura, Koji; Oide, Takashi; Tanaka, Tomoaki; Nihei, Naoki; Suzuki, Hiroyoshi; Nakatani, Yukio; Ichikawa, Tomohiko

2016-07-01

Adrenal tumors with more than one cellular component are uncommon. Furthermore, an adrenal tumor composed of a pheochromocytoma and a malignant peripheral nerve sheath tumor is extremely rare. A composite pheochromocytoma with malignant peripheral nerve sheath tumor in a 42-year-old man is reported here. After adequate preoperative control, left adrenalectomy was performed simultaneously with resection of the ipsilateral kidney for spontaneous rupture of the left adrenal tumor. Pathological findings demonstrated pheochromocytoma and malignant peripheral nerve sheath tumor in a ruptured adrenal tumor. To date, there have been only four reported cases of composite pheochromocytoma with malignant peripheral nerve sheath tumor, so the present case is only the fifth case in the world. Despite the very poor prognosis of patients with pheochromocytoma and malignant peripheral nerve sheath tumors reported in the literature, the patient remains well without evidence of recurrence or new metastatic lesions at 36 months postoperatively. Copyright © 2012. Published by Elsevier Taiwan.

MRI abnormalities of peripheral nerve and muscle are common in amyotrophic lateral sclerosis and share features with multifocal motor neuropathy

PubMed Central

Staff, Nathan P.; Amrami, Kimberly K.; Howe, Benjamin M.

2015-01-01

Introduction MRI of peripheral nerve and muscle in patients with ALS may be performed to investigate alternative diagnoses including multifocal motor neuropathy (MMN). MRI findings of peripheral nerve and muscle are not well described in these conditions, making interpretation of results difficult. Methods We examined systematically the peripheral nerve and muscle MRI findings in patients with ALS (n=60) and MMN (n=8). Results In patients with ALS and MMN, abnormal MRIs were common (85% and 75%, respectively) but did not correlate with disease severity. Peripheral nerve MRI abnormalities were similar in frequency (ALS: 58% vs. MMN: 63%) with most changes being of mild-to-moderate severity. Muscle MRI changes were more common in ALS (57% vs. 33%), and no muscle atrophy was seen in patients with MMN. Discussion MRI abnormalities of peripheral nerve and muscle in ALS and MMN are common and share some features. PMID:25736373

Drug Distribution into Peripheral Nerve.

PubMed

Liu, Houfu; Chen, Yan; Huang, Liang; Sun, Xueying; Fu, Tingting; Wu, Shengqian; Zhu, Xiaoyan; Zhen, Wei; Liu, Jihong; Lu, Gang; Cai, Wei; Yang, Ting; Zhang, Wandong; Yu, Xiaohong; Wan, Zehong; Wang, Jianfei; Summerfield, Scott G; Dong, Kelly; Terstappen, Georg C

2018-05-01

Little is known about the impact of the blood-nerve barrier (BNB) on drug distribution into peripheral nerves. In this study, we examined the peripheral nerve penetration in rats of 11 small-molecule drugs possessing diverse physicochemical and transport properties and ProTx-II, a tarantula venom peptide with molecular mass of 3826 Daltons. Each drug was administered as constant rate intravenous infusion for 6 hours (small molecules) or 24 hours (ProTx-II). Blood and tissues including brain, spinal cord, sciatic nerve, and dorsal root ganglion (DRG) were collected for drug concentration measurements. Unbound fractions of a set of compounds were determined by equilibrium dialysis method in rat blood, brains, spinal cords, sciatic nerves, and DRG. We also investigated the influence of N -[4-[2-(6,7-dimethoxy-3,4-dihydro-1 H -isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10 H -acridine-4-carboxamide (GF120918), a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor, on the peripheral nerve and central nervous system (CNS) tissue penetration of imatinib. We found that: 1) the unbound fraction in brain tissue homogenate highly correlates with that in the spinal cord, sciatic nerve, and DRG for a set of compounds and thus provides a good surrogate for spinal cord and peripheral nerve tissues, 2) small-molecule drugs investigated can penetrate the DRG and sciatic nerve, 3) P-gp and BCRP have a limited impact on the distribution of small-molecule drugs into peripheral nerves, and 4) DRG is permeable to ProTx-II, but its distribution into sciatic nerve and CNS tissues is restricted. These results demonstrate that small-molecule drugs investigated can penetrate peripheral nerve tissues, and P-gp/BCRP may not be a limiting factor at the BNB. Biologics as large as ProTx-II can access the DRG but not sciatic nerve and CNS tissues. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

The utility of ultrasound in the assessment of traumatic peripheral nerve lesions: report of 4 cases.

PubMed

Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D

2015-09-01

Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.

CORRELATION BETWEEN MARKERS OF PERIPHERAL NERVE FUNCTION AND STRUCTURE IN TYPE 1 DIABETES.

PubMed

Borire, Adeniyi A; Issar, Tushar; Kwai, Natalie C; Visser, Leo H; Simon, Neil G; Poynten, Ann M; Kiernan, Matthew C; Krishnan, Arun V

2018-06-01

Clinical and experimental studies in patients with type 1 and type 2 diabetes have demonstrated changes in ion channel function and nerve structure. In this study, we investigated the relationship between axonal dysfunction and morphological change in diabetic polyneuropathy using neuromuscular ultrasound and nerve excitability techniques. We also explored possible differences in this relationship between type 1 and type 2 diabetes. Nerve ultrasound and corresponding motor excitability studies were undertaken in 110 diabetes patients (50 type 1;60 type 2) and 60 age-matched controls (30 for each group). Neuropathy severity was assessed using Total Neuropathy Score. Median and tibial nerve cross-sectional areas were measured at non-entrapment sites using high resolution linear probe. Median and tibial nerve cross-sectional areas were significantly higher in diabetes patients compared to controls: Type1 (Median=7.6±0.2mm 2 vs. 6.3±0.1mm 2 ; Tibial=14.5±0.7mm 2 vs. 10.8±0.3mm 2 ,p<0.05) and Type 2 (Median=9.1±0.3mm 2 vs. 7.2±0.1mm 2 ; Tibial=18.5±1.0mm 2 vs. 12.8±0.5mm 2 ,p<0.05). In the type 1 cohort, significant correlations were found between nerve cross-sectional area and excitability parameters including resting current-threshold slope (Median: r=0.523,p<0.0001; Tibial: r=-0.571,p=0.004) and depolarizing threshold electrotonus at 90-100ms (Median: 0.424,p<0.01; Tibial: r=0.435,p=0.030). In contrast, there was no relationship between excitability values and nerve cross-sectional area in the type 2 cohort. This study has identified correlation between markers of axonal membrane function and structural abnormalities in peripheral nerves of type 1 diabetes patients. The differential relationship in nerve function and structure between Type 1 and Type 2 diabetes provides clinical evidence that different pathophysiological mechanisms underlie the development of neuropathy in these patient groups. This article is protected by copyright. All rights reserved.

Types of neural guides and using nanotechnology for peripheral nerve reconstruction

PubMed Central

Biazar, Esmaeil; Khorasani, MT; Montazeri, Naser; Pourshamsian, Khalil; Daliri, Morteza; T, Mostafa Rezaei; B, Mahmoud Jabarvand; Khoshzaban, Ahad; K, Saeed Heidari; Jafarpour, Mostafa; Roviemiab, Ziba

2010-01-01

Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Different methods, such as conventional allograft procedures and use of biologic tubes present problems when used for damaged peripheral nerve reconstruction. Designed scaffolds comprised of natural and synthetic materials are now widely used in the reconstruction of damaged tissues. Utilization of absorbable and nonabsorbable synthetic and natural polymers with unique characteristics can be an appropriate solution to repair damaged nerve tissues. Polymeric nanofibrous scaffolds with properties similar to neural structures can be more effective in the reconstruction process. Better cell adhesion and migration, more guiding of axons, and structural features, such as porosity, provide a clearer role for nanofibers in the restoration of neural tissues. In this paper, basic concepts of peripheral nerve injury, types of artificial and natural guides, and methods to improve the performance of tubes, such as orientation, nanotechnology applications for nerve reconstruction, fibers and nanofibers, electrospinning methods, and their application in peripheral nerve reconstruction are reviewed. PMID:21042546

Physiological and pharmacologic aspects of peripheral nerve blocks

PubMed Central

Vadhanan, Prasanna; Tripaty, Debendra Kumar; Adinarayanan, S.

2015-01-01

A successful peripheral nerve block not only involves a proper technique, but also a thorough knowledge and understanding of the physiology of nerve conduction and pharmacology of local anesthetics (LAs). This article focuses on what happens after the block. Pharmacodynamics of LAs, underlying mechanisms of clinically observable phenomena such as differential blockade, tachyphylaxis, C fiber resistance, tonic and phasic blockade and effect of volume and concentration of LAs. Judicious use of additives along with LAs in peripheral nerve blocks can prolong analgesia. An entirely new group of drugs-neurotoxins has shown potential as local anesthetics. Various methods are available now to prolong the duration of peripheral nerve blocks. PMID:26330722

Necrotizing Fasciitis as a Complication of a Continuous Sciatic Nerve Catheter Using the Lateral Popliteal Approach.

PubMed

Dott, Daltry; Canlas, Christopher; Sobey, Christopher; Obremskey, William; Thomson, Andrew Brian

Necrotizing fasciitis is an infection of the soft tissue that is characterized by rapidly spreading inflammation and subsequent necrosis. It is a rare complication of peripheral nerve blocks. We report a rare case of necrotizing fasciitis after placement of a peripheral nerve catheter. A 58-year-old woman presented for an elective right second metatarsal resection and received a sciatic nerve catheter for postoperative pain control. On postoperative day 7, clinical examination and imaging supported the diagnosis of necrotizing fasciitis. Multiple reports have been published of necrotizing fasciitis after single-shot peripheral nerve block injections, neuraxial anesthesia, and intramuscular injections. This case highlights the potential for the rare complication of necrotizing fasciitis after peripheral nerve catheter placement.

Peripheral nerve conduits: technology update

PubMed Central

Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

2014-01-01

Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis.

PubMed

Koff, Matthew D; Cohen, Jeffrey A; McIntyre, John J; Carr, Charles F; Sites, Brian D

2008-02-01

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.

Habilitation of facial nerve dysfunction after resection of a vestibular schwannoma.

PubMed

Rudman, Kelli L; Rhee, John S

2012-04-01

Facial nerve dysfunction after resection of a vestibular schwannoma is one of the most common indications for facial nerve habilitation. This article presents an overview of common and emerging management options for facial habilitation following resection of a vestibular schwannoma. Immediate and delayed nerve repair options, as well as adjunctive surgical, medical, and physical therapies for facial nerve dysfunction, are discussed. Two algorithms are provided as guides for the assessment and treatment of facial nerve paralysis after resection of vestibular schwannoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

PubMed Central

Ogawa, Teruyuki; Miyazato, Minoru; Kitta, Takeya; Furuta, Akira; Chancellor, Michael B.; Tyagi, Pradeep

2014-01-01

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed. PMID:24578802

21 CFR 868.2775 - Electrical peripheral nerve stimulator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... a device used to apply an electrical current to a patient to test the level of pharmacological... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve...

21 CFR 868.2775 - Electrical peripheral nerve stimulator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... a device used to apply an electrical current to a patient to test the level of pharmacological... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve...

Advances and Future Applications of Augmented Peripheral Nerve Regeneration

PubMed Central

Jones, Salazar; Eisenberg, Howard M.; Jia, Xiaofeng

2016-01-01

Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested. PMID:27618010

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath (MPNST) Tumors and Plexiform Neurofibromas (PN)

DTIC Science & Technology

2012-09-01

TITLE: Convection-Enhanced Delivery ( CED ) in an Animal Model of Malignant Peripheral Nerve Sheath ( MPNST ) Tumors and Plexiform Neurofibromas (PN...within the sciatic nerve. 15. SUBJECT TERMS Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas...determine the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural

Electrodiagnosis and nerve conduction studies.

PubMed

Posuniak, E A

1984-08-01

The use of electrodiagnostic techniques in evaluation of complaints in the lower extremities provides an objective method of assessment. A basic understanding of principles of neurophysiology, EMG and NCV methodology, and neuropathology of peripheral nerves greatly enhances physical diagnosis and improves the state of the art in treatment of the lower extremity, especially foot and ankle injuries. Familiarity with the method of reporting electrodiagnostic studies and appreciation of the electromyographer's interpretation of the EMG/NCV studies also reflects an enhanced fund of knowledge, skills, and attitudes as pertains to one's level of professional expertise. Information regarding the etiology of positive sharp waves, fibrillation potentials, fasciculation, and normal motor action potentials and conduction studies serves as a sound basis for the appreciation of the categories of nerve injury. Competence in understanding the degree of axonal or myelin function or dysfunction in a nerve improve one's effectiveness not only in medical/surgical treatment but in prognostication of recovery of function. A review of the entrapment syndromes in the lower extremity with emphasis on tarsal tunnel syndrome summarizes the most common nerve entrapments germane to the practice of podiatry. With regard to tarsal tunnel syndrome, the earliest electrodiagnostic study to suggest compression was reported to be the EMG of the foot and leg muscles, even before prolonged nerve latency was noted.

Electrochemical skin conductance to detect sudomotor dysfunction, peripheral neuropathy and the risk of foot ulceration among Saudi patients with diabetes mellitus.

PubMed

Sheshah, Eman; Madanat, Amal; Al-Greesheh, Fahad; Al-Qaisi, Dalal; Al-Harbi, Mohammad; Aman, Reem; Al-Ghamdi, Abdul Aziz; Al-Madani, Khaled

2015-01-01

Sudomotor dysfunction is manifested clinically as abnormal sweating leading to dryness of feet skin and increased risk of foot ulceration. The aim of this study was to test the performance of foot electrochemical skin conductance (ESC) to detect diabetic peripheral neuropathy and the risk of foot ulceration against traditional methods in Saudi patients with diabetes mellitus. This cross-sectional study was conducted on 296 Saudi patients with diabetes mellitus. Painful neuropathic symptoms were evaluated using the neuropathy symptom score (NSS). The risk of foot ulceration and diabetic peripheral neuropathy were determined using the neuropathy disability score (NDS). Vibration perception threshold (VPT) was assessed using neurothesiometer. Neurophysiological assessment of the right and left sural, peroneal and tibial nerves was performed in 222 participants. Diabetic peripheral neuropathy was defined according to the definition of the American Academy of Neurology. ESC was measured with Sudoscan. Feet-ESC decreased as the scores of sensory and motor function tests increased. Feet-ESC decreased as the NSS, NDS and severity of diabetic peripheral neuropathy increased. Sensitivity of feet-ESC < 50μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 90.1, 61 and 63.8 % respectively and specificity 77, 85 and 81.9 % respectively. Sensitivity of feet-ESC < 70μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 100, 80.6 and 80.9 % respectively. Sensitivity and specificity of feet-ESC < 70μS to detect confirmed-diabetic peripheral neuropathy were 67.5 and 58.9 % respectively. Sudoscan a simple and objective tool can be used to detect diabetic peripheral neuropathy and the risk of foot ulceration among patients with diabetes mellitus. Prospective studies to confirm our results are warranted.

Resident Exposure to Peripheral Nerve Surgical Procedures During Residency Training

PubMed Central

Gil, Joseph A.; Daniels, Alan H.; Akelman, Edward

2016-01-01

Background Variability in case exposures has been identified for orthopaedic surgery residents. It is not known if this variability exists for peripheral nerve procedures. Objective The objective of this study was to assess ACGME case log data for graduating orthopaedic surgery, plastic surgery, general surgery, and neurological surgery residents for peripheral nerve surgical procedures and to evaluate intraspecialty and interspecialty variability in case volume. Methods Surgical case logs from 2009 to 2014 for the 4 specialties were compared for peripheral nerve surgery experience. Peripheral nerve case volume between specialties was performed utilizing a paired t test, 95% confidence intervals were calculated, and linear regression was calculated to assess the trends. Results The average number of peripheral nerve procedures performed per graduating resident was 54.2 for orthopaedic surgery residents, 62.8 for independent plastic surgery residents, 84.6 for integrated plastic surgery residents, 22.4 for neurological surgery residents, and 0.4 for surgery residents. Intraspecialty comparison of the 10th and 90th percentile peripheral nerve case volume in 2012 revealed remarkable variability in training. There was a 3.9-fold difference within orthopaedic surgery, a 5.0-fold difference within independent plastic surgery residents, an 8.8-fold difference for residents from integrated plastic surgery programs, and a 7.0-fold difference within the neurological surgery group. Conclusions There is interspecialty and intraspecialty variability in peripheral nerve surgery volume for orthopaedic, plastic, neurological, and general surgery residents. Caseload is not the sole determinant of training quality as mentorship, didactics, case breadth, and complexity play an important role in training. PMID:27168883

Comparison of Nerve Excitability Testing, Nerve Conduction Velocity, and Behavioral Observations for Acrylamide Induced Peripheral Neuropathy

EPA Science Inventory

Nerve excitability (NE) testing is a sensitive method to test for peripheral neurotoxicity in humans,and may be more sensitive than compound nerve action potential (CNAP) or nerve conduction velocity (NCV).We used acrylamide to compare the NE and CNAP/NCV methods. Behavioral test...

Optical cuff for optogenetic control of the peripheral nervous system.

PubMed

Michoud, Frédéric; Sottas, Loïc; Browne, Liam E; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J; Lacour, Stéphanie P

2018-02-01

Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Here, we propose an optical peripheral nerve interface-an optocuff-, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

Optical cuff for optogenetic control of the peripheral nervous system

NASA Astrophysics Data System (ADS)

Michoud, Frédéric; Sottas, Loïc; Browne, Liam E.; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J.; Lacour, Stéphanie P.

2018-02-01

Objective. Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Approach. Here, we propose an optical peripheral nerve interface—an optocuff—, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Main results. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. Significance. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

Ultrasound-guided peripheral nerve interventions for common pain disorders

PubMed Central

Krishna Prasad, B P; Joy, Binu; Raghavendra, Vijayakumar A; Toms, Ajith; George, Danny; Ray, Brijesh

2018-01-01

There are a number of common pain disorders that can be managed effectively by injections around or ablation of peripheral nerves. Ultrasound is a universally available imaging tool, is safe, cost-effective, and is excellent in imaging many peripheral nerves and guiding needles to the site of the nerves. This article aims to present an overview of indications and techniques of such procedures that can be effectively performed by a radiologist. PMID:29692534

Debates to personal conclusion in peripheral nerve injury and reconstruction: A 30-year experience at Chang Gung Memorial Hospital

PubMed Central

Chuang, David Chwei-Chin

2016-01-01

Significant progress has been achieved in the science and management of peripheral nerve injuries over the past 40 years. Yet there are many questions and few answers. The author, with 30 years of experience in treating them at the Chang Gung Memorial Hospital, addresses debates on various issues with personal conclusions. These include: (1) Degree of peripheral nerve injury, (2) Timing of nerve repair, (3)Technique of nerve repair, (4) Level of brachial plexus injury,(5) Level of radial nerve injury,(6) Traction avulsion amputation of major limb, (7) Proximal Vs distal nerve transfers in brachial plexus injuries and (8) Post paralysis facial synkinesis. PMID:27833273

Updating the mild encephalitis hypothesis of schizophrenia.

PubMed

Bechter, K

2013-04-05

Schizophrenia seems to be a heterogeneous disorder. Emerging evidence indicates that low level neuroinflammation (LLNI) may not occur infrequently. Many infectious agents with low overall pathogenicity are risk factors for psychoses including schizophrenia and for autoimmune disorders. According to the mild encephalitis (ME) hypothesis, LLNI represents the core pathogenetic mechanism in a schizophrenia subgroup that has syndromal overlap with other psychiatric disorders. ME may be triggered by infections, autoimmunity, toxicity, or trauma. A 'late hit' and gene-environment interaction are required to explain major findings about schizophrenia, and both aspects would be consistent with the ME hypothesis. Schizophrenia risk genes stay rather constant within populations despite a resulting low number of progeny; this may result from advantages associated with risk genes, e.g., an improved immune response, which may act protectively within changing environments, although they are associated with the disadvantage of increased susceptibility to psychotic disorders. Specific schizophrenic symptoms may arise with instances of LLNI when certain brain functional systems are involved, in addition to being shaped by pre-existing liability factors. Prodrome phase and the transition to a diseased status may be related to LLNI processes emerging and varying over time. The variability in the course of schizophrenia resembles the varying courses of autoimmune disorders, which result from three required factors: genes, the environment, and the immune system. Preliminary criteria for subgrouping neurodevelopmental, genetic, ME, and other types of schizophrenias are provided. A rare example of ME schizophrenia may be observed in Borna disease virus infection. Neurodevelopmental schizophrenia due to early infections has been estimated by others to explain approximately 30% of cases, but the underlying pathomechanisms of transition to disease remain in question. LLNI (e.g. from reactivation related to persistent infection) may be involved and other pathomechanisms including dysfunction of the blood-brain barrier or the blood-CSF barrier, CNS-endogenous immunity and the volume transmission mode balancing wiring transmission (the latter represented mainly by synaptic transmission, which is often described as being disturbed in schizophrenia). Volume transmission is linked to CSF signaling; and together could represent a common pathogenetic link for the distributed brain dysfunction, dysconnectivity, and brain structural abnormalities observed in schizophrenia. In addition, CSF signaling may extend into peripheral tissues via the CSF outflow pathway along brain nerves and peripheral nerves, and it may explain the peripheral topology of neuronal dysfunctions found, like in olfactory dysfunction, dysautonomia, and even in peripheral tissues, i.e., the muscle lesions that were found in 50% of cases. Modulating factors in schizophrenia, such as stress, hormones, and diet, are also modulating factors in the immune response. Considering recent investigations of CSF, the ME schizophrenia subgroup may constitute approximately 40% of cases. Copyright © 2012 Elsevier Inc. All rights reserved.

Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

PubMed

Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

2017-04-01

Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

Emerging nanotechnology approaches in tissue engineering for peripheral nerve regeneration.

PubMed

Cunha, Carla; Panseri, Silvia; Antonini, Stefania

2011-02-01

Effective nerve regeneration and functional recovery subsequent to peripheral nerve injury is still a clinical challenge. Autologous nerve graft transplantation is a feasible treatment in several clinical cases, but it is limited by donor site morbidity and insufficient donor tissue, impairing complete functional recovery. Tissue engineering has introduced innovative approaches to promote and guide peripheral nerve regeneration by using biomimetic conduits creating favorable microenvironments for nervous ingrowth, but despite the development of a plethora of nerve prostheses, few approaches have as yet entered the clinic. Promising strategies using nanotechnology have recently been proposed, such as the use of scaffolds with functionalized cell-binding domains, the use of guidance channels with cell-scale internally oriented fibers, and the possibility of sustained release of neurotrophic factors. This review addresses the fabrication, advantages, drawbacks, and results achieved by the most recent nanotechnology approaches in view of future solutions for peripheral nerve repair. Peripheral nerve repair strategies are very limited despite numerous advances on the field of neurosciences and regenerative medicine. This review discusses nanotechnology based strategies including scaffolds with functionalized cell binding domains, the use of guidance channels, and the potential use of sustained release neurotropic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway.

PubMed

Jiang, Bo; Zhang, Yong; She, Chang; Zhao, Jiaju; Zhou, Kailong; Zuo, Zhicheng; Zhou, Xiaozhong; Wang, Peiji; Dong, Qirong

2017-09-01

It is well known that moderate to high doses of ionizing radiation have a toxic effect on the organism. However, there are few experimental studies on the mechanisms of LDR ionizing radiation on nerve regeneration after peripheral nerve injury. We established the rats' peripheral nerve injury model via repaired Peripheral nerve injury nerve, vascular endothelial growth factor a and Growth associated protein-43 were detected from different treatment groups. We performed transcriptome sequencing focusing on investigating the differentially expressed genes and gene functions between the control group and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA-seq) technologies. The results showed the 1Gy group to be the most effective promoting repair. RNA-sequencing identified 619 differently expressed genes between control and treated groups. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways. Among them, candidate genes associated with nerve repair were identified. Pathways involved in cell-substrate adhesion, vascular smooth muscle contraction and cell adhesion molecule signaling may be involved in recovery from peripheral nerve injury. Copyright © 2017. Published by Elsevier B.V.

In vivo targeted peripheral nerve imaging with a nerve-specific nanoscale magnetic resonance probe.

PubMed

Zheng, Linfeng; Li, Kangan; Han, Yuedong; Wei, Wei; Zheng, Sujuan; Zhang, Guixiang

2014-11-01

Neuroimaging plays a pivotal role in clinical practice. Currently, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET) are applied in the clinical setting as neuroimaging modalities. There is no optimal imaging modality for clinical peripheral nerve imaging even though fluorescence/bioluminescence imaging has been used for preclinical studies on the nervous system. Some studies have shown that molecular and cellular MRI (MCMRI) can be used to visualize and image the cellular and molecular level of the nervous system. Other studies revealed that there are different pathological/molecular changes in the proximal and distal sites after peripheral nerve injury (PNI). Therefore, we hypothesized that in vivo peripheral nerve targets can be imaged using MCMRI with specific MRI probes. Specific probes should have higher penetrability for the blood-nerve barrier (BNB) in vivo. Here, a functional nanometre MRI probe that is based on nerve-specific proteins as targets, specifically, using a molecular antibody (mAb) fragment conjugated to iron nanoparticles as an MRI probe, was constructed for further study. The MRI probe allows for imaging the peripheral nerve targets in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synovial sarcoma of nerve.

PubMed

Scheithauer, Bernd W; Amrami, Kimberly K; Folpe, Andrew L; Silva, Ana I; Edgar, Mark A; Woodruff, James M; Levi, Allan D; Spinner, Robert J

2011-04-01

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome. Copyright © 2011. Published by Elsevier Inc.

Phrenic nerve palsy associated with birth trauma--case reports and a literature review.

PubMed

Shiohama, Tadashi; Fujii, Katsunori; Hayashi, Masaharu; Hishiki, Tomoro; Suyama, Maiko; Mizuochi, Hiromi; Uchikawa, Hideki; Yoshida, Shigetoshi; Yoshida, Hideo; Kohno, Yoichi

2013-04-01

Phrenic nerve palsy is a peripheral nerve disorder caused by excessive cervical extension due to birth trauma or cardiac surgery. We describe two new patients with phrenic nerve palsy associated with birth trauma. Both patients exhibited profound dyspnea and general hypotonia immediately after birth. A chest roentgenogram and fluoroscopy revealed elevation of the diaphragm, leading to a diagnosis of phrenic nerve palsy associated with birth trauma. Since they had intermittently exhibited dyspnea and recurrent infection, we performed video-assisted thoracoscopic surgery (VATS) plication in both cases, at an early and a late stage, respectively. Both patients subsequently exhibited a dramatic improvement in dyspnea and recurrent respiratory infection. Interestingly, the late stage operated infant exhibited spontaneous recovery at 7 months with cessation of mechanical ventilation once. However, this recovery was transient and subsequently led to an increased ventilation volume demand, finally resulting in surgical treatment at 15 months. Histological examination of the diaphragm at this time showed grouped muscle atrophy caused by phrenic nerve degeneration. To our knowledge, this is the first pathologically proven report of grouped muscle atrophy of the diaphragm due to phrenic nerve degeneration, suggesting that partial impairment of phrenic nerves resulted in respiratory dysfunction with incomplete recovery. We conclude that recently developed VATS plication is a safe and effective treatment for infants with phrenic nerve palsy, and should be considered as a surgical treatment at an early period. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A study of tapping by the unaffected finger of patients presenting with central and peripheral nerve damage.

PubMed

Zhang, Lingli; Han, Xiuying; Li, Peihong; Liu, Yang; Zhu, Yulian; Zou, Jun; Yu, Zhusheng

2015-01-01

Whether the unaffected function of the hand of patients presenting with nerve injury is affected remains inconclusive. We aimed to evaluate whether there are differences in finger tapping following central or peripheral nerve injury compared with the unaffected hand and the ipsilateral hand of a healthy subject. Thirty right brain stroke patients with hemiplegia, 30 left arm peripheral nerve injury cases, and 60 healthy people were selected. We tested finger tapping of the right hands, and each subject performed the test twice. Finger tapping following peripheral nerve injury as compared with the unaffected hand and the dominant hand of a healthy person was markedly higher than was found for central nerve injury (P < 0.05). Finger tapping of the male peripheral group's unaffected hand and the control group's dominant hand was significantly higher than the central group (P < 0.001). However, finger tapping of the female control group's dominant hand was significantly higher than the central group's unaffected hand (P < 0.01, P = 0.002), the peripheral group's unaffected hand (P < 0.05, P = 0.034). The unaffected function of the hand of patients with central and peripheral nerve injury was different as compared with the ipsilateral hand of healthy individuals. The rehabilitation therapist should intensify the practice of normal upper limb fine activities and coordination of the patient.

[Blood-nerve barrier and peripheral nerve regeneration].

PubMed

Kanda, Takashi

2013-01-01

Blood-nerve barrier (BNB) restricts the movement of soluble mediators and leukocytes from the blood contents to the peripheral nervous system (PNS) parenchyma and thus maintains the endoneurial homeostasis. However, it interferes the supply of various neurotrophic factors from the blood constituents and stops the drainage of toxic substances out of the PNS parenchyma, resulting in the inhibition of peripheral nerve regeneration. If the manipulation of BNB function is possible, regeneration of peripheral nerve may be facilitated via the alteration of peripheral nerve microenvironment and ample supply of neurotrophic substances. A possible method to manipulate the BNB for therapeutic purposes is to modify the endothelial function using siRNAs, oligonucleotides and virus vectors. Another possible method is to modify BNB pericytes: small hydrophobic substances that can reach the pericyte membrane through the endothelial monolayer and strengthen the pericytic activity, including the release of various cytokines/chemokines that influence endothelial function, may also be useful as drug candidates to control the BNB function.

A silk sericin/silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve.

PubMed

Xie, Hongjian; Yang, Wen; Chen, Jianghai; Zhang, Jinxiang; Lu, Xiaochen; Zhao, Xiaobo; Huang, Kun; Li, Huili; Chang, Panpan; Wang, Zheng; Wang, Lin

2015-10-28

Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.

PubMed

Sugimura-Wakayama, Yukiko; Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Ogata, Kenichi; Sakaguchi, Kohei; Hibi, Hideharu

2015-11-15

Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

Stimulating effect of thyroid hormones in peripheral nerve regeneration: research history and future direction toward clinical therapy

PubMed Central

Barakat-Walter, I.; Kraftsik, R.

2018-01-01

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions. Despite extensive investigation, testing various surgical repair techniques and neurotrophic molecules, at present, a satisfactory method to ensuring successful recovery does not exist. For successful molecular therapy in nerve regeneration, it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth. Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination. Therefore, any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration. Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system, so they could be candidates for nervous system regeneration. This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration. Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves. We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves, and accelerates functional recovering. This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves. The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells. PMID:29722302

Nervous system (image)

MedlinePlus

Peripheral Neuropathy is not a distinct disease, but the manifestation of many conditions that damage the peripheral nerves ( ... abnormal. Damaged motor nerves impair movement or function. Peripheral neuropathy may be caused by direct or indirect injury, ...

Benign Peripheral Nerve Sheath Tumor in a Wild Toco Toucan ( Ramphastos toco ).

PubMed

Carvalho, Marcelo P N; Fernandes, Natalia C C A; Nemer, Viviane C; Neto, Ramiro N Dias; Teixeira, Rodrigo H F; Miranda, Bruna S; Mamprim, Maria J; Catão-Dias, José L; Réssio, Rodrigo A

2016-09-01

Peripheral nerve sheath tumors are a heterogeneous group of neoplasms that comprise neurofibromas, schwannomas, neurilemmomas, and perineuromas. In animals, peripheral nerve sheath neoplasms are most commonly diagnosed in dogs and cattle, followed by horses, goats, and cats, but their occurrence is uncommon in birds. An adult, free-living, male toco (common) toucan ( Ramphastos toco ) was admitted to the zoo animal clinic with weight loss, dehydration, and presence of a soft nodule adhered to the medial portion of the left pectoral muscle. Clinical, cytologic, and computed tomography scan results were indicative of a neoplasm. The toucan died during surgical resection of the mass. Necropsy, histopathologic, and immunohistochemical findings confirmed the diagnosis of benign peripheral nerve sheath tumor. To our knowledge, benign peripheral nerve sheath tumor has not previously been reported in a toucan or any other species in the order Piciformes.

Overview of pediatric peripheral facial nerve paralysis: analysis of 40 patients.

PubMed

Özkale, Yasemin; Erol, İlknur; Saygı, Semra; Yılmaz, İsmail

2015-02-01

Peripheral facial nerve paralysis in children might be an alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery, and hypertension. The cases of 40 consecutive children and adolescents who were diagnosed with peripheral facial nerve paralysis at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. We determined that the most common cause was Bell palsy, followed by infection, tumor lesion, and suspected chemotherapy toxicity. We noted that younger patients had generally poorer outcome than older patients regardless of disease etiology. Peripheral facial nerve paralysis has been reported in many countries in America and Europe; however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. The present study demonstrated that Bell palsy and infection were the most common etiologies of peripheral facial nerve paralysis. © The Author(s) 2014.

Stem cell and peripheral nerve injury and repair.

PubMed

Dong, Ming-min; Yi, Tian-hua

2010-10-01

Peripheral motor nerve injuries are a significant source of morbidity. Neural stem cells (NSCs), a group of relatively primitive cells, possess self-renewal ability and multidifferentiation potential. NSCs may be successfully separated from the human embryo and central nervous system (CNS) and differentiated into mature neurons and gliacytes by in vitro induction or transplantation into the body and may be differentiated into Schwann-like cells under specific conditions. It has been demonstrated that the ability of peripheral nerves to regenerate is mainly attributable to Schwann cells. NSC transplantation can promote peripheral nerve regeneration and provide a new means for treatment of peripheral nerve injury. In recent years, the study of NSCs has become a focus of many laboratories, but the biological characteristics and differentiation regulation mechanisms are not fully clear. In this article, we provide a brief review of NSC characteristics, cultivation, oriented differentiation, and clinical application. © Thieme Medical Publishers.

Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

DTIC Science & Technology

2016-04-01

faster regeneration and functional recovery. Peripheral nerve injury is a common complication of complex tissue trauma and often results in significant...having poor regeneration overall, the areas of regenerating nerve tissue could often be found in sections of the nerve guide where luminal spaces of...conducted in this Aim also provided important insight into the NGC design parameters necessary to allow for maximum nerve tissue ingrowth and regeneration

Quantitative magnetic resonance (MR) neurography for evaluation of peripheral nerves and plexus injuries

PubMed Central

Barousse, Rafael; Socolovsky, Mariano; Luna, Antonio

2017-01-01

Traumatic conditions of peripheral nerves and plexus have been classically evaluated by morphological imaging techniques and electrophysiological tests. New magnetic resonance imaging (MRI) studies based on 3D fat-suppressed techniques are providing high accuracy for peripheral nerve injury evaluation from a qualitative point of view. However, these techniques do not provide quantitative information. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are functional MRI techniques that are able to evaluate and quantify the movement of water molecules within different biological structures. These techniques have been successfully applied in other anatomical areas, especially in the assessment of central nervous system, and now are being imported, with promising results for peripheral nerve and plexus evaluation. DWI and DTI allow performing a qualitative and quantitative peripheral nerve analysis, providing valuable pathophysiological information about functional integrity of these structures. In the field of trauma and peripheral nerve or plexus injury, several derived parameters from DWI and DTI studies such as apparent diffusion coefficient (ADC) or fractional anisotropy (FA) among others, can be used as potential biomarkers of neural damage providing information about fiber organization, axonal flow or myelin integrity. A proper knowledge of physical basis of these techniques and their limitations is important for an optimal interpretation of the imaging findings and derived data. In this paper, a comprehensive review of the potential applications of DWI and DTI neurographic studies is performed with a focus on traumatic conditions, including main nerve entrapment syndromes in both peripheral nerves and brachial or lumbar plexus. PMID:28932698

4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury

PubMed Central

Boyer, Richard B.; Kelm, Nathaniel D.; Riley, D. Colton; Sexton, Kevin W.; Pollins, Alonda C.; Shack, R. Bruce; Dortch, Richard D.; Nanney, Lillian B.; Does, Mark D.; Thayer, Wesley P.

2015-01-01

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries. PMID:26323827

Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies.

PubMed

Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki

2011-06-01

Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

The first radiographic image of a peripheral nerve disorder? Lipomatous macrodactyly (unrecognized lipomatosis of nerve).

PubMed

Mahan, Mark A; Prasad, Nikhil; Spinner, Robert J

2015-06-01

Lipomatosis of nerves (LN) involves benign fibro-fatty infiltration and is often associated with territorial overgrowth of soft tissue and bone; this distinctive disease pattern can be visualized on plain radiographs. We recently discovered a case (presented by Sir Robert Jones in 1898 to the Pathological Society of London) that indirectly represents a historical landmark in the imaging of peripheral nerves. The clinical findings and image, with obvious soft tissue and bone overgrowth, are pathognomonic for LN, making this one of the earliest radiological observations of a peripheral nerve lesion.

A Bionic Neural Link for peripheral nerve repair.

PubMed

Xu, Yong Ping; Yen, Shih-Cheng; Ng, Kian Ann; Liu, Xu; Tan, Ter Chyan

2012-01-01

Peripheral nerve injuries with large gaps and long nerve regrowth paths are difficult to repair using existing surgical techniques, due to nerve degeneration and muscle atrophy. This paper proposes a Bionic Neural Link (BNL) as an alternative way for peripheral nerve repair. The concept of the BNL is described, along with the hypothetical benefits. A prototype monolithic single channel BNL has been developed, which consists of 16 neural recording channels and one stimulation channel, and is implemented in a 0.35-µm CMOS technology. The BNL has been tested in in-vivo animal experiments. Full function of the BNL chip has been demonstrated.

Clinical neurophysiology and quantitative sensory testing in the investigation of orofacial pain and sensory function.

PubMed

Jääskeläinen, Satu K

2004-01-01

Chronic orofacial pain represents a diagnostic and treatment challenge for the clinician. Some conditions, such as atypical facial pain, still lack proper diagnostic criteria, and their etiology is not known. The recent development of neurophysiological methods and quantitative sensory testing for the examination of the trigeminal somatosensory system offers several tools for diagnostic and etiological investigation of orofacial pain. This review presents some of these techniques and the results of their application in studies on orofacial pain and sensory dysfunction. Clinical neurophysiological investigation has greater diagnostic accuracy and sensitivity than clinical examination in the detection of the neurogenic abnormalities of either peripheral or central origin that may underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological testing may also reveal trigeminal pathology when magnetic resonance imaging has failed to detect it, so these methods should be considered complementary to each other in the investigation of orofacial pain patients. The blink reflex, corneal reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the recording of trigeminal somatosensory-evoked potentials with near-nerve stimulation have all proved to be sensitive and reliable in the detection of dysfunction of the myelinated sensory fibers of the trigeminal nerve or its central connections within the brainstem. With appropriately small thermodes, thermal quantitative sensory testing is useful for the detection of trigeminal small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most sensitive to lesions causing axonal injury. By combining different techniques for investigation of the trigeminal system, an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. Neurophysiological and quantitative sensory tests have already highlighted some similarities among various orofacial pain conditions and have shown heterogeneity within clinical diagnostic categories. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.

Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

PubMed

Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

2015-12-01

During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The prevalence of early subclinical somatic neuropathy in children and adolescents with Type 1 diabetes mellitus and its association with the persistence of autoantibodies to glutamic acid decarboxylase (GAD) and islet antigen-2 (IA-2).

PubMed

Louraki, Maria; Katsalouli, Marina; Kanaka-Gantenbein, Christina; Kafassi, Nikolitsa; Critselis, Eleni; Kallinikou, Dimitra; Tsentidis, Charalampos; Karavanaki, Kyriaki

2016-07-01

To evaluate the prevalence of early somatic neuropathy in children and adolescents with Type 1 diabetes mellitus (Type 1 DM) and its association with the presence of glutamic acid decarboxylase and islet antigen-2 autoantibodies (GADA and IA-2A). A cross-sectional study was conducted in a hospital-based cohort of pediatric Type 1 DM patients (n=85, mean(±SD) age: 13.5±3.4years, mean(±SD) disease duration 5.5±3.4years). Peripheral neuropathy was assessed with nerve conduction studies (NCS). GADA and IA-2A titers were measured with radioligand assays. Among the study population, 34.1% had at least one abnormal electrophysiological parameter, although predominantly asymptomatic. The highest rates of abnormality were detected in sensory peroneal nerve (25.9%) followed by sural nerve (15.3%). Affected patients were not different in terms of age, diabetes duration or glycaemic control. Among the participants, 62.4% had positive GADA, 58.8% positive IA-2A and 42.4% double antibody positivity. Abnormal NCS correlated neither with GADA nor with IA-2A levels or positivity. However lower sensory nerve action potential in the peroneal nerve, indicative of early axonal dysfunction, was observed in patients with GADA or IA-2A positivity. Absence of both antibodies was associated with better action potentials in all the examined nerves of the lower limbs. Impaired indices of subclinical peripheral primarily sensory neuropathy were present among one third of Type 1 DM children and adolescents, with no impact of diabetes duration or glycaemic control. GADA and IA-2A seem to be involved in the development of axonal degeneration, in a pathway which remains to be identified. Copyright © 2016. Published by Elsevier Ireland Ltd.

[Correlation between facial nerve functional evaluation and efficacy evaluation of acupuncture treatment for Bell's palsy].

PubMed

Zhou, Zhang-ling; Li, Cheng-xin; Jiang, Yue-bo; Zuo, Cong; Cai, Yun; Wang, Rui

2012-09-01

To assess and grade facial nerve dysfunction according to the extent of facial paralysis in the clinical course of acupuncture treatment for Bell's palsy, and to observe the interrelationship between the grade, the efficacy and the period of treatment, as well as the effect on prognosis. The authors employed the House-Brackmann scale, a commonly used evaluation scale for facial paralysis motor function, and set standards for eye fissure and lips. According to the improved scale, the authors assessed and graded the degree of facial paralysis in terms of facial nerve dysfunction both before and after treatment. The grade was divided into five levels: mild, moderate, moderately severe, severe dysfunction and complete paralysis. The authors gave acupuncture treatment according to the state of the disease without artificially setting the treatment period. The observation was focused on the efficacy and the efficacy was evaluated throughout the entire treatment process. Fifty-three cases out of 68 patients with Bell's palsy were cured and the overall rate of efficacy was 97%. Statistically significant differences (P<0.01) were perceived among the efficacy of five levels of facial nerve dysfunction. Efficacy was correlated with the damage level of the disease (correlation coefficient r=0.423, P<0.01). The course of treatment also extended with the severity of facial nerve dysfunction (P<0.01). Differences exist in patients with Bell's palsy in terms of severity of facial nerve dysfunction. Efficacy is reduced in correlation with an increase in facial nerve dysfunction, and the period of treatment varies in need of different levels of facial nerve dysfunction. It is highly necessary to assess and grade patients before observation and treatment in clinical study, and choose corresponding treatment according to severity of damage of the disease.

Health effect of agricultural pesticide use in China: implications for the development of GM crops

PubMed Central

Zhang, Chao; Hu, Ruifa; Huang, Jikun; Huang, Xusheng; Shi, Guanming; Li, Yifan; Yin, Yanhong; Chen, Zhaohui

2016-01-01

It is notable that the adoption of GM glyphosate-tolerant crops increases glyphosate use but reduces non-glyphosate herbicide use; and adoption of GM insect-resistant crops significantly reduces insecticide use. While the health hazard of pesticide use has been well documented, little literature evaluates the health effects of different pesticides related to GM crops in an integrated framework. This study aims to associate the uses of different pesticides related to GM crops with the blood chemistry panel and peripheral nerve conduction of Chinese farmers. Pesticides used by farmers were recorded and classified as glyphosate, non-glyphosate herbicides, chemical lepidopteran insecticides, biological lepidopteran insecticides, non-lepidopteran insecticides and fungicides. The multivariate regression results show that none of the examined 35 health indicators was associated with glyphosate use, while the use of non-glyphosate herbicides was likely to induce renal dysfunction and decrease of serum folic acid. The use of chemical lepidopteran insecticides might be associated with hepatic dysfunction, serum glucose elevation, inflammation and even severe nerve damage. In this context, if GM crops are adopted, the alterations in pesticide use may benefit farmer health in China and globe, which has positive implications for the development of GM crops. PMID:27721390

[Clinical report of hereditary motor and sensory neuropathy with proximal dominance in Shiga prefecture].

PubMed

Takahashi, Mitsuo; Mitsui, Yoshiyuki; Yorifuji, Shiro; Nakamura, Yuusaku; Tsukamoto, Yoshihumi; Nishimoto, Kazuhiro

2007-09-01

We followed eight hereditary motor and sensory neuropathy patients with proximal dominance (HMSN-P) in Shiga prefecture from 1984 to 2007. There were 4 men and 4 women from two families showing autosomal and dominant prepotency. These families were related by marriage. The average onset of disease was at 53.4 +/- 8.9 (40-68) years-old. Initial symptoms were difficulty of standing up, difficulty elevating their arms, limping, or numbness. The main feature was neurogenic muscular atrophy with proximal dominance. All deep tendon reflexes were decreased or nonexistent. Paresthesia in the hands and feet and/or decreased vibratory sense in the legs were found in six patients. High CK blood levels were recognized in three patients. EMG in four patients revealed neurogenic pattern. Nerve conduction study was conducted in two patients. MCV of the median nerve and of the tibial posterior nerve, also SCV of the median nerve and of the sural nerve were within normal range in all nerves. Amplitudes of sensory action potential or of M wave were decreased or nonexistent in five of eight nerves, and distal latency of M waves was delayed in three of four nerves. These data suggests dysfunction of distal parts of the peripheral nerve fibers and axonal degeneration of the nerve trunk. Seven patients have died, and their average death age was 69.1 +/- 8.2 (52-77) years-old. Their average affected period was 16.6 (4-30) years. Their clinical history resembles Okinawa-type HMSN-P, but without the painful muscle cramps which are distinctive Okinawa-type signs.

A 3D-engineered porous conduit for peripheral nerve repair

PubMed Central

Tao, Jie; Hu, Yu; Wang, Shujuan; Zhang, Jiumeng; Liu, Xuan; Gou, Zhiyuan; Cheng, Hao; Liu, Qianqi; Zhang, Qianqian; You, Shenglan; Gou, Maling

2017-01-01

End-to-end neurorrhaphy is the most commonly used method for treating peripheral nerve injury. However, only 50% of patients can regain useful function after treating with neurorrhaphy. Here, we constructed a 3D-engineered porous conduit to promote the function recovery of the transected peripheral nerve after neurorrhaphy. The conduit that consisted of a gelatin cryogel was prepared by molding with 3D-printed moulds. Due to its porous structure and excellent mechanical properties, this conduit could be collapsed by the mechanical force and resumed its original shape after absorption of normal saline. This shape-memory property allowed a simply surgery process for installing the conduits. Moreover, the biodegradable conduit could prevent the infiltration of fibroblasts and reduce the risk of scar tissue, which could provide an advantageous environment for nerve regeneration. The efficiency of the conduits in assisting peripheral nerve regeneration after neurorrhaphy was evaluated in a rat sciatic nerve transected model. Results indicated that conduits significantly benefitted the recovery of the transected peripheral nerve after end-to-end neurorrhaphy on the static sciatic index (SSI), electrophysiological results and the re-innervation of the gastrocnemius muscle. This work demonstrates a biodegradable nerve conduit that has potentially clinical application in promoting the neurorrhaphy. PMID:28401914

Radial nerve dysfunction (image)

MedlinePlus

The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

PubMed Central

Deng, Jiu-xu; Zhang, Dian-yin; Li, Ming; Weng, Jian; Kou, Yu-hui; Zhang, Pei-xun; Han, Na; Chen, Bo; Yin, Xiao-feng; Jiang, Bao-guo

2017-01-01

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification’ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect. PMID:29323049

Near-infrared signals associated with electrical stimulation of peripheral nerves

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

2009-02-01

We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration.

PubMed

Chang, Wei; Shah, Munish B; Lee, Paul; Yu, Xiaojun

2018-06-01

Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve. Results from this study can help further optimize tissue engineering strategies for peripheral nerve repair. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Use of Nerve Conduction Velocity to Assess Peripheral Nerve Health in Aging Mice

PubMed Central

Walsh, Michael E.; Sloane, Lauren B.; Fischer, Kathleen E.; Austad, Steven N.; Richardson, Arlan

2015-01-01

Nerve conduction velocity (NCV), the speed at which electrical signals propagate along peripheral nerves, is used in the clinic to evaluate nerve function in humans. A decline in peripheral nerve function is associated with a number of age-related pathologies. While several studies have shown that NCV declines with age in humans, there is little information on the effect of age on NCV in peripheral nerves in mice. In this study, we evaluated NCV in male and female C57Bl/6 mice ranging from 4 to 32 months of age. We observed a decline in NCV in both male and female mice after 20 months of age. Sex differences were detected in sensory NCV as well as the rate of decline during aging in motor nerves; female mice had slower sensory NCV and a slower age-related decline in motor nerves compared with male mice. We also tested the effect of dietary restriction on NCV in 30-month-old female mice. Dietary restriction prevented the age-related decline in sciatic NCV but not other nerves. Because NCV is clinically relevant to the assessment of nerve function, we recommend that NCV be used to evaluate healthspan in assessing genetic and pharmacological interventions that increase the life span of mice. PMID:25477428

Sensory and motor peripheral nerve function and lower-extremity quadriceps strength: the health, aging and body composition study.

PubMed

Strotmeyer, Elsa S; de Rekeneire, Nathalie; Schwartz, Ann V; Resnick, Helaine E; Goodpaster, Bret H; Faulkner, Kimberly A; Shorr, Ronald I; Vinik, Aaron I; Harris, Tamara B; Newman, Anne B

2009-11-01

To determine whether sensory and motor nerve function is associated cross-sectionally with quadriceps or ankle dorsiflexion strength in an older community-based population. Cross-sectional analyses within a longitudinal cohort study. Two U.S. clinical sites. Two thousand fifty-nine Health, Aging and Body Composition Study (Health ABC) participants (49.5% male, 36.7% black, aged 73-82) in 2000/01. Quadriceps and ankle strength were measured using an isokinetic dynamometer. Sensory and motor peripheral nerve function in the legs and feet was assessed using 10-g and 1.4-g monofilaments, vibration threshold, and peroneal motor nerve conduction amplitude and velocity. Monofilament insensitivity, poorest vibration threshold quartile (>60 mu), and poorest motor nerve conduction amplitude quartile (<1.7 mV) were associated with 11%, 7%, and 8% lower quadriceps strength (all P<.01), respectively, than in the best peripheral nerve function categories in adjusted linear regression models. Monofilament insensitivity and lowest amplitude quartile were both associated with 17% lower ankle strength (P<.01). Multivariate analyses were adjusted for demographic characteristics, diabetes mellitus, body composition, lifestyle factors, and chronic health conditions and included all peripheral nerve measures in the same model. Monofilament insensitivity (beta=-7.19), vibration threshold (beta=-0.097), and motor nerve conduction amplitude (beta=2.01) each contributed independently to lower quadriceps strength (all P<.01). Monofilament insensitivity (beta=-5.29) and amplitude (beta=1.17) each contributed independently to lower ankle strength (all P<.01). Neither diabetes mellitus status nor lean mass explained the associations between peripheral nerve function and strength. Reduced sensory and motor peripheral nerve function is related to poorer lower extremity strength in older adults, suggesting a mechanism for the relationship with lower extremity disability.

Peripheral nerve injuries secondary to missiles.

PubMed

Katzman, B M; Bozentka, D J

1999-05-01

Peripheral nerve injuries secondary to missiles can present some of the most challenging problems faced by hand surgeons. This article reviews the pertinent neural anatomy, injury classifications, and repair techniques. Options in the management of nerve gaps are presented including the use of vascularized nerve grafts. The results are discussed and a treatment algorithm is presented.

Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-13-1-0309 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Thomas L. Smith, PhD RECIPIENT: Wake Forest University Health Sciences

Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review

PubMed Central

Ghafoor, Usman; Kim, Sohee; Hong, Keum-Shik

2017-01-01

For those individuals with upper-extremity amputation, a daily normal living activity is no longer possible or it requires additional effort and time. With the aim of restoring their sensory and motor functions, theoretical and technological investigations have been carried out in the field of neuroprosthetic systems. For transmission of sensory feedback, several interfacing modalities including indirect (non-invasive), direct-to-peripheral-nerve (invasive), and cortical stimulation have been applied. Peripheral nerve interfaces demonstrate an edge over the cortical interfaces due to the sensitivity in attaining cortical brain signals. The peripheral nerve interfaces are highly dependent on interface designs and are required to be biocompatible with the nerves to achieve prolonged stability and longevity. Another criterion is the selection of nerves that allows minimal invasiveness and damages as well as high selectivity for a large number of nerve fascicles. In this paper, we review the nerve-machine interface modalities noted above with more focus on peripheral nerve interfaces, which are responsible for provision of sensory feedback. The invasive interfaces for recording and stimulation of electro-neurographic signals include intra-fascicular, regenerative-type interfaces that provide multiple contact channels to a group of axons inside the nerve and the extra-neural-cuff-type interfaces that enable interaction with many axons around the periphery of the nerve. Section Current Prosthetic Technology summarizes the advancements made to date in the field of neuroprosthetics toward the achievement of a bidirectional nerve-machine interface with more focus on sensory feedback. In the Discussion section, the authors propose a hybrid interface technique for achieving better selectivity and long-term stability using the available nerve interfacing techniques. PMID:29163122

Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

ERIC Educational Resources Information Center

Gordon, Tessa; Gordon, Karen

2010-01-01

Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

Neurophysiological mechanism of possibly confounding peripheral activation of the facial nerve during corticobulbar tract monitoring.

PubMed

Téllez, Maria J; Ulkatan, Sedat; Urriza, Javier; Arranz-Arranz, Beatriz; Deletis, Vedran

2016-02-01

To improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring. We applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract. A single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation. Our results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli. This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring. The failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Combining Gene and Stem Cell Therapy for Peripheral Nerve Tissue Engineering.

PubMed

Busuttil, Francesca; Rahim, Ahad A; Phillips, James B

2017-02-15

Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical challenge. Nerve regeneration following injury is dependent on Schwann cells, the supporting cells in the peripheral nervous system. Following nerve injury, Schwann cells adopt a proregenerative phenotype, which supports and guides regenerating nerves. However, this phenotype may not persist long enough to ensure functional recovery. Tissue-engineered nerve repair devices containing therapeutic cells that maintain the appropriate phenotype may help enhance nerve regeneration. The combination of gene and cell therapy is an emerging experimental strategy that seeks to provide the optimal environment for axonal regeneration and reestablishment of functional circuits. This review aims to summarize current preclinical evidence with potential for future translation from bench to bedside.

Interactive modeling and simulation of peripheral nerve cords in virtual environments

NASA Astrophysics Data System (ADS)

Ullrich, Sebastian; Frommen, Thorsten; Eckert, Jan; Schütz, Astrid; Liao, Wei; Deserno, Thomas M.; Ntouba, Alexandre; Rossaint, Rolf; Prescher, Andreas; Kuhlen, Torsten

2008-03-01

This paper contributes to modeling, simulation and visualization of peripheral nerve cords. Until now, only sparse datasets of nerve cords can be found. In addition, this data has not yet been used in simulators, because it is only static. To build up a more flexible anatomical structure of peripheral nerve cords, we propose a hierarchical tree data structure where each node represents a nerve branch. The shape of the nerve segments itself is approximated by spline curves. Interactive modeling allows for the creation and editing of control points which are used for branching nerve sections, calculating spline curves and editing spline representations via cross sections. Furthermore, the control points can be attached to different anatomic structures. Through this approach, nerve cords deform in accordance to the movement of the connected structures, e.g., muscles or bones. As a result, we have developed an intuitive modeling system that runs on desktop computers and in immersive environments. It allows anatomical experts to create movable peripheral nerve cords for articulated virtual humanoids. Direct feedback of changes induced by movement or deformation is achieved by visualization in real-time. The techniques and the resulting data are already used for medical simulators.

A magnetically responsive nanocomposite scaffold combined with Schwann cells promotes sciatic nerve regeneration upon exposure to magnetic field

PubMed Central

Huang, Liangliang; Sun, Zhen; Zeng, Wen; Huang, Jinghui; Luo, Zhuojing

2017-01-01

Peripheral nerve repair is still challenging for surgeons. Autologous nerve transplantation is the acknowledged therapy; however, its application is limited by the scarcity of available donor nerves, donor area morbidity, and neuroma formation. Biomaterials for engineering artificial nerves, particularly materials combined with supportive cells, display remarkable promising prospects. Schwann cells (SCs) are the absorbing seeding cells in peripheral nerve engineering repair; however, the attenuated biologic activity restricts their application. In this study, a magnetic nanocomposite scaffold fabricated from magnetic nanoparticles and a biodegradable chitosan–glycerophosphate polymer was made. Its structure was evaluated and characterized. The combined effects of magnetic scaffold (MG) with an applied magnetic field (MF) on the viability of SCs and peripheral nerve injury repair were investigated. The magnetic nanocomposite scaffold showed tunable magnetization and degradation rate. The MGs synergized with the applied MF to enhance the viability of SCs after transplantation. Furthermore, nerve regeneration and functional recovery were promoted by the synergism of SCs-loaded MGs and MF. Based on the current findings, the combined application of MGs and SCs with applied MF is a promising therapy for the engineering of peripheral nerve regeneration. PMID:29123395

The pattern of peripheral nerve injuries among Pakistani soldiers in the war against terror.

PubMed

Razaq, Sarah; Yasmeen, Rehana; Butt, Aamir Waheed; Akhtar, Noreen; Mansoor, Sahibzada Nasir

2015-05-01

To determine the pattern of peripheral nerve injuries in Pakistani soldiers in the War against terror. Case series. Department of Electrodiagnosis at Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi, Pakistan, from June 2008 to June 2011. All new cases of war wounded soldiers with peripheral nerve injuries were consecutively enrolled. Physical examination and electrodiagnostic study was carried out by experienced physiatrists. Data was entered in pretested especially designed questionnaire which was analysed using SPSS version 17.0. Seddon's classification system was used to assess the severity of injury. There were 418 cases of peripheral nerve injuries with 504 different nerve segments. Mean age was 29.41 ±8 years. Blast was the main cause of nerve injury in 244 (48.5%) cases followed by gunshot in 215 (42.7%) and 45 (8.9%) cases had nerve injuries secondary to fall, burial under debris and motor vehicle accidents. Eighty six (17%) cases had multiple nerve injuries. Most commonly injured nerve was ulnar (20.6%) followed by sciatic (16.7%), median (16.5%), radial (16.3%), peroneal (8.7%), brachial plexus (8.5%), axillary (4.8%), tibial (2%), femoral (1.8%), long thoracic (0.4%) and others (3.8%). Axonotmesis was seen in 459 (91.1%) cases, 44 (8.7%) cases revealed neurotmesis and 1 (0.2%) case had neuropraxia. Peripheral nerve injuries are a major component of war related injuries mainly involving the upper limbs. Electrodiagnostic studies help in assessing severity and determining prognosis. Precise documentation of severity of nerve injuries is important to estimate the burden on our resources and to extend rehabilitation services.

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

PubMed Central

Galor, A; Levitt, R C; Felix, E R; Martin, E R; Sarantopoulos, C D

2015-01-01

Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain. PMID:25376119

ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.

PubMed

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-11-08

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD.

ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density

PubMed Central

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-01-01

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD. PMID:24136731

The Relationship of Reduced Peripheral Nerve Function and Diabetes With Physical Performance in Older White and Black Adults

PubMed Central

Strotmeyer, Elsa S.; de Rekeneire, Nathalie; Schwartz, Ann V.; Faulkner, Kimberly A.; Resnick, Helaine E.; Goodpaster, Bret H.; Shorr, Ronald I.; Vinik, Aaron I.; Harris, Tamara B.; Newman, Anne B.

2008-01-01

OBJECTIVE—Poor peripheral nerve function is prevalent in diabetes and older populations, and it has great potential to contribute to poor physical performance. RESEARCH DESIGN AND METHODS—Cross-sectional analyses were done for the Health, Aging, and Body Composition (Health ABC) Study participants (n = 2,364; 48% men; 38% black; aged 73–82 years). Sensory and motor peripheral nerve function in legs/feet was assessed by 10- and 1.4-g monofilament perception, vibration detection, and peroneal motor nerve conduction amplitude and velocity. The Health ABC lower-extremity performance battery was a supplemented version of the Established Populations for the Epidemiologic Studies of the Elderly battery (chair stands, standing balance, and 6-m walk), adding increased stand duration, single foot stand, and narrow walk. RESULTS—Diabetic participants had fewer chair stands (0.34 vs. 0.36 stands/s), shorter standing balance time (0.69 vs. 0.75 ratio), slower usual walking speed (1.11 vs. 1.14 m/s), slower narrow walking speed (0.80 vs. 0.90 m/s), and lower performance battery score (6.43 vs. 6.93) (all P < 0.05). Peripheral nerve function was associated with each physical performance measure independently. After addition of peripheral nerve function in fully adjusted models, diabetes remained significantly related to a lower performance battery score and slower narrow walking speed but not to chair stands, standing balance, or usual walking speed. CONCLUSIONS—Poor peripheral nerve function accounts for a portion of worse physical performance in diabetes and may be directly associated with physical performance in older diabetic and nondiabetic adults. The impact of peripheral nerve function on incident disability should be evaluated in older adults. PMID:18535192

Fate of combat nerve injury.

PubMed

Beltran, Michael J; Burns, Travis C; Eckel, Tobin T; Potter, Benjamin K; Wenke, Joseph C; Hsu, Joseph R

2012-11-01

Assess a cohort of combat-related type III open tibia fractures with peripheral nerve injury to determine the injury mechanism and likelihood for recovery or improvement in nerve function. Retrospective study. Three military medical centers. Out of a study cohort of 213 type III open tibia fractures, 32 fractures (in 32 patients) with a total of 43 peripheral nerve injuries (peroneal or tibial) distal to the popliteal fossa met inclusion criteria and were available for follow-up at an average of 20 months (range, 2-48 months). Clinical assessment of motor and sensory nerve improvement. There was a 22% incidence of peripheral nerve injury in the study cohort. At an average follow-up of 20 months (range, 2-48 months), 89% of injured motor nerves were functional, whereas the injured sensory nerves had function in 93%. Fifty percent and 27% of motor and sensory injuries demonstrated improvement, respectively (P = 0.043). With the numbers available, there was no difference in motor or sensory improvement based on mechanism of injury, fracture severity or location, soft tissue injury, or specific nerve injured. In the subset of patients with an initially impaired sensory examination, full improvement was related to fracture location (P = 0.0164). Type III open tibia fractures sustained in combat are associated with a 22% incidence of peripheral nerve injury, and the majority are due to multiple projectile penetrating injury. Despite the severe nature of these injuries, the vast majority of patients had a functional nerve status by an average of 2-year follow-up. Based on these findings, discussions regarding limb salvage and amputation should not be overly influenced by the patient's peripheral nerve status. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Mitchell's influence on European studies of peripheral nerve injuries during World War I.

PubMed

Koehler, Peter J; Lanska, Douglas J

2004-12-01

Describe the influence of S. Weir Mitchell's (1829-1914) work, and in particular his ideas on causalgia, on European physicians who treated peripheral nerve injuries during World War I (WWI). During the American Civil War (1861-1865), Mitchell studied peripheral nerve injuries with colleagues George Read Morehouse and William Williams Keen. Three monographs resulted from this work. All were important landmarks in the evolution of knowledge of peripheral nerve injuries. A subsequent occasion to improve knowledge came in WWI. The most important European monographs or series on peripheral nerve injuries from WWI were studied with special interest in references to causalgia and Mitchell's works on peripheral nerve injuries. We included works by Tinel, Athanassio-Benisty, Purves-Stewart & Evans and Carter, Foerster and Oppenheim. Tinel and Athanassio-Benisty provided the most detailed information on peripheral nerve injuries and causalgia and often referred to Mitchell. Both mentioned a possible sympathetic origin. Athanassio-Benisty described tremor and other movement disorders in relation to causalgia. Purves-Stewart and Evans mentioned Mitchell and causalgia in the second edition of their book. They advocated the term "thermalgia." Carter, who had access to data of many cases, concentrated his work on causalgia, referring to Mitchell. Foerster provided data of a great number of peripheral nerve injuries, but did not refer to Mitchell. However, he described the symptoms of causalgia cursorily, applying the term Reflexschmerz (reflexpain). Oppenheim was particularly interested in muscle innervation and referred to Mitchell with respect to hypertrichosis and glossy skin. Oppenheim did not use the term causalgia, although he described the syndrome in some of his patients. It wasn't until around 1920 that German physicians devoted significant attention to causalgia and began using the term. Knowledge of peripheral nerve injuries was greatly advanced during and after WWI. Mitchell's influence was mainly found in the French medical literature, where his findings provided the basis for further research on the origin of causalgia. In England, Mitchell and causalgia were also well-known. We found evidence to suggest that some of the English knowledge came from French physicians. German physicians described the symptoms of causalgia, but did not use the term, nor did they refer to Mitchell. This variation in Mitchell's influence by country probably reflects the fact that Mitchell's Injuries of nerves and their consequences was translated into French but not German.

Diabetes and nerve damage

MedlinePlus

Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... pubmed/27979897 . Boulton AJM, Malik RA. Diabetes mellitus: ... of peripheral nerves. In: Daroff RB, Jankovic J, Mazziotta JC, ...

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

DTIC Science & Technology

2015-10-01

Modulated Sensory Feedback from, a Hand Prosthesis PRINCIPAL INVESTIGATOR: Bradley Greger, PhD CONTRACTING ORGANIZATION: Arizona State University...Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis 5a. CONTRACT NUMBER 5b. GRANT...Peripheral Nerve Interface, Prosthetic Hand, Neural Prosthesis , Sensory Feedback, Micro-stimulation, Electrophysiology, Action Potentials, Micro

A Novel Internal Fixator Device for Peripheral Nerve Regeneration

PubMed Central

Chuang, Ting-Hsien; Wilson, Robin E.; Love, James M.; Fisher, John P.

2013-01-01

Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension—traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration. PMID:23102114

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

Neural tissue engineering options for peripheral nerve regeneration.

PubMed

Gu, Xiaosong; Ding, Fei; Williams, David F

2014-08-01

Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...5b. GRANT NUMBER W81XWH-15-2-0026 CClinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...co- treatments of a commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with

Current Concept in Adult Peripheral Nerve and Brachial Plexus Surgery.

PubMed

Rasulic, Lukas

2017-01-01

Peripheral nerve injuries and brachial plexus injuries are relatively frequent. Significance of these injuries lies in the fact that the majority of patients with these types of injuries constitute working population. Since these injuries may create disability, they present substantial socioeconomic problem nowadays. This article will present current state-of-the-art achievements of minimal invasive brachial plexus and peripheral nerve surgery. It is considered that the age of the patient, the mechanism of the injury, and the associated vascular and soft-tissue injuries are factors that primarily influence the extent of recovery of the injured nerve. The majority of patients are treated using classical open surgical approach. However, new minimally invasive open and endoscopic approaches are being developed in recent years-endoscopic carpal and cubital tunnel release, targeted minimally invasive approaches in brachial plexus surgery, endoscopic single-incision sural nerve harvesting, and there were even attempts to perform endoscopic brachial plexus surgery. The use of the commercially available nerve conduits for bridging short nerve gap has shown promising results. Multidisciplinary approach individually designed for every patient is of the utmost importance for the successful treatment of these injuries. In the future, integration of biology and nanotechnology may fabricate a new generation of nerve conduits that will allow nerve regeneration over longer nerve gaps and start new chapter in peripheral nerve surgery.

Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain.

PubMed

Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

2016-10-01

Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

The effects of repetitive vibration on sensorineural function: biomarkers of sensorineural injury in an animal model of metabolic syndrome

PubMed Central

Kiedrowski, Megan; Waugh, Stacey; Miller, Roger; Johnson, Claud; Krajnak, Kristine

2016-01-01

Exposure to hand-transmitted vibration in the work-place can result in the loss of sensation and pain in workers. These effects may be exacerbated by pre-existing conditions such as diabetes or the presence of primary Raynaud's phenomena. The goal of these studies was to use an established model of vibration-induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile, while obese Zucker rats display symptoms of metabolic disorder or Type II diabetes. This study examined the effects of vibration in obese and lean rats. Zucker rats were exposed to 4 h of vibration for 10 consecutive days at a frequency of 125 Hz and acceleration of 49 m/s2 for 10 consecutive days. Sensory function was checked using transcutaneous electrical stimulation on days 1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves, dorsal root ganglia and spinal cord were dissected, and levels of various transcripts involved in sensorineural dysfunction were measured. Sensorineural dysfunction was assessed using transcutaneous electrical stimulation. Obese Zucker rats displayed very few changes in sensorineural function. However they did display significant changes in transcript levels for factors involved in synapse formation, peripheral nerve remodeling, and inflammation. The changes in transcript levels suggested that obese Zucker rats had some level of sensory nerve injury prior to exposure, and that exposure to vibration activated pathways involved in injury and re-innervation. PMID:26433044

Neuroanatomy and neurophysiology related to sexual dysfunction in male neurogenic patients with lesions to the spinal cord or peripheral nerves.

PubMed

Everaert, K; de Waard, W I Q; Van Hoof, T; Kiekens, C; Mulliez, T; D'herde, C

2010-03-01

Review article. The neuroanatomy and physiology of psychogenic erection, cholinergic versus adrenergic innervation of emission and the predictability of outcome of vibration and electroejaculation require a review and synthesis. University Hospital Belgium. We reviewed the literature with PubMed 1973-2008. Erection, emission and ejaculation are separate phenomena and have different innervations. It is important to realize, which are the afferents and efferents and where the motor neuron of the end organ is located. When interpreting a specific lesion it is important to understand if postsynaptic fibres are intact or not. Afferents of erection, emission and ejaculation are the pudendal nerve and descending pathways from the brain. Erection is cholinergic and NO-mediated. Emission starts cholinergically (as a secretion) and ends sympathetically (as a contraction). Ejaculation is mainly adrenergic and somatic. For vibratory-evoked ejaculation, the reflex arch must be complete; for electroejaculation, the postsynaptic neurons (paravertebral ganglia) must be intact. Afferents of erection, emission and ejaculation are the pudendal nerve and descending pathways from the brain. Erection is cholinergic and NO-mediated. Emission starts cholinergically (as a secretion) and ends sympathetically (as a contraction). Ejaculation is mainly adrenergic and somatic. In neurogenic disease, a good knowledge of neuroanatomy and physiology makes understanding of sexual dysfunction possible and predictable. The minimal requirement for the success of penile vibration is a preserved reflex arch and the minimal requirement for the success of electroejaculation is the existence of intact post-ganglionic fibres.

MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

PubMed

Zhou, Nan; Hao, Shuang; Huang, Zongqiang; Wang, Weiwei; Yan, Penghui; Zhou, Wei; Zhu, Qihang; Liu, Xiaokang

2018-01-01

Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3'UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

Sonographic identification of peripheral nerves in the forearm

PubMed Central

Jackson, Saundra A.; Derr, Charlotte; De Lucia, Anthony; Harris, Marvin; Closser, Zuheily; Miladinovic, Branko; Mhaskar, Rahul; Jorgensen, Theresa; Green, Lori

2016-01-01

Background: With the growing utilization of ultrasonography in emergency medicine combined with the concern over adequate pain management in the emergency department (ED), ultrasound guidance for peripheral nerve blockade in ED is an area of increasing interest. The medical literature has multiple reports supporting the use of ultrasound guidance in peripheral nerve blocks. However, to perform a peripheral nerve block, one must first be able to reliably identify the specific nerve before the procedure. Objective: The primary purpose of this study is to describe the number of supervised peripheral nerve examinations that are necessary for an emergency medicine physician to gain proficiency in accurately locating and identifying the median, radial, and ulnar nerves of the forearm via ultrasound. Methods: The proficiency outcome was defined as the number of attempts before a resident is able to correctly locate and identify the nerves on ten consecutive examinations. Didactic education was provided via a 1 h lecture on forearm anatomy, sonographic technique, and identification of the nerves. Participants also received two supervised hands-on examinations for each nerve. Count data are summarized using percentages or medians and range. Random effects negative binomial regression was used for modeling panel count data. Results: Complete data for the number of attempts, gender, and postgraduate year (PGY) training year were available for 38 residents. Nineteen males and 19 females performed examinations. The median PGY year in practice was 3 (range 1–3), with 10 (27%) in year 1, 8 (22%) in year 2, and 19 (51%) in year 3 or beyond. The median number (range) of required supervised attempts for radial, median, and ulnar nerves was 1 (0–12), 0 (0–10), and 0 (0–17), respectively. Conclusion: We can conclude that the maximum number of supervised attempts to achieve accurate nerve identification was 17 (ulnar), 12 (radial), and 10 (median) in our study. The only significant association was found between years in practice and proficiency (P = 0.025). We plan to expound upon this research with an additional future study that aims to assess the physician's ability to adequately perform peripheral nerve blocks in efforts to decrease the need for more generalized procedural sedation. PMID:27904260

A Fully Implanted Drug Delivery System for Peripheral Nerve Blocks in Behaving Animals

PubMed Central

Pohlmeyer, Eric A.; Jordon, Luke R.; Kim, Peter; Miller, Lee E.

2009-01-01

Inhibiting peripheral nerve function can be useful for many studies of the nervous system or motor control. Accomplishing this in a temporary fashion in animal models by using peripheral nerve blocks permits studies of the immediate effects of the loss, and/or any resulting short-term changes and adaptations in behavior or motor control, while avoiding the complications commonly associated with permanent lesions, such as sores or self-mutilation. We have developed a method of quickly and repeatedly inducing temporary, controlled motor deficits in rhesus macaque monkeys via a chronically implanted drug delivery system. This assembly consists of a nerve cuff and a subdermal injection dome, and has proved effective for delivering local anesthetics directly to peripheral nerves for many months. Using this assembly for median and ulnar nerve blocks routinely resulted in over 80% losses in hand and wrist strength for rhesus monkeys. The assembly was also effective for inducing ambulatory motor deficits in rabbits through blocks of the sciatic nerve. Interestingly, while standard anesthetics were sufficient for the rabbit nerve blocks, the inclusion of epinephrine was essential for achieving significant motor blockade in the monkeys. PMID:19524613

Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lei; Liu, Yi; Zhao, Hua

Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediatedmore » transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a promising strategy for peripheral nerve repair.« less

A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

PubMed

Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

2018-01-19

OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

Paeoniae alba Radix Promotes Peripheral Nerve Regeneration

PubMed Central

Huang, Kun-Shan; Lin, Jaung-Geng; Lee, Han-Chung; Tsai, Fuu-Jen; Bau, Da-Tian; Huang, Chih-Yang; Yao, Chun-Hsu; Chen, Yueh-Sheng

2011-01-01

The present study provides in vitro and in vivo evaluation of Paeoniae alba Radix (PR) on peripheral nerve regeneration. In the in vitro study, we found the PR caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as their expression of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with the PR water extract were used to bridge a 10-mm sciatic nerve defect in rats. At the conclusion of 8 weeks, regenerated nerves in the PR groups, especially at 1.25 mg ml−1 had a higher rate of successful regeneration across the wide gap, relatively larger mean values of total nerve area, myelinated axon count and blood vessel number, and a significantly larger nerve conductive velocity compared to the control group (P  <  .05). These results suggest that the PR extract can be a potential nerve growth-promoting factor, being salutary in aiding the growth of injured peripheral nerve. PMID:19687191

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision.

PubMed

2010-12-01

A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment. © 2010 Peripheral Nerve Society.

Exploration of a Novel Persistent Reversal of Pathological Pain: Mechanisms and Mediators

DTIC Science & Technology

2015-04-01

ability of a single IT ATL313 dose to reverse neuropathic pain from traumatic peripheral neuropathy . Milestone 2 is complete. We determined that 1 pmol...cord injury; to prevent and reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ...ATL313 can reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ) injections. We also

Cross sectional study to evaluate the effect of duration of type 2 diabetes mellitus on the nerve conduction velocity in diabetic peripheral neuropathy.

PubMed

Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal

2014-01-01

To study the nerve conduction velocity in clinically undetectable and detectable peripheral neuropathy in type 2 diabetes mellitus with variable duration. This cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups: Group I (n=37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n=27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with T2DM patients (n=22) without clinical neuropathy. Clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Nerve conduction velocity was measured in both upper and lower limbs. Median, ulnar, common peroneal and posterior tibial nerves were selected for motor nerve conduction study and median and sural nerves were selected for sensory nerve conduction study. The comparisons were done between nerve conduction velocities of motor and sensory nerves in patients of clinically detectable neuropathy and patients without neuropathy in type 2 diabetes mellitus population. This study showed significant electrophysiological changes with duration of disease. Nerve conduction velocities in lower limbs were significantly reduced even in patients of shorter duration with normal upper limb nerve conduction velocities. Diabetic neuropathy symptom score (NSS) and neuropathy disability score (NDS) can help in evaluation of diabetic sensorimotor polyneuropathy though nerve conduction study is more powerful test and can help in diagnosing cases of neuropathy. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Pathology in practice: Peripheral nerve sheath tumor in a Shubunkin goldfish

USDA-ARS?s Scientific Manuscript database

Peripheral nerve sheath tumors (PNSTs) have been detected in many fish species, including goldfish, several species of snapper, coho salmon, the bicolor damselfish, and rainbow smelt. They originate from neural crest cells and generally occur along the subcutaneous nerves. A viral etiology has bee...

Lipid-lowering drugs (statins) and peripheral neuropathy.

PubMed

Emad, Mohammadreza; Arjmand, Hosein; Farpour, Hamid Reza; Kardeh, Bahareh

2018-03-01

Peripheral neuropathy is a disorder with often unknown causes. Some drugs, including statins, are proposed to be among the causes of peripheral neuropathy. This study aimed at evaluating this condition by electrodiagnostic study among patients who had received statins. This case-control study was conducted in Shiraz, Iran in 2015, and included 39 patients aged 35-55 who had received statins for at least 6 months, and 39 healthy matched controls. Using electrodiagnosis, the sensory and motor wave features (amplitude, latency and nerve conduction velocity) of the peripheral nerves (Median, Ulnar, Tibial, Sural, and Peroneal) were evaluated among the subjects. Data were analyzed using SPSS software and p<0.05 was considered statistically significant. Regarding the occurrence of neuropathy, there were no significant differences in any of the definitions presented for peripheral neuropathy. However, the difference was close to significance for one definition [2 abnormalities in 2 nerves (p=0.055)]. Regarding mean values of the features, significant differences were observed in two features: amplitude of the peroneal motor nerve (p=0.048) and amplitude of the sural sensory nerve (p=0.036). Since statins are widely used, awareness regarding their side-effects would lead to better treatment. Even though no significant differences were found between the groups regarding the occurrence of peripheral neuropathy, there were significant differences in amplitudes of the sural sensory response and the peroneal motor response. This indicates the involvement of peripheral nerves. Therefore, we recommend that patients and physicians should be informed about the possible symptoms of this condition.

Reflex effects on components of synchronized renal sympathetic nerve activity.

PubMed

DiBona, G F; Jones, S Y

1998-09-01

The effects of peripheral thermal receptor stimulation (tail in hot water, n = 8, anesthetized) and cardiac baroreceptor stimulation (volume loading, n = 8, conscious) on components of synchronized renal sympathetic nerve activity (RSNA) were examined in rats. The peak height and peak frequency of synchronized RSNA were determined. The renal sympathoexcitatory response to peripheral thermal receptor stimulation was associated with an increase in the peak height. The renal sympathoinhibitory response to cardiac baroreceptor stimulation was associated with a decrease in the peak height. Although heart rate was significantly increased with peripheral thermal receptor stimulation and significantly decreased with cardiac baroreceptor stimulation, peak frequency was unchanged. As peak height reflects the number of active fibers, reflex increases and decreases in synchronized RSNA are mediated by parallel increases and decreases in the number of active renal nerve fibers rather than changes in the centrally based rhythm or peak frequency. The increase in the number of active renal nerve fibers produced by peripheral thermal receptor stimulation reflects the engagement of a unique group of silent renal sympathetic nerve fibers with a characteristic response pattern to stimulation of arterial baroreceptors, peripheral and central chemoreceptors, and peripheral thermal receptors.

Compartment syndrome after total knee arthroplasty: regarding a clinical case☆

PubMed Central

Pinheiro, Ana Alexandra da Costa; Marques, Pedro Miguel Dantas Costa; Sá, Pedro Miguel Gomes; Oliveira, Carolina Fernandes; da Silva, Bruno Pombo Ferreira; de Sousa, Cristina Maria Varino

2015-01-01

Although compartment syndrome is a rare complication of total knee arthroplasty, it is one of the most devastating complications. It is defined as a situation of increased pressure within a closed osteofascial space that impairs the circulation and the functioning of the tissues inside this space, thereby leading to ischemia and tissue dysfunction. Here, a clinical case of a patient who was followed up in orthopedic outpatient consultations due to right gonarthrosis is presented. The patient had a history of arthroscopic meniscectomy and presented knee flexion of 10° before the operation, which consisted of total arthroplasty of the right knee. The operation seemed to be free from intercurrences, but the patient evolved with compartment syndrome of the ipsilateral leg after the operation. Since compartment syndrome is a true surgical emergency, early recognition and treatment of this condition through fasciotomy is crucial in order to avoid amputation, limb dysfunction, kidney failure and death. However, it may be difficult to make the diagnosis and cases may not be recognized if the cause of compartment syndrome is unusual or if the patient is under epidural analgesia and/or peripheral nerve block, which thus camouflages the main warning sign, i.e. disproportional pain. In addition, edema of the limb that underwent the intervention is common after total knee arthroplasty operations. This study presents a review of the literature and signals that the possible rarity of cases is probably due to failure to recognize this condition in a timely manner and to placing these patients in other diagnostic groups that are less likely, such as neuropraxia caused by using a tourniquet or peripheral nerve injury. PMID:26401507

Lack of Neuropathy-Related Phenotypes in Hint1 Knockout Mice

PubMed Central

Seburn, Kevin L.; Morelli, Kathryn H.; Jordanova, Albena; Burgess, Robert W.

2014-01-01

Mutations in HINT1, the gene encoding histidine triad nucleotide-binding protein 1 (HINT1), cause a recessively inherited peripheral neuropathy that involves primarily motor dysfunction and is usually associated with neuromyotonia, i.e. prolonged muscle contraction resulting from hyperexcitability of the peripheral nerve. Because these mutations are hypothesized to cause loss of function, we analyzed Hint1 knockout mice for their relevance as a disease model. Mice lacking Hint1 were normal in appearance and in behavioral tests or motor performance, although they moved slower and for a smaller fraction of time than wild-type (WT) mice in an open field arena. Muscles, neuromuscular junctions, and nodes of Ranvier are anatomically normal and did not show evidence of degeneration or regeneration. Axon numbers and myelination in peripheral nerves were normal at 4 and 13 months of age. Axons were slightly smaller than those in WT mice at 4 months of age, but this did not cause a decrease in conduction velocity, and no differences in axon diameters were detected at 13 months. Using electromyography, we were unable to detect neuromyotonia, even using supra-physiological stimuli and stressors such as reduced temperature or 3,4 diaminopyridine to block potassium channels. Therefore, we conclude that Hint1 knockout mice may be useful for studying the biochemical activities of HINT1, but these mice do not provide a disease model or a means for investigating the basis of HINT1-associated neuropathy and neuromyotonia. PMID:24918641

Electron microscopy of human peripheral nerves of clinical relevance to the practice of nerve blocks. A structural and ultrastructural review based on original experimental and laboratory data.

PubMed

Reina, M A; Arriazu, R; Collier, C B; Sala-Blanch, X; Izquierdo, L; de Andrés, J

2013-12-01

The goal is to describe the ultrastructure of normal human peripheral nerves, and to highlight key aspects that are relevant to the practice of peripheral nerve block anaesthesia. Using samples of sciatic nerve obtained from patients, and dural sac, nerve root cuff and brachial plexus dissected from fresh human cadavers, an analysis of the structure of peripheral nerve axons and distribution of fascicles and topographic composition of the layers that cover the nerve is presented. Myelinated and unmyelinated axons, fascicles, epineurium, perineurium and endoneurium obtained from patients and fresh cadavers were studied by light microscopy using immunohistochemical techniques, and transmission and scanning electron microscopy. Structure of perineurium and intrafascicular capillaries, and its implications in blood-nerve barrier were revised. Each of the anatomical elements is analyzed individually with regard to its relevance to clinical practice to regional anaesthesia. Routine practice of regional anaesthetic techniques and ultrasound identification of nerve structures has led to conceptions, which repercussions may be relevant in future applications of these techniques. In this regard, the ultrastructural and histological perspective accomplished through findings of this study aims at enlightening arising questions within the field of regional anaesthesia. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Silicone Molding and Lifetime Testing of Peripheral Nerve Interfaces for Neuroprostheses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupte, Kimaya; Tolosa, Vanessa

Implantable peripheral nerve cuffs have a large application in neuroprostheses as they can be used to restore sensation to those with upper limb amputations. Modern day prosthetics, while lessening the pain associated with phantom limb syndrome, have limited fine motor control and do not provide sensory feedback to patients. Sensory feedback with prosthetics requires communication between the nervous system and limbs, and is still a challenge to accomplish with amputees. Establishing this communication between the peripheral nerves in the arm and artificial limbs is vital as prosthetics research aims to provide sensory feedback to amputees. Peripheral nerve cuffs restore sensationmore » by electrically stimulating certain parts of the nerve in order to create feeling in the hand. Cuff electrodes have an advantage over standard electrodes as they have high selective stimulation by bringing the electrical interface close to the neural tissue in order to selectively activate targeted regions of a peripheral nerve. In order to further improve the selective stimulation of these nerve cuffs, there is need for finer spatial resolution among electrodes. One method to achieve a higher spatial resolution is to increase the electrode density on the cuff itself. Microfabrication techniques can be used to achieve this higher electrode density. Using L-Edit, a layout editor, microfabricated peripheral nerve cuffs were designed with a higher electrode density than the current model. This increase in electrode density translates to an increase in spatial resolution by at least one order of magnitude. Microfabricated devices also have two separate components that are necessary to understand before implantation: lifetime of the device and assembly to prevent nerve damage. Silicone molding procedures were optimized so that devices do not damage nerves in vivo, and lifetime testing was performed on test microfabricated devices to determine their lifetime in vivo. Future work of this project would include fabricating some of the designed devices and seeing how they compare to the current cuffs in terms of their electrical performance, lifetime, shape, and mechanical properties.« less

Mechanical Loading for Peripheral Nerve Stabilization and Regeneration

DTIC Science & Technology

2012-10-01

Dahlin, L., Johansson, F., Lindwall, C., and Kanje, M. Chapter 28: Future perspective in peripheral nerve reconstruction . Int Rev Neurobiol 87, 507...Genden, E.M., MacKinnon, S.E., Doolabh, V.B., and Hunter, D.A. Regeneration through long nerve grafts in the swine model. Microsurgery 18, 379, 1998. 12

Video Head Impulse Test to Preoperatively Identify the Nerve of Origin of Vestibular Schwannomas.

PubMed

Constanzo, Felipe; Sens, Patricia; Teixeira, Bernardo Corrêa de Almeida; Ramina, Ricardo

2018-05-10

Identification of the nerve of origin in vestibular schwannoma (VS) is an important prognostic factor for hearing preservation surgery. Thus far, vestibular functional tests and magnetic resonance imaging have not yielded reliable results to preoperatively evaluate this information. The development of the video head impulse test (vHIT) has allowed a precise evaluation of each semicircular canal, and its localizing value has been tested for some peripheral vestibular diseases, but not for VS. To correlate patterns of semicircular canal alteration on vHIT to intraoperative identification of the nerve of origin of VSs. A total 31 patients with sporadic VSs were preoperatively evaluated with vHIT (gain of vestibule-ocular reflex, overt and covert saccades on each semicircular canal) and then the nerve of origin was surgically identified during surgical resection via retrosigmoid approach. vHIT results were classified as normal, isolated superior vestibular nerve (SVN) pattern, isolated inferior vestibular nerve (IVN) pattern, predominant SVN pattern, and predominant IVN pattern. Hannover classification, cystic component, and distance between the tumor and the end of the internal auditory canal were also considered for analysis. Three patients had a normal vHIT, 12 had an isolated SVN pattern, 5 had an isolated IVN pattern, 7 had a predominant SVN pattern, and 4 had a predominant IVN pattern. vHIT was able to correctly identify the nerve of origin in 89.7% of cases (100% of altered exams). The pattern of semicircular canal dysfunction on vHIT has a localizing value to identify the nerve of origin in VSs.

Novel Therapeutic Development of NF1-Associated Malignant Peripheral Nerve Sheath Tumor (MPNST)

DTIC Science & Technology

2016-08-01

peripheral nerve sheath tumor (MPSNT)”, 11/5/2015, SARC-CTOS (Connective Tissue Oncology Society) Symposium, Salt Lake City, Utah b) “PRC2 loss in...of malignant peripheral nerve sheath tumor (MPSNT)”, 11/5/2015, SARC-CTOS (Connective Tissue Oncology Society) Symposium, Salt Lake City, Utah 2...Medical Oncology Service FROM: Roger S Wilson, MD Chairman, Institutional Review Board/Privacy Board-A DATE: 02/11/2016 RE: Protocol # 16-052 Your

Sodium-dependent Vitamin C transporter 2 deficiency impairs myelination and remyelination after injury: Roles of collagen and demethylation.

PubMed

Röhr, Dominik; Halfter, Hartmut; Schulz, Jörg B; Young, Peter; Gess, Burkhard

2017-07-01

Peripheral nerve myelination involves rapid production of tightly bound lipid layers requiring cholesterol biosynthesis and myelin protein expression, but also a collagen-containing extracellular matrix providing mechanical stability. In previous studies, we showed a function of ascorbic acid in peripheral nerve myelination and extracellular matrix formation in adult mice. Here, we sought the mechanism of action of ascorbic acid in peripheral nerve myelination using different paradigms of myelination in vivo and in vitro. We found impaired myelination and reduced collagen expression in Sodium-dependent Vitamin C Transporter 2 heterozygous mice (SVCT2 +/- ) during peripheral nerve development and after peripheral nerve injury. In dorsal root ganglion (DRG) explant cultures, hypo-myelination could be rescued by precoating with different collagen types. The activity of the ascorbic acid-dependent demethylating Ten-eleven-translocation (Tet) enzymes was reduced in ascorbic acid deprived and SVCT2 +/- DRG cultures. Further, in ascorbic acid-deprived DRG cultures, methylation of a CpG island in the collagen alpha1 (IV) and alpha2 (IV) bidirectional promoter region was increased compared to wild-type and ascorbic acid treated controls. Taken together, these results provide further evidence for the function of ascorbic acid in myelination and extracellular matrix formation in peripheral nerves and suggest a putative molecular mechanism of ascorbic acid function in Tet-dependent demethylation of collagen promoters. © 2017 Wiley Periodicals, Inc.

Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nerves.

PubMed

Sun, Yuan-Ting; Lin, Thy-Sheng; Tzeng, Shun-Fen; Delpire, Eric; Shen, Meng-Ru

2010-10-01

Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K(+)-Cl(-) cotransporter (KCC) family includes four isoforms (KCC1-4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K(+) and Cl(-) with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2-4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na(+)-K(+)-2Cl(-)-cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3(-/-) mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3(-/-) mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K(+)-Cl(-) cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. (c) 2010 Wiley-Liss, Inc.

Lower-extremity peripheral nerve blocks in the perioperative pain management of orthopaedic patients: AAOS exhibit selection.

PubMed

Stein, Benjamin E; Srikumaran, Umasuthan; Tan, Eric W; Freehill, Michael T; Wilckens, John H

2012-11-21

The utilization of peripheral nerve blocks in orthopaedic surgery has paralleled the rise in the number of ambulatory surgical procedures performed. Optimization of pain control in the perioperative orthopaedic patient contributes to improved patient satisfaction, early mobilization, decreased length of hospitalization, and decreased associated hospital and patient costs. Our purpose was to provide a concise, pertinent review of the use of peripheral nerve blocks in various orthopaedic procedures of the lower extremity, with specific focus on procedural anatomy, indications, patient outcome measures, and complications. We reviewed the literature and reference textbooks on commonly performed lower-extremity peripheral nerve block procedures in orthopaedic surgery, focusing on those most commonly used. The use of lower-extremity peripheral nerve blocks is a safe and effective approach to perioperative pain management. Different techniques and timing can have an important impact on patient satisfaction, and each technique has specific indications and complications. For major hip surgery, one of the most commonly used is the lumbar plexus block, which can result in early mobilization, reduced postoperative pain, and decreased opioid-associated adverse events. Associated complications include epidural spread of anesthesia, retroperitoneal hematoma formation, and postoperative falls. For arthroscopic and open knee procedures, the femoral nerve block is frequently used adjunctively. It provides improved early postoperative pain control, early mobilization with therapy, and increased patient satisfaction compared with intra-articular or intravenous opioids alone; it also provides cost savings. However, some studies have shown no significant difference in outcome measures compared with intra-articular opioids alone for arthroscopic anterior cruciate ligament reconstruction. Associated complications include nerve injury, intravascular injection, and postoperative falls. The use of peripheral nerve blocks in lower-extremity surgery is becoming a mainstay of perioperative pain management strategy.

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

PubMed

Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D

1991-04-22

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)

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy.

PubMed

Tang, Wei; Chen, Xiangfang; Liu, Haoqi; Lv, Qian; Zou, Junjie; Shi, Yongquan; Liu, Zhimin

2018-04-26

High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury. © 2018 The Author(s). Published by S. Karger AG, Basel.

Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinsella, T.J.; DeLuca, A.M.; Barnes, M.

1991-04-01

Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers andmore » perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.« less

Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome.

PubMed

O'Malley, Dervla

2016-11-01

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain, bloating, and disturbed bowel habit, symptoms that impact the quality of life of sufferers. The pathophysiological changes underlying this multifactorial condition are complex and include increased sensitivity to luminal and mucosal factors, resulting in altered colonic transit and visceral pain. Moreover, dysfunctional communication in the bidirectional signaling axis between the brain and the gut, which involves efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones, and local paracrine and neurocrine factors, including immune and perhaps even microbial signaling molecules, has a role to play in this disorder. This minireview will examine recent advances in our understanding of the pathophysiology of IBS and assess how cross talk between hormones, immune, and microbe-derived factors and their neuromodulatory effects on peripheral nerves may underlie IBS symptomatology. Copyright © 2016 the American Physiological Society.

Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

PubMed

Allbright, Kassandra O; Bliley, Jacqueline M; Havis, Emmanuelle; Kim, Deok-Yeol; Dibernardo, Gabriella A; Grybowski, Damian; Waldner, Matthias; James, Isaac B; Sivak, Wesley N; Rubin, J Peter; Marra, Kacey G

2018-02-06

Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

Artificial sensory organs: latest progress.

PubMed

Nakamura, Tatsuo; Inada, Yuji; Shigeno, Keiji

2018-03-01

This study introduces the latest progress on the study of artificial sensory organs, with a special emphasis on the clinical results of artificial nerves and the concept of in situ tissue engineering. Peripheral nerves have a strong potential for regeneration. An artificial nerve uses this potential to recover a damaged peripheral nerve. The polyglycolic acid collagen tube (PGA-C tube) is a bio-absorbable tube stuffed with collagen of multi-chamber structure that consists of thin collagen films. The clinical application of the PGA-C tube began in 2002 in Japan. The number of PGA-C tubes used is now beyond 300, and satisfactory results have been reported on peripheral nerve repairs. This PGA-C tube is also effective for patients suffering from neuropathic pain.

Motor Nerve Conduction Velocity In Postmenopausal Women with Peripheral Neuropathy.

PubMed

Singh, Akanksha; Asif, Naiyer; Singh, Paras Nath; Hossain, Mohd Mobarak

2016-12-01

The post-menopausal phase is characterized by a decline in the serum oestrogen and progesterone levels. This phase is also associated with higher incidence of peripheral neuropathy. To explore the relationship between the peripheral motor nerve status and serum oestrogen and progesterone levels through assessment of Motor Nerve Conduction Velocity (MNCV) in post-menopausal women with peripheral neuropathy. This cross-sectional study was conducted at Jawaharlal Nehru Medical College during 2011-2013. The study included 30 post-menopausal women with peripheral neuropathy (age: 51.4±7.9) and 30 post-menopausal women without peripheral neuropathy (control) (age: 52.5±4.9). They were compared for MNCV in median, ulnar and common peroneal nerves and serum levels of oestrogen and progesterone estimated through enzyme immunoassays. To study the relationship between hormone levels and MNCV, a stepwise linear regression analysis was done. The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum oestrogen and progesterone levels as compared to control subjects. Stepwise linear regression analysis showed oestrogen with main effect on MNCV. The findings of the present study suggest that while the post-menopausal age group is at a greater risk of peripheral neuropathy, it is the decline in the serum estrogen levels which is critical in the development of peripheral neuropathy.

Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

PubMed Central

Sánchez, Mikel; Garate, Ane; Delgado, Diego; Padilla, Sabino

2017-01-01

Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery. PMID:28250739

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model.

PubMed

Huisman, Merel; Staruch, Robert M; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A; Burns, Dennis K; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining. All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection.

Pulsed laser versus electrical energy for peripheral nerve stimulation

PubMed Central

Wells, Jonathon; Konrad, Peter; Kao, Chris; Jansen, E. Duco; Mahadevan-Jansen, Anita

2010-01-01

Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods can selectively excite functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits some advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future. PMID:17537515

Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise

PubMed Central

Gordon, Tessa; English, Arthur W.

2015-01-01

Enhancing the regeneration of axons is often considered a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise, and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients, is explored. The rationale, effectiveness, and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins, and androgens are considered common requirements. Similar, gender-specific requirements are found for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem ready to be translated to clinical use. PMID:26121368

Influence of peripheral magnetic stimulation of soleus muscle on H and M waves.

PubMed

Matsuda, Tadamitsu; Kurayama, Taichi; Tagami, Miki; Fujino, Yuji; Manji, Atsushi; Kusumoto, Yasuaki; Amimoto, Kazu

2018-05-01

[Purpose] This study evaluated the effects of repetitive peripheral magnetic stimulation of the soleus muscle on spinal cord and peripheral motor nerve excitability. [Subjects and Methods] Twelve healthy adults (mean age 22 years) who provided written informed consent were administered repetitive peripheral magnetic stimulation for 10 min. Pre-and post-stimulation latencies and amplitudes of H- and M-waves of the soleus muscle were measured using electromyography and compared using paired t-tests. [Results] Pre- and post-stimulation latencies (28.3 ± 3.3 vs. 29.1 ± 1.3 ms, respectively) and amplitudes (35.8 ± 1.3 vs. 35.8 ± 1.1 mV, respectively) of H-waves were similar. Pre-stimulation latencies of M-waves were significantly higher than post-stimulation latencies (6.1 ± 2.2 vs. 5.0 ± 0.9 ms, respectively), although pre- and post-stimulation amplitudes were similar (12.2 ± 1.4 vs. 12.2 ± 1.3 mV, respectively). Motor neuron excitability, based on the excitability of motor nerves and peripheral nerve action, was increased by M-waves following magnetic stimulation. [Conclusion] The lack of effect of magnetic stimulation on the amplitude and latency of the H-reflex suggests that magnetic stimulation did not activate sensory nerve synapses of α motor neurons in the spinal cord. However, because motor nerves were stimulated together with sensory nerves, the increased H-wave amplitude may have reflected changes in peripheral rather than in α motor nerves.

Usefulness of sural nerve biopsy in the genomic era.

PubMed

Kanda, Takashi

2009-08-01

The value of peripheral nerve biopsy is now sometimes questioned due to the high complication rate and the recent development of noninvasive molecular techniques for diagnosis of hereditary neuropathy. However, the disorders that can be diagnosed by genetic analysis are limited and sural nerve biopsy is still a powerful tool for making a correct diagnosis of peripheral neuropathy. Histological evaluation of the sural nerve has long focused on changes of the two major components of peripheral nerves, axons and myelin, as well as on the detection of diagnostic changes such as amyloid deposits, sarcoid tubercles, and vasculitis. In addition to these components, the sural nerve biopsy specimen contains various important cells, including perineurial cells, mast cells, endothelial cells, pericytes, and lymphocytes. Among these cells, the endothelial cells and pericytes form the blood-nerve barrier (BNB) and investigation of these cells can reveal important information, especially in inflammatory neuropathies. To better understand the biological basis of BNB, we established rat and human immortal cell lines from the endothelial cells and pericytes of endoneurial microvessels. Characterization of these cell lines is now underway at our laboratory. These BNB cell lines should provide useful information concerning the pathophysiology of peripheral neuropathy, and we should obtain a new perspective for the investigation of nerve biopsy specimens after understanding the molecular background of the BNB.

Spatial and Functional Selectivity of Peripheral Nerve Signal Recording With the Transversal Intrafascicular Multichannel Electrode (TIME).

PubMed

Badia, Jordi; Raspopovic, Stanisa; Carpaneto, Jacopo; Micera, Silvestro; Navarro, Xavier

2016-01-01

The selection of suitable peripheral nerve electrodes for biomedical applications implies a trade-off between invasiveness and selectivity. The optimal design should provide the highest selectivity for targeting a large number of nerve fascicles with the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME), transversally inserted in the peripheral nerve, has been shown to be useful for the selective activation of subsets of axons, both at inter- and intra-fascicular levels, in the small sciatic nerve of the rat. In this study we assessed the capabilities of TIME for the selective recording of neural activity, considering the topographical selectivity and the distinction of neural signals corresponding to different sensory types. Topographical recording selectivity was proved by the differential recording of CNAPs from different subsets of nerve fibers, such as those innervating toes 2 and 4 of the hindpaw of the rat. Neural signals elicited by sensory stimuli applied to the rat paw were successfully recorded. Signal processing allowed distinguishing three different types of sensory stimuli such as tactile, proprioceptive and nociceptive ones with high performance. These findings further support the suitability of TIMEs for neuroprosthetic applications, by exploiting the transversal topographical structure of the peripheral nerves.

[Features of peripheral nerve injuries in workers exposed to vibration: an analysis of 197 cases].

PubMed

Situ, J; Lin, C M; Qin, Z H; Zhu, D X; Lin, H; Zhang, F F; Zhang, J J

2016-12-20

Objective: To investigate the features of peripheral nerve injuries in workers exposed to vibration. Methods: A total of 197 male workers [median age: 34 years (21 - 50 years) ; median working years of vibration exposure: 7.3 years (1 - 20 years) ] engaged in grinding in an enterprise were enrolled. Their clinical data and electromyography results were analyzed to investigate the features of peripheral nerve impairment. Results: Of all workers, 96 (48.73%) had abnormal electromyography results. Of all workers, 88 (44.7%) had simple mild median nerve injury in the wrist, who accounted for 91.7% (88/96) of all workers with abnormal electromy-ography results. Six workers had ulnar nerve injury, superficial radial nerve injury, or/and superficial peroneal nerve injury and accounted for 6.3% of all workers with abnormal electromyography results. Of all workers, 88 had a reduced amplitude of median nerve sensory transduction, and 28 had slowed median nerve sensory transduction. A total of 46 workers were diagnosed with occupational hand-arm vibration disease and hospitalized for treatment. They were followed up for more than 4 months after leaving their jobs, and most of them showed improvements in neural electromyography results and returned to a normal state. Conclusion: Workers exposed to vibration have a high incidence rate of nerve injury in the hand, mainly sensory function impairment at the distal end of the median nerve, and all injuries are mild peripheral nerve injuries. After leaving the vibration job and being treated, most workers can achieve improvements and return to a normal state.

Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.

PubMed

Verheij, Johanna B G M; Sival, Deborah A; van der Hoeven, Johannes H; Vos, Yvonne J; Meiners, Linda C; Brouwer, Oebele F; van Essen, Anthonie J

2006-01-01

Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

PubMed

Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

2016-10-01

This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

Burning Feet

MedlinePlus

... are most often a sign of nerve damage (peripheral neuropathy). Nerve damage has many different causes, including diabetes, ... if any of the various conditions that cause peripheral neuropathy are to blame. Eleftheriadou I, et al. A ...

Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery

PubMed Central

Knipfer, Christian; Hadlock, Tessa

2016-01-01

Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration. PMID:27556032

Whole-Mount Adult Ear Skin Imaging Reveals Defective Neuro-Vascular Branching Morphogenesis in Obese and Type 2 Diabetic Mouse Models.

PubMed

Yamazaki, Tomoko; Li, Wenling; Yang, Ling; Li, Ping; Cao, Haiming; Motegi, Sei-Ichiro; Udey, Mark C; Bernhard, Elise; Nakamura, Takahisa; Mukouyama, Yoh-Suke

2018-01-11

Obesity and type 2 diabetes are frequently associated with peripheral neuropathy. Though there are multiple methods for diagnosis and analysis of morphological changes of peripheral nerves and blood vessels, three-dimensional high-resolution imaging is necessary to appreciate the pathogenesis with an anatomically recognizable branching morphogenesis and patterning. Here we established a novel technique for whole-mount imaging of adult mouse ear skin to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels. Whole-mount immunostaining of adult mouse ear skin showed that peripheral sensory and sympathetic nerves align with large-diameter blood vessels. Diet-induced obesity (DIO) mice exhibit defective vascular smooth muscle cells (VSMCs) coverage, while there is no significant change in the amount of peripheral nerves. The leptin receptor-deficient db/db mice, a severe obese and type 2 diabetic mouse model, exhibit defective VSMC coverage and a large increase in the amount of smaller-diameter nerve bundles with myelin sheath and unmyelinated nerve fibers. Interestingly, an increase in the amount of myeloid immune cells was observed in the DIO but not db/db mouse skin. These data suggest that our whole-mount imaging method enables us to investigate the neuro-vascular and neuro-immune phenotypes in the animal models of obesity and diabetes.

Aging-associated sensory neuropathy alters pressure-induced vasodilation in humans.

PubMed

Fromy, Bérengère; Sigaudo-Roussel, Dominique; Gaubert-Dahan, Marie-Line; Rousseau, Pascal; Abraham, Pierre; Benzoni, Daniel; Berrut, Gilles; Saumet, Jean Louis

2010-03-01

Healthy skin is protected from pressure-induced ischemic damage because of the presence of pressure-induced vasodilation (PIV). PIV relies on small sensory nerve fibers and endothelial function. Since aging alters both nervous and vascular functions, we hypothesized that PIV is altered with aging. We compared PIV in non-neuropathic and neuropathic older subjects (60-75 years) with that of young subjects (20-35 years). Laser Doppler flowmetry was used to evaluate the cutaneous responses to local pressure application, acetylcholine, and local heating. Quantitative sensory tests were used to evaluate sensory-nerve-fiber function. The non-neuropathic older subjects had an impaired PIV (12+/-7% increase in blood flow with pressure) compared with young subjects (62+/-4%, P<0.001). In the presence of peripheral neuropathy, the older subjects were totally deprived of PIV, leading to early pressure-induced cutaneous ischemia (-31+/-10%, P<0.001). This inability of the skin to adapt to localized pressure in older subjects is related to the severity of the sensory-fiber dysfunction rather than to endothelial dysfunction, which was comparable between the non-neuropathic (141+/-19% increased blood flow with acetylcholine, P<0.05) and neuropathic older subjects (145+/-28% increase, P<0.05) compared with young subjects (234+/-25% increase).

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

PubMed

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-03-28

To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.

Acute lower motor neuron tetraparesis.

PubMed

Añor, Sònia

2014-11-01

Flaccid nonambulatory tetraparesis or tetraplegia is an infrequent neurologic presentation; it is characteristic of neuromuscular disease (lower motor neuron [LMN] disease) rather than spinal cord disease. Paresis beginning in the pelvic limbs and progressing to the thoracic limbs resulting in flaccid tetraparesis or tetraplegia within 24 to 72 hours is a common presentation of peripheral nerve or neuromuscular junction disease. Complete body flaccidity develops with severe decrease or complete loss of spinal reflexes in pelvic and thoracic limbs. Animals with acute generalized LMN tetraparesis commonly show severe motor dysfunction in all limbs and severe generalized weakness in all muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic inflammatory polyneuropathy

MedlinePlus

... to nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy means several nerves are involved. CIDP often ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

Assessment of vascularization and myelination following peripheral nerve repair using angiographic and polarization sensitive optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nam, Ahhyun S.; Chico-Calero, Isabel; Easow, Jeena M.; Villiger, Martin; Welt, Jonathan; Winograd, Jonathan M.; Randolph, Mark A.; Redmond, Robert W.; Vakoc, Benjamin J.

2017-02-01

A severe traumatic injury to a peripheral nerve often requires surgical graft repair. However, functional recovery after these surgical repairs is often unsatisfactory. To improve interventional procedures, it is important to understand the regeneration of the nerve grafts. The rodent sciatic nerve is commonly used to investigate these parameters. However, the ability to longitudinally assess the reinnervation of injured nerves are limited, and to our knowledge, no methods currently exist to investigate the timing of the revascularization in functional recovery. In this work, we describe the development and use of angiographic and polarization-sensitive (PS) optical coherence tomography (OCT) to visualize the vascularization, demyelination and remyelination of peripheral nerve healing after crush and transection injuries, and across a variety of graft repair methods. A microscope was customized to provide 3.6 cm fields of view along the nerve axis with a capability to track the nerve height to maintain the nerve within the focal plane. Motion artifact rejection was implemented in the angiography algorithm to reduce degradation by bulk respiratory motion in the hindlimb site. Vectorial birefringence imaging methods were developed to significantly enhance the accuracy of myelination measurements and to discriminate birefringent contributions from the myelin and epineurium. These results demonstrate that the OCT platform has the potential to reveal new insights in preclinical studies and may ultimately provide a means for clinical intra-surgical assessment of peripheral nerve function.

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

PubMed Central

Gonzalez, Eric J.; Merrill, Liana

2014-01-01

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

Peripheral choline acetyltransferase in rat skin demonstrated by immunohistochemistry.

PubMed

Hanada, Keiji; Kishimoto, Saburo; Bellier, Jean-Pierre; Kimura, Hiroshi

2013-03-01

Conventional choline acetyltransferase immunohistochemistry has been used widely for visualizing central cholinergic neurons and fibers but not often for labeling peripheral structures, probably because of their poor staining. The recent identification of the peripheral type of choline acetyltransferase (pChAT) has enabled the clear immunohistochemical detection of many known peripheral cholinergic elements. Here, we report the presence of pChAT-immunoreactive nerve fibers in rat skin. Intensely stained nerve fibers were distributed in association with eccrine sweat glands, blood vessels, hair follicles and portions just beneath the epidermis. These results suggest that pChAT-positive nerves participate in the sympathetic cholinergic innervation of eccrine sweat glands. Moreover, pChAT also appears to play a role in cutaneous sensory nerve endings. These findings are supported by the presence of many pChAT-positive neuronal cells in the sympathetic ganglion and dorsal root ganglion. Thus, pChAT immunohistochemistry should provide a novel and unique tool for studying cholinergic nerves in the skin.

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

PubMed Central

Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

2015-01-01

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

NASA Astrophysics Data System (ADS)

Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

2014-08-01

Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves.

PubMed

Meyer, Cora; Stenberg, Lena; Gonzalez-Perez, Francisco; Wrobel, Sandra; Ronchi, Giulia; Udina, Esther; Suganuma, Seigo; Geuna, Stefano; Navarro, Xavier; Dahlin, Lars B; Grothe, Claudia; Haastert-Talini, Kirsten

2016-01-01

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Damage to cranial and peripheral nerves following patency restoration of the internal carotid artery].

PubMed

Myrcha, P; Ciostek, P; Szopiński, P; Noszczyk, W

2001-01-01

The aim of the study was an assessment of the incidence of injury to cranial and peripheral nerves as complication of patency restoration of the internal carotid artery, and analysis of the effect of peripheral nerve injury on the results of carotid patency restoration. From Oct 1987 to Sept 1999 543 procedures were carried out for restoration of patency of the internal carotid artery. After the operation hypoglossus nerve injury was found in 7 cases (1.4%), vagus injury in 9 (1.8%). Signs of exclusively recurrent laryngeal nerve damage were found in 6 cases (1.2%). Glossopharyngeus nerve was damaged in 2 cases (0.4%), transient phrenic nerve palsy as a result of conduction anaesthesia was noted in 2 cases (0.4%). Damage to the transverse cervical nerve was found in 96 cases (60%). In 2 patients (1.2%) lower position of mouth angle was due to section of the mandibular ramus of the facial nerve. In another 2 cases skin sensation disturbances were a consequence of lesion of the auricularis magnus nerve and always they coexisted with signs of transverse cervical nerve damage. damage to the cranial nerves during operation for carotid patency restoration are frequent but mostly they are not connected with any health risks and often they regress spontaneously.

Role of Neuroactive Steroids in the Peripheral Nervous System

PubMed Central

Melcangi, Roberto Cosimo; Giatti, Silvia; Pesaresi, Marzia; Calabrese, Donato; Mitro, Nico; Caruso, Donatella; Garcia-Segura, Luis Miguel

2011-01-01

Several reviews have so far pointed out on the relevant physiological and pharmacological role exerted by neuroactive steroids in the central nervous system. In the present review we summarize observations indicating that synthesis and metabolism of neuroactive steroids also occur in the peripheral nerves. Interestingly, peripheral nervous system is also a target of their action. Indeed, as here reported neuroactive steroids are physiological regulators of peripheral nerve functions and they may also represent interesting therapeutic tools for different types of peripheral neuropathy. PMID:22654839

Scaffolds for peripheral nerve repair and reconstruction.

PubMed

Yi, Sheng; Xu, Lai; Gu, Xiaosong

2018-06-02

Trauma-associated peripheral nerve defect is a widespread clinical problem. Autologous nerve grafting, the current gold standard technique for the treatment of peripheral nerve injury, has many internal disadvantages. Emerging studies showed that tissue engineered nerve graft is an effective substitute to autologous nerves. Tissue engineered nerve graft is generally composed of neural scaffolds and incorporating cells and molecules. A variety of biomaterials have been used to construct neural scaffolds, the main component of tissue engineered nerve graft. Synthetic polymers (e.g. silicone, polyglycolic acid, and poly(lactic-co-glycolic acid)) and natural materials (e.g. chitosan, silk fibroin, and extracellular matrix components) are commonly used along or together to build neural scaffolds. Many other materials, including the extracellular matrix, glass fabrics, ceramics, and metallic materials, have also been used to construct neural scaffolds. These biomaterials are fabricated to create specific structures and surface features. Seeding supporting cells and/or incorporating neurotrophic factors to neural scaffolds further improve restoration effects. Preliminary studies demonstrate that clinical applications of these neural scaffolds achieve satisfactory functional recovery. Therefore, tissue engineered nerve graft provides a good alternative to autologous nerve graft and represents a promising frontier in neural tissue engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

Immunohistochemical Analysis of the Structure of Injured Peripheral Nerve Neuroma after Electrosurgical Welding Intervention.

PubMed

Korsak, A V; Chaikovskii, Yu B

2015-10-01

Immunohistochemical analysis of changes in neuroma after surgical treatment of damaged peripheral nerve with the use of high frequency electrosurgical device for high frequency current welding of soft tissues was carried out. No adverse effects of this technology and the bipolar instrument on degeneration and regeneration of damaged nerve stem were detected.

Different effects of astrocytes and Schwann cells on regenerating retinal axons.

PubMed

Campbell, Gregor; Kitching, Juliet; Anderson, Patrick N; Lieberman, A Robert

2003-11-14

Following a crush injury of the optic nerve in adult rats, the axons of retinal ganglion cells, stimulated to regenerate by a lens injury and growing within the optic nerve, are associated predominantly with astrocytes: they remain of small diameter (0.1-0.5 microm) and unmyelinated for > or = 2 months after the operation. In contrast, when the optic nerve is cut and a segment of a peripheral nerve is grafted to the ocular stump of the optic nerve, the regenerating retinal axons are associated predominantly with Schwann cells: they are of larger diameter than in the previous experiment and include unmyelinated axons (0.2-2.5 microm) and myelinated axons (mean diameter 2.3 microm). Thus, the grafted peripheral nerve, and presumably its Schwann cells, stimulate enlargement of the regenerating retinal axons leading to partial myelination, whereas the injured optic nerve itself, and presumably its astrocytes, does not. The result points to a marked difference of peripheral (Schwann cells) and central (astrocytes) glia in their effect on regenerating retinal axons.

Gene probe for P0 messenger RNA used to index acrylamide toxic neuropathy in rats.

PubMed

Veronesi, B; Jones, K; Gupta, S; Pringle, J; Mezei, C

1991-01-01

Cumulative exposure to the neurotoxicant acrylamide produces axonal damage in the distal ends of both central (CNS) and peripheral (PNS) nerve fibers and subsequent hind-limb paralysis. The messenger RNA which codes for the PNS myelin glycoprotein P0 (P0-mRNA) was used to monitor this toxic neuropathy in Sprague Dawley rats prior to, concurrent with, and subsequent to, ultrastructurally and immunocytochemically defined nerve damage. Rats were dosed every other day with acrylamide (50 mg/kg, IP) and sampled intermittently throughout a 4 week exposure period. Slot blot and Northern gel analyses of the proximal and distal sciatic nerve were used to determine a quantitated measure of P0-mRNA. Twenty-four hours after the first treatment, in the absence of ultrastructural damage, P0-mRNA increased 55% over control levels in the distal sciatic nerve. After 12 treatments, and concomitant with the appearance of spinal cord and PNS neuropathic damage and hindlimb dysfunction, P0-mRNA decreased 45% below control levels. Levels of P0-mRNA from rats exposed to 12 treatments of acrylamide but allowed to recover for 40 days, returned to 79% of control values to reflect the regeneration and remyelination occurring in the distal sciatic nerve. In spite of these fluctuations in levels of P0-mRNA, immunocytochemical staining of P0 protein in plastic sections of the distal sciatic nerve was present throughout all sample times. These results suggest that changes in neural specific mRNAs are sensitive to neurotoxic damage and can be used to monitor the pathogenesis of nerve degeneration.

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

PubMed

Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly. Copyright © 2018 the authors 0270-6474/18/384610-11$15.00/0.

Use of paper for treatment of a peripheral nerve trauma in the rat.

PubMed

Kauppila, T; Jyväsjärvi, E; Murtomäki, S; Mansikka, H; Pertovaara, A; Virtanen, I; Liesi, P

1997-09-29

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

Evaluation of tissue components in the peripheral nervous system using Sirius red staining and immunohistochemistry: a comparative study (human, pig, rat).

PubMed

Kaemmer, D; Bozkurt, A; Otto, J; Junge, K; Klink, C; Weis, J; Sellhaus, B; O'Dey, D M; Pallua, N; Jansen, M; Schumpelick, V; Klinge, U

2010-06-30

Little is known about species differences in the peripheral nerve system and quantitative evaluation of main tissue components has rarely been done. Nevertheless, animal models are used for example in pain research without exact knowledge of degree of fibrosis in pathological states which would determine possible treatment options. It would therefore be of crucial interest to describe the degree of fibrosis and the remaining functional nerve tissue as exact as possible. In the present study we evaluated collagen (stroma) and nerve fiber (parenchyma) composition of peripheral nerves in three species (human, rat, pig) and used digital colour-separation and analysis for collagen type differentiation and quantification of immuno-positive-stained area. We found similar ratios of collagen types I and III in epineurium and similar immuno-positive area for staining of neurofilament and S-100beta. In contrast, we measured significantly different ratios of collagen type I to type III in the endoneurium. This combined analysis of the main tissue components of peripheral nerves could be an easy-to-use tool in evaluating changes during damage caused by scaring, systemic disease or compression syndromes. The calculated collagen type I/III ratio may serve as an objective diagnostic value for the description or as prognostic marker for therapeutic approaches in peripheral nerve pathology. However, in particular studies of collagen accumulation in nerves, species dependant differences have to be considered. Copyright 2010 Elsevier B.V. All rights reserved.

Occipital peripheral nerve stimulation in the management of chronic intractable occipital neuralgia in a patient with neurofibromatosis type 1: a case report.

PubMed

Skaribas, Ioannis; Calvillo, Octavio; Delikanaki-Skaribas, Evangelia

2011-05-10

Occipital peripheral nerve stimulation is an interventional pain management therapy that provides beneficial results in the treatment of refractory chronic occipital neuralgia. Herein we present a first-of-its-kind case study of a patient with neurofibromatosis type 1 and bilateral occipital neuralgia treated with occipital peripheral nerve stimulation. A 42-year-old Caucasian woman presented with bilateral occipital neuralgia refractory to various conventional treatments, and she was referred for possible treatment with occipital peripheral nerve stimulation. She was found to be a suitable candidate for the procedure, and she underwent implantation of two octapolar stimulating leads and a rechargeable, programmable, implantable generator. The intensity, severity, and frequency of her symptoms resolved by more than 80%, but an infection developed at the implantation site two months after the procedure that required explantation and reimplantation of new stimulating leads three months later. To date she continues to experience symptom resolution of more than 60%. These results demonstrate the significance of peripheral nerve stimulation in the management of refractory occipital neuralgias in patients with neurofibromatosis type 1 and the possible role of neurofibromata in the development of occipital neuralgia in these patients.

Peripheral neuropathy

MedlinePlus

... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

Chondroitinase C Selectively Degrades Chondroitin Sulfate Glycosaminoglycans that Inhibit Axonal Growth within the Endoneurium of Peripheral Nerve.

PubMed

Graham, James B; Muir, David

2016-01-01

The success of peripheral nerve regeneration is highly dependent on the regrowth of axons within the endoneurial basal lamina tubes that promote target-oriented pathfinding and appropriate reinnervation. Restoration of nerve continuity at this structural level after nerve transection injury by direct repair and nerve grafting remains a major surgical challenge. Recently, biological approaches that alter the balance of growth inhibitors and promoters in nerve have shown promise to improve appropriate axonal regeneration and recovery of peripheral nerve function. Chondroitin sulfate proteoglycans (CSPGs) are known inhibitors of axonal growth. This growth inhibition is mainly associated with a CSPG's glycosaminoglycan chains. Enzymatic degradation of these chains with chondroitinase eliminates this inhibitory activity and, when applied in vivo, can improve the outcome of nerve repair. To date, these encouraging findings were obtained with chondroitinase ABC (a pan-specific chondroitinase). The aim of this study was to examine the distribution of CSPG subtypes in rodent, rabbit, and human peripheral nerve and to test more selective biological enzymatic approaches to improve appropriate axonal growth within the endoneurium and minimize aberrant growth. Here we provide evidence that the endoneurium, but not the surrounding epineurium, is rich in CSPGs that have glycosaminoglycan chains readily degraded by chondroitinase C. Biochemical studies indicate that chondroitinase C has degradation specificity for 6-sulfated glycosaminoglycans found in peripheral nerve. We found that chondroitinase C degrades and inactivates inhibitory CSPGs within the endoneurium but not so much in the surrounding nerve compartments. Cryoculture bioassays (neurons grown on tissue sections) show that chondroitinase C selectively and significantly enhanced neuritic growth associated with the endoneurial basal laminae without changing growth-inhibiting properties of the surrounding epineurium. Interestingly, chondroitinase ABC treatment increased greatly the growth-promoting properties of the epineurial tissue whereas chondroitinase C had little effect. Our evidence indicates that chondroitinase C effectively degrades and inactivates inhibitory CSPGs present in the endoneurial Schwann cell basal lamina and does so more specifically than chondroitinase ABC. These findings are discussed in the context of improving nerve repair and regeneration and the growth-promoting properties of processed nerve allografts.

Primary Motor Cortex Representation of Handgrip Muscles in Patients with Leprosy

PubMed Central

Rangel, Maria Luíza Sales; Sanchez, Tiago Arruda; Moreira, Filipe Azaline; Hoefle, Sebastian; Souto, Inaiacy Bittencourt; da Cunha, Antônio José Ledo Alves

2015-01-01

Background Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. Our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic stimulation (TMS). Methods In a cross-sectional study design, we mapped bilaterally in the primary motor cortex (M1) the representations of the hand flexor digitorum superficialis (FDS), as well as of the intrinsic hand muscles abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM). All participants underwent clinical assessment, handgrip dynamometry and motor and sensory nerve conduction exams 30 days before mapping. Wilcoxon signed rank and Mann-Whitney tests were performed with an alpha-value of p<0.05. Findings Dynamometry performance of the patients’ most affected hand (MAH), was worse than that of the less affected hand (LAH) and of healthy controls participants (p = 0.031), confirming handgrip impairment. Motor threshold (MT) of the FDS muscle was higher in both hemispheres in patients as compared to controls, and lower in the hemisphere contralateral to the MAH when compared to that of the LAH. Moreover, motor evoked potential (MEP) amplitudes collected in the FDS of the MAH were higher in comparison to those of controls. Strikingly, MEPs in the intrinsic hand muscle FDI had lower amplitudes in the hemisphere contralateral to MAH as compared to those of the LAH and the control group. Taken together, these results are suggestive of a more robust representation of an extrinsic hand flexor and impaired intrinsic hand muscle function in the hemisphere contralateral to the MAH due to leprosy. Conclusion Decreased sensory-motor function induced by leprosy affects handgrip muscle representation in M1. PMID:26203653

Circadian Rhythm Influences the Promoting Role of Pulsed Electromagnetic Fields on Sciatic Nerve Regeneration in Rats

PubMed Central

Zhu, Shu; Ge, Jun; Liu, Zhongyang; Liu, Liang; Jing, Da; Ran, Mingzi; Wang, Meng; Huang, Liangliang; Yang, Yafeng; Huang, Jinghui; Luo, Zhuojing

2017-01-01

Circadian rhythm (CR) plays a critical role in the treatment of several diseases. However, the role of CR in the treatment of peripheral nerve defects has not been studied. It is also known that the pulsed electromagnetic fields (PEMF) can provide a beneficial microenvironment to quicken the process of nerve regeneration and to enhance the quality of reconstruction. In this study, we evaluate the impact of CR on the promoting effect of PEMF on peripheral nerve regeneration in rats. We used the self-made “collagen-chitosan” nerve conduits to bridge the 15-mm nerve gaps in Sprague-Dawley rats. Our results show that PEMF stimulation at daytime (DPEMF) has most effective outcome on nerve regeneration and rats with DPEMF treatment achieve quickly functional recovery after 12 weeks. These findings indicate that CR is an important factor that determines the promoting effect of PEMF on peripheral nerve regeneration. PEMF exposure in the daytime enhances the functional recovery of rats. Our study provides a helpful guideline for the effective use of PEMF mediations experimentally and clinically. PMID:28360885

Cochlear implantation in chronic demyelinating inflammatory polyneuropathy.

PubMed

Mowry, Sarah E; King, Sarah

2017-03-01

To describe a case of chronic inflammatory demyelinating polyneuropathy (CDIP) with bilateral sudden sensorineural hearing loss who subsequently benefited from unilateral cochlear implantation. case history review and review of the literature for the terms CDIP, hearing loss, cochleovestibular dysfunction, and cochlear implantation. A 49-year-old woman presented with bilateral rapidly progressive sensorineural hearing loss (SNHL) 1 month after an upper respiratory tract infection. Hearing loss was not responsive to high-dose steroids and there were no other laboratory abnormalities or physical findings. Within 1 month, she developed ascending motor palsy, requiring long-term ventilator support. This neurologic condition was diagnosed as CDIP and she was successfully treated with plasmapheresis and intravenous immunoglobulin. Her hearing never recovered. At the time of cochlear implant, she had no response at the limits of the audiometer and obtained 0% on AzBio testing. No ABR could be recorded preoperatively. She underwent uneventful cochlear implantation with a perimodilar electrode. One year after activation, she had a PTA of 20 dB and 40% on AzBio sentence testing. Her eABR demonstrated a neuropathy pattern. Only two other cases of CDIP associated with dysfunction of the eighth nerve have been described, and neither had documented profound hearing loss. Severe SNHL associated with CDIP is rare. Although this patient has good access to sound, speech discrimination is poor at 1-year post implantation. This outcome may be due to incomplete recovery of myelination of the eighth nerve. Other possibilities include loss of peripheral nerve fibers due to the initial viral upper respiratory infection, which may lead to less neural substrate to stimulate.

Limb myokymia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albers, J.W.; Allen, A.A.; Bastron, J.A.

Thirty-eight patients with myokymic discharges localized to limb muscles on needle electromyography had various neurologic lesions, both acute and chronic. Of the 38 patients, 27 had had previous radiation therapy and the clinical diagnosis of radiation-induced plexopathy, myelopathy, or both. For the remaining 11 patients, the diagnoses included multiple sclerosis, inflammatory polyradiculoneuropathy, ischemic neuropathy, inflammatory myopathy, and chronic disorders of the spinal cord and peripheral nerves. The clinical presentations and results of local ischemia, peripheral nerve block, and percutaneous stimulation suggest that most limb myokymic discharges arise focally at the site of a chronic peripheral nerve lesion.

F wave index: A diagnostic tool for peripheral neuropathy.

PubMed

Sathya, G R; Krishnamurthy, N; Veliath, Susheela; Arulneyam, Jayanthi; Venkatachalam, J

2017-03-01

Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy.

Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

NASA Astrophysics Data System (ADS)

Sharma, Anup Dutt

Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats.

PubMed

Gonzalez-Perez, Francisco; Cobianchi, Stefano; Heimann, Claudia; Phillips, James B; Udina, Esther; Navarro, Xavier

2017-03-01

Autograft is still the gold standard technique for the repair of long peripheral nerve injuries. The addition of biologically active scaffolds into the lumen of conduits to mimic the endoneurium of peripheral nerves may increase the final outcome of artificial nerve devices. Furthermore, the control of the orientation of the collagen fibers may provide some longitudinal guidance architecture providing a higher level of mesoscale tissue structure. To evaluate the regenerative capabilities of chitosan conduits enriched with extracellular matrix-based scaffolds to bridge a critical gap of 15 mm in the rat sciatic nerve. The right sciatic nerve of female Wistar Hannover rats was repaired with chitosan tubes functionalized with extracellular matrix-based scaffolds fully hydrated or stabilized and rolled to bridge a 15 mm nerve gap. Recovery was evaluated by means of electrophysiology and algesimetry tests and histological analysis 4 months after injury. Stabilized constructs enhanced the success of regeneration compared with fully hydrated scaffolds. Moreover, fibronectin-enriched scaffolds increased muscle reinnervation and number of myelinated fibers compared with laminin-enriched constructs. A mixed combination of collagen and fibronectin may be a promising internal filler for neural conduits for the repair of peripheral nerve injuries, and their stabilization may increase the quality of regeneration over long gaps. Copyright © 2017 by the Congress of Neurological Surgeons

Are Human Peripheral Nerves Sensitive to X-Ray Imaging?

PubMed Central

Scopel, Jonas Francisco; de Souza Queiroz, Luciano; O’Dowd, Francis Pierce; Júnior, Marcondes Cavalcante França; Nucci, Anamarli; Hönnicke, Marcelo Gonçalves

2015-01-01

Diagnostic imaging techniques play an important role in assessing the exact location, cause, and extent of a nerve lesion, thus allowing clinicians to diagnose and manage more effectively a variety of pathological conditions, such as entrapment syndromes, traumatic injuries, and space-occupying lesions. Ultrasound and nuclear magnetic resonance imaging are becoming useful methods for this purpose, but they still lack spatial resolution. In this regard, recent phase contrast x-ray imaging experiments of peripheral nerve allowed the visualization of each nerve fiber surrounded by its myelin sheath as clearly as optical microscopy. In the present study, we attempted to produce high-resolution x-ray phase contrast images of a human sciatic nerve by using synchrotron radiation propagation-based imaging. The images showed high contrast and high spatial resolution, allowing clear identification of each fascicle structure and surrounding connective tissue. The outstanding result is the detection of such structures by phase contrast x-ray tomography of a thick human sciatic nerve section. This may further enable the identification of diverse pathological patterns, such as Wallerian degeneration, hypertrophic neuropathy, inflammatory infiltration, leprosy neuropathy and amyloid deposits. To the best of our knowledge, this is the first successful phase contrast x-ray imaging experiment of a human peripheral nerve sample. Our long-term goal is to develop peripheral nerve imaging methods that could supersede biopsy procedures. PMID:25757086

Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

PubMed Central

Zhu, Yiqian; Wang, Aijun; Patel, Shyam; Kurpinski, Kyle; Diao, Edward; Bao, Xuan; Kwong, George; Young, William L.

2011-01-01

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID:21501089

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Peripheral Nerve Disorders

MedlinePlus

... outlet syndrome. In some cases, like complex regional pain syndrome and brachial plexus injuries, the problem begins after an injury. Some people are born with peripheral nerve disorders. Symptoms often start gradually, and then ... Burning or tingling Muscle weakness Sensitivity to touch ...

Identification of PN1, a Predominant Voltage-Dependent Sodium Channel Expressed Principally in Peripheral Neurons

NASA Astrophysics Data System (ADS)

Toledo-Aral, Juan J.; Moss, Brenda L.; He, Zhi-Jun; Koszowski, Adam G.; Whisenand, Teri; Levinson, Simon R.; Wolf, John J.; Silos-Santiago, Inmaculada; Halegoua, Simon; Mandel, Gail

1997-02-01

Membrane excitability in different tissues is due, in large part, to the selective expression of distinct genes encoding the voltage-dependent sodium channel. Although the predominant sodium channels in brain, skeletal muscle, and cardiac muscle have been identified, the major sodium channel types responsible for excitability within the peripheral nervous system have remained elusive. We now describe the deduced primary structure of a sodium channel, peripheral nerve type 1 (PN1), which is expressed at high levels throughout the peripheral nervous system and is targeted to nerve terminals of cultured dorsal root ganglion neurons. Studies using cultured PC12 cells indicate that both expression and targeting of PN1 is induced by treatment of the cells with nerve growth factor. The preferential localization suggests that the PN1 sodium channel plays a specific role in nerve excitability.

Motor-commands decoding using peripheral nerve signals: a review

NASA Astrophysics Data System (ADS)

Hong, Keum-Shik; Aziz, Nida; Ghafoor, Usman

2018-06-01

During the last few decades, substantial scientific and technological efforts have been focused on the development of neuroprostheses. The major emphasis has been on techniques for connecting the human nervous system with a robotic prosthesis via natural-feeling interfaces. The peripheral nerves provide access to highly processed and segregated neural command signals from the brain that can in principle be used to determine user intent and control muscles. If these signals could be used, they might allow near-natural and intuitive control of prosthetic limbs with multiple degrees of freedom. This review summarizes the history of neuroprosthetic interfaces and their ability to record from and stimulate peripheral nerves. We also discuss the types of interfaces available and their applications, the kinds of peripheral nerve signals that are used, and the algorithms used to decode them. Finally, we explore the prospects for future development in this area.

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2014-10-01

Shahani B. Peripheral-nerve allotransplantation in rats immunosuppressed with transient or long-term FK-506. Journal of reconstructive microsurgery ...multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions . Microsurgery . 2012 Jan;32(1):1-14. PubMed PMID: 22121093...PTB method can provide fixation strengths 6 approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in

Microsurgical Outcome of Post-traumatic Peripheral Nerve Injuries: An Experience of 23 Cases and Review of Literature.

PubMed

Garg, Kanwaljeet; Sinha, Sumit; Satyarthee, Guru Dutta; Agarwal, Deepak; Gupta, Deepak Kumar; Sharma, Bhawani; Mahapatra, Ashok Kumar

2016-01-01

The present study aimed to evaluate the microsurgical outcome in post-traumatic peripheral nerve injuries and its correlation with time since injury and the type of the operative procedure performed. All the patients admitted to our center with the diagnosis of post-traumatic peripheral nerve injury were included in the study. The data of all patients was retrospectively analysed from the computerized database of our hospital. The time period of the study was from January 2008 to March 2011. A total of 23 patients were included in the study. The interval between injury and surgery was 28.8 weeks (range: 1 day - 70 weeks). The most common mode of injury was road traffic accidents (39%, n=9). The mean follow up was 24.7 ± 11.3 months (range 9-45 months). Six (60%) patients had a good outcome. There was no statistically significant correlation between outcome and time since injury or type of operative procedure performed (p > 0.05). Post-traumatic peripheral nerve injury is a rare form of nerve injury. There is no correlation between the surgical outcome and time since injury. Some of the nerves have a better outcome as compared to others.

A Pilot Study of a Novel Automated Somatosensory Evoked Potential (SSEP) Monitoring Device for Detection and Prevention of Intraoperative Peripheral Nerve Injury in Total Shoulder Arthroplasty Surgery.

PubMed

Chui, Jason; Murkin, John M; Drosdowech, Darren

2018-05-21

Peripheral nerve injury is a potentially devastating complication after total shoulder arthroplasty (TSA) surgery. This pilot study aimed to assess the feasibility of using an automated somatosensory evoked potential (SSEP) device to provide a timely alert/intervention to minimize intraoperative nerve insults during TSA surgery. A prospective, single-arm, observational study was conducted in a single university hospital. The attending anesthesiologist monitored the study participants using the EPAD automated SSEP device and an intervention was made if there was an alert during TSA surgery. The median, radial, and ulnar nerve SSEP on the operative arm, as well as the median nerve SSEP of the nonoperative arm were monitored for each patient. All patients were evaluated for postoperative neurological deficits 6 weeks postoperatively. In total, 21 patients were consented and were successfully monitored. In total, 4 (19%) patients developed intraoperative abnormal SSEP signal changes in the operative arm, in which 3 were reversible and 1 was irreversible till the end of surgery. Median and radial nerves were mostly involved (3/4 patients). The mean cumulative duration of nerve insult (abnormal SSEP) was 21.7±26.2 minutes. Univariate analysis did not identify predictor of intraoperative nerve insults. No patients demonstrated postoperative peripheral neuropathy at 6 weeks. A high incidence (19%) of intraoperative nerve insult was observed in this study demonstrating the feasibility of using an automated SSEP device to provide a timely alert and enable an intervention in order to minimize peripheral nerve injury during TSA. Further randomized studies are warranted.

An in vivo study of tricalcium phosphate and glutaraldehyde crosslinking gelatin conduits in peripheral nerve repair.

PubMed

Chen, Ming-Hong; Chen, Pei-Ru; Chen, Mei-Hsiu; Hsieh, Sung-Tsang; Huang, Jing-Shan; Lin, Feng-Huei

2006-04-01

In order to modulate the mechanical properties of gelatin, we previously developed a biodegradable composite composed by tricalcium phosphate and glutaraldehyde crosslinking gelatin (GTG) feasible for surgical manipulation. In this study, we evaluated the in vivo applications of GTG conduit for peripheral nerve repair. The effect of sciatic nerve reconstruction was compared between resorbable permeable GTG conduits and durable impermeable silicone tubes. Traditional methods of assessing nerve recovery following peripheral nerve repair including histomorphometric and electrophysiologic features were conducted in our study. In addition, autotomy score and sciatic function index (SFI) in walking tract analysis were used as additional parameters for assessing the return of nerve function. Twenty-four weeks after sciatic nerve repair, the GTG conduits were harvested. Microscopically, regeneration of nerves was observed in the cross-section at the mid portion of all implanted GTG conduits. The cross-sectional area of regenerated nerve of the GTG group was significant larger than that of the silicone group. In the compound muscle action potentials (CMAP), the mean recovery index of CMAP amplitude was 0.24 +/- 0.02 for the silicone group, 0.41 +/- 0.07 for the GTG group. The mean SFI increased with time in the GTG group during the evaluation period until 24 weeks. Walking tract analysis showed a higher SFI score in the GTG group at both 12 and 24 weeks. The difference reached a significant level at 24 weeks. Thus, the histomorphometric, electrophysiologic, and functional assessments demonstrate that GTG can be a candidate for peripheral nerve repair.

Effect of Platelet-Rich Fibrin on Peripheral Nerve Regeneration.

PubMed

Şenses, Fatma; Önder, Mustafa E; Koçyiğit, Ismail D; Kul, Oğuz; Aydin, Gülümser; Inal, Elem; Atil, Fethi; Tekin, Umut

2016-10-01

This study aimed to evaluate the effect of platelet-rich fibrin (PRF) on peripheral nerve regeneration on the sciatic nerve of rats by using functional, histopathologic, and electrophysiologic analyses. Thirty female Wistar rats were divided randomly into 3 experimental groups. In group 1 (G1), which was the control group, the sciatic nerve was transected and sutured (n = 10). In group 2 (G2), the sciatic nerve was transected, sutured, and then covered with PRF as a membrane (n = 10). In group 3 (G3), the sciatic nerve was transected, sutured by leaving a 5-mm gap, and then covered by PRF as a nerve guide (n = 10). Functional, histopathologic, and electrophysiologic analyses were performed. The total histopathologic semiquantitative score was significantly higher in G1 compared to G2 and G3 (P < 0.05). Myelin thickness and capillaries were significantly lower in G3 compared to G1 (P < 0.05). There was no statistically significant difference between the groups with regard to the functional and electrophysiologic results. The study results suggest that PRF decreases functional recovery in sciatic nerve injury. Further studies are required to determine the efficacy of PRF on peripheral nerve regeneration.

[Peripheral nerve repair: 30 centuries of scientific research].

PubMed

Desouches, C; Alluin, O; Mutaftschiev, N; Dousset, E; Magalon, G; Boucraut, J; Feron, F; Decherchi, P

2005-11-01

Nerve injury compromises sensory and motor functions. Techniques of peripheral nerve repair are based on our knowledge regarding regeneration. Microsurgical techniques introduced in the late 1950s and widely developed for the past 20 years have improved repairs. However, functional recovery following a peripheral mixed nerve injury is still incomplete. Good motor and sensory function after nerve injury depends on the reinnervation of the motor end plates and sensory receptors. Nerve regeneration does not begin if the cell body has not survived the initial injury or if it is unable to initiate regeneration. The regenerated axons must reach and reinnervate the appropriate target end-organs in a timely fashion. Recovery of motor function requires a critical number of motor axons reinnervating the muscle fibers. Sensory recovery is possible if the delay in reinnervation is short. Many additional factors influence the success of nerve repair or reconstruction. The timing of the repair, the level of injury, the extent of the zone of injury, the technical skill of the surgeon, and the method of repair and reconstruction contribute to the functional outcome after nerve injury. This review presents the recent advances in understanding of neural regeneration and their application to the management of primary repairs and nerve gaps.

In vivo predegeneration of peripheral nerves: an effective technique to obtain activated Schwann cells for nerve conduits.

PubMed

Keilhoff, G; Fansa, H; Schneider, W; Wolf, G

1999-07-01

In vivo predegeneration of peripheral nerves is presented as a convenient and effective method to obtain activated Schwann cells and an enhanced cell yield following in vitro cultivation. The experiments conducted in rats were aimed at clinical use in gaining Schwann cell suspensions for filling artificial conduits in order to bridge peripheral nerve gaps. The rat sciatic nerve used as a model was transected distally to the spinal ganglia. Predegeneration in vivo was allowed to take place for 1, 2, 3 and 4 days and up to 1, 2 and 3 weeks. The nerve was then resected and prepared for cell cultivation. Schwann cells cultivated from the contralateral untreated nerve served as control. Immunostaining for S100, nerve growth factor receptor and the adhesion molecules N-cadherin and L1 was used to characterize the general state of the cultures. Viability was assessed by fluorescein fluorescence staining, and the proliferation index was determined by bromodeoxyuridine-DNA incorporation. The Schwann cells from predegenerated nerves revealed an increased proliferation rate compared to the control, whereas fibroblast contamination was decreased. Best results were obtained 1 week after predegeneration.

Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs.

PubMed

Cui, Yi; Yao, Yao; Zhao, Yannan; Xiao, Zhifeng; Cao, Zongfu; Han, Sufang; Li, Xing; Huan, Yong; Pan, Juli; Dai, Jianwu

2018-05-01

Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5-cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC-MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC-MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC-MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC-MSCs might have therapeutic potential for the treatment of peripheral nerve injury. Copyright © 2018 John Wiley & Sons, Ltd.

Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

PubMed Central

Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothstein, Jeffrey D.

2014-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

PubMed

Morrison, Brett M; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Rothstein, Jeffrey D

2015-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. Copyright © 2014 Elsevier Inc. All rights reserved.

Sequential variation in brain functional magnetic resonance imaging after peripheral nerve injury: A rat study.

PubMed

Onishi, Okihiro; Ikoma, Kazuya; Oda, Ryo; Yamazaki, Tetsuro; Fujiwara, Hiroyoshi; Yamada, Shunji; Tanaka, Masaki; Kubo, Toshikazu

2018-04-23

Although treatment protocols are available, patients experience both acute neuropathic pain and chronic neuropathic pain, hyperalgesia, and allodynia after peripheral nerve injury. The purpose of this study was to identify the brain regions activated after peripheral nerve injury using functional magnetic resonance imaging (fMRI) sequentially and assess the relevance of the imaging results using histological findings. To model peripheral nerve injury in male Sprague-Dawley rats, the right sciatic nerve was crushed using an aneurysm clip, under general anesthesia. We used a 7.04T MRI system. T 2 * weighted image, coronal slice, repetition time, 7 ms; echo time, 3.3 ms; field of view, 30 mm × 30 mm; pixel matrix, 64 × 64 by zero-filling; slice thickness, 2 mm; numbers of slices, 9; numbers of average, 2; and flip angle, 8°. fMR images were acquired during electrical stimulation to the rat's foot sole; after 90 min, c-Fos immunohistochemical staining of the brain was performed in rats with induced peripheral nerve injury for 3, 6, and 9 weeks. Data were pre-processed by realignment in the Statistical Parametric Mapping 8 software. A General Linear Model first level analysis was used to obtain T-values. One week after the injury, significant changes were detected in the cingulate cortex, insular cortex, amygdala, and basal ganglia; at 6 weeks, the brain regions with significant changes in signal density were contracted; at 9 weeks, the amygdala and hippocampus showed activation. Histological findings of the rat brain supported the fMRI findings. We detected sequential activation in the rat brain using fMRI after sciatic nerve injury. Many brain regions were activated during the acute stage of peripheral nerve injury. Conversely, during the chronic stage, activation of the amygdala and hippocampus may be related to chronic-stage hyperalgesia, allodynia, and chronic neuropathic pain. Copyright © 2018 Elsevier B.V. All rights reserved.

Preoperative percutaneous cranial nerve mapping in head and neck surgery.

PubMed

Park, Jung I

2003-01-01

To identify and map the course of the peripheral branches of the cranial nerve preoperatively and percutaneously. Prospective study. Preoperative percutaneous nerve mapping performed prior to the operation under deep sedation or general anesthesia without muscle paralysis. Private office surgery suite, freestanding surgery center, and regional medical centers. A total of 142 patients undergoing head and neck surgery and facial plastic surgery between August 1994 and July 1999. Monopolar probe was used for nerve stimulation. Electromyographic reading was done through intramuscular bipolar recording electrodes. The equipment used was a nerve monitor. The mandibular divisions were tested in 142 cases, the frontal division in 60 cases, the accessory nerve in 12 cases, and the hypoglossal nerve in 3 cases. Satisfactory mappings were obtained in 115 cases of the mandibular division, 49 cases of the frontal division, 8 cases of the accessory division, and 1 case of the hypoglossal nerve. Preoperative percutaneous nerve mapping is a new method of identifying the location of the peripheral branches of the cranial nerves. Identifying and mapping the course of peripheral branches of the cranial nerves safely assists the head and neck surgeon in the placement of incisions in a favorable location and in the dissection of the area involving the nerves. Mapping alerts the surgeon to an area containing a nerve and allows the surgeon to avoid just the specific area where a nerve is present, preventing large-scale abandonment of unmapped areas for fear of potential nerve damage.

Promoting peripheral nerve regeneration with biodegradable poly (DL-lactic acid) films

PubMed Central

Li, Ruijun; Chen, Lei; Fu, Jinling; Liu, Zhigang; Wang, Shuang; Pan, Yuehai

2015-01-01

Regeneration and repair of peripheral nerve injury has always been a major problem in the clinic. The conventional technique based on suturing the nerve ends to each other coupled with the implantation of nerve conduits outside is associated with postoperative adhesions and scar problems. Recently, a novel biodegradable poly (DL-lactic acid) (PDLLA) film has been introduced. This novel anti-adhesion film has a porous structure with better mechanical properties, better flexibility, and more controllable degradation as compared to traditional non-porous nerve conduits. However, little is known about the effects of such PDLLA films on regeneration and repair of peripheral nerve injury in vivo. In this study, we evaluated the effects of PDLLA films implantation after sciatic nerve transection and anastomosis on subsequent sciatic nerve regeneration in vivo, using a rat sciatic nerve injury model. Sciatic nerve transection surgery coupled with direct suturing only, suturing and wrapping with traditional nerve conduits, or suturing and wrapping with PDLLA films was performed on adult Wistar rats. The additional wrapping with PDLLA films inhibited the nerve adhesion after 12 weeks recovery from surgery. It also increased the compound muscle action potentials and tibialis and gastrocnemius muscle wet weight ratio following 8 weeks recovery from surgery. Regenerated nerve fibers were relatively straight and the aligned structure was complete in rats with implantations of PDLLA films. The results suggested that PDLLA films can improve the nutritional status in the muscles innervated by the damaged nerves and promote nerve regeneration in vivo. PMID:26339372

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

PubMed Central

Huisman, Merel; Staruch, Robert M.; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A.; Burns, Dennis K.; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Purpose Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Methods Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160–300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson’s trichrome and toluidine blue staining. Results All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Conclusion Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection. PMID:26659073

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

PubMed Central

Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

2011-01-01

Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

Is Local Infiltration Analgesia Superior to Peripheral Nerve Blockade for Pain Management After THA: A Network Meta-analysis.

PubMed

Jiménez-Almonte, José H; Wyles, Cody C; Wyles, Saranya P; Norambuena-Morales, German A; Báez, Pedro J; Murad, Mohammad H; Sierra, Rafael J

2016-02-01

Local infiltration analgesia and peripheral nerve blocks are common methods for pain management in patients after THA but direct head-to-head, randomized controlled trials (RCTs) have not been performed. A network meta-analysis allows indirect comparison of individual treatments relative to a common comparator; in this case placebo (or no intervention), epidural analgesia, and intrathecal morphine, yielding an estimate of comparative efficacy. We asked, when compared with a placebo, (1) does use of local infiltration analgesia reduce patient pain scores and opioid consumption, (2) does use of peripheral nerve blocks reduce patient pain scores and opioid consumption, and (3) is local infiltration analgesia favored over peripheral nerve blocks for postoperative pain management after THA? We searched six databases, from inception through June 30, 2014, to identify RCTs comparing local infiltration analgesia or peripheral nerve block use in patients after THA. A total of 35 RCTs at low risk of bias based on the recommended Cochrane Collaboration risk assessment tool were included in the network meta-analysis (2296 patients). Primary outcomes for this review were patient pain scores at rest and cumulative opioid consumption, both assessed at 24 hours after THA. Because of substantial heterogeneity (variation of outcomes between studies) across included trials, a random effect model for meta-analysis was used to estimate the weighted mean difference (WMD) and 95% CI. The gray literature was searched with the same inclusion criteria as published trials. Only one unpublished trial (published abstract) fulfilled our criteria and was included in this review. All other studies included in this systematic review were full published articles. Bayesian network meta-analysis included all RCTs that compared local infiltration analgesia or peripheral nerve blocks with placebo (or no intervention), epidural analgesia, and intrathecal morphine. Compared with placebo, local infiltration analgesia reduced patient pain scores (WMD, -0.61; 95% CI, -0.97 to -0.24; p = 0.001) and opioid consumption (WMD, -7.16 mg; 95% CI, -11.98 to -2.35; p = 0.004). Peripheral nerve blocks did not result in lower pain scores or reduced opioid consumption compared with placebo (WMD, -0.43; 95% CI, -0.99 to 0.12; p = 0.12 and WMD, -3.14 mg, 95% CI, -11.30 to 5.02; p = 0.45). However, network meta-analysis comparing local infiltration analgesia with peripheral nerve blocks through common comparators showed no differences between postoperative pain scores (WMD, -0.36; 95% CI, -1.06 to 0.31) and opioid consumption (WMD, -4.59 mg; 95% CI, -9.35 to 0.17), although rank-order analysis found local infiltration analgesia to be ranked first in more simulations than peripheral nerve blocks, suggesting that it may be more effective. Using the novel statistical network meta-analysis approach, we found no differences between local infiltration analgesia and peripheral nerve blocks in terms of analgesia or opioid consumption 24 hours after THA; there was a suggestion of a slight advantage to peripheral nerve blocks based on rank-order analysis, but the effect size in question is likely not large. Given the slight difference between interventions, clinicians may choose to focus on other factors such as cost and intervention-related complications when debating which analgesic treatment to use after THA. Level I, therapeutic study.

Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes.

PubMed

Hinder, Lucy M; Vivekanandan-Giri, Anuradha; McLean, Lisa L; Pennathur, Subramaniam; Feldman, Eva L

2013-01-01

Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted liquid chromatography-tandem mass spectrometry (LC/MS/MS) to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve, and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Lepr(db); db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, and lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve, and DRG from diabetic mice. Utilizing LC/electrospray ionization/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids) in db/db tissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerves to rely on truncated TCA cycle metabolism in the type 2 diabetes environment.

Human amniotic fluid mesenchymal stem cells in combination with hyperbaric oxygen augment peripheral nerve regeneration.

PubMed

Pan, Hung-Chuan; Chin, Chun-Shih; Yang, Dar-Yu; Ho, Shu-Peng; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou

2009-07-01

Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.

Relationship between sensorimotor peripheral nerve function and indicators of cardiovascular autonomic function in older adults from the Health, Aging and Body Composition Study.

PubMed

Lange-Maia, Brittney S; Newman, Anne B; Jakicic, John M; Cauley, Jane A; Boudreau, Robert M; Schwartz, Ann V; Simonsick, Eleanor M; Satterfield, Suzanne; Vinik, Aaron I; Zivkovic, Sasa; Harris, Tamara B; Strotmeyer, Elsa S

2017-10-01

Age-related peripheral nervous system (PNS) impairments are highly prevalent in older adults. Although sensorimotor and cardiovascular autonomic function have been shown to be related in persons with diabetes, the nature of the relationship in general community-dwelling older adult populations is unknown. Health, Aging and Body Composition participants (n=2399, age=76.5±2.9years, 52% women, 38% black) underwent peripheral nerve testing at the 2000/01 clinic visit. Nerve conduction amplitude and velocity were measured at the peroneal motor nerve. Sensory nerve function was assessed with vibration detection threshold and monofilament (1.4-g/10-g) testing at the big toe. Symptoms of lower-extremity peripheral neuropathy were collected by self-report. Cardiovascular autonomic function indicators included postural hypotension, resting heart rate (HR), as well as HR response to and recovery from submaximal exercise testing (400m walk). Multivariable modeling adjusted for demographic/lifestyle factors, medication use and comorbid conditions. In fully adjusted models, poor motor nerve conduction velocity (<40m/s) was associated with greater odds of postural hypotension, (OR=1.6, 95% CI: 1.0-2.5), while poor motor amplitude (<1mV) was associated with 2.3beats/min (p=0.003) higher resting HR. No associations were observed between sensory nerve function or symptoms of peripheral neuropathy and indicators of cardiovascular autonomic function. Motor nerve function and indicators of cardiovascular autonomic function remained significantly related even after considering many potentially shared risk factors. Future studies should investigate common underlying processes for developing multiple PNS impairments in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of a Peripheral Nerve Neurite Growth-Promoting Activity by Development and Use of an in vitro Bioassay

NASA Astrophysics Data System (ADS)

Sandrock, Alfred W.; Matthew, William D.

1987-10-01

The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay.

Sciatica

MedlinePlus

... sciatic nerve; Sciatic nerve dysfunction; Low back pain - sciatica; LBP - sciatica; Lumbar radiculopathy - sciatica ... Sciatica occurs when there is pressure or damage to the sciatic nerve. This nerve starts in the ...

Middle ear osteoma causing progressive facial nerve weakness: a case report.

PubMed

Curtis, Kate; Bance, Manohar; Carter, Michael; Hong, Paul

2014-09-18

Facial nerve weakness is most commonly due to Bell's palsy or cerebrovascular accidents. Rarely, middle ear tumor presents with facial nerve dysfunction. We report a very unusual case of middle ear osteoma in a 49-year-old Caucasian woman causing progressive facial nerve deficit. A subtle middle ear lesion was observed on otoscopy and computed tomographic images demonstrated an osseous middle ear tumor. Complete surgical excision resulted in the partial recovery of facial nerve function. Facial nerve dysfunction is rarely caused by middle ear tumors. The weakness is typically due to a compressive effect on the middle ear portion of the facial nerve. Early recognition is crucial since removal of these lesions may lead to the recuperation of facial nerve function.

Acceleration of Regeneration of Large Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W811XWH-13-1-0310 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Zhongyu Li, MD, PhD RECIPIENT: Wake Forest University Health Sciences...REPORT DATE September 2016 2. REPORT TYPE Annual 3. DATES COVERED 1Sep2015 - 31Aug2016 4. TITLE AND SUBTITLE Acceleration of Regeneration of Large

Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

DTIC Science & Technology

2017-09-01

AFS seeded ANA used for nerve repair resulted in an improved functional outcome for the rats compared to ANA alone and were equivalent to those...junction morphology were equivalent between the AFS seeded ANA. Additional studies investigated the use of post-partum acellular materials to promote...techniques for repairing large-gap (6 cm) nerve injuries in non -human primates. This pre-clinical model represents a more translational model of peripheral

Takotsubo cardiomyopathy associated with Miller-Fisher syndrome.

PubMed

Gill, Dalvir; Liu, Kan

2017-07-01

51-year-old female who presented with progressive paresthesia, numbness of the lower extremities, double vision, and trouble walking. Physical exam was remarkable for areflexia, and ptosis. Her initial EKG showed nonspecific ST segment changes and her Troponin T was elevated to 0.41ng/mL which peaked at 0.66ng/mL. Echocardiogram showed a depressed left ventricular ejection fraction to 35% with severely hypokinetic anterior wall and left ventricular apex was severely hypokinetic. EMG nerve conduction study showed severely decreased conduction velocity and prolonged distal latency in all nerves consistent with demyelinating disease. She was treated with 5days of intravenous immunoglobulin therapy to which she showed significant improvement in strength in her lower extremities. Echocardiogram repeated 4days later showing an improved left ventricular ejection fraction of 55% and no left ventricular wall motion abnormalities. Takotsubo cardiomyopathy is a rare complication of Miller-Fisher syndrome and literature review did not reveal any cases. Miller-Fisher syndrome is an autoimmune process that affects the peripheral nervous system causing autonomic dysfunction which may involve the heart. Due to significant autonomic dysfunction in Miller-Fisher syndrome, it could lead to arrhythmias, blood pressure changes, acute coronary syndrome and myocarditis, Takotsubo cardiomyopathy can be difficult to distinguish. The treatment of Takotsubo cardiomyopathy is supportive with beta-blockers and angiotensin-converting enzyme inhibitors are recommended until left ventricle ejection fraction improvement. Takotsubo cardiomyopathy is a rare complication during the acute phase of Miller-Fisher syndrome and must be distinguished from autonomic dysfunction as both diagnoses have different approaches to treatment. Published by Elsevier Inc.

Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

PubMed

Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2016-05-27

Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

Patterns of innervation of neurones in the inferior mesenteric ganglion of the cat.

PubMed Central

Julé, Y; Krier, J; Szurszewski, J H

1983-01-01

The patterns of peripheral and central synaptic input to non-spontaneous, irregular discharging and regular discharging neurones in the inferior mesenteric ganglion of the cat were studied in vitro using intracellular recording techniques. All three types of neurones in rostral and caudal lobes received central synaptic input primarily from L3 and L4 spinal cord segments. Since irregular discharging neurones received synaptic input from intraganglionic regular discharging neurones, some of the central input to irregular discharging neurones may have been relayed through the regular discharging neurones. In the rostral lobes of the ganglion, more than 70% of the non-spontaneous and irregular discharging neurones tested received peripheral synaptic input from the lumbar colonic, intermesenteric and left and right hypogastric nerves. Most of the regular discharging neurones tested received synaptic input from the intermesenteric and lumbar colonic nerves; none of the regular discharging neurones received synaptic input from the hypogastric nerves. Some of the peripheral synaptic input from the lumbar colonic and intermesenteric nerves to irregular discharging neurones may have been relayed through the regular discharging neurones. Axons of non-spontaneous and irregular discharging neurones located in the rostral lobes travelled to the periphery exclusively in the lumbar colonic nerves. Antidromic responses were not observed in regular discharging neurones during stimulation of any of the major peripheral nerve trunks. This suggests these neurones were intraganglionic. In the caudal lobes, irregular discharging neurones received a similar pattern of peripheral synaptic input as did irregular discharging neurones located in the rostral lobes. The majority of irregular discharging neurones in the caudal lobes projected their axons to the periphery through the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes, in contrast to those located in the rostral lobes, received peripheral synaptic input primarily from the hypogastric nerves. Axons of the majority of non-spontaneous neurones located in the caudal lobes travelled to the periphery through hypogastric nerves. The results suggest that non-spontaneous neurones and irregular discharging neurones in the rostral lobes and the majority of irregular discharging neurones in the caudal lobes transact and integrate neural commands destined for abdominal viscera supplied by the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes transact and integrate neural commands destined for pelvic viscera supplied by the hypogastric nerves. PMID:6655582

Patterns of innervation of neurones in the inferior mesenteric ganglion of the cat.

PubMed

Julé, Y; Krier, J; Szurszewski, J H

1983-11-01

The patterns of peripheral and central synaptic input to non-spontaneous, irregular discharging and regular discharging neurones in the inferior mesenteric ganglion of the cat were studied in vitro using intracellular recording techniques. All three types of neurones in rostral and caudal lobes received central synaptic input primarily from L3 and L4 spinal cord segments. Since irregular discharging neurones received synaptic input from intraganglionic regular discharging neurones, some of the central input to irregular discharging neurones may have been relayed through the regular discharging neurones. In the rostral lobes of the ganglion, more than 70% of the non-spontaneous and irregular discharging neurones tested received peripheral synaptic input from the lumbar colonic, intermesenteric and left and right hypogastric nerves. Most of the regular discharging neurones tested received synaptic input from the intermesenteric and lumbar colonic nerves; none of the regular discharging neurones received synaptic input from the hypogastric nerves. Some of the peripheral synaptic input from the lumbar colonic and intermesenteric nerves to irregular discharging neurones may have been relayed through the regular discharging neurones. Axons of non-spontaneous and irregular discharging neurones located in the rostral lobes travelled to the periphery exclusively in the lumbar colonic nerves. Antidromic responses were not observed in regular discharging neurones during stimulation of any of the major peripheral nerve trunks. This suggests these neurones were intraganglionic. In the caudal lobes, irregular discharging neurones received a similar pattern of peripheral synaptic input as did irregular discharging neurones located in the rostral lobes. The majority of irregular discharging neurones in the caudal lobes projected their axons to the periphery through the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes, in contrast to those located in the rostral lobes, received peripheral synaptic input primarily from the hypogastric nerves. Axons of the majority of non-spontaneous neurones located in the caudal lobes travelled to the periphery through hypogastric nerves. The results suggest that non-spontaneous neurones and irregular discharging neurones in the rostral lobes and the majority of irregular discharging neurones in the caudal lobes transact and integrate neural commands destined for abdominal viscera supplied by the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes transact and integrate neural commands destined for pelvic viscera supplied by the hypogastric nerves.

Microscale Electrode Implantation during Nerve Repair: Effects on Nerve Morphology, Electromyography, and Recovery of Muscle Contractile Function

PubMed Central

Urbanchek, Melanie G; Wei, Benjamin; Egeland, Brent M; Abidian, Mohammad R; Kipke, Daryl R; Cederna, Paul S

2011-01-01

Background Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration. Methods A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery. Results Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements. Conclusions The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves. PMID:21921739

Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits

PubMed Central

Anderson, Matthew; Shelke, Namdev B.; Manoukian, Ohan S.; Yu, Xiaojun; McCullough, Louise D.; Kumbar, Sangamesh G.

2017-01-01

Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration. PMID:27278739

Evidence for a systemic regulation of neurotrophin synthesis in response to peripheral nerve injury.

PubMed

Shakhbazau, Antos; Martinez, Jose A; Xu, Qing-Gui; Kawasoe, Jean; van Minnen, Jan; Midha, Rajiv

2012-08-01

Up-regulation of neurotrophin synthesis is an important mechanism of peripheral nerve regeneration after injury. Neurotrophin expression is regulated by a complex series of events including cell interactions and multiple molecular stimuli. We have studied neurotrophin synthesis at 2 weeks time-point in a transvertebral model of unilateral or bilateral transection of sciatic nerve in rats. We have found that unilateral sciatic nerve transection results in the elevation of nerve growth factor (NGF) and NT-3, but not glial cell-line derived neurotrophic factor or brain-derived neural factor, in the uninjured nerve on the contralateral side, commonly considered as a control. Bilateral transection further increased NGF but not other neurotrophins in the nerve segment distal to the transection site, as compared to the unilateral injury. To further investigate the distinct role of NGF in regeneration and its potential for peripheral nerve repair, we transduced isogeneic Schwann cells with NGF-encoding lentivirus and transplanted the over-expressing cells into the distal segment of a transected nerve. Axonal regeneration was studied at 2 weeks time-point using pan-neuronal marker NF-200 and found to directly correlate with NGF levels in the regenerating nerve. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Bridging extra large defects of peripheral nerves: possibilities and limitations of alternative biological grafts from acellular muscle and Schwann cells.

PubMed

Keilhoff, Gerburg; Prätsch, Florian; Wolf, Gerald; Fansa, Hisham

2005-01-01

Defects of peripheral nerves are bridged with autologous nerve grafts. Tissue-engineered nerve grafts offer a laboratory-based alternative to overcome limited donor nerve availability. Our objective was to evaluate whether a graft made from acellular muscle enriched with cultivated Schwann cells can bridge extra large gaps where conventional conduits usually fail. Our well-established rat sciatic nerve model was used with an increased gap length of 50 mm. The conduits consisted of freeze-thawed or chemically extracted homologous acellular rat rectus muscles and implanted Schwann cells. Autologous nerve grafts were used for control purposes. Biocompatibility of the grafts was demonstrated by Schwann cell settlement, revascularization, and macrophage recruitment. After 12 weeks regeneration was assessed clinically, histologically, and morphometrically. The control group showed superior results regarding axon counts, histologic appearance, and functional recovery compared with the muscle grafts. The chemically extracted conduits completely failed to support nerve regeneration. They were not stable enough to bridge longer nerve gaps with an expanded regeneration time. On the basis of morphological parameters freeze-thawed muscle grafts were, however, able to support peripheral nerve regeneration even over the extralong distance of 50 mm, and therefore are of potential benefit for new therapeutic strategies.

Avulsion of the brachial plexus in a great horned owl (Bubo virginaus)

USGS Publications Warehouse

Moore, M.P.; Stauber, E.; Thomas, N.J.

1989-01-01

Avulsion of the brachial plexus was documented in a Great Horned Owl (Bubo virginianus). A fractured scapula was also present. Cause of these injuries was not known but was thought to be due to trauma. Differentiation of musculoskeletal injury from peripheral nerve damage can be difficult in raptors. Use of electromyography and motor nerve conduction velocity was helpful in demonstrating peripheral nerve involvement. A brachial plexus avulsion was suspected on the basis of clinical signs, presence of electromyographic abnormalities in all muscles supplied by the nerves of the brachial plexus and absence of median-ulnar motor nerve conduction velocities.

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

PubMed Central

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-01-01

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions. PMID:29599609

[Artificial control of blood-nerve barrier: a novel therapeutic approach to peripheral neuropathies].

PubMed

Kanda, Takashi

2011-11-01

Blood-nerve barrier (BNB) is a "Janus-faced" structure for the peripheral nerve parenchyma. Healthy BNB may contribute to stabilize the internal milleu of peripheral nervous system (PNS) and to stop the entrance of toxic substances and harmful leukocytes into nerve parenchyma. On the other hand, healthy BNB may sometimes be a drawback because the peripheral nerve parenchyma cannot receive enough amount of nutrients and growth factors and cannot excrete toxic substances into systemic circulation because of its presence. Here we present a future therapeutic strategy to control BNB function, based on the basic knowledge acquired from recently developed human immortalized cell lines of BNB origin. If we can artificially regulate the BNB permeability and the expression of adhesion molecules on the surface of BNB-forming endothelial cells, and stop the entrance of toxic substances as well as pathogenic leukocytes into PNS parenchyma, the treatment of inflammatory neuropathies may make great progresses. For hereditary, metabolic and ischemic neuropathies, the promotion of the entrance of growth factors into PNS parenchyma and of the excretion of toxic substances should powerfully encourage the regeneration of axons.

The effects of picric acid (2,4,6-trinitrophenol) and a bite-deterrent chemical (denatonium benzoate) on autotomy in rats after peripheral nerve lesion.

PubMed

Firouzi, Matin Sadat; Firouzi, Masoumeh; Nabian, Mohammad Hossein; Zanjani, Leila Oryadi; Zadegan, Shayan Abdollah; Kamrani, Reza Shahryar; Rahimi-Movaghar, Vafa

2015-04-01

Denervation of the hind limb is a technique used to study peripheral nerve regeneration. Autotomy or autophagia is an undesirable response to denervation in such studies. Application of a commercially available lotion used to deter nail biting in humans reduced autotomy in rats after denervation but did not completely prevent it. In this study, this authors evaluated the application of picric acid to prevent autotomy in rats in peripheral nerve experiments. They carried out sciatic nerve transection in 41 adult female Wistar rats and then applied either bite-deterrent lotion (n = 26) or saturated picric acid solution (n = 15) topically to the affected hind limb immediately after surgery and every day for 1 month. Autotomy scores were lower for rats treated with picric acid than for rats treated with bite-deterrent lotion 1 week and 2 weeks after surgery but were not different between the two groups 4 weeks after surgery. The authors conclude that application of picric acid could be used as an alternative strategy to prevent autotomy in peripheral nerve studies.

Central and peripheral nervous systems: master controllers in cancer metastasis.

PubMed

Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

2013-12-01

Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

Nerve regeneration with aid of nanotechnology and cellular engineering.

PubMed

Sedaghati, Tina; Yang, Shi Yu; Mosahebi, Afshin; Alavijeh, Mohammad S; Seifalian, Alexander M

2011-01-01

Repairing nerve defects with large gaps remains one of the most operative challenges for surgeons. Incomplete recovery from peripheral nerve injuries can produce a diversity of negative outcomes, including numbness, impairment of sensory or motor function, possibility of developing chronic pain, and devastating permanent disability. In the last few years, numerous microsurgical techniques, such as coaptation, nerve autograft, and different biological or polymeric nerve conduits, have been developed to reconstruct a long segment of damaged peripheral nerve. A few of these techniques are promising and have become popular among surgeons. Advancements in the field of tissue engineering have led to development of synthetic nerve conduits as an alternative for the nerve autograft technique, which is the current practice to bridge nerve defects with gaps larger than 30 mm. However, to date, despite significant progress in this field, no material has been found to be an ideal alternative to the nerve autograft. This article briefly reviews major up-to-date published studies using different materials as an alternative to the nerve autograft to bridge peripheral nerve gaps in an attempt to assess their ability to support and enhance nerve regeneration and their prospective drawbacks, and also highlights the promising hope for nerve regeneration with the next generation of nerve conduits, which has been significantly enhanced with the tissue engineering approach, especially with the aid of nanotechnology in development of the three-dimensional scaffold. The goal is to determine potential alternatives for nerve regeneration and repair that are simply and directly applicable in clinical conditions. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Ultrasound-guided peripheral nerve blockade.

PubMed

Chin, Ki Jinn; Chan, Vincent

2008-10-01

The use of ultrasound for peripheral nerve blockade is becoming popular. Although the feasibility of ultrasound-guided nerve blockade is now clear, it is uncertain at this time whether it represents the new standard for regional anesthesia in terms of efficacy and safety. The ability to visualize nerve location, needle advancement, needle-nerve interaction, and local anesthetic spread makes ultrasound-guided nerve block an attractive option. Study results indicate that these advantages can improve the ease of block performance, block success rates, and complications. At the same time there is evidence that ultrasound-guided regional anesthesia is a unique skill in its own right, and that proficiency in it requires training and experience. Ultrasound is a valuable tool that is now available to the regional anesthesiologist, and it is fast becoming a standard part of practice. It promises to be of especial value to the less experienced practitioner. Ultrasound does not in itself, however, guarantee the efficacy and safety of peripheral nerve blockade. Proper training in its use is required and we can expect to see the development of formal standards and guidelines in this regard.

Differential involvement of forearm muscles in ALS does not relate to sonographic structural nerve alterations.

PubMed

Schreiber, Stefanie; Schreiber, Frank; Debska-Vielhaber, Grazyna; Garz, Cornelia; Hensiek, Nathalie; Machts, Judith; Abdulla, Susanne; Dengler, Reinhard; Petri, Susanne; Nestor, Peter J; Vielhaber, Stefan

2018-07-01

We aimed to assess whether differential peripheral nerve involvement parallels dissociated forearm muscle weakness in amyotrophic lateral sclerosis (ALS). The analysis comprised 41 ALS patients and 18 age-, sex-, height- and weight-matched healthy controls. Strength of finger-extension and -flexion was measured using the Medical Research Council (MRC) scale. Radial, median and ulnar nerve sonographic cross-sectional area (CSA) and echogenicity, expressed by the hypoechoic fraction (HF), were determined. In ALS, finger extensors were significantly weaker than finger flexors. Sonographic evaluation revealed peripheral nerve atrophy, affecting various nerve segments in ALS. HF was unaltered. This systematic study confirmed a long-observed physical examination finding in ALS - weakness in finger-extension out of proportion to finger-flexion. This phenomenon was not related to any particular sonographic pattern of upper limb peripheral nerve alteration. In ALS, dissociated forearm muscle weakness could aid in the disease's diagnosis. Nerve ultrasound did not provide additional information on the differential involvement of finger-extension and finger-flexion strength. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

NASA Astrophysics Data System (ADS)

Downs, Matthew E.; Lee, Stephen A.; Yang, Georgiana; Kim, Seaok; Wang, Qi; Konofagou, Elisa E.

2018-02-01

Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons. Here, for the first time, noninvasive stimulation of the sciatic nerve eliciting a physiological response in vivo is demonstrated with FUS. FUS was applied on the sciatic nerve in mice with simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals were detected during or directly after ultrasound stimulation along with observable muscle contraction of the hind limb. Transecting the sciatic nerve downstream of FUS stimulation eliminated EMG activity during FUS stimulation. Peak-to-peak EMG response amplitudes and latency were found to be comparable to conventional electrical stimulation methods. Histology along with behavioral and thermal testing did not indicate damage to the nerve or surrounding regions. The findings presented herein demonstrate that FUS can serve as a targeted, safe and non-invasive alternative to conventional peripheral nervous system stimulation to treat peripheral neuropathic diseases in the clinic.

Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat.

PubMed

Bester, H; Allchorne, A J; Woolf, C J

1998-12-01

Peripheral nerve injury leads to substantial alterations in injured sensory neurons. These include cell death, phenotypic modifications, and regeneration. Primary sensory neurons have recently been shown not to die until a time beyond 4 months following a nerve crush or ligation and this loss is, moreover, limited to cells with unmyelinated axons, the C-fibers. The late loss of C-fibers may be due to a lack of target reinnervation during the regenerative phase. In order to investigate this, we have used a particular peripheral function, unique to C-fibers, as a measure of peripheral reinnervation: an increase in capillary permeability on antidromic activation of C-fibers, i.e., neurogenic extravasation. This was investigated in rats that had received a nerve crush injury 1 to 50 weeks earlier. Some recovery of the capacity of C-fibers to generate extravasation was detected at 8-10 weeks, which increased further at 12-14 weeks, and then plateaued at this level with no further recovery at 30 or 50 weeks. In intact and damaged sciatic nerves, A beta-fibers never induced extravasation. These findings are compatible with the hypothesis that those C-fibers which make it back to their peripheral targets do not subsequently die and those that do not, may die. Copyright 1998 Academic Press.

“Can't Walk Nor Raise Arms to Head”

PubMed Central

Pendleton, Courtney; Dorsi, Michael J.; Belzberg, Allan J.; Cohen-Gadol, Aaron A.; Quiñones-Hinojosa, Alfredo

2015-01-01

Study Design This study was a retrospective chart review for patients undergoing operative treatment by Dr. Harvey Cushing at the Johns Hopkins Hospital between 1896 and 1912. Objective To illustrate the early use of peripheral nerve anastomoses for the treatment of postpoliomyelitis paralysis. Summary of Background Data At the turn of the 20th century, poliomyelitis was recognized as a disease of neurons; neurological surgeons sought to find a surgical cure for the paralysis occurring after the disease onset. Peripheral nerve anastomoses were an attractive option employed during this time. Methods Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital from 1896 to 1912 were reviewed. A single case of peripheral nerve anastomosis for the treatment of postpoliomyelitis paralysis was selected for further analysis. Results Cushing performed a multiple peripheral nerve anastomoses in a 3-year-old girl. Although the patient experienced no postoperative complications, there was no improvement in her function at the time of discharge from the hospital, and no long-term follow-up was available. Conclusion While unsuccessful, Cushing's use of peripheral nerve anastomoses to restore motor function in the pediatric patient described here demonstrates his commitment to pushing the boundaries of neurological surgery at the turn of the 20th century. PMID:21301395

"Can't walk nor raise arms to head": Harvey Cushing's surgical treatment of poliomyelitis.

PubMed

Pendleton, Courtney; Dorsi, Michael J; Belzberg, Allan J; Cohen-Gadol, Aaron A; Quiñones-Hinojosa, Alfredo

2012-02-15

This study was a retrospective chart review for patients undergoing operative treatment by Dr. Harvey Cushing at the Johns Hopkins Hospital between 1896 and 1912. To illustrate the early use of peripheral nerve anastomoses for the treatment of postpoliomyelitis paralysis. At the turn of the 20th century, poliomyelitis was recognized as a disease of neurons; neurological surgeons sought to find a surgical cure for the paralysis occurring after the disease onset. Peripheral nerve anastomoses were an attractive option employed during this time. Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital from 1896 to 1912 were reviewed. A single case of peripheral nerve anastomosis for the treatment of postpoliomyelitis paralysis was selected for further analysis. Cushing performed a multiple peripheral nerve anastomoses in a 3-year-old girl. Although the patient experienced no postoperative complications, there was no improvement in her function at the time of discharge from the hospital, and no long-term follow-up was available. While unsuccessful, Cushing's use of peripheral nerve anastomoses to restore motor function in the pediatric patient described here demonstrates his commitment to pushing the boundaries of neurological surgery at the turn of the 20th century.

Occipital peripheral nerve stimulation in the management of chronic intractable occipital neuralgia in a patient with neurofibromatosis type 1: a case report

PubMed Central

2011-01-01

Introduction Occipital peripheral nerve stimulation is an interventional pain management therapy that provides beneficial results in the treatment of refractory chronic occipital neuralgia. Herein we present a first-of-its-kind case study of a patient with neurofibromatosis type 1 and bilateral occipital neuralgia treated with occipital peripheral nerve stimulation. Case presentation A 42-year-old Caucasian woman presented with bilateral occipital neuralgia refractory to various conventional treatments, and she was referred for possible treatment with occipital peripheral nerve stimulation. She was found to be a suitable candidate for the procedure, and she underwent implantation of two octapolar stimulating leads and a rechargeable, programmable, implantable generator. The intensity, severity, and frequency of her symptoms resolved by more than 80%, but an infection developed at the implantation site two months after the procedure that required explantation and reimplantation of new stimulating leads three months later. To date she continues to experience symptom resolution of more than 60%. Conclusion These results demonstrate the significance of peripheral nerve stimulation in the management of refractory occipital neuralgias in patients with neurofibromatosis type 1 and the possible role of neurofibromata in the development of occipital neuralgia in these patients. PMID:21569290

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

PubMed Central

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463

A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

PubMed

Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

2011-01-01

A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

Peripheral neuromodulation: a review.

PubMed

Goroszeniuk, Teodor; Pang, David

2014-05-01

Peripheral nerve stimulation (PNS) is likely the most diverse and rapidly expanding area of neuromodulation. Its expansion has become possible due to both technological and clinical advances in pain medicine. The first implantable systems were surgically placed. However, it is currently commonplace to use percutaneous leads, as this approach has become instrumental in its expansion. The first percutaneous peripheral nerve stimulators were reported in 1999. Cylindrical leads were implanted to stimulate the greater occipital nerve to manage intractable headache. It has been expanded into other individual nerves or nerve plexuses to treat neuropathic, visceral, cardiac, abdominal, low back and facial pain. The use of PNS in modulating organ function in treatment of syndromes such as epilepsy, incontinence and obesity with vagal, tibial and gastric stimulation is under extensive investigation. New technologies that allow easier and safer electrode placement are expected to further expand the uses of PNS. A noninvasive stimulation will open this treatment modality to more clinicians of varying backgrounds.

Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

PubMed

Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

Karolinska Institutet 200-Year Anniversary. Symposium on Traumatic Injuries in the Nervous System: Injuries to the Spinal Cord and Peripheral Nervous System – Injuries and Repair, Pain Problems, Lesions to Brachial Plexus

PubMed Central

Sköld, Mattias K.; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented. PMID:21629875

Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury.

PubMed

Gordon, Tessa; Chan, K Ming; Sulaiman, Olawale A R; Udina, Esther; Amirjani, Nasim; Brushart, Thomas M

2009-10-01

Injured peripheral nerves regenerate at very slow rates. Therefore, proximal injury sites such as the brachial plexus still present major challenges, and the outcomes of conventional treatments remain poor. This is in part attributable to a progressive decline in the Schwann cells' ability to provide a supportive milieu for the growth cone to extend and to find the appropriate target. These challenges are compounded by the often considerable delay of regeneration across the site of nerve laceration. Recently, low-frequency electrical stimulation (as brief as an hour) has shown promise, as it significantly accelerated regeneration in animal models through speeding of axon growth across the injury site. To test whether this might be a useful clinical tool, we carried out a randomized controlled trial in patients who had experienced substantial axonal loss in the median nerve owing to severe compression in the carpal tunnel. To further elucidate the potential mechanisms, we applied rolipram, a cyclic adenosine monophosphate agonist, to rats after axotomy of the femoral nerve. We demonstrated that effects similar to those observed in animal studies could also be attained in humans. The mechanisms of action of electrical stimulation likely operate through up-regulation of neurotrophic factors and cyclic adenosine monophosphate. Indeed, the application of rolipram significantly accelerated nerve regeneration. With new mechanistic insights into the influencing factors of peripheral nerve regeneration, the novel treatments described above could form part of an armament of synergistic therapies that could make a meaningful difference to patients with peripheral nerve injuries.

Sciatic Nerve Intrafascicular Lidocaine Injection-induced Peripheral Neuropathic Pain: Alleviation by Systemic Minocycline Administration.

PubMed

Cheng, Kuang-I; Wang, Hung-Chen; Wu, Yi-Chia; Tseng, Kuang-Yi; Chuang, Yi-Ta; Chou, Chao-Wen; Chen, Ping-Luen; Chang, Lin-Li; Lai, Chung-Sheng

2016-06-01

Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration. A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28. On the basis of the results in experiment 1, rats in experiment 2 were divided into sham, extraneural, intrafascicular, peri-injury minocycline, and postinjury minocycline groups. Behavioral responses, macrophage recruitment, expression changes of myelin basic protein and Schwann cells in the sciatic nerve, dysregulated expression of ATF-3 in the DRG, and activated glial cells in L5 SDH were assessed on days 7 and 14. Intrafascicular lidocaine induced mechanical allodynia, downregulated Nav1.8, increased ATF-3 expression in the DRG, and activated glial cells in the SDH. Increased expression of macrophages, Schwann cells, and myelin basic protein was found in the sciatic nerve. Minocycline attenuated intrafascicular lidocaine-induced neuropathic pain and nerve damage significantly. Peri-injury minocycline was better than postinjury minocycline administration in alleviating mechanical behaviors, mitigating macrophage recruitment into the sciatic nerve, and suppressing activated microglial cells in the spinal cord. Systemic minocycline administration alleviates intrafascicular lidocaine injection-induced peripheral nerve damage.

Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

PubMed

Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

2018-03-28

Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

PubMed

Linnemann, Christoph; Tezenas du Montcel, Sophie; Rakowicz, Maryla; Schmitz-Hübsch, Tanja; Szymanski, Sandra; Berciano, Jose; van de Warrenburg, Bart P; Pedersen, Karine; Depondt, Chantal; Rola, Rafal; Klockgether, Thomas; García, Antonio; Mutlu, Gurkan; Schöls, Ludger

2016-04-01

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

Connexin32 expression in central and peripheral nervous systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

1994-09-01

Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show thatmore » Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.« less

Diaphragmatic height index: new diagnostic test for phrenic nerve dysfunction.

PubMed

Pornrattanamaneewong, Chaturong; Limthongthang, Roongsak; Vathana, Torpon; Kaewpornsawan, Kamolporn; Songcharoen, Panupan; Wongtrakul, Saichol

2012-11-01

The diaphragmatic height index (DHI) was developed to measure the difference in diaphragm levels. The purpose of this study was to set definite DHI values and test the accuracy of these values for use as a new diagnostic test for phrenic nerve dysfunction. All data for this study were obtained from medical charts and retrospectively reviewed. One hundred sixty-five patients with brachial plexus injury who had undergone nerve transfers between 2005 and 2008 were divided into Groups A and B. Group A consisted of 40 patients (mean age 28.0 years) who had sustained concomitant injury of the brachial plexus and phrenic nerves. Patients in Group A1 had right phrenic nerve injury and those in Group A2 had left phrenic nerve injury. Intraoperative direct electrical stimulation of the phrenic nerve was considered the gold standard in assessing nerve function in all patients with brachial plexus injury. Group B consisted of 125 patients (mean age 28.7 years) with brachial plexus injury and normal phrenic nerve function. Group C, the control group, consisted of 80 patients with nonbrachial plexus injury (mean age 34.0 years) who had undergone other kinds of orthopedic operations between April and June 2009. Standard posteroanterior chest radiographs were blindly interpreted using the Siriraj inhouse picture archiving and communication system in all 245 patients in the study. First, a reference line (R line) was drawn along the inferior endplate of T-10. Then, 2 lines (lines A and B) were drawn through the highest point of each diaphragm and parallel to the R line. The difference between these 2 lines divided by the height of T-10 was defined as the DHI. The cutoff points of the DHI for diagnosing right and left phrenic nerve dysfunction were analyzed with a receiver operating characteristic curve. The accuracy of these DHI values was then evaluated. The DHI in Group C was 0.64 ± 0.44, slightly higher than the DHI in Group B, with no significant difference. Diaphragmatic height indexes in Groups A1 and A2 were 2.0 ± 0.99 and -1.04 ± 0.83, respectively, which were significantly different from those in Groups B and C (p < 0.05). The cutoff point of the DHI for diagnosing right phrenic nerve dysfunction was > 1.1, and that for left phrenic nerve dysfunction was < 0.2. The sensitivity and specificity of right and left DHI values were 90.5% and 86.3%, and 94.7 and 88.3%, respectively. Data in this study show that diaphragm paralysis can be simply and reliably predicted by the DHI. Diaphragmatic height index values > 1.1 and < 0.2 are proposed as the new diagnostic test for right and left phrenic nerve dysfunction with a high degree of accuracy. This index is applicable in diagnosing phrenic nerve dysfunction that occurs concomitantly with brachial plexus injury or from other etiologies.

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons near the implanted electrode shanks, along with dense cellular accumulations near the implant site. Scanning electron microscopy (SEM) showed alterations of the electrode insulation and deformation of electrode shanks. Significance. We describe a comprehensive testing platform with applicability to electrodes that record from the peripheral nerves. This study assesses the long term safety and performance of electrodes in the peripheral nerves using a rodent model. Under this animal test platform, FMA electrodes record single unit action potentials but have limited chronic reliability due to structural weaknesses. Future work will apply these methods to other commercially-available and novel peripheral electrode technologies. This research was carried out in the Division of Biomedical Physics, Office of Science and Engineering Laboratory, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

NASA Astrophysics Data System (ADS)

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-03-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

PubMed Central

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-01-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

PubMed

Das, H K; Das, D; Doley, R; Sahu, P P

2016-03-02

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration.

PubMed

Li, Wen-Yuan; Zhang, Wei-Ting; Cheng, Yong-Xia; Liu, Yan-Cui; Zhai, Feng-Guo; Sun, Ping; Li, Hui-Ting; Deng, Ling-Xiao; Zhu, Xiao-Feng; Wang, Ying

2018-06-01

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

Peripheral nerve regeneration using a microporous polylactic acid asymmetric conduit in a rabbit long-gap sciatic nerve transection model.

PubMed

Hsu, Shan-Hui; Chan, Shan-Ho; Chiang, Chih-Ming; Chen, Clayton Chi-Chang; Jiang, Ching-Fen

2011-05-01

The performance of an asymmetric conduit made of microporous polylactic acid (PLA) in promoting the long-term peripheral nerve regeneration across a 20-mm-long sciatic nerve gap was evaluated by a rabbit sciatic nerve transection model. Magnetic resonance imaging (MRI) was employed to monitor the nerve regeneration process. The extents of nerve regeneration and conduit degradation were quantified by image analysis. Functional and histological analyses were followed to assess nerve reinnervation. MR images showed that the transected nerve was connected at about 4 months. The diameter of the regenerated nerve continued to increase while the conduit was gradually degraded. The conduit was completely degraded in 18 months. The degradation kinetics in vivo was estimated based on MR images. The functional recovery after 18 months was ∼82% based on electrophysiology. The extension range of the operated limb was slowly recuperated to ∼81% at 18 months. Histology showed that nerve bundles were self-assembled after 16-18 months, but the morphologies were still different from those of normal sciatic nerve. This was the first work on the long-term evaluation of peripheral nerve regeneration in a rabbit model, and the first to report the use of MRI to obtain the real-time images of regenerated nerve in a biomaterial conduit as well as to define the degradation rate of the conduit in vivo. The platform established in this study serves to evaluate the regeneration of larger-diameter (>3-mm) nerve across a long-gap bridged by a conduit. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2018-06-20

High Grade Sarcoma; Metastatic Leiomyosarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Recurrent Leiomyosarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Synovial Sarcoma; Recurrent Undifferentiated Pleomorphic Sarcoma; Uterine Corpus Leiomyosarcoma

Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

PubMed

Liu, Harry; Wu, Chengbiao

2017-02-04

Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B) is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s) enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF) in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A "gain of toxicity" model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s) causes a "loss of function", resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons) of CMT2B are needed to precisely define the disease mechanisms.

Optimal conditions for peripheral nerve storage in green tea polyphenol: an experimental study in animals.

PubMed

Matsumoto, Taiichi; Kakinoki, Ryosuke; Ikeguchi, Ryosuke; Hyon, Suong-Hyu; Nakamura, Takashi

2005-06-30

Our previous study demonstrated successful peripheral nerve storage for 1 month using polyphenol solution. We here report two studies to solve residual problems in using polyphenols as a storage solution for peripheral nerves. Study 1 was designed to determine the optimal concentration of the polyphenol solution and the optimal immersion period for nerve storage. Rat sciatic nerve segments were immersed in polyphenol solution at three different concentrations (2.5, 1.0, and 0.5 mg/ml) for three different periods (1, 7, and 26 days). Electrophysiological and morphological studies demonstrated that nerve regeneration from nerve segments that had been immersed in 1mg/ml polyphenol solution for 1 week and in Dulbecco's modified Eagle's medium (DMEM) for the subsequent 3 weeks was superior to the regeneration in other treatment groups. In study 2, the permeability of nerve tissue to polyphenol solution was investigated using canine sciatic nerve segments stored in 1.0mg/ml polyphenol solution for 1 week and in DMEM for the subsequent 3 weeks. Electron microscopy revealed that the Schwann cell structure within 500-700 microm of the perineurium was preserved, but cells deeper than 500-700 microm were badly damaged or had disappeared. The infiltration limit for polyphenol solution into neural tissue is inferred to be 500-700 microm.

Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

PubMed Central

Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.

2013-01-01

Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. PMID:23659607

Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

PubMed

Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

2011-09-01

The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. © 2011 Peripheral Nerve Society.

Review: peripheral nerve regeneration using non-tubular alginate gel crosslinked with covalent bonds.

PubMed

Hashimoto, Tadashi; Suzuki, Yoshihisa; Suzuki, Kyoko; Nakashima, Toshihide; Tanihara, Masao; Ide, Chizuka

2005-06-01

We have developed a nerve regeneration material consisting of alginate gel crosslinked with covalent bonds. in the first part of this study, we attempted to analyze nerve regeneration through alginate gel in the early stages within 2 weeks. in the second part, we tried to regenerate cat peripheral nerve by using alginate tubular or non-tubular nerve regeneration devices, and compared their efficacies. Four days after surgery, regenerating axons grew without Schwann cell investment through the partially degraded alginate gel, being in direct contact with the alginate without a basal lamina covering. One to 2 weeks after surgery, regenerating axons were surrounded by common Schwann cells, forming small bundles, with some axons at the periphery being partly in direct contact with alginate. At the distal stump, numerous Schwann cells had migrated into the alginate 8-14 days after surgery. Remarkable restorations of the 50-mm gap in cat sciatic nerve were obtained after a long term by using tubular or non-tubular nerve regeneration material consisting mainly of alginate gel. However, there was no significant difference between both groups at electrophysiological and morphological evaluation. Although, nowadays, nerve regeneration materials being marketed mostly have a tubular structure, our results suggest that the tubular structure is not indispensable for peripheral nerve regeneration.

Malignant nerve sheath tumor involving glossopharyngeal, vagus and spinal nerve with intracranial-extracranial extension and systemic metastases in a patient with type 1 neurofibromatosis: A case report.

PubMed

Guerra-Mora, José Raúl; Del Castillo-Calcáneo, Juan D; Córdoba-Mosqueda, María Elena; Yáñez-Castro, Jorge; García-González, Ulises; Soriano-Navarro, Eduardo; Llamas-Ceras, Leticia; Vicuña-González, Rosa María

2016-01-01

Intracranial malignant peripheral nerve sheath tumors are an extremely rare pathology with a high morbidity and mortality. Epidemiological, clinical and prognostic data are scarce and with little certainty in the literature. The aim of this paper is to report for first time in English literature, the case of a patient with type 1 neurofibromatosis, who presented a malignant peripheral nerve sheath tumor that involved the left glossopharyngeal, vagus and spinal nerves with intracranial and extracranial extension through jugular foramen and systemic metastases. A 37 years-old female patient with malnutrition and Villaret́s syndrome. It was confirmed by brain magnetic resonance imaging and PET-CT the presence of a neoplasic lesion which was radiologically compatible with malignant peripheral nerve sheath tumor with systemic metastases. Partial surgical resection was performed; the patient postoperative course was without significant clinical improvement but with added peripheral facial palsy. The patient did not accept adjuvant management because of personal reasons. Behavior therapy is unclear due to the low frequency of the disease and the lack of case series, representing a challenge for the physician in its approach and a poor prognosis for the patient. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of Netrin-1 Signaling in Nerve Regeneration

PubMed Central

Dun, Xin-Peng; Parkinson, David B.

2017-01-01

Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

Lycium barbarum polysaccharide encapsulated Poly lactic-co-glycolic acid Nanofibers: cost effective herbal medicine for potential application in peripheral nerve tissue engineering.

PubMed

Wang, Jing; Tian, Lingling; He, Liumin; Chen, Nuan; Ramakrishna, Seeram; So, Kwok-Fai; Mo, Xiumei

2018-06-06

Nerve regeneration is a serious clinical challenge following peripheral nerve injury. Lycium barbarum polysaccharide (LBP) is the major component of wolfberry extract, which has been shown to be neuroprotective and promising in nerve recovery in many studies. Electrospun nanofibers, especially core-shell structured nanofibers being capable of serving as both drug delivery system and tissue engineering scaffolds, are well known to be suitable scaffolds for regeneration of peripheral nerve applications. In this study, LBP was incorporated into core-shell structured nanofibrous scaffolds via coaxial electrospinning. Alamar blue assays were performed to investigate the proliferation of both PC12 and Schwann cells cultured on the scaffolds. The neuronal differentiation of PC12 cells was evaluated by NF200 expression with immunostaining and morphology changes observed by SEM. The results indicated that the released LBP dramatically enhanced both proliferation and neuronal differentiation of PC12 cells induced by NGF. Additionally, the promotion of Schwann cells myelination and neurite outgrowth of DRG neurons were also observed on LBP loaded scaffolds by LSCM with immunostaining. In summary, LBP, as a drug with neuroprotection, encapsulated into electrospun nanofibers could be a potential candidate as tissue engineered scaffold for peripheral nerve regeneration.

Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series.

PubMed

Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F

2016-09-01

Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID:26355598

Sandwich technique, peripheral nerve stimulation, peripheral field stimulation and hybrid stimulation for inguinal region and genital pain.

PubMed

Shaw, Andrew; Sharma, Mayur; Zibly, Zion; Ikeda, Daniel; Deogaonkar, Milind

2016-12-01

Ilioinguinal neuralgia (IG) and genitofemoral (GF) neuralgia following inguinal hernia repair is a chronic and debilitating neuropathic condition. Recently, peripheral nerve stimulation has become an effective and minimally invasive option for the treatment of refractory pain. Here we present a retrospective case series of six patients who underwent placement of peripheral nerve stimulation electrodes using various techniques for treatment of refractory post-intervention inguinal region pain. Six patients with post-intervention inguinal, femoral or GF neuropathic pain were evaluated for surgery. Either octopolar percutaneous electrodes or combination of paddle and percutaneous electrodes were implanted in the area of their pain. Pain visual analog scores (VAS), surgical complication rate, preoperative symptom duration, degree of pain relief, preoperative and postoperative work status, postoperative changes in medication usage, and overall degree of satisfaction with this therapy was assessed. All six patients had an average improvement of 62% in the immediate post-operative follow-up. Four patients underwent stimulation for IG, one for femoral neuralgia, and another for GF neuralgia. Peripheral nerve stimulation provided at least 50% pain relief in all the six patients with post-intervention inguinal region pain. 85% of patients indicated they were completely satisfied with the therapy overall. There was one treatment failure with an acceptable complication rate. Peripheral nerve or field stimulation for post-intervention inguinal region pain is a safe and effective treatment for this refractory and complex problem for patients who have exhausted other management options.

[Treatment of painful neuromas via end-to-side neurorraphy].

PubMed

Aszmann, O C; Moser, V; Frey, M

2010-08-01

Management of the painful neuroma has been subject to controversy since the earliest descriptions of this disabling problem. Today, treatment is limited to resection of the neuroma and implantation of the nerve in a muscle at a location where it is safe from irritation and trauma. This however is not attainable in many cases and it is our clinical experience, that nerves without a target remain a source of constant discomfort and pain. Recently we reported of the feasibility of neuroma prevention through end-to-side neurorraphy into adjacent sensory and/or motor nerves to provide a target for axons deprived of their endorgan. Here we report of our first clinical experience with this method in sixteen patients with longstanding upper and lower extremity neuromas. 16 patients were included in this study. All had neuromas of different sensory nerves of both the upper and lower extremity. 11 were of iatrogenic origin, 5 were caused by different traumas. 8 had previous attempts to surgically treat the neuroma. Finally, all were treated by end-to-side neurorraphy into adjacent nerves. Postoperatively quantitative sensorymotor testing was performed to evaluate possible changes of nerve function of the recipient nerves. Pain was evaluated by visual analogue score and changes in pain medication. In no patient a sensory or motor deficit or painful sensations were induced in the target area of the recipient nerve. Some had dysaesthesias for about 6 months, which finally subsided. All but 1 patient improved in their symptoms at a follow-up of more than 2 years. Previous experimental work and present clinical results suggest that axons of a severed peripheral nerve that are provided with a pathway and target through an end-to-side coaptation will either be pruned or establish some type of end-organ contact so that a neuroma can be prevented without inducing sensory or motor dysfunctions in the recipient nerve. Georg Thieme Verlag KG Stuttgart New York.

Impairments in Motor Neurons, Interneurons and Astrocytes Contribute to Hyperexcitability in ALS: Underlying Mechanisms and Paths to Therapy.

PubMed

Do-Ha, Dzung; Buskila, Yossi; Ooi, Lezanne

2018-02-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of motor neurons leading to progressive paralysis and death. Using transcranial magnetic stimulation (TMS) and nerve excitability tests, several clinical studies have identified that cortical and peripheral hyperexcitability are among the earliest pathologies observed in ALS patients. The changes in the electrophysiological properties of motor neurons have been identified in both sporadic and familial ALS patients, despite the diverse etiology of the disease. The mechanisms behind the change in neuronal signalling are not well understood, though current findings implicate intrinsic changes in motor neurons and dysfunction of cells critical in regulating motor neuronal excitability, such as astrocytes and interneurons. Alterations in ion channel expression and/or function in motor neurons has been associated with changes in cortical and peripheral nerve excitability. In addition to these intrinsic changes in motor neurons, inhibitory signalling through GABAergic interneurons is also impaired in ALS, likely contributing to increased neuronal excitability. Astrocytes have also recently been implicated in increasing neuronal excitability in ALS by failing to adequately regulate glutamate levels and extracellular K + concentration at the synaptic cleft. As hyperexcitability is a common and early feature of ALS, it offers a therapeutic and diagnostic target. Thus, understanding the underlying pathways and mechanisms leading to hyperexcitability in ALS offers crucial insight for future development of ALS treatments.

Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

PubMed Central

Shakespeare, C. F.; Katritsis, D.; Crowther, A.; Cooper, I. C.; Coltart, J. D.; Webb-Peploe, M. W.

1994-01-01

BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction. Images PMID:8297687

Premature aging-related peripheral neuropathy in a mouse model of progeria.

PubMed

Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

2011-08-01

Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Bone marrow-derived mesenchymal stem/stromal cells reverse the sensorial diabetic neuropathy via modulation of spinal neuroinflammatory cascades.

PubMed

Evangelista, Afrânio Ferreira; Vannier-Santos, Marcos André; de Assis Silva, Gessica Sabrina; Silva, Daniela Nascimento; Juiz, Paulo José Lima; Nonaka, Carolina Kymie Vasques; Dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira; Villarreal, Cristiane Flora

2018-06-22

Diabetic neuropathy (DN) is a frequent and debilitating manifestation of diabetes mellitus, to which there are no effective therapeutic approaches. Mesenchymal stem/stromal cells (MSC) have a great potential for the treatment of this syndrome, possibly through regenerative actions on peripheral nerves. Here, we evaluated the therapeutic effects of MSC on spinal neuroinflammation, as well as on ultrastructural aspects of the peripheral nerve in DN-associated sensorial dysfunction. C57Bl/6 mice were treated with bone marrow-derived MSC (1 × 10 6 ), conditioned medium from MSC cultures (CM-MSC) or vehicle by endovenous route following the onset of streptozotocin (STZ)-induced diabetes. Paw mechanical and thermal nociceptive thresholds were evaluated by using von Frey filaments and Hargreaves test, respectively. Morphological and morphometric analysis of the sciatic nerve was performed by light microscopy and transmission electron microscopy. Mediators and markers of neuroinflammation in the spinal cord were measured by radioimmunoassay, real-time PCR, and immunofluorescence analyses. Diabetic mice presented behavioral signs of sensory neuropathy, mechanical allodynia, and heat hypoalgesia, which were completely reversed by a single administration of MSC or CM-MSC. The ultrastructural analysis of the sciatic nerve showed that diabetic mice exhibited morphological and morphometric alterations, considered hallmarks of DN, such as degenerative changes in axons and myelin sheath, and reduced area and density of unmyelinated fibers. In MSC-treated mice, these structural alterations were markedly less commonly observed and/or less pronounced. Moreover, MSC transplantation inhibited multiple parameters of spinal neuroinflammation found in diabetic mice, causing the reduction of activated astrocytes and microglia, oxidative stress signals, galectin-3, IL-1β, and TNF-α production. Conversely, MSC increased the levels of anti-inflammatory cytokines, IL-10, and TGF-β. The present study described the modulatory effects of MSC on spinal cord neuroinflammation in diabetic mice, suggesting new mechanisms by which MSC can improve DN.

Tissue engineering and peripheral nerve reconstruction: an overview.

PubMed

Geuna, Stefano; Gnavi, Sara; Perroteau, Isabelle; Tos, Pierluigi; Battiston, Bruno

2013-01-01

Nerve repair is no more regarded as merely a matter of microsurgical reconstruction. To define this evolving reconstructive/regenerative approach, the term tissue engineering is being increasingly used since it reflects the search for interdisciplinary and integrated treatment strategies. However, the drawback of this new approach is its intrinsic complexity, which is the result of the variety of scientific disciplines involved. This chapter presents a synthetic overview of the state of the art in peripheral nerve tissue engineering with a look forward at the most promising innovations emerging from basic science investigation. This review is intended to set the stage for the collection of papers in the thematic issue of the International Review of Neurobiology that is focused on the various interdisciplinary approaches in peripheral nerve tissue engineering. © 2013 Elsevier Inc. All rights reserved.

A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

PubMed

Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

2014-09-01

This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems.

Arterial and venous plasma levels of bupivacaine following peripheral nerve blocks.

PubMed

Moore, D C; Mather, L E; Bridenbaugh, L D; Balfour, R I; Lysons, D F; Horton, W G

1976-01-01

Mean arterial plasma (MAP) and peripheral mean venous plasma (MVP) levels of bupivacaine were ascertained in 3 groups of 10 patients each for: (1) intercostal nerve block, 400 mg; (2) block of the sciatic, femoral, and lateral femoral cutaneous nerves, with or without block of the obturator nerve, 400 mg; and (3) supraclavicular brachial plexus block, 300 mg. MAP levels were consistently higher than simultaneously sampled MVP levels, the highest levels occurring from bilateral intercostal nerve block. No evidence of systemic toxicity was observed. The results suggest that bupivacaine has a much wider margin of safety in humans than is now stated.

Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

PubMed

Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

2018-06-01

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy of decellularized nerve allograft for nerve regeneration, with limited success. Xenogeneic decellularized tissue matrices or hydrogels have been widely used for surgical applications owing to their ease of harvesting and low immunogenicity. Moreover, decellularized tissue matrix hydrogels show good biocompatibility and are highly tunable. In this study, we prepared a porcine decellularized nerve matrix (pDNM-G) and evaluated its potential for promoting nerve regeneration. Our results demonstrate that pDNM-G can support Schwann cell proliferation and peripheral nerve regeneration by means of residual primary extracellular matrix components and nano-fibrous structure features. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Remodeling of peripheral nerve ensheathment during the larval-to-adult transition in Drosophila.

PubMed

Subramanian, Aswati; Siefert, Matthew; Banerjee, Soumya; Vishal, Kumar; Bergmann, Kayla A; Curts, Clay C M; Dorr, Meredith; Molina, Camillo; Fernandes, Joyce

2017-10-01

Over the course of a 4-day period of metamorphosis, the Drosophila larval nervous system is remodeled to prepare for adult-specific behaviors. One example is the reorganization of peripheral nerves in the abdomen, where five pairs of abdominal nerves (A4-A8) fuse to form the terminal nerve trunk. This reorganization is associated with selective remodeling of four layers that ensheath each peripheral nerve. The neural lamella (NL), is the first to dismantle; its breakdown is initiated by 6 hours after puparium formation, and is completely removed by the end of the first day. This layer begins to re-appear on the third day of metamorphosis. Perineurial glial (PG) cells situated just underneath the NL, undergo significant proliferation on the first day of metamorphosis, and at that stage contribute to 95% of the glial cell population. Cells of the two inner layers, Sub-Perineurial Glia (SPG) and Wrapping Glia (WG) increase in number on the second half of metamorphosis. Induction of cell death in perineurial glia via the cell death gene reaper and the Diptheria toxin (DT-1) gene, results in abnormal bundling of the peripheral nerves, suggesting that perineurial glial cells play a role in the process. A significant number of animals fail to eclose in both reaper and DT-1 targeted animals, suggesting that disruption of PG also impacts eclosion behavior. The studies will help to establish the groundwork for further work on cellular and molecular processes that underlie the co-ordinated remodeling of glia and the peripheral nerves they ensheath. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1144-1160, 2017. © 2017 Wiley Periodicals, Inc.

Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury.

PubMed

Jones, Iwan; Novikova, Liudmila N; Novikov, Lev N; Renardy, Monika; Ullrich, Andreas; Wiberg, Mikael; Carlsson, Leif; Kingham, Paul J

2018-04-01

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair. © 2018 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

Six cases of sporadic schwannomatosis: Topographic distribution and outcomes of peripheral nerve tumors.

PubMed

Chick, G; Victor, J; Hollevoet, N

2017-10-01

The diagnosis of schwannomatosis is often overestimated and is based on the existence of multiple peripheral nerve tumors composed exclusively of schwannomas, in the absence of clinical signs of neurofibromatosis type 2 (NF2). Sporadic forms are much more frequent than familial forms. The objective of this study was to describe the distribution of peripheral nerve tumors and investigate the outcomes of schwannomas in the context of sporadic schwannomatosis. We conducted a retrospective study of patients who fulfilled clinical diagnostic criteria for sporadic schwannomatosis. Six patients were reviewed with a mean follow-up of 38.5months (27-60months). Patients' demographic, clinical, radiographic, and pathologic data were extracted. All patients underwent slit-lamp examination, enhanced brain magnetic resonance imaging (MRI) and a spinal MRI. Enucleation that preserved nerve continuity was performed in symptomatic patients. On average, patients were 36years of age at the time of diagnosis with no sex predominance. The topographic distribution of the peripheral nerve tumors was always unilateral and most frequently targeted the upper limb. In four cases, the tumors involved the same peripheral nerve exclusively. The average number of nerve tumors observed per patient was 4.7 (2-8). The outcome after enucleation was marked by the systematic appearance of new tumors. After enucleation, no recurrence or malignant transformation was observed at the final follow-up. There was no transition to a NF2 configuration. The absence of neurofibroma and NF2 criteria makes schwannomatosis a diagnosis of exclusion. While a good prognosis can be expected following enucleation, two risks related to neurofibromatosis type 3 (NF3) are worth monitoring: the transition to NF2, particularly in young patients, and the appearance of new tumors. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

POEMS Syndrome Diagnosed 10 Years after Disabling Peripheral Neuropathy.

PubMed

Nguyen, Viet H

2011-01-01

Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF.

POEMS Syndrome Diagnosed 10 Years after Disabling Peripheral Neuropathy

PubMed Central

Nguyen, Viet H.

2011-01-01

Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF. PMID:22013451

New synthetic prosthesis for peripheral nerve injuries: an experimental pilot study.

PubMed

Uranüs, Selman; Bretthauer, Georg; Nagele-Moser, Doris; Saliba, Sarah; Tomasch, Gordana; Rafolt, Dietmar; Justich, Ivo; Waldert, Jörg; Berghold, Andrea; Kleinert, Reinhold; Becker, Heinz; Voges, Udo; Wiederstein-Grasser, Iris; Koch, Horst

2013-04-01

Even the most modern technology has failed to induce satisfactory functional regeneration of traumatically severed peripheral nerves. Delayed neural regeneration and in consequence, slower neural conduction seriously limit muscle function in the area supplied by the injured nerve. This study aimed to compare a new nerve coaptation system involving an innovative prosthesis with the classical clinical method of sutured nerve coaptation. Besides the time and degree of nerve regeneration, the influence of electrostimulation was also tested. The sciatic nerve was severed in 14 female Göttingen minipigs with an average weight of 40.4 kg. The animals were randomized into 2 groups: One group received the new prosthesis and the other underwent microsurgical coaptation. In each group, according to the randomization a part of the animals received postoperative electrostimulation. Postoperative monitoring and the stimulation schedule covered a period of 9 months, during which axonal budding was evaluated monthly. The data from the pilot study indicate that results with the nerve prosthesis were comparable with those of conventional coaptation. The results indicate that implantation of the nerve prosthesis allows for good and effective neural regeneration. This new and simple treatment option for peripheral nerve injuries can be performed in any hospital with surgical facilities as it does not involve the demanding microsurgical suture technique that can only be performed in specialized centers.

The incidental finding of elevated anti GQ1B antibodies in a patient with selective small fiber neuropathy.

PubMed

Favoni, Valentina; Liguori, Rocco; Incensi, Alex; Fileccia, Enrico; Donadio, Vincenzo

2018-05-15

Small fiber neuropathy (SFN) selectively affects small diameter sensory and/or autonomic axons. Pain and autonomic dysfunctions are the most common symptoms. SFN occurs in several autoimmune diseases and autoantibodies against neuronal proteins may play a role in SFN pathophysiology. Anti-GQ1b antibody has been associated with Miller Fisher syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoplegia, pharyngeal-cervical-brachial weakness and peripheral neuropathy involving large fibers. Isolated SFN associated with anti-GQ1b antibodies has not been previously reported. Here we report a 45-year-old woman presenting with highly positive anti-GQ1b titer and selective SFN without central nervous system or peripheral large nerve involvement. She improved upon administration of adalizumab. Further studies will clarify a possible pathogenetic role of antiganglioside antibodies in SFN. Moreover, the recognition of antiganglioside antibodies in SFN may have therapeutic consequences with patients who would benefit from immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

P02.05 Peripheral Nerve Sheath Tumor Epidemiology in the South Central Hospital of High Specialty from PEMEX in Mexico

PubMed Central

Guerra Mora, J.; Cordoba Mosqueda, M.; Hernandez Resendiz, R.; Loya Aguilar, I.; Vicuña Gonzalez, R.; Garcia Gonzalez, U.

2016-01-01

Abstract Introduction: The peripheral sheath tumors are part of a large group of neoplasms that range from biologically benign with minimal disorders in life quality to highly malign with life quality deterioration and high mortality. There are subtypes with high prevalence like Schwannomas and some much rarer like the intracranial peripheral nerve sheath tumor which happen to have very bad prognosis. The aim of this study is to describe the epidemiologic and clinical characteristics of patients with peripheral nerve sheat tumors in a hospital of high specialty. Method and materials: Observational study with patients from March 1999 to March 2016 with confirmed diagnosis of peripheral nerve sheath tumor in the electronic files of the South Central Hospital of High Specialty PEMEX. A statistical analysis is made through the SPSS Statistics of the disease in this Institution program. Results: There were 84 patients with the diagnosis of peripheral nerve sheath tumor with a median age of 48.04 years, 65.5% were males, the most common histological type found was the Schwannoma with a 72.6%, followed by senescent Schwannoma 13.1%, neurofibroma 8.3%, and malign peripheral nerve sheath tumor 2.4%. The most frequent location was at the site of cranial nerves, followed by cervical level 27.4%, lumbar 16.7% and thoracic 9.5%. The most common initial symptom was pain in 23.8% of the patients, and the time of the onset of symptoms to the diagnosis was 31.6 months. From the total of patients 8.3% had neurofibromatosis type 1, 6.0% neurofibromatosis type 2. Conclusions: We realized in our series of reported cases that the frequency is similar to those reported in worldwide population; nevertheless the time between the onset of symptoms and the diagnosis is much higher in our cases as well as the population of patients with neurofibromatosis. This study justifies the need of attention quality improvement and the knowledge of this information the medical doctor of first contact so that the right diagnosis can be made and the treatment given in the shortest time possible.

Peripheral Nerve Blocks for the Treatment of Headache in Older Adults: A Retrospective Study.

PubMed

Hascalovici, Jacob R; Robbins, Matthew S

2017-01-01

The objective of this study is to provide demographical and clinical descriptions of patients age 65 years old and older who were treated with peripheral nerve blocks (PNBs) at our institution and evaluate the safety and efficacy of this treatment. Headache disorders are common, disabling chronic neurological diseases that often persist with advancing age. Geriatric headache management poses unique therapeutic challenges because of considerations of comorbidity, drug interactions, and adverse effects. Peripheral nerve blocks are commonly used for acute and short-term prophylactic treatment for headache disorders and may be a safer alternative to standard pharmacotherapy in this demographic. We performed a single center, retrospective chart review of patients at least 65 years of age who received peripheral nerve blocks for headache management over a 6 year period. Sixty-four patients were mostly female (78%) with an average age of 71 years (range 65-94). Representative headache diagnoses were chronic migraine 50%, episodic migraine 12.5%, trigeminal autonomic cephalalgia 9.4%, and occipital neuralgia 7.8%. Average number of headache days/month was 23. Common comorbidities were hypertension 48%, hyperlipidemia 42%, arthritis 27%, depression 47%, and anxiety 33%. Eighty-nine percent were prescribed at least 1 medication fulfilling the Beers criteria. The average number of peripheral nerve blocks per patient was 4. Peripheral nerve blocks were felt to be effective in 73% for all headaches, 81% for chronic migraine, 75% for episodic migraine, 67% for chronic tension type headache, 67% for new daily persistent headache, and 60% for occipital neuralgia. There were no adverse events related to PNBs reported. PNBs might be a safe and effective alternative headache management strategy for older adults. Medical and psychiatric comorbidities, medication overuse, and Beers list medication rates were extraordinarily high, giving credence to the use of peripherally administered therapies in the geriatric population that may be better tolerated and safer. © 2016 American Headache Society.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

PubMed

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

2017-01-01

To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

Controversies related to electromagnetic field exposure on peripheral nerves.

PubMed

Say, Ferhat; Altunkaynak, Berrin Zuhal; Coşkun, Sina; Deniz, Ömür Gülsüm; Yıldız, Çağrı; Altun, Gamze; Kaplan, Arife Ahsen; Kaya, Sefa Ersan; Pişkin, Ahmet

2016-09-01

Electromagnetic field (EMF) is a pervasive environmental presence in modern society. In recent years, mobile phone usage has increased rapidly throughout the world. As mobile phones are generally held close to the head while talking, studies have mostly focused on the central and peripheral nervous system. There is a need for further research to ascertain the real effect of EMF exposure on the nervous system. Several studies have clearly demonstrated that EMF emitted by cell phones could affect the systems of the body as well as functions. However, the adverse effects of EMF emitted by mobile phones on the peripheral nerves are still controversial. Therefore, this review summarizes current knowledge on the possible positive or negative effects of electromagnetic field on peripheral nerves. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural parameters of collagen nerve grafts influence peripheral nerve regeneration.

PubMed

Stang, Felix; Fansa, Hisham; Wolf, Gerald; Reppin, Michael; Keilhoff, Gerburg

2005-06-01

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.

Lower limb and back pain in Guillain-Barré syndrome and associated contrast enhancement in MRI of the cauda equina.

PubMed

Wilmshurst, J M; Thomas, N H; Robinson, R O; Bingham, J B; Pohl, K R

2001-06-01

This study assesses the frequency of lower limb and back pain in children with Guillain-Barré syndrome and reviews the magnetic resonance imaging results of those undergoing spinal imaging. Over an 8-y period, nine children presented with various combinations of severe back pain, leg pains, impairment of gait and bladder dysfunction. Guillain-Barré syndrome was confirmed on clinical examination and peripheral electrophysiology (n = 8). Magnetic resonance imaging in four patients, following contrast injection, showed enhancement of the cauda equine and, additionally, of the cervical nerve roots in one of the patients. A further patient, who was not scanned with contrast, had abnormal thickening of the lumbar roots. Carbamazepine and steroids were effectively used for analgesia in three cases. All the patients recovered. Guillain-Barré syndrome should be considered in the differential diagnosis of children presenting with back and/or leg pain. Early diagnosis ensures prompt monitoring for autonomic dysfunction and respiratory compromise.

Rehabilitation of brachial plexus and peripheral nerve disorders.

PubMed

Scott, Kevin R; Ahmed, Aiesha; Scott, Linda; Kothari, Milind J

2013-01-01

Peripheral nerve lesions are common and can present in a variety of ways. Peripheral nerve injury can result from a broad spectrum of causes. For the majority of patients, rehabilitation is generally indicated regardless of etiology. Evaluation and treatment by a multidisciplinary team including neurologists, psychiatrists, surgeons, occupational and physical therapists, and therapists with specialized training in orthotics maximizes the potential for recovery. This chapter will focus on those upper and lower extremity neuropathies that are most commonly seen in clinical practice. In addition, we discuss various rehabilitative strategies designed to improve function and quality of life. Copyright © 2013 Elsevier B.V. All rights reserved.

Axonal regeneration through acellular muscle grafts

PubMed Central

HALL, SUSAN

1997-01-01

The management of peripheral nerve injury remains a major clinical problem. Progress in this field will almost certainly depend upon manipulating the pathophysiological processes which are triggered by traumatic injuries. One of the most important determinants of functional outcome after the reconstruction of a transected peripheral nerve is the length of the gap between proximal and distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit in order to support axonal regrowth. This review examines the cellular and acellular elements which facilitate axonal regrowth and the use of acellular muscle grafts in the repair of injuries in the peripheral nervous system. PMID:9034882

Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Lihua; Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053; Gan, Li

Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were appliedmore » to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide conduits in the field of nerve tissue engineering. - Highlights: • A novel nerve conduit was constructed and applied to repair nerve defect in rats. • Transparent hollow cellulose/soy protein isolate tube was used as conduit matrix. • Pyrroloquinoline quinine was adsorbed into the hollow tube as nerve growth factor. • Schwann cells were cultured into the hollow tube as seed cells. • The new nerve conduit could repair and reconstruct the peripheral nerve defects.« less

High mortality from Guillain-Barré syndrome in Bangladesh.

PubMed

Ishaque, Tanveen; Islam, Mohammad B; Ara, Gulshan; Endtz, Hubert P; Mohammad, Quazi D; Jacobs, Bart C; Islam, Zhahirul

2017-06-01

Although Guillain-Barré syndrome (GBS) has higher incidence and poor outcome in Bangladesh, mortality from GBS in Bangladesh has never been explored before. We sought to explore the frequency, timing, and risk factors for deaths from GBS in Bangladesh. We conducted a prospective study on 407 GBS patients who were admitted to Dhaka Medical College Hospital, Dhaka, Bangladesh from 2010 to 2013. We compared deceased and alive patients to identify risk factors. Cox regression model was used to adjust for confounders. Of the 407 GBS patients, 50 (12%) died, with the median time interval between the onset of weakness and death of 18 days. Among the fatal cases, 24 (48%) were ≥40 years, 36 (72%) had a Medical Research Council sum score ≤20 at entry, 33 (66%) had a progressive phase <8 days, and 27 (54%) required ventilation support. Ten patients (20%) died due to unavailability of ventilator. The strongest risk factor for deaths was lack of ventilator support when it was required (HR: 11.9; 95% confidence interval [CI]: 4.6-30.7). Other risk factors for death included age ≥40 years (HR: 5.9; 95% CI: 2.1-16.7), mechanical ventilation (HR: 2.3; 95% CI: 1.02-5.2), longer progressive phase (>8 days) (HR: 2.06; 95% CI: 1.1-3.8), autonomic dysfunction (HR: 1.9; 95% CI: 1.05-3.6), and bulbar nerve involvement (HR: 5.4; 95% CI: 1.5-19.2). In Bangladesh, GBS is associated with higher mortality rates, which is related to lack of ventilator support, disease severity, longer progressive phase of the disease, autonomic dysfunction, and involvement of the bulbar nerves. © 2017 Peripheral Nerve Society.

A cross-sectional electromyography assessment in linear scleroderma patients

PubMed Central

2014-01-01

Background Muscle atrophy and asymmetric extremity growth is a common feature of linear scleroderma (LS). Extra-cutaneous features are also common and primary neurologic involvement, with sympathetic dysfunction, may have a pathogenic role in subcutaneous and muscle atrophy. The aim was investigate nerve conduction and muscle involvement by electromyography in pediatric patients with LS. Methods We conducted a retrospective review of LS pediatric patients who had regular follow up at a single pediatric center from 1997–2013. We selected participants if they had consistently good follow up and enrolled consecutive patients in the study. We examined LS photos as well as clinical, serological and imaging findings. Electromyograms (EMG) were performed with bilateral symmetric technique, using surface and needle electrodes, comparing the affected side with the contralateral side. Abnormal muscle activity was categorized as a myopathic or neurogenic pattern. Results Nine LS subjects were selected for EMG, 2 with Parry-Romberg/Hemifacial Atrophy Syndrome, 7 linear scleroderma of an extremity and 2 with mixed forms (linear and morphea). Electromyogram analysis indicated that all but one had asymmetric myopathic pattern in muscles underlying the linear streaks. Motor and sensory nerve conduction was also evaluated in upper and lower limbs and one presented a neurogenic pattern. Masticatory muscle testing showed a myopathic pattern in the atrophic face of 2 cases with head and face involvement. Conclusion In our small series of LS patients, we found a surprising amount of muscle dysfunction by EMG. The muscle involvement may be possibly related to a secondary peripheral nerve involvement due to LS inflammation and fibrosis. Further collaborative studies to confirm these findings are needed. PMID:25053924

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2013-02-01

successfully establish the xenograft within the sciatic nerve. Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform...intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1 MPNST and PNs in scid mice as described by Perrin et...using convection-enhanced delivery ( CED ). Relative Growth of MPNST cells in vivo treated with rapamycin, imatinib or erlotinib: Elotinib

Alterations in the Local Axonal Environment Influence Target Reinnervation and Neuronal Survival After PostnataI Axotomy

DTIC Science & Technology

2000-06-21

2000 Dissertation directed by: Rosemary C. Borke, Ph.D. Professor Department of Anatomy and Cell Biology Following peripheral nerve injury in adult...augmented at the injury site and the neuromuscular junction (NMJ) following sciatic nerve axotomy. The current work determined that SC apoptosis occurs in...related and location-specific response to peripheral nerve injury . Apoptotic SC were found in two strategic locations for guiding axonal outgrowth during

Bell palsy in lyme disease-endemic regions of canada: a cautionary case of occult bilateral peripheral facial nerve palsy due to Lyme disease.

PubMed

Ho, Karen; Melanson, Michel; Desai, Jamsheed A

2012-09-01

Lyme disease caused by the spirochete Borrelia burgdorferi is a multisystem disorder characterized by three clinical stages: dermatologic, neurologic, and rheumatologic. The number of known Lyme disease-endemic areas in Canada is increasing as the range of the vector Ixodes scapularis expands into the eastern and central provinces. Southern Ontario, Nova Scotia, southern Manitoba, New Brunswick, and southern Quebec are now considered Lyme disease-endemic regions in Canada. The use of field surveillance to map risk and endemic regions suggests that these geographic areas are growing, in part due to the effects of climate warming. Peripheral facial nerve palsy is the most common neurologic abnormality in the second stage of Lyme borreliosis, with up to 25% of Bell palsy (idiopathic peripheral facial nerve palsy) occurring due to Lyme disease. Here we present a case of occult bilateral facial nerve palsy due to Lyme disease initially diagnosed as Bell palsy. In Lyme disease-endemic regions of Canada, patients presenting with unilateral or bilateral peripheral facial nerve palsy should be evaluated for Lyme disease with serologic testing to avoid misdiagnosis. Serologic testing should not delay initiation of appropriate treatment for presumed Bell palsy.

Receptor Tyrosine Kinases as Targets for Treatment of Peripheral Nerve Sheath Tumors in NF 1 Patients

DTIC Science & Technology

2007-03-01

EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms ...Armstrong,F., Delsol,G., Dastugue,N. and Brousset,P. (2003) Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth

HCV RNA Genomic sequences and HCV-E2 glycoprotein in sural nerve biopsies from HCV-infected patients with peripheral neuropathy.

PubMed

Russi, S; Sansonno, D; Monaco, S; Mariotto, S; Ferrari, S; Pavone, F; Lauletta, G; Dammacco, F

2018-06-01

Peripheral neuropathy (PN), the major neurological complication of chronic HCV infection, is frequently associated with mixed cryoglobulinaemia (MC) and small-vessel systemic vasculitis. While humoral and cell-mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of HCV remains largely speculative. The possible demonstration of HCV in peripheral nerve tissue would obviously assume important pathogenic implications. We studied sural nerve biopsies from 11 HCV-positive patients with neuropathic symptoms: five with and six without MC. In situ hybridization (ISH) and immunofluorescence studies were carried out to detect genomic and antigenomic HCV RNA sequences and HCV-encoded E2-glycoprotein, respectively. Epineurial vascular deposits of E2-glycoprotein were found in four (80%) MC and in two (33.3%) non-MC patients, respectively. These findings were enhanced by the perivascular deposition of positive-, though not negative-strand replicative RNA, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and/or complement proteins were revealed around small vessels, without distinct vasculitis changes between MC and non-MC patients. These results indicate that nerve vascular HCV RNA/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically HCV-infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate HCV productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus-triggered immune-mediated mechanisms. © 2017 British Neuropathological Society.

Novel drug delivering conduit for peripheral nerve regeneration

NASA Astrophysics Data System (ADS)

Labroo, Pratima; Shea, Jill; Edwards, Kyle; Ho, Scott; Davis, Brett; Sant, Himanshu; Goodwin, Isak; Gale, Bruce; Agarwal, Jay

2017-12-01

Objective. This paper describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA) based nerve guide conduit for controlled local delivery of nerve growth factor (NGF) and application in peripheral nerve gap injury. Approach. An NGF dosage curve was acquired to determine the minimum in vitro concentration for optimal neurite outgrowth of dorsal root ganglion (DRG) cells; PLGA based drug delivery devices were then designed and tested in vitro and in vivo across 15 mm rat sciatic nerve gap injury model. Main results. The drug delivery nerve guide was able to release NGF for 28 d at concentrations (0.1-10 ng ml-1) that were shown to enhance DRG neurite growth. Furthermore, the released NGF was bioactive and able to enhance DRG neurite growth. Following these tests, optimized NGF-releasing nerve conduits were implanted across 15 mm sciatic nerve gaps in a rat model, where they demonstrated significant myelination and muscle innervation in vivo as compared to empty nerve conduits (p  <  0.05). This drug delivery nerve guide can release NGF for extended periods of time and enhance axon growth in vitro and in vivo and has the potential to improve nerve regeneration following a peripheral nerve injury. Significance. This integrated drug delivering nerve guide simplifies the design process and provides increased versatility for releasing a variety of different growth factors. This innovative device has the potential for broad applicability and allows for easier customization to change the type of drugs and dosage of individual drugs without devising a completely new biomaterial-drug conjugate each time.

An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries.

PubMed

Patel, Nitesh P; Lyon, Kristopher A; Huang, Jason H

2018-05-01

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

The role of precisely matching fascicles in the quick recovery of nerve function in long peripheral nerve defects

PubMed Central

Yan, Liwei; Yao, Zhi; Lin, Tao; Zhu, Qingtang; Qi, Jian; Gu, Liqiang; Fang, Jintao; Zhou, Xiang

2017-01-01

Peripheral nerve injury therapy in the clinic remains less than satisfactory. The gold standard of treatment for long peripheral nerve defects is autologous nerve grafts; however, numerous clinical complications are associated with this treatment. As tissue engineering has developed, tissue-engineered nerve grafts (TENGs) have shown potential applications as alternatives to autologous nerve grafts. To verify the important role of the biomimetic pathway of fascicle design in TENGs, we designed an animal model to study the role of the precise matching of fascicles in the effectiveness of nerve function recovery. 24 Sprague-Dawley rats were divided randomly into three groups (eight/group) that corresponded to 100% fascicle matching (100%FM), 50%FM and 0%FM. We selected Sprague–Dawley rat long-gap (15 mm) sciatic nerve defects. In the 6 weeks after surgery, we found that the 100%FM group showed the most effective functional recovery among the three groups. The 100%FM group showed better functional recovery on the basis of the sciatic functional index than the 50%FM and 0%FM groups. According to histological evaluation, the 100%FM group showed more regenerating nerve fibres. Moreover, in terms of the prevention of muscle atrophy, the 100%FM group showed excellent physiological outcomes. The 100%FM as tissue-engineered scaffolds can enhance nerve regeneration and effective functional recovery after the repair of large nerve defects. The results of this study provide a theoretical basis for future TENG designs including biomimetic fascicle pathways for repairing long nerve defects. PMID:28914740

Rapid and accurate peripheral nerve detection using multipoint Raman imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kumamoto, Yasuaki; Minamikawa, Takeo; Kawamura, Akinori; Matsumura, Junichi; Tsuda, Yuichiro; Ukon, Juichiro; Harada, Yoshinori; Tanaka, Hideo; Takamatsu, Tetsuro

2017-02-01

Nerve-sparing surgery is essential to avoid functional deficits of the limbs and organs. Raman scattering, a label-free, minimally invasive, and accurate modality, is one of the best candidate technologies to detect nerves for nerve-sparing surgery. However, Raman scattering imaging is too time-consuming to be employed in surgery. Here we present a rapid and accurate nerve visualization method using a multipoint Raman imaging technique that has enabled simultaneous spectra measurement from different locations (n=32) of a sample. Five sec is sufficient for measuring n=32 spectra with good S/N from a given tissue. Principal component regression discriminant analysis discriminated spectra obtained from peripheral nerves (n=863 from n=161 myelinated nerves) and connective tissue (n=828 from n=121 tendons) with sensitivity and specificity of 88.3% and 94.8%, respectively. To compensate the spatial information of a multipoint-Raman-derived tissue discrimination image that is too sparse to visualize nerve arrangement, we used morphological information obtained from a bright-field image. When merged with the sparse tissue discrimination image, a morphological image of a sample shows what portion of Raman measurement points in arbitrary structure is determined as nerve. Setting a nerve detection criterion on the portion of "nerve" points in the structure as 40% or more, myelinated nerves (n=161) and tendons (n=121) were discriminated with sensitivity and specificity of 97.5%. The presented technique utilizing a sparse multipoint Raman image and a bright-field image has enabled rapid, safe, and accurate detection of peripheral nerves.

Echogenicity and ultrasound visibility of peripheral nerves of the upper extremity.

PubMed

Stolz, Lori A; Acuna, Josie Galarza; Gaskin, Kevin; Murphy, Amanda M; Friedman, Lucas; Stears-Ellis, Summer; Javedani, Parisa; Stolz, Uwe; Adhikari, Srikar

2018-05-02

Regional anesthesia with ultrasound-guidance is an excellent option for pain control if nerves are adequately visualized. Gender, body mass index (BMI), history of diabetes, neck and forearm circumference may affect echotexture and visualization. This study evaluates patient characteristics for their ability to predict the echogenicity or visibility of upper extremity peripheral nerves. This is a prospective observational study. A convenience sample of adult emergency department patients were enrolled. Gender, BMI, history of diabetes, neck circumference and arm circumference were recorded. Sonographic images of the brachial plexus at interscalene and supraclavicular levels, the median, the radial and ulnar nerves were recorded. Three reviewers independently graded the echogenicity and visibility using subjective scales. 395 peripheral nerves were included. Nerves of the forearm (median, ulnar, radial nerves) were found to be more echogenic (OR=9.3; 95% CI: 5.7, 15.3) and visible (OR=10.0; 6.3, 16.0) than more proximal nerves (brachial plexus at interscalene and supraclavicular levels). Gender, BMI, and history of diabetes mellitus were not significantly related to nerve visibility (p=0.9, 0.2, 0.2, respectively) or echogenicity (p=0.3, 0.8, 0.3). Neck circumference was not related to visibility or echogenicity of proximal nerves. Increased forearm circumference improved echogenicity (OR=1.25; 1.09, 1.43) but not visibility of forearm nerves. Gender, BMI and presence of diabetes were not related to echogenicity or visibility of upper extremity nerves. Increasing forearm circumference was associated with increased echogenicity of the adjacent nerves, but not visibility. Neck circumference was not associated with either nerve visibility or echogenicity of brachial plexus nerve bundles.

Effect of diet induced obesity or type 1 or type 2 diabetes on corneal nerves and peripheral neuropathy in C57Bl/6J mice

PubMed Central

Yorek, Matthew S.; Obrosov, Alexander; Shevalye, Hanna; Holmes, Amey; Harper, Matthew M.; Kardon, Randy H.; Yorek, Mark A.

2015-01-01

We determined the impact diet induced obesity (DIO) and types 1 and 2 diabetes has on peripheral neuropathy with emphasis on corneal nerve structural changes in C57Bl/6J mice. Endpoints examined included nerve conduction velocity, response to thermal and mechanical stimuli and innervation of the skin and cornea. DIO mice and to a greater extent type 2 diabetic mice were insulin resistant. DIO and both types 1 and 2 diabetic mice developed motor and sensory nerve conduction deficits. In the cornea of DIO and type 2 diabetic mice there was a decrease in sub-epithelial corneal nerves, innervation of the corneal epithelium and corneal sensitivity. Type 1 diabetic mice did not present with any significant changes in corneal nerve structure until after 20 weeks of hyperglycemia. DIO and type 2 diabetic mice developed corneal structural damage more rapidly than type 1 diabetic mice even though hemoglobin A1C values were significantly higher in type 1 diabetic mice. This suggests that DIO with or without hyperglycemia contributes to development and progression of peripheral neuropathy and nerve structural damage in the cornea. PMID:25858759

What is the Best Strategy on Detection of Cornea Neuropathy in People with Diabetes? Recent Advances in Potential Measurements.

PubMed

Lv, Ying; Zhao, Shaozhen

2018-03-26

There are well-acknowledged clinical or pre-clinical measurements concerning diabetic peripheral neuropathy(DPN). The current gold standard for diagnosis of diabetic peripheral neuropathy is nerve conduction suitable for detecting large nerve fiber function[1] and intraepidermal nerve fiber density assessment for small fiber damage evaluation[2]. The lack of a sensitive, non-invasive, and repeatable endpoint to measure changes in small nerve fibers is a major factor holding back clinical trials for the treatment of diabetic peripheral neuropathy. As cornea is the most densely innerved tissue, assessing corneal nerves' structure and function will be promising to predict and assess the degree of DPN [3]. In the diabetic micro-environment, damaged corneal nerves lead to decreased corneal sensitivity, both of which resulting in abnormal tear function. According to this theory, the measurements of nerve structure, corneal sensitivity, tear secretion and tear components, to some extent, can reveal and assess the state of corneal neuropathy. This review focuses on summarizing the knowledge of the latest detective methods of diabetic corneal neuropathy, popular in use or possible to further in study and be applied into clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Sonographic evaluation of peripheral nerves in subtypes of Guillain-Barré syndrome.

PubMed

Mori, Atsuko; Nodera, Hiroyuki; Takamatsu, Naoko; Maruyama-Saladini, Keiko; Osaki, Yusuke; Shimatani, Yoshimitsu; Kaji, Ryuji

2016-05-15

Sonography of peripheral nerves can depict alteration of nerve sizes that could reflect inflammation and edema in inflammatory and demyelinating neuropathies. Guillain-Barré syndrome (GBS). Information on sonographic comparison of an axonal subtype (acute motor [and sensory] axonal neuropathy [AMAN and AMSAN]) and a demyelinating subtype (acute inflammatory demyelinating polyneuropathy [AIDP]) has been sparse. Sonography of peripheral nerves and cervical nerve roots were prospectively recorded in patients with GBS who were within three weeks of disease onset. Five patients with AIDP and nine with AMAN (n=6)/AMSAN (n=3) were enrolled. The patients with AIDP showed evidence of greater degrees of demyelination (e.g., slower conduction velocities and increased distal latencies) than those with AMAN/AMSAN. The patients with AIDP tended to show enlarged nerves in the proximal segments and in the cervical roots, whereas the patients with AMAN/AMSAN had greater enlargement in the distal neve segment, especially in the median nerve (P = 0.03; Wrist-axilla cross-sectional ratio). In this small study, two subtypes of GBS showed different patterns of involvement that might reflect different pathomechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration

NASA Astrophysics Data System (ADS)

Gao, Mingyong; Lu, Paul; Lynam, Dan; Bednark, Bridget; Campana, W. Marie; Sakamoto, Jeff; Tuszynski, Mark

2016-12-01

Objective. We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. Approach. 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site. Main results. Twelve weeks after injury, scaffolds supported highly linear regeneration of host axons across the 15 mm lesion gap. The incorporation of BDNF-secreting cells into scaffolds significantly increased axonal regeneration, and additional injection of viral vectors expressing BDNF into the distal segment of the transected nerve significantly enhanced axonal regeneration beyond the lesion. Significance. Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.

Evaluation of central and peripheral neuropathy in patients with chronic obstructive pulmonary disease.

PubMed

Aras, Yeşim Güzey; Aydemir, Yusuf; Güngen, Belma Doğan; Güngen, Adil Can

2018-01-01

The aim of the study was to investigate the frequency and characteristics of peripheral nervous system (PNS) and central nervous system (CNS) involvement in COPD. The study included 41 COPD patients and 41 healthy volunteers. Electrophysiological studies were carried out: electromyography (EMG) and visual evoked potentials (VEPs). The median nerve, ulnar nerve, common peroneal nerve, and tibial nerve were evaluated for latency, amplitude, and conduction velocity. The mean age of patients with COPD was 61.8 years and disease duration 10.3 years. There was no difference between patient and control groups in terms of age, BMI, smoking status, or biochemical parameters. Upon VEP examination, latencies were significantly prolonged and amplitudes shortened in the patient group compared to the control group. In EMG measurements, conduction velocity and amplitudes in all nerves were low in the patient group. Similarly, latencies in all nerves were higher in patients with COPD. Central and peripheral nervous system involvement could develop in patients with moderate-severe COPD, and these patients should be monitored for neuropathic changes in combination with neurological examination.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

Multifunctional Silk Nerve Guides for Axon Outgrowth

NASA Astrophysics Data System (ADS)

Tupaj, Marie C.

Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long (> 3 cm) peripheral nerve gaps.

Effects of nerve cells and adhesion molecules on nerve conduit for peripheral nerve regeneration

PubMed Central

Fiorellini, Joseph P.

2017-01-01

Background For peripheral nerve regeneration, recent attentions have been paid to the nerve conduits made by tissue-engineering technique. Three major elements of tissue-engineering are cells, molecules, and scaffolds. Methods In this study, the attachments of nerve cells, including Schwann cells, on the nerve conduit and the effects of both growth factor and adhesion molecule on these attachments were investigated. Results The attachment of rapidly-proliferating cells, C6 cells and HS683 cells, on nerve conduit was better than that of slowly-proliferating cells, PC12 cells and Schwann cells, however, the treatment of nerve growth factor improved the attachment of slowly-proliferating cells. In addition, the attachment of Schwann cells on nerve conduit coated with fibronectin was as good as that of Schwann cells treated with glial cell line-derived neurotrophic factor (GDNF). Conclusions Growth factor changes nerve cell morphology and affects cell cycle time. And nerve growth factor or fibronectin treatment is indispensable for Schwann cell to be used for implantation in artificial nerve conduits. PMID:29090249

Biomechanical and functional variation in rat sciatic nerve following cuff electrode implantation

PubMed Central

2014-01-01

Background Nerve cuff electrodes are commonly and successfully used for stimulating peripheral nerves. On the other hand, they occasionally induce functional and morphological changes following chronic implantation, for reasons not always clear. We hypothesize that restriction of nerve mobility due to cuff implantation may alter nerve conduction. Methods We quantified acute changes in nerve-muscle electrophysiology, using electromyography, and nerve kinematics in anesthetized Sprague Dawley rat sciatic nerves during controlled hindlimb joint movement. We compared electrophysiological and biomechanical response in uncuffed nerves and those secured within a cuff electrode using analysis of variance (ANOVA) and regression analysis. Results Tethering resulting from cuff implantation resulted in altered nerve strain and a complex biomechanical environment during joint movement. Coincident with biomechanical changes, electromyography revealed significantly increased variability in the response of conduction latency and amplitude in cuffed, but not free, nerves following joint movement. Conclusion Our findings emphasize the importance of the mechanical interface between peripheral nerves and their devices on neurophysiological performance. This work has implications for nerve device design, implantation, and prediction of long-term efficacy. PMID:24758405

Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve Barrier.

PubMed

Morris, Angela D; Lewis, Gwendolyn M; Kucenas, Sarah

2017-05-03

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation, and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury, and function were altered compared with wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor-β1 as a partial mediator of perineurial glial development. Together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations. SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction, and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve barrier, are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally derived myelin, demonstrating that, although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve barrier is compromised in the presence of ectopic OPCs. Copyright © 2017 the authors 0270-6474/17/374790-18$15.00/0.

The neurotrophic effects of different human dental mesenchymal stem cells.

PubMed

Kolar, Mallappa K; Itte, Vinay N; Kingham, Paul J; Novikov, Lev N; Wiberg, Mikael; Kelk, Peyman

2017-10-03

The current gold standard treatment for peripheral nerve injury is nerve grafting but this has disadvantages such as donor site morbidity. New techniques focus on replacing these grafts with nerve conduits enhanced with growth factors and/or various cell types such as mesenchymal stem cells (MSCs). Dental-MSCs (D-MSCs) including stem cells obtained from apical papilla (SCAP), dental pulp stem cells (DPSC), and periodontal ligament stem cells (PDLSC) are potential sources of MSCs for nerve repair. Here we present the characterization of various D-MSCs from the same human donors for peripheral nerve regeneration. SCAP, DPSC and PDLSC expressed BDNF, GDNF, NGF, NTF3, ANGPT1 and VEGFA growth factor transcripts. Conditioned media from D-MSCs enhanced neurite outgrowth in an in vitro assay. Application of neutralizing antibodies showed that brain derived neurotrophic factor plays an important mechanistic role by which the D-MSCs stimulate neurite outgrowth. SCAP, DPSC and PDLSC were used to treat a 10 mm nerve gap defect in a rat sciatic nerve injury model. All the stem cell types significantly enhanced axon regeneration after two weeks and showed neuroprotective effects on the dorsal root ganglia neurons. Overall the results suggested SCAP to be the optimal dental stem cell type for peripheral nerve repair.

Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies.

PubMed

Wieringa, Paul A; Gonçalves de Pinho, Ana Rita; Micera, Silvestro; van Wezel, Richard J A; Moroni, Lorenzo

2018-04-01

Biofabrication techniques have endeavored to improve the regeneration of the peripheral nervous system (PNS), but nothing has surpassed the performance of current clinical practices. However, these current approaches have intrinsic limitations that compromise patient care. The "gold standard" autograft provides the best outcomes but requires suitable donor material, while implantable hollow nerve guide conduits (NGCs) can only repair small nerve defects. This review places emphasis on approaches that create structural cues within a hollow NGC lumen in order to match or exceed the regenerative performance of the autograft. An overview of the PNS and nerve regeneration is provided. This is followed by an assessment of reported devices, divided into three major categories: isotropic hydrogel fillers, acting as unstructured interluminal support for regenerating nerves; fibrous interluminal fillers, presenting neurites with topographical guidance within the lumen; and patterned interluminal scaffolds, providing 3D support for nerve growth via structures that mimic native PNS tissue. Also presented is a critical framework to evaluate the impact of reported outcomes. While a universal and versatile nerve repair strategy remains elusive, outlined here is a roadmap of past, present, and emerging fabrication techniques to inform and motivate new developments in the field of peripheral nerve regeneration. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of barrier coatings on kink-resistant peripheral nerve conduits

PubMed Central

Clements, Basak Acan; Bushman, Jared; Murthy, N Sanjeeva; Ezra, Mindy; Pastore, Christopher M; Kohn, Joachim

2016-01-01

Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1) electrospinning a layer of polymer fibers onto the surface of the conduit and (2) coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery. PMID:26977288

Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration.

PubMed

Wong, Kah-Hui; Kanagasabapathy, Gowri; Naidu, Murali; David, Pamela; Sabaratnam, Vikineswary

2016-10-01

To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice.

PubMed

Homayouni Moghadam, Farshad; Dehghan, Maryam; Zarepur, Ehsan; Dehlavi, Reyhaneh; Ghaseminia, Fatemeh; Ehsani, Shima; Mohammadzadeh, Golnaz; Barzegar, Kazem

2014-05-28

According to the Chinese, European, Iranian and Indian traditional medicines, oleo gum resin of Ferula assa-foetida (asafoetida) has therapeutic effects on different kinds of diseases. Some of these effects are related to the diseases of nervous system such as hysteresis and convulsion. In recent studies, some anti-epileptic and neuroprotective roles were also considered for it and we examined its possible role on treatment of peripheral neuropathy. in vitro studies were carried out to identify the response of isolated sciatic nerves to different concentrations of oleo gum resin of asafoetida solved in Lock׳s solution. Then, in vivo studies were conducted to evaluate its effect on amelioration of peripheral neuropathy in mice. Peripheral neuropathy was induced by intraperiotoneal injection of high doses of pyridoxine in adult Balb/c male mice. Tail flick tests were performed to identify the incidence of neuropathy in animals. After 10 days treatment with asafoetida, the efficiency of treatment was assessed by behavioral, electrophysiological and histological studies. in vitro experiments confirmed that incubating the nerves in aqueous extract of oleo gum rein of asafoetida increased the amplitude and decreased the latent period of nerve compound action potential (CAP). Nerve conduction velocity (NCV) and amplitude of CAP also improved in asafoetida treated animals. Histological and behavioral studies showed that asafoetida was able to facilitate the healing process in peripheral nerves. in vitro experiments showed that asafoetida is a nerve stimulant and its administration in neuropathic mice exerted neuroprotecting effects through stimulating axonal regeneration and remyelination and decrement of lymphocyte infiltration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Biophysical characterization of interactions between the C-termini of peripheral nerve claudins and the PDZ₁ domain of zonula occludens.

PubMed

Wu, Jiawen; Peng, Dungeng; Zhang, Yang; Lu, Zhenwei; Voehler, Markus; Sanders, Charles R; Li, Jun

2015-03-27

Our recent study has shown that cellular junctions in myelin and in the epi-/perineruium that encase nerve fibers regulate the permeability of the peripheral nerves. This permeability may affect propagation of the action potential. Direct interactions between the PDZ₁ domain of zonula occludens (ZO₁ or ZO₂) and the C-termini of claudins are known to be crucial for the formation of tight junctions. Using the purified PDZ₁ domain of ZO₂ and a variety of C-terminal mutants of peripheral nerve claudins (claudin-1, claudin-2, claudin-3, claudin-5 in epi-/perineurium; claudin-19 in myelin), we have utilized NMR spectroscopy to determine specific roles of the 3 C-terminal claudin residues (position -2, -1, 0) for their interactions with PDZ₁ of ZO₂. In contrast to the canonical model that emphasizes the importance of residues at the -2 and 0 positions, our results demonstrate that, for peripheral nerve claudins, the residue at position -1 plays a critical role in association with PDZ₁, while the side-chain of residue 0 plays a significant but lesser role. Surprisingly, claudin-19, the most abundant claudin in myelin, exhibited no binding to ZO₂. These findings reveal that the binding mechanism of claudin/ZO in epi-/perineurium is distinct from the canonical interactions between non-ZO PDZ-containing proteins with their ligands. This observation provides the molecular basis for a strategy to develop drugs that target tight junctions in the epi-/perineurium of peripheral nerves. Published by Elsevier Inc.

Development of regenerative peripheral nerve interfaces for motor control of neuroprosthetic devices

NASA Astrophysics Data System (ADS)

Kemp, Stephen W. P.; Urbanchek, Melanie G.; Irwin, Zachary T.; Chestek, Cynthia A.; Cederna, Paul S.

2017-05-01

Traumatic peripheral nerve injuries suffered during amputation commonly results in debilitating neuropathic pain in the affected limb. Modern prosthetic technologies allow for intuitive, simultaneous control of multiple degrees of freedom. However, these state-of-the-art devices require separate, independent control signals for each degree of freedom, which is currently not possible. As a result, amputees reject up to 75% of myoelectric devices preferring instead to use body-powered artificial limbs which offer subtle sensory feedback. Without meaningful and intuitive sensory feedback, even the most advanced myoelectric prostheses remain insensate, burdensome, and are associated with enormous cognitive demand and mental fatigue. The ideal prosthetic device is one which is capable of providing intuitive somatosensory feedback essential for interaction with the environment. Critical to the design of such a bioprosthetic device is the development of a reliable biologic interface between human and machine. This ideal patient-prosthetic interface allows for transmission of both afferent somatosensory information and efferent motor signals for a closed-loop feedback system of neural control. Our lab has developed the Regenerative Peripheral Nerve Interface (RPNI) as a biologic nerve interface designed for stable integration of a prosthetic device with transected peripheral nerves in a residual limb. The RPNI is constructed by surgically implanting the distal end of a transected peripheral nerve into an autogenous muscle graft. Animal experiments in our lab have shown recording of motor signals from RPNI's implanted into both rodents and monkeys. Here, we achieve high amplitude EMG signals with a high signal to noise (SNR) ratio.

Nerve Entrapment in Ankle and Foot: Ultrasound Imaging.

PubMed

Chari, Basavaraj; McNally, Eugene

2018-07-01

Peripheral nerve entrapment of the ankle and foot is relatively uncommon and often underdiagnosed because electrophysiologic studies may not contribute to the diagnosis. Anatomy of the peripheral nerves is variable and complex, and along with a comprehensive physical examination, a thorough understanding of the applied anatomy is essential. Several studies have helped identify specific areas in which nerves are commonly compressed. Identified secondary causes of nerve compression include previous trauma, osteophytes, ganglion cysts, edema, accessory muscles, tenosynovitis, vascular lesions, and a primary nerve tumor. Imaging plays a key role in identifying primary and secondary causes of nerve entrapment, specifically ultrasound (US) and magnetic resonance imaging. US is a dynamic imaging modality that is cost effective and offers excellent resolution. Symptoms of nerve entrapment may mimic other common foot and ankle conditions such as plantar fasciitis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia.

PubMed

Daulatzai, Mak Adam

2015-01-01

The non-celiac gluten sensitivity (NCGS) is a chronic functional gastrointestinal disorder which is very common world wide. The human gut harbors microbiota which has a wide variety of microbial organisms; they are mainly symbiotic and important for well being. However, "dysbiosis" - i.e. an alteration in normal commensal gut microbiome with an increase in pathogenic microbes, impacts homeostasis/health. Dysbiosis in NCGS causes gut inflammation, diarrhea, constipation, visceral hypersensitivity, abdominal pain, dysfunctional metabolic state, and peripheral immune and neuro-immune communication. Thus, immune-mediated gut and extra-gut dysfunctions, due to gluten sensitivity with comorbid diarrhea, may last for decades. A significant proportion of NCGS patients may chronically consume alcohol, non-steroidal anti-inflammatory drugs, and fatty diet, as well as suffer from various comorbid disorders. The above pathophysiological substrate and dysbiosis are underpinned by dysfunctional bidirectional "Gut-Brain Axis" pathway. Pathogenic gut microbiota is known to upregulate gut- and systemic inflammation (due to lipopolysaccharide from pathogenic bacteria and synthesis of pro-inflammatory cytokines); they enhance energy harvest, cause obesity, insulin resistance, and dysfunctional vago-vagal gut-brain axis. Conceivably, the above cascade of pathology may promote various pathophysiological mechanisms, neuroinflammation, and cognitive dysfunction. Hence, dysbiosis, gut inflammation, and chronic dyshomeostasis are of great clinical relevance. It is argued here that we need to be aware of NCGS and its chronic pathophysiological impact. Therapeutic measures including probiotics, vagus nerve stimulation, antioxidants, alpha 7 nicotinic receptor agonists, and corticotropin-releasing factor receptor 1 antagonist may ameliorate neuroinflammation and oxidative stress in NCGS; they may therefore, prevent cognitive dysfunction and vulnerability to Alzheimer's disease.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

PubMed Central

Marshall, Andrew G.; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N.; Ponirakis, Georgios; Fineman, Mark S.; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jolivalt, Corinne G.; Boulton, Andrew J.M.; Efron, Nathan; Calcutt, Nigel A.

2017-01-01

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. PMID:28202580

Challenges for Nerve Repair Using Chitosan-Siloxane Hybrid Porous Scaffolds

PubMed Central

Shirosaki, Yuki; Hayakawa, Satoshi; Osaka, Akiyoshi; Lopes, Maria A.; Santos, José D.; Geuna, Stefano; Mauricio, Ana C.

2014-01-01

The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton's jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration. PMID:25054129

Peripheral nerve regeneration with conduits: use of vein tubes

PubMed Central

Sabongi, Rodrigo Guerra; Fernandes, Marcela; dos Santos, João Baptista Gomes

2015-01-01

Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit. PMID:26170802

Peripheral nerve regeneration with conduits: use of vein tubes.

PubMed

Sabongi, Rodrigo Guerra; Fernandes, Marcela; Dos Santos, João Baptista Gomes

2015-04-01

Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit.

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

PubMed

Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

2018-05-01

Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

Intelligence, Reaction Times, and Peripheral Nerve Conduction Velocity.

ERIC Educational Resources Information Center

Vernon, Philip A.; Mori, Monica

1992-01-01

In 2 studies with 85 and 88 undergraduates, respectively, peripheral nerve conduction velocity (NCV) was significantly correlated with IQ score and reaction times, and NCV and reaction time contributed significantly, in combination, to prediction of IQ. Results are interpreted in terms of a neural efficiency model of intelligence. (Author/SLD)

Peripheral neurostimulation for control of intractable occipital neuralgia.

PubMed

Weiner, R L; Reed, K L

1999-07-01

Objective. To present a novel approach for treatment of intractable occipital neuralgia using percutaneous peripheral nerve electrostimulation techniques. Methods. Thirteen patients underwent 17 implant procedures for medically refractory occipital neuralgia. A subcutaneous electrode placed transversely at the level of C1 across the base of the occipital nerve trunk produced paresthesias and pain relief covering the regions of occipital nerve pain Results. With follow-up ranging from 1-½ to 6 years, 12 patients continue to report good to excellent response with greater than 50% pain control and requiring little or no additional medications. The 13th patient (first in the series) was subsequently explanted following symptom resolution. Conclusions. In patients with medically intractable occipital neuralgia, peripheral nerve electrostimulation subcutaneously at the level of C1 appears to be a reasonable alternative to more invasive surgical procedures following failure of more conservative therapies.

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

PubMed

Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Transdermal optogenetic peripheral nerve stimulation

NASA Astrophysics Data System (ADS)

Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

2017-06-01

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

PubMed

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

NASA Astrophysics Data System (ADS)

Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

2016-08-01

Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use.

Iodine and freeze-drying enhanced high-resolution MicroCT imaging for reconstructing 3D intraneural topography of human peripheral nerve fascicles.

PubMed

Yan, Liwei; Guo, Yongze; Qi, Jian; Zhu, Qingtang; Gu, Liqiang; Zheng, Canbin; Lin, Tao; Lu, Yutong; Zeng, Zitao; Yu, Sha; Zhu, Shuang; Zhou, Xiang; Zhang, Xi; Du, Yunfei; Yao, Zhi; Lu, Yao; Liu, Xiaolin

2017-08-01

The precise annotation and accurate identification of the topography of fascicles to the end organs are prerequisites for studying human peripheral nerves. In this study, we present a feasible imaging method that acquires 3D high-resolution (HR) topography of peripheral nerve fascicles using an iodine and freeze-drying (IFD) micro-computed tomography (microCT) method to greatly increase the contrast of fascicle images. The enhanced microCT imaging method can facilitate the reconstruction of high-contrast HR fascicle images, fascicle segmentation and extraction, feature analysis, and the tracing of fascicle topography to end organs, which define fascicle functions. The complex intraneural aggregation and distribution of fascicles is typically assessed using histological techniques or MR imaging to acquire coarse axial three-dimensional (3D) maps. However, the disadvantages of histological techniques (static, axial manual registration, and data instability) and MR imaging (low-resolution) limit these applications in reconstructing the topography of nerve fascicles. Thus, enhanced microCT is a new technique for acquiring 3D intraneural topography of the human peripheral nerve fascicles both to improve our understanding of neurobiological principles and to guide accurate repair in the clinic. Additionally, 3D microstructure data can be used as a biofabrication model, which in turn can be used to fabricate scaffolds to repair long nerve gaps. Copyright © 2017 Elsevier B.V. All rights reserved.

Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

PubMed

Atkinson, M E; Shehab, S A

1986-12-01

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides.

PubMed

Stenberg, Lena; Stößel, Maria; Ronchi, Giulia; Geuna, Stefano; Yin, Yaobin; Mommert, Susanne; Mårtensson, Lisa; Metzen, Jennifer; Grothe, Claudia; Dahlin, Lars B; Haastert-Talini, Kirsten

2017-07-18

Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes. In short and long-term investigations, we comprehensively analyzed the performance of one-chambered hollow CNGs (hCNGs) and two-chambered CNGs (CFeCNGs) in which a chitosan film has been longitudinally introduced. Additionally, we investigated in vitro the immunomodulatory effect provided by the chitosan film. Both types of nerve guides, i.e. hCNGs and CFeCNGs, enabled moderate morphological and functional nerve regeneration after reconstruction that was delayed for 45 days. These positive findings were detectable in generally healthy as well as in diabetic Goto-Kakizaki rats (for the latter only in short-term studies). The regenerative outcome did not reach the degree as recently demonstrated after immediate reconstruction using hCNGs and CFeCNGs. CFeCNG-treatment, however, enabled tissue regrowth in all animals (hCNGs: only in 80% of animals). CFeCNGs did further support with an increased vascularization of the regenerated tissue and an enhanced regrowth of motor axons. One mechanism by which the CFeCNGs potentially support successful regeneration is an immunomodulatory effect induced by the chitosan film itself. Our in vitro results suggest that the pro-regenerative effect of chitosan is related to the differentiation of chitosan-adherent monocytes into pro-healing M2 macrophages. No considerable differences appear for the delayed nerve regeneration process related to healthy and diabetic conditions. Currently available chitosan nerve grafts do not support delayed nerve regeneration to the same extent as they do after immediate nerve reconstruction. The immunomodulatory characteristics of the biomaterial may, however, be crucial for their regeneration supportive effects.

BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury.

PubMed

Lopes, Cátia D F; Gonçalves, Nádia P; Gomes, Carla P; Saraiva, Maria J; Pêgo, Ana P

2017-03-01

Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

PubMed Central

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

2017-01-01

Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

Bioengineered nerve regeneration and muscle reinnervation

PubMed Central

Kingham, Paul J; Terenghi, Giorgio

2006-01-01

The peripheral nervous system has the intrinsic capacity to regenerate but the reinnervation of muscles is often suboptimal and results in limited recovery of function. Injuries to nerves that innervate complex organs such as the larynx are particularly difficult to treat. The many functions of the larynx have evolved through the intricate neural regulation of highly specialized laryngeal muscles. In this review, we examine the responses of nerves and muscles to injury, focusing on changes in the expression of neurotrophic factors, and highlight differences between the skeletal limb and laryngeal muscle systems. We also describe how artificial nerve conduits have become a useful tool for delivery of neurotrophic factors as therapeutic agents to promote peripheral nerve repair and might eventually be useful in the treatment of laryngeal nerve injury. PMID:17005023

[Scalp neuralgia and headache elicited by cranial superficial anatomical causes: supraorbital neuralgia, occipital neuralgia, and post-craniotomy headache].

PubMed

Shimizu, Satoru

2014-01-01

Most scalp neuralgias are supraorbital or occipital. Although they have been considered idiopathic, recent studies revealed that some were attributable to mechanical irritation with the peripheral nerve of the scalp by superficial anatomical cranial structures. Supraorbital neuralgia involves entrapment of the supraorbital nerve by the facial muscle, and occipital neuralgia involves entrapment of occipital nerves, mainly the greater occipital nerve, by the semispinalis capitis muscle. Contact between the occipital artery and the greater occipital nerve in the scalp may also be causative. Decompression surgery to address these neuralgias has been reported. As headache after craniotomy is the result of iatrogenic injury to the peripheral nerve of the scalp, post-craniotomy headache should be considered as a differential diagnosis.

Recognizing schwannomatosis and distinguishing it from neurofibromatosis type 1 or 2.

PubMed

Westhout, Franklin D; Mathews, Marlon; Paré, Laura S; Armstrong, William B; Tully, Patricia; Linskey, Mark E

2007-06-01

Schwannomatosis has become a newly recognized classification of neurofibromatosis. Although the genetic loci are on chromosome 22, it lacks the classic bilateral vestibular schwannomas as seen in NF-2. We present the surgical treatment of 4 patients with schwannomatosis, including a brother and sister. Case 1 presented with multiple progressively enlarging peripheral nerve sheath tumors. Case 4 presented with a trigeminal schwannoma and a vagal nerve schwannoma. Three of 4 patients had spinal intradural, extramedullary nerve sheath tumors. Surgery in all was multistaged and consisted of spinal laminectomies, site-specific explorations, and microsurgical tumor dissection and resection, with intraoperative neurophysiologic monitoring (including somatosensory-evoked and motor-evoked potentials, upper extremity electromyography and intraoperative nerve action potential monitoring, as appropriate). Intraoperatively the schwannomas had cystic and solid features and in all surgical cases the tumors arose from discrete fascicles of sensory nerve roots or sensory peripheral nerve branches. None of the patients experienced neurologic worsening as a result of their resections. Pathologic analysis of specimens from all cases demonstrated schwannoma. Not all patients with multiple schwannomas of cranial nerve, spinal nerve root, or peripheral nerve origin have NF-1 or NF-2. In schwannomatosis, these lesions are present in the absence of cutaneous stigmata, neurofibromas, vestibular schwannomas, or parenchymal brain tumors. Schwannomas in schwannomatosis can be large, cystic, and multiple. However, the predominant nerve involvement seems to be sensory and discrete fascicular in origin, facilitating microsurgical resection with minimal deficit.

Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease

PubMed Central

Lin, Chin-Hsien; Chao, Chi-Chao; Wu, Shao-Wei; Hsieh, Paul-Chen; Feng, Fang-Ping; Lin, Yea-Huey; Chen, Ya-Mei; Wu, Ruey-Meei; Hsieh, Sung-Tsang

2016-01-01

Abstract Sensory symptoms are frequent nonmotor complaints in patients with Parkinson's disease (PD). However, few investigations integrally explored the physiology and pathology of the thermonociceptive pathway in PD. We aim to investigate the involvement of the thermonociceptive pathway in PD. Twenty-eight PD patients (16 men, with a mean age and standard deviation of 65.6 ± 10.7 years) free of neuropathic symptoms and systemic disorders were recruited for the study and compared to 23 age- and gender-matched control subjects (12 men, with a mean age and standard deviation of 65.1 ± 9.9 years). We performed skin biopsy, contact heat-evoked potential (CHEP), and quantitative sensory tests (QST) to study the involvement of the thermonociceptive pathway in PD. The duration of PD was 7.1 ± 3.2 (range 2–17 years) years and the UPDRS part III score was 25.6 ± 9.7 (range 10–48) during the off period. Compared to control subjects, PD patients had reduced intra-epidermal nerve fiber (IENF) density (2.48 ± 1.65 vs 6.36 ± 3.19 fibers/mm, P < 0.001) and CHEP amplitude (18.02 ± 10.23 vs 33.28 ± 10.48 μV, P < 0.001). Twenty-three patients (82.1%) had abnormal IENF densities and 18 (64.3%) had abnormal CHEP. Nine patients (32.1%) had abnormal thermal thresholds in the feet. In total 27 patients (96.4%) had at least 1 abnormality in IENF, CHEP, or thermal thresholds of the foot, indicating dysfunctions in the small-fiber nerve system. In control subjects, CHEP amplitude linearly correlated with IENF density (P < 0.001). In contrast, this relationship disappeared in PD (P = 0.312) and CHEP amplitude was negatively correlated with motor severity of PD independent of age, gender, and anti-PD medication dose (P = 0.036), suggesting the influences of central components on thermonociceptive systems in addition to peripheral small-fiber nerves in PD. The present study suggested impairment of small-fiber sensory system at both peripheral and central levels is an intrinsic feature of PD, and skin biopsy, CHEP, and QST provided an integral approach for assessing such dysfunctions. PMID:26962835

Epithelioid Malignant Peripheral Nerve Sheath Tumor Arising in a Schwannoma, in a Patient with “Neuroblastoma-like” Schwannomatosis and a Novel Germline SMARCB1 mutation

PubMed Central

Carter, Jodi M.; O'Hara, Carolyn; Dundas, George; Gilchrist, Dawna; Collins, Mark S.; Eaton, Katherine; Judkins, Alexander R.; Biegel, Jaclyn A.; Folpe, Andrew L.

2011-01-01

Epithelioid malignant peripheral nerve sheath tumors arising in pre-existing schwannomas are extremely rare. We report an unusual example occurring in a patient with multiple schwannomas (schwannomatosis), all but one of which showed “neuroblastoma-like” histology. By immunohistochemistry, both the epithelioid malignant peripheral nerve sheath tumor and the schwannomas showed a complete loss of the Smarcb1 protein. Subsequent genetic evaluation revealed the presence of a novel germline mutation in the SMARCB1/INI1 gene in the patient and three of her children, two of whom were diagnosed with atypical teratoid/rhabdoid tumors of the brain. PMID:22082606

Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2016-04-01

Page 1 AWARD NUMBER: W81XWH-14-1-0073 TITLE: Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral...COVERED 04/01/2015 to 03/31/2016 4. TITLE AND SUBTITLE Prevention and Treatment of Neurofibromatosis Type 1- 5a. CONTRACT NUMBER W81XWH-14-1-0073...ABSTRACT The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is malignant peripheral nerve sheath tumor (MPNST). MPNSTs are

Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

PubMed Central

Rodriguez, Fausto J.; Stratakis, Constantine A.; Evans, D Gareth

2013-01-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

PubMed

Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

2012-03-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

The effects of hemostatic agents on peripheral nerve function: an experimental study.

PubMed

Alkan, Alper; Inal, Samet; Yildirim, Mehmet; Baş, Burcu; Ağar, Erdal

2007-04-01

In the practice of oral and maxillofacial surgery, hemostatic agents are sometimes placed in close proximity to peripheral nerves. In the present study, we evaluated immediate and delayed effects of 4 hemostatic agents (oxidized regenerated cellulose, 5% colloid silver-added gelatine sponge, bovine collagen, bone wax) on peripheral nerve function. A total of 25 rat sciatic nerves were prepared, and the amplitudes were recorded with a physiological data acquisition system. Animals were randomly assigned to 5 groups: control, oxidized regenerated cellulose, gelatine sponge, bone wax, and bovine collagen. The first hour records are defined as immediate effects of these hemostatic agents on nerve function. The animals were then allowed to recover for 4 weeks. At the end of this period, the same surgical and recording procedures were performed. These final records are defined as delayed effects of hemostatic agents on nerve function. According to nerve conduction velocity (NCV) and compound action potential (CAP) values of the experimental groups, early and delayed effects of each hemostatic agent were statistically compared with Bonferroni corrected test (P < .05). Statistically, NCV was significantly reduced, and the CAP was significantly increased 1 hour after surgery (P < .05) in the group of oxidized regenerated cellulose. However, there were no significant differences after 4 weeks compared with the first records. In the gelatine sponge group, CAP was significantly increased 4 weeks after the application. In the bovine collagen and bone wax groups, NCV and CAP values (1 hour and 4 weeks after the application) were not statistically significant compared with initial control records. The present study shows that bovine collagen is the most suitable hemostatic agent applicable for peripheral nerves.

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats.

PubMed

Li, Rui; Li, Yiyang; Wu, Yanqing; Zhao, Yingzheng; Chen, Huanwen; Yuan, Yuan; Xu, Ke; Zhang, Hongyu; Lu, Yingfeng; Wang, Jian; Li, Xiaokun; Jia, Xiaofeng; Xiao, Jian

2018-06-01

Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p < 0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of peripheral microcirculation improvement of foot after tarsal tunnel release in diabetic patients by transcutaneous oximetry.

PubMed

Trignano, Emilio; Fallico, Nefer; Chen, Hung-Chi; Faenza, Mario; Bolognini, Alfonso; Armenti, Andrea; Santanelli Di Pompeo, Fabio; Rubino, Corrado; Campus, Gian Vittorio

2016-01-01

According to recent studies, peripheral nerve decompression in diabetic patients seems to not only improve nerve function, but also to increase microcirculation; thus decreasing the incidence of diabetic foot wounds and amputations. However, while the postoperative improvement of nerve function is demonstrated, the changes in peripheral microcirculation have not been demonstrated yet. The aim of this study is to assess the degree of microcirculation improvement of foot after the tarsal tunnel release in the diabetic patients by using transcutaneous oximetry. Twenty diabetic male patients aged between 43 and 72 years old (mean age 61.2 years old) suffering from diabetic peripheral neuropathy with superimposed nerve compression underwent transcutaneous oximetry (PtcO2) before and after tarsal tunnel release by placing an electrode on the skin at the level of the dorsum of the foot. Eight lower extremities presented diabetic foot wound preoperatively. Thirty-six lower extremities underwent surgical release of the tibialis posterior nerve only, whereas four lower extremities underwent the combined release of common peroneal nerve, anterior tibialis nerve, and posterior tibialis nerve. Preoperative values of transcutaneous oximetry were below the critical threshold, that is, lower than 40 mmHg (29.1 ± 5.4 mmHg). PtcO2 values at one month after surgery (45.8 ± 6.4 mmHg) were significantly higher than the preoperative ones (P = 0.01). The results of postoperative increase in PtcO2 values demonstrate that the release of the tarsal tunnel determines a relevant increase in microcirculation in the feet of diabetic patients. © 2015 Wiley Periodicals, Inc.

Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

PubMed

St John Smith, Ewan; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-08-15

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Specific Paucity of Unmyelinated C-Fibers in Cutaneous Peripheral Nerves of the African Naked-Mole Rat: Comparative Analysis Using Six Species of Bathyergidae

PubMed Central

Smith, Ewan S; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-01-01

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. J. Comp. Neurol. 520:2785–2803, 2012. © 2012 Wiley Periodicals, Inc. PMID:22528859

Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance.

PubMed

Schmid, C D; Stienekemeier, M; Oehen, S; Bootz, F; Zielasek, J; Gold, R; Toyka, K V; Schachner, M; Martini, R

2000-01-15

The adhesive cell surface molecule P(0) is the most abundant glycoprotein in peripheral nerve myelin and fulfills pivotal functions during myelin formation and maintenance. Mutations in the corresponding gene cause hereditary demyelinating neuropathies. In mice heterozygously deficient in P(0) (P(0)(+/-) mice), an established animal model for a subtype of hereditary neuropathies, T-lymphocytes are present in the demyelinating nerves. To monitor the possible involvement of the immune system in myelin pathology, we cross-bred P(0)(+/-) mice with null mutants for the recombination activating gene 1 (RAG-1) or with mice deficient in the T-cell receptor alpha-subunit. We found that in P(0)(+/-) mice myelin degeneration and impairment of nerve conduction properties is less severe when the immune system is deficient. Moreover, isolated T-lymphocytes from P(0)(+/-) mice show enhanced reactivity to myelin components of the peripheral nerve, such as P(0), P(2), and myelin basic protein. We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy.

The effect of interleukin-2 on canine peripheral nerve sheath tumours after marginal surgical excision: a double-blind randomized study

PubMed Central

2013-01-01

Background The objective of this study was to evaluate the effect on outcomes of intraoperative recombinant human interleukin-2 injection after surgical resection of peripheral nerve sheath tumours. In this double-blind trial, 40 patients due to undergo surgical excision (<5 mm margins) of presumed peripheral nerve sheath tumours were randomized to receive intraoperative injection of interleukin-2 or placebo into the wound bed. Results There were no significant differences in any variable investigated or in median survival between the two groups. The median recurrence free interval was 874 days (range 48–2141 days), The recurrence-free interval and overall survival time were significantly longer in dogs that undergone the primary surgery by a specialist-certified surgeon compared to a referring veterinarian regardless of whether additional adjunct therapy was given. Conclusion Overall, marginal excision of peripheral nerve sheath tumours in dogs resulted in a long survival time, but adjuvant treatment with recombinant human interleukin-2 (rhIL-2) did not provide a survival advantage. PMID:23927575

[Neuroimmunological diseases associated with VGKC complex antibodies].

PubMed

Watanabe, Osamu

2013-05-01

Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability.

High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study.

PubMed

Walter-Höliner, Isabella; Barbarini, Daniela Seick; Lütschg, Jürg; Blassnig-Ezeh, Anya; Zanier, Ulrike; Saely, Christoph H; Simma, Burkhard

2018-03-01

In this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. A total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. At baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). The prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly. Copyright © 2017 Elsevier Inc. All rights reserved.

Biocompatible Electroactive Tetra(aniline)-Conjugated Peptide Nanofibers for Neural Differentiation.

PubMed

Arioz, Idil; Erol, Ozlem; Bakan, Gokhan; Dikecoglu, F Begum; Topal, Ahmet E; Urel, Mustafa; Dana, Aykutlu; Tekinay, Ayse B; Guler, Mustafa O

2018-01-10

Peripheral nerve injuries cause devastating problems for the quality of patients' lives, and regeneration following damage to the peripheral nervous system is limited depending on the degree of the damage. Use of nanobiomaterials can provide therapeutic approaches for the treatment of peripheral nerve injuries. Electroactive biomaterials, in particular, can provide a promising cure for the regeneration of nerve defects. Here, a supramolecular electroactive nanosystem with tetra(aniline) (TA)-containing peptide nanofibers was developed and utilized for nerve regeneration. Self-assembled TA-conjugated peptide nanofibers demonstrated electroactive behavior. The electroactive self-assembled peptide nanofibers formed a well-defined three-dimensional nanofiber network mimicking the extracellular matrix of the neuronal cells. Neurite outgrowth was improved on the electroactive TA nanofiber gels. The neural differentiation of PC-12 cells was more advanced on electroactive peptide nanofiber gels, and these biomaterials are promising for further use in therapeutic neural regeneration applications.

Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

NASA Technical Reports Server (NTRS)

Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

1998-01-01

Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

PubMed

Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

Novel mutation in the replication focus targeting sequence domain of DNMT1 causes hereditary sensory and autonomic neuropathy IE.

PubMed

Yuan, Junhui; Higuchi, Yujiro; Nagado, Tatsui; Nozuma, Satoshi; Nakamura, Tomonori; Matsuura, Eiji; Hashiguchi, Akihiro; Sakiyama, Yusuke; Yoshimura, Akiko; Takashima, Hiroshi

2013-03-01

DNMT1, encoding DNA methyltransferase 1 (Dnmt1), is a critical enzyme which is mainly responsible for conversion of unmethylated DNA into hemimethylated DNA. To date, two phenotypes produced by DNMT1 mutations have been reported, including hereditary sensory and autonomic neuropathy (HSAN) type IE with mutations in exon 20, and autosomal dominant cerebellar ataxia, deafness, and narcolepsy caused by mutations in exon 21. We report a sporadic case in a Japanese patient with loss of pain and vibration sense, chronic osteomyelitis, autonomic system dysfunctions, hearing loss, and mild dementia, but without definite cerebellar ataxia. Electrophysiological studies revealed absent sensory nerve action potential with nearly normal motor nerve conduction studies. Brain magnetic resonance imaging revealed mild diffuse cerebral and cerebellar atrophy. Using a next-generation sequencing system, 16 candidate genes were analyzed and a novel missense mutation, c.1706A>G (p.His569Arg), was identified in exon 21 of DNMT1. Our findings suggest that mutation in exon 21 of DNMT1 may also produce a HSAN phenotype. Because all reported mutations of DNMT1 are concentrated in exons 20 and 21, which encode the replication focus targeting sequence (RFTS) domain of Dnmt1, the RFTS domain could be a mutation hot spot. © 2013 Peripheral Nerve Society.

Temporal prolongation of decreased skin blood flow causes cold limbs in Parkinson's disease.

PubMed

Shindo, Kazumasa; Kobayashi, Fumikazu; Miwa, Michiaki; Nagasaka, Takamura; Takiyama, Yoshihisa; Shiozawa, Zenji

2013-03-01

To unravel the pathogenesis of cold limbs in Parkinson's disease, we evaluated cutaneous vasomotor neural function in 25 Parkinson's disease patients with or without cold limbs and 20 healthy controls. We measured resting skin sympathetic nerve activity, as well as reflex changes of skin blood flow and skin sympathetic nerve activity after electrical stimulation, with the parameters including skin sympathetic nerve activity frequency at rest, the amplitude of reflex bursts, the absolute decrease and percent reduction of blood flow, and the recovery time which was calculated as the interval from the start of blood flow reduction until the return to baseline cutaneous blood flow. The resting frequency of skin sympathetic nerve activity was significantly lower in patients with Parkinson's disease than in controls (p < 0.01). There were no significant differences between the patients and controls with respect to the amplitude of skin sympathetic nerve activity and the absolute decrease or percent reduction of blood flow volume. In the controls, the recovery time (9.4 ± 1.2), which was similar to Parkinson's disease patients without cold limbs (9.0 ± 0.7), while the recovery time ranged (15.7 ± 3.2) in Parkinson's disease patients with cold limbs. Recovery was significantly slower in these patients compared with the other groups (p < 0.05). It is possible that cold limbs might arise due to impaired circulation based on prolonged vasoconstriction by peripheral autonomic impairments, in addition to central autonomic dysfunction in Parkinson's disease.

Transformation of synaptic vesicle phenotype in the intramedullary axonal arbors of cat spinal motoneurons following peripheral nerve injury.

PubMed

Havton, L A; Kellerth, J O

2001-08-01

Permanent transection of a peripheral motor nerve induces a gradual elimination of whole axon collateral systems in the axotomized spinal motoneurons. There is also an initial concurrent decrease in the amount of recurrent inhibition exerted by these arbors in the spinal cord for up to 6 weeks after the injury, whereas the same reflex action returns to normal by the 12-week postoperative state. The aim of the present investigation was to study the fine structure of the intramedullary axonal arbors of axotomized alpha-motoneurons in the adult cat spinal cord following a permanent peripheral motor nerve lesion. For this purpose, single axotomized alpha-motoneurons were labeled intracellularly with horseradish peroxidase at 12 weeks after permanent transection of their peripheral motor nerve. The intramedullary portions of their motor axon and axon collateral arbors were first reconstructed at the light microscopic level and subsequently studied ultrastructurally. This study shows that the synaptic contacts made by the intramedullary axon collateral arbors of axotomized motoneurons have undergone a change in synaptic vesicle ultrastructure from spherical and clear vesicles to spherical and dense-cored vesicles at 12 weeks after the transection of their peripheral axons. We suggest that the present transformation in synaptic vesicle fine structure may also correspond to a change in the contents of these boutons. This may, in turn, be responsible for the strengthening and recovery of the recurrent inhibitory reflex action exerted by the axotomized spinal motoneurons following a prolonged permanent motor nerve injury.

A forgotten facial nerve tumour: granular cell tumour of the parotid and its implications for treatment.

PubMed

Lerut, B; Vosbeck, J; Linder, T E

2011-04-01

We present a rare case of a facial nerve granular cell tumour in the right parotid gland, in a 10-year-old boy. A parotid or neurogenic tumour was suspected, based on magnetic resonance imaging. Intra-operatively, strong adhesions to surrounding structures were found, and a midfacial nerve branch had to be sacrificed for complete tumour removal. Recent reports verify that granular cell tumours arise from Schwann cells of peripheral nerve branches. The rarity of this tumour within the parotid gland, its origin from peripheral nerves, its sometimes misleading imaging characteristics, and its rare presentation with facial weakness and pain all have considerable implications on the surgical strategy and pre-operative counselling. Fine needle aspiration cytology may confirm the neurogenic origin of this lesion. When resecting the tumour, the surgeon must anticipate strong adherence to the facial nerve and be prepared to graft, or sacrifice, certain branches of this nerve.

A pediatric case with peripheral facial nerve palsy caused by a granulomatous lesion associated with cat scratch disease.

PubMed

Nakamura, Chizuko; Inaba, Yuji; Tsukahara, Keiko; Mochizuki, Mie; Sawanobori, Emi; Nakazawa, Yozo; Aoyama, Kouki

2018-02-01

Cat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown. A previously healthy 7-year-old boy presented with fever, cervical lymphadenopathy, and peripheral facial nerve palsy associated with serologically confirmed cat scratch disease. The stapedius muscle reflex was absent on the left side and brain magnetic resonance imaging revealed a mass lesion at the left internal auditory meatus. The patient's symptoms and imaging findings were gradually resolved after the antibiotics and corticosteroids treatment. The suspected granulomatous lesion was considered to have resulted from the host's immune reaction to Bartonella infection and impaired the facial nerve. This is the first case report providing direct evidence of peripheral facial nerve palsy caused by a suspected granulomatous lesion associated with cat scratch disease and its treatment course. Copyright © 2017. Published by Elsevier B.V.

Electrically stimulated signals from a long-term Regenerative Peripheral Nerve Interface.

PubMed

Langhals, Nicholas B; Woo, Shoshana L; Moon, Jana D; Larson, John V; Leach, Michelle K; Cederna, Paul S; Urbanchek, Melanie G

2014-01-01

Despite modern technological advances, the most widely available prostheses provide little functional recovery beyond basic grasping. Although sophisticated upper extremity prostheses are available, optimal prosthetic interfaces which give patients high-fidelity control of these artificial limbs are limited. We have developed a novel Regenerative Peripheral Nerve Interface (RPNI), which consists of a unit of free muscle that has been neurotized by a transected peripheral nerve. In conjunction with a biocompatible electrode on the muscle surface, the RPNI facilitates signal transduction from a residual peripheral nerve to a neuroprosthetic limb. The purpose of this study was to explore signal quality and reliability in an RPNI following an extended period of implantation. Following a 14-month maturation period, electromyographic signal generation was evaluated via electrical stimulation of the innervating nerve. The long-term RPNI was viable and healthy, as demonstrated by evoked compound muscle action potentials as well as histological tissue analysis. Signals exceeding 4 mV were successfully acquired and amplitudes were consistent across multiple repetitions of applied stimuli. There were no evident signs of muscle denervation, significant scar tissue, or muscle necrosis. This study provides further evidence that after a maturation period exceeding 1 year, reliable and consistent signals can still be acquired from an RPNI.

Social impact of peripheral nerve injuries.

PubMed

Wojtkiewicz, Danielle M; Saunders, James; Domeshek, Leahthan; Novak, Christine B; Kaskutas, Vicki; Mackinnon, Susan E

2015-06-01

Disorders involving the peripheral nervous system can have devastating impacts on patients' daily functions and routines. There is a lack of consideration of the impact of injury on social/emotional well-being and function. We performed a retrospective database and chart review of adult patients presenting between 2010 and 2012 with peripheral nerve compression, brachial plexus injury, thoracic outlet syndrome (TOS), or neuromas. At the initial assessment, patients completed a questionnaire used to obtain demographic and psychosocial variable data including the (1) average level of pain over the last month, (2) self-perceived depression, (3) how much pain impacts quality of life (QoL), (4) current level of stress, and (5) ability to cope with stress. Statistical analyses were used to assess the differences between the dependent variables and diagnostic and demographic groups. This study included 490 patients (mean age 50 ± 15 years); the most common diagnosis was single nerve compression (n = 171). Impact on QoL was significantly greater in patients with TOS, cutaneous peroneal compressions, and neuroma versus single site nerve compressions. Average pain, impact on QoL, and stress at home were significantly higher in females versus males. Impact on QoL was correlated with average pain, depression, stress at home, and ability to cope with stress at home. Our study demonstrates that patients with single site nerve compression neuropathies experience fewer negative psychosocial effects compared to patients with more proximal upper extremity peripheral nerve disorders and neuromas. The impact on QoL was strongly correlated with pain and depression, where patients with neuromas and painful peroneal nerve entrapments reported greater detriments to QoL.

Sensorimotor Peripheral Nerve Function and the Longitudinal Relationship with Endurance Walking in the Health, Aging and Body Composition Study

PubMed Central

Lange-Maia, Brittney S.; Newman, Anne B.; Cauley, Jane A.; Boudreau, Robert M.; Jakicic, John M.; Caserotti, Paolo; Glynn, Nancy W.; Harris, Tamara B.; Kritchevsky, Stephen B.; Schwartz, Ann V.; Satterfield, Suzanne; Simonsick, Eleanor M.; Vinik, Aaron I.; Zivkovic, Sasa; Strotmeyer, Elsa S.

2015-01-01

Objectives To determine whether lower extremity sensorimotor peripheral nerve deficits are associated with reduced walking endurance in older adults. Design Prospective cohort study with six years of follow-up. Setting Two U.S. clinical sites in (Pittsburgh, PA and Memphis, TN). Participants Community-dwelling older adults enrolled in Health, Aging and Body Composition study from the 2000/01 annual clinical examination (n=2393; age 76.5 ± 2.9 years; 48.2% male; 38.2% black) and subset with longitudinal data (n=1,178). Interventions Not applicable Main Outcome Measures Participants underwent peripheral nerve function examination in 2000/01, including peroneal motor nerve conduction amplitude and velocity, vibration perception threshold, and monofilament testing. Symptoms of lower-extremity peripheral neuropathy included numbness or tingling and sudden stabbing, burning, pain, or aches in the feet or legs. The long distance corridor walk (LDCW; 400m) was administered in 2000/01 and every two years afterwards for 6 years to assess endurance walking performance over time. Results In separate fully adjusted linear mixed models poor vibration threshold (>130 microns), 10-g and 1.4-g monofilament insensitivity were each associated with slower LDCW completion time (16.0, 14.1, and 6.7, seconds slower, respectively, P<.05 for each). Poor motor amplitude (<1mV), poor vibration perception threshold, and 10-g monofilament insensitivity were related to greater slowing/year (4.7, 4.3, and 4.3 additional seconds/year, respectively, P<.05), though poor motor amplitude was not associated with initial completion time. Conclusions Poorer sensorimotor peripheral nerve function is related to slower endurance walking and greater slowing longitudinally. Interventions to reduce the burden of sensorimotor peripheral nerve function impairments should be considered in order to help older adults to maintain walking endurance—a critical component for remaining independent in the community. PMID:26343170

Peripheral changes in endometriosis-associated pain

PubMed Central

Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

2014-01-01

BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between elevated neurotrophin levels and pain severity seems to exist, suggesting the involvement of other mediators in the modulation of pain. CONCLUSIONS The increased expression of neuotrophic factors and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum imply a role of such peripheral changes in the pathogenesis of endometriosis-associated pain. However, a clear link between these findings and pain in patients with endometriosis has so far not been demonstrated. PMID:24859987

Posterior tibial nerve stimulation vs parasacral transcutaneous neuromodulation for overactive bladder in children.

PubMed

Barroso, Ubirajara; Viterbo, Walter; Bittencourt, Joana; Farias, Tiago; Lordêlo, Patrícia

2013-08-01

Parasacral transcutaneous electrical nerve stimulation and posterior tibial nerve stimulation have emerged as effective methods to treat overactive bladder in children. However, to our knowledge no study has compared the 2 methods. We evaluated the results of parasacral transcutaneous electrical nerve stimulation and posterior tibial nerve stimulation in children with overactive bladder. We prospectively studied children with overactive bladder without dysfunctional voiding. Success of treatment was evaluated by visual analogue scale and dysfunctional voiding symptom score, and by level of improvement of each specific symptom. Parasacral transcutaneous electrical nerve stimulation was performed 3 times weekly and posterior tibial nerve stimulation was performed once weekly. A total of 22 consecutive patients were treated with posterior tibial nerve stimulation and 37 with parasacral transcutaneous electrical nerve stimulation. There was no difference between the 2 groups regarding demographic characteristics or types of symptoms. Concerning the evaluation by visual analogue scale, complete resolution of symptoms was seen in 70% of the group undergoing parasacral transcutaneous electrical nerve stimulation and in 9% of the group undergoing posterior tibial nerve stimulation (p = 0.02). When the groups were compared, there was no statistically significant difference (p = 0.55). The frequency of persistence of urgency and diurnal urinary incontinence was nearly double in the group undergoing posterior tibial nerve stimulation. However, this difference was not statistically significant. We found that parasacral transcutaneous electrical nerve stimulation is more effective in resolving overactive bladder symptoms, which matches parental perception. However, there were no statistically significant differences in the evaluation by dysfunctional voiding symptom score, or in complete resolution of urgency or diurnal incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

PubMed

Li, Guicai; Xiao, Qinzhi; Zhang, Luzhong; Zhao, Yahong; Yang, Yumin

2017-09-01

Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

PubMed

Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

2017-06-01

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

Motor neuron activation in peripheral nerves using infrared neural stimulation

NASA Astrophysics Data System (ADS)

Peterson, E. J.; Tyler, D. J.

2014-02-01

Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.

Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival.

PubMed

Renault, Marie-Ange; Chapouly, Candice; Yao, Qinyu; Larrieu-Lahargue, Frédéric; Vandierdonck, Soizic; Reynaud, Annabel; Petit, Myriam; Jaspard-Vinassa, Béatrice; Belloc, Isabelle; Traiffort, Elisabeth; Ruat, Martial; Duplàa, Cécile; Couffinhal, Thierry; Desgranges, Claude; Gadeau, Alain-Pierre

2013-03-01

Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves. The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia. We induced hindlimb ischemia in wild-type and Dhh(-/-) mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh(-/-). By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle. This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.

Sequential involvement of the nervous system in subacute combined degeneration.

PubMed

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han; Sunwoo, Il-Nam

2012-03-01

Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Motor Neuron Activation in Peripheral Nerves Using Infrared Neural Stimulation

PubMed Central

Peterson, EJ; Tyler, DJ

2014-01-01

Objective Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach The rabbit sciatic nerve was stimulated extraneurally with 1875 nm-wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results 81% of nerves tested were sensitive to INS, with 1.7± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2–9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance The observed selectivity of INS indicates it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS. PMID:24310923

[Evaluating the risk of sciatic nerve damage in the rabbit by administration of low and intermediate energy extracorporeal shock waves].

PubMed

Rompe, J D; Bohl, J; Riehle, H M; Schwitalle, M; Krischek, O

1998-01-01

The aim of the study was to evaluate the likeliness for peripheral nerve lesions following extracorporeal shock wave application. 82 rabbit sciatic nerves were randomized to undergo low-energetic (0.08 mJ/mm2), middle-energetic (0.28 mJ/mm2) or no (controls) shock wave therapy. After 1 to 28 days an independent neuropathologist checked the specimen for signs of neural lesions. Only after 14 and 28 days vacuolic swelling of the axons was noted, somewhat pronounced in the middle-energetic group. In no case was there any disruption of the nerve's continuity. We did not observe any neurapraxia. Shock wave application does not threaten peripheral nerve integrity in an animal model.

Sciatic nerve regeneration in rats subjected to ketogenic diet.

PubMed

Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

2016-01-01

Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

[Peripheral Regional Anesthesia Without Any Complications - a Dream Comes True?!

PubMed

Wiesmann, Thomas; Döffert, Jens; Steinfeldt, Thorsten

2018-04-01

Peripheral regional anesthesia procedures, such as femoral nerve block, are relatively safe procedures in clinical anesthesia. Nevertheless, it may lead to typical, usually transient and rarely even persistent complications. This article aims to highlight key aspects of complications in peripheral regional anesthesia and, in particular, strategies to reduce risk. Moreover, beside general complications, which might potentially occur in any peripheral nerve blockade ("bleeding/infection/nerve damage"), accidental co-blockades of other nerval structures are discussed using the example of the brachial plexus. In addition to the presentation of the possible complications, this article discusses improvements in the techniques during the last two decades. Due to the use of ultrasound, some side effects nowadays are supposed to occur less likely. An outlook into the future will inform the reader about improved or more selective blockages. Georg Thieme Verlag KG Stuttgart · New York.

Focus on autonomic dysfunction in familial amyloidotic polyneuropathy (FAP).

PubMed

Obayashi, Konen; Ando, Yukio

2012-06-01

It is well known that autonomic dysfunction in familial amyloidotic polyneuropathy (FAP) is the most serious problem, because it restricts the daily life of these patients. The detail mechanisms of the onset are not well understood in FAP and domino liver transplantation-induced amyloid neuropathy. As autonomic disturbances play an important role in the symptomatology of FAP, further studies of autonomic dysfunction in these patients may lead the pathogenesis of FAP. Autonomic dysfunction is often observed before sensory and motor nerve dysfunction in FAP. This can be attributed to the morphological characteristics of the nerves. Unmyelinated, small myelinated, and large myelinated fibers tend to become impaired in that order. Although the reasons of susceptibility to amyloid infiltration and injury are not known, studies of autopsied FAP patients have revealed heavy infiltration of amyloid in autonomic ganglions. Moreover, spinal ganglion and posterior loot of the spine had severe amyloid deposits than did the anterior root of the spine or the motor nerves. It is well known that autonomic dysfunction is the most serious problem, because it restricts the daily life of FAP patients. However, we have four major questions about autonomic dysfunction in clinical. In this manuscript, we discuss about the answers of these questions.

Bidirectional peripheral nerve interface and applications.

PubMed

Thakor, Nitish V; Qihong Wang; Greenwald, Elliot

2016-08-01

Peripheral nerves, due to their small size and complex innervation to organs and complex physiology, pose particularly significant challenges towards interfacing electrodes and electronics to enable neuromodulation. Here, we present a review of the technology for building such interface, including recording and stimulating electrodes and low power electronics, as well as powering. Of particular advantage to building a miniature implanted device is a "bidirectional" system that both senses from the nerves or surrogate organs and stimulates the nerves to affect the organ function. This review and presentation will cover a range of electrodes, electronics, wireless power and data schemes and system integration, and will end with some examples and applications.

Comparative Evaluation of Chitosan Nerve Guides with Regular or Increased Bendability for Acute and Delayed Peripheral Nerve Repair: A Comprehensive Comparison with Autologous Nerve Grafts and Muscle-in-Vein Grafts.

PubMed

Stößel, Maria; Wildhagen, Vivien M; Helmecke, Olaf; Metzen, Jennifer; Pfund, Charlotte B; Freier, Thomas; Haastert-Talini, Kirsten

2018-05-08

Reconstruction of joint-crossing digital nerves requires the application of nerve guides with a much higher flexibility than used for peripheral nerve repair along larger bones. Nevertheless, collapse-resistance should be preserved to avoid secondary damage to the regrowing nerve tissue. In recent years, we presented chitosan nerve guides (CNGs) to be highly supportive for the regeneration of critical gap length peripheral nerve defects in the rat. Now, we evidently increased the bendability of regular CNGs (regCNGs) by developing a wavy wall structure, that is, corrugated CNGs (corrCNGs). In a comprehensive in vivo study, we compared both types of CNGs with clinical gold standard autologous nerve grafts (ANGs) and muscle-in-vein grafts (MVGs) that have recently been highlighted in the literature as a suitable alternative to ANGs. We reconstructed rat sciatic nerves over a critical gap length of 15 mm either immediately upon transection or after a delay period of 45 days. Electrodiagnostic measurements were applied to monitor functional motor recovery at 60, 90, 120, and 150 (only delayed repair) days postreconstruction. Upon explanation, tube properties were analyzed. Furthermore, distal nerve ends were evaluated using histomorphometry, while connective tissue specimens were subjected to immunohistological stainings. After 120 days (acute repair) or 150 days (delayed repair), respectively, compression-stability of regCNGs was slightly increased while it remained stable in corrCNGs. In both substudies, regCNGs and corrCNGs supported functional recovery of distal plantar muscles in a similar way and to a greater extent when compared with MVGs, while ANGs demonstrated the best support of regeneration. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits.

PubMed

Wang, Chunyang; Jia, Yachao; Yang, Weichao; Zhang, Cheng; Zhang, Kuihua; Chai, Yimin

2018-07-01

Silk fibroin (SF)-based nerve conduits have been widely used to bridge peripheral nerve defects. Our previous study showed that nerve regeneration in a SF-blended poly (l-lactide-co-ɛ-caprolactone) [P(LLA-CL)] nerve conduit is better than that in a P(LLA-CL) conduit. However, the involved mechanisms remain unclarified. Because angiogenesis within a nerve conduit plays an important role in nerve regeneration, vascularization of SF/P(LLA-CL) and P(LLA-CL) conduits was compared both in vitro and in vivo. In the present study, we observed that SF/P(LLA-CL) nanofibers significantly promoted fibroblast proliferation, and vascular endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA-CL) nanofibers was more than seven-fold higher than that in P(LLA-CL) nanofibers. Conditioned medium of fibroblasts in the SF/P(LLA-CL) group stimulated more human umbilical vein endothelial cells (HUVEC) to form capillary-like networks and promoted faster HUVEC migration. The two kinds of nerve conduits were used to bridge 10-mm-length nerve defects in rats. At 3 weeks of reparation, the blood vessel area in the SF/P(LLA-CL) group was significantly larger than that in the P(LLA-CL) group. More regenerated axons and Schwann cells were also observed in the SF/P(LLA-CL) group, which was consistent with the results of blood vessels. Collectively, our data revealed that the SF/P(LLA-CL) nerve conduit enhances peripheral nerve regeneration by improving angiogenesis within the conduit. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070-2077, 2018. © 2018 Wiley Periodicals, Inc.

Tissue resident macrophages are sufficient for demyelination during peripheral nerve myelin induced experimental autoimmune neuritis?

PubMed

Taylor, Jude Matthew

2017-12-15

The contribution of resident endoneurial tissue macrophages versus recruited monocyte derived macrophages to demyelination and disease during Experimental Autoimmune Neuritis (EAN) was investigated using passive transfer of peripheral nerve myelin (PNM) specific serum antibodies or adoptive co-transfer of PNM specific T and B cells from EAN donors to leukopenic and normal hosts. Passive transfer of PNM specific serum antibodies or adoptive co-transfer of myelin specific T and B cells into leukopenic recipients resulted in a moderate reduction in nerve conduction block or in the disease severity compared to the normal recipients. This was despite at least a 95% decrease in the number of circulating mononuclear cells during the development of nerve conduction block and disease and a 50% reduction in the number of infiltrating endoneurial macrophages in the nerve lesions of the leukopenic recipients. These observations suggest that during EAN in Lewis rats actively induced by immunization with peripheral nerve myelin, phagocytic macrophages originating from the resident endoneurial population may be sufficient to engage in demyelination initiated by anti-myelin antibodies in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of the effects of peripheral nerves injury on the muscle control - A review

NASA Astrophysics Data System (ADS)

Cabaj, Anna; Zmyslowski, Wojciech

2011-01-01

Impairment of motor function following peripheral nerve injury is a serious clinical problem. Generally nerve injury leads to erroneous control of muscle activity that results in gait and voluntary movement abnormalities followed by muscle atrophy. This article presents a review of studies on the effects of peripheral nerve injury on the motor system performed on animal models. We focused our attention on the results that are fundamental for better understanding of the degenerative and regenerative processes induced by nerve injury as well as of the mechanisms of structural changes in neuronal networks controlling movement. Quoted results are also important for clinical applications because they allow to develop new diagnostic and therapeutic techniques that can be used after nerve injury inducing motor deficits. However, till now no efficient therapy inducing satisfactory recovery was found. There is still a need to continue an advanced basic research directed to develop effective therapies. Thus the aim of this review is to compare the results of recent studies performed on various animal models in order to propose new methods for identification of mechanisms responsible for muscle deficits and propose targets for new pharmacological therapies.

Effect of Limb Lengthening on Internodal Length and Conduction Velocity of Peripheral Nerve

PubMed Central

Gillingwater, Thomas H.; Anderson, Heather; Cottrell, David; Sherman, Diane L.; Ribchester, Richard R.; Brophy, Peter J.

2013-01-01

The influences of axon diameter, myelin thickness, and internodal length on the velocity of conduction of peripheral nerve action potentials are unclear. Previous studies have demonstrated a strong dependence of conduction velocity on internodal length. However, a theoretical analysis has suggested that this relationship may be lost above a nodal separation of ∼0.6 mm. Here we measured nerve conduction velocities in a rabbit model of limb lengthening that produced compensatory increases in peripheral nerve growth. Divided tibial bones in one hindlimb were gradually lengthened at 0.7 mm per day using an external frame attached to the bone. This was associated with a significant increase (33%) of internodal length (0.95–1.3 mm) in axons of the tibial nerve that varied in proportion to the mechanical strain in the nerve of the lengthened limb. Axonal diameter, myelin thickness, and g-ratios were not significantly altered by limb lengthening. Despite the substantial increase in internodal length, no significant change was detected in conduction velocity (∼43 m/s) measured either in vivo or in isolated tibial nerves. The results demonstrate that the internode remains plastic in the adult but that increases in internodal length of myelinated adult nerve axons do not result in either deficiency or proportionate increases in their conduction velocity and support the view that the internodal lengths of nerves reach a plateau beyond which their conduction velocities are no longer sensitive to increases in internodal length. PMID:23467369

[Preliminary investigation of treatment of ulnar nerve defect by end-to-side neurorrhaphy].

PubMed

Luo, Y; Wang, T; Fang, H

1997-11-01

In the repair of the defect of peripheral nerve, it was necessary to find an operative method with excellent therapeutic effect but simple technique. Based on the experimental study, one case of old injury of the ulnar nerve was treated by end-to-side neurorraphy with the intact median nerve. In this case the nerve defect was over 3 cm and unable to be sutured directly. The patient was followed up for fourteen months after the operation. The recovery of the sensation and the myodynamia was evaluated. The results showed that: the sensation and the motor function innervated by ulnar nerve were recovered. The function of the hand was almost recovered to be normal. It was proved that the end-to-side neurorraphy between the distal stump with the intact median nerve to repair the defect of the ulnar nerve was a new operative procedure for nerve repair. Clinically it had good effect with little operative difficulty. This would give a bright prospect to repair of peripheral nerve defect in the future.

Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury.

PubMed

Chen, Wayne A; Luo, T David; Barnwell, Jonathan C; Smith, Thomas L; Li, Zhongyu

2017-12-01

Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion. Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period. Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance. The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.

Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated peripheral neuropathy.

PubMed

Al-Zuhairy, Ali; Schrøder, Henrik Daa; Plesner, Torben; Abildgaard, Niels; Sindrup, Søren H

2015-02-15

For several decades an association between MGUS, IgM-MGUS in particular, and peripheral neuropathy has been suspected. Several histopathology studies have shown binding of IgM to myelin and a secondary widening of myelin lamellae in cutaneous nerves and in the sural nerve of patients with IgM-MGUS, or Waldenström's Macroglobulinaemia (WM), and peripheral neuropathy. In this retrospective study we investigated the value of skin biopsy examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy. A total of 117 patients, who were examined for an M-component in serum with associated nerve symptoms, had a skin biopsy taken and examined for immunoglobulin deposition in cutaneous nerves. Thirty-five patients were diagnosed with MGUS or WM and peripheral neuropathy with no other cause of neuropathy. Nineteen patients had MGUS but no peripheral neuropathy. Of the 35 patients with MGUS or WM and peripheral neuropathy, four had immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy. In the control group of 19 without peripheral neuropathy, three had immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both groups, there was a trend towards higher IgM blood levels in patients with immunoglobulin deposition. Half of the patients with IgM gammopathy in the neuropathy group had anti-MAG reactivity, whereas only one in the control group had weak anti-MAG reactivity. Our study indicates that examination of skin biopsies for immunoglobulin deposition does not add significant diagnostic value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM immunoglobulin deposition in skin biopsy might merely be an epiphenomenon secondary to high IgM blood levels. Copyright © 2014 Elsevier B.V. All rights reserved.

Low-intensity pulsed ultrasound treatment improved the rate of autograft peripheral nerve regeneration in rat

PubMed Central

Jiang, Wenli; Wang, Yuexiang; Tang, Jie; Peng, Jiang; Wang, Yu; Guo, Quanyi; Guo, Zhiyuan; Li, Pan; Xiao, Bo; Zhang, Jinxing

2016-01-01

Low intensity pulsed ultrasound (LIPUS) has been widely used in clinic for the treatment of repairing pseudarthrosis, bone fractures and of healing in various soft tissues. Some reports indicated that LIPUS accelerated peripheral nerve regeneration including Schwann cells (SCs) and injured nerves. But little is known about its appropriate intensities on autograft nerves. This study was to investigate which intensity of LIPUS improved the regeneration of gold standard postsurgical nerves in experimental rat model. Sprague-Dawley rats were made into 10 mm right side sciatic nerve reversed autologous nerve transplantation and randomly treated with 250 mW/cm2, 500 mW/cm2 or 750 mW/cm2 LIPUS for 2–12 weeks after operation. Functional and pathological results showed that LIPUS of 250 mW/cm2 significantly induced faster rate of axonal regeneration. This suggested that autograft nerve regeneration was improved. PMID:27102358

Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

PubMed Central

Hulse, Elspeth J.; Davies, James O. J.; Simpson, A. John; Sciuto, Alfred M.

2014-01-01

Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities. PMID:25419614

A complicated case of metastatic thymoma.

PubMed

Mather, Harriet

2016-03-01

This report describes the case of a 49-year-old man who presented to the hospice with severe neuropathic pain, cramps, muscle twitching, generalised sweating, insomnia and anxiety in the context of metastatic thymoma. The symptoms were exquisitely corticosteroid sensitive raising the possibility of an immunogenic aetiology. Morvan's syndrome, a paraneoplastic, immune-mediated syndrome characterised by peripheral nerve hyperexcitability, dysautonomia and central nervous system dysfunction was thus considered. Nerve conduction studies and electromyography were negative as were initial serological assays. Subsequent assays for antibodies to leucine-rich, glioma inactivated one protein and contactin-associated protein-2, recently discovered to be associated with Morvan's syndrome, confirmed the diagnosis. By the time the diagnosis of Morvan's syndrome was reached the patient was too unwell to receive disease-modifying treatments. An awareness of Morvan's syndrome in Palliative and Supportive care is essential to improve the outcome of patients with this devastating syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Peripheral nerve blocks for paediatric day-stay surgery: one year's experience in a district general hospital.

PubMed Central

Keohane, M.; McAuley, D.; Ardill, A. C.

1995-01-01

Two hundred children underwent day-care surgery using peripheral nerve blockade as an adjunct to general anaesthesia during a twelve month period. Total post-operative analgesia was achieved in 86%, simple oral analgesia was needed in 9% and the remaining 5% of patients required systemic opiate administration for pain. PMID:7502400

Ultrasound-Guided Cryoanalgesia of Peripheral Nerve Lesions.

PubMed

Djebbar, Sahlya; Rossi, Ignacio M; Adler, Ronald S

2016-11-01

The real-time nature of ultrasound makes it ideally suited to provide guidance for a variety of musculoskeletal interventional procedures involving peripheral nerves. Continuous observation of the needle ensures proper placement and allows continuous monitoring when performing localized ablative therapy and therefore more accurate positioning of a cryoprobe, use of smaller needles, as well as access to small structures. We describe our experience performing cryoablative procedures. Patients undergoing cryoneurolysis have largely reported varying degrees of long-term pain relief and improvement in function; no serious complications have yet been identified. Ultrasound-guided cryoneurolysis can provide a useful, safe alternative to other ablative techniques to achieve long-term analgesia from painful peripheral nerve lesions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Physiology in Medicine: neuromuscular consequences of diabetic neuropathy

PubMed Central

Doherty, Timothy J.; Rice, Charles L.; Kimpinski, Kurt

2016-01-01

Diabetic polyneuropathy (DPN) refers to peripheral nerve dysfunction as a complication of diabetes mellitus. This condition is relatively common and is likely a result of vascular and/or metabolic disturbances related to diabetes. In the early or less severe stages of DPN it typically results in sensory impairments but can eventually lead to major dysfunction of the neuromuscular system. Some of these impairments may include muscle atrophy and weakness, slowing of muscle contraction, and loss of power and endurance. Combined with sensory deficits these changes in the motor system can contribute to decreased functional capacity, impaired mobility, altered gait, and increased fall risk. There is no pharmacological disease-modifying therapy available for DPN and the mainstay of treatment is linked to treating the diabetes itself and revolves around strict glycemic control. Exercise therapy (including aerobic, strength, or balance training-based exercise) appears to be a promising preventative and treatment strategy for patients with DPN and those at risk. The goal of this Physiology in Medicine article is to highlight important and overlooked dysfunction of the neuromuscular system as a result of DPN with an emphasis on the physiologic basis for that dysfunction. Additionally, we sought to provide information that clinicians can use when following patients with diabetes or DPN including support for the inclusion of exercise-based therapy as an effective, accessible, and inexpensive form of treatment. PMID:26989220

Physiology in Medicine: neuromuscular consequences of diabetic neuropathy.

PubMed

Allen, Matti D; Doherty, Timothy J; Rice, Charles L; Kimpinski, Kurt

2016-07-01

Diabetic polyneuropathy (DPN) refers to peripheral nerve dysfunction as a complication of diabetes mellitus. This condition is relatively common and is likely a result of vascular and/or metabolic disturbances related to diabetes. In the early or less severe stages of DPN it typically results in sensory impairments but can eventually lead to major dysfunction of the neuromuscular system. Some of these impairments may include muscle atrophy and weakness, slowing of muscle contraction, and loss of power and endurance. Combined with sensory deficits these changes in the motor system can contribute to decreased functional capacity, impaired mobility, altered gait, and increased fall risk. There is no pharmacological disease-modifying therapy available for DPN and the mainstay of treatment is linked to treating the diabetes itself and revolves around strict glycemic control. Exercise therapy (including aerobic, strength, or balance training-based exercise) appears to be a promising preventative and treatment strategy for patients with DPN and those at risk. The goal of this Physiology in Medicine article is to highlight important and overlooked dysfunction of the neuromuscular system as a result of DPN with an emphasis on the physiologic basis for that dysfunction. Additionally, we sought to provide information that clinicians can use when following patients with diabetes or DPN including support for the inclusion of exercise-based therapy as an effective, accessible, and inexpensive form of treatment. Copyright © 2016 the American Physiological Society.

Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

PubMed

Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

2017-09-01

Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

Biochemical factors modulating female genital sexual arousal physiology.

PubMed

Traish, Abdulmaged M; Botchevar, Ella; Kim, Noel N

2010-09-01

Female genital sexual arousal responses are complex neurophysiological processes consisting of central and peripheral components that occur following sexual stimulation. The peripheral responses in sexual arousal include genital vasocongestion, engorgement and lubrication resulting from a surge of vaginal and clitoral blood flow. These hemodynamic events are mediated by a host of neurotransmitters and vasoactive agents. To discuss the role of various biochemical factors modulating female genital sexual arousal responses. A comprehensive literature review was conducted using the PubMed database and citations were selected, based on topical relevance, and examined for study methodology and major findings. Data from peer-reviewed publications. Adrenergic as well as non-adrenergic non-cholinergic neurotransmitters play an important role in regulating genital physiological responses by mediating vascular and non-vascular smooth muscle contractility. Vasoactive peptides and neuropeptides also modulate genital sexual responses by regulating vascular and non-vascular smooth muscle cells and epithelial function. The endocrine milieu, particularly sex steroid hormones, is critical in the maintenance of tissue structure and function. Reduced levels of estrogens and androgen are associated with dramatic alterations in genital tissue structure, including the nerve network, as well as the response to physiological modulators. Furthermore, estrogen and androgen deficiency is associated with reduced expression of sex steroid receptors and most importantly with attenuated genital blood flow and lubrication in response to pelvic nerve stimulation. This article provides an integrated framework describing the physiological and molecular basis of various pathophysiological conditions associated with female genital sexual arousal dysfunction. © 2010 International Society for Sexual Medicine.

Peripheral nervous system insulin resistance in ob/ob mice

PubMed Central

2013-01-01

Background A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. Results The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. Conclusions These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy. PMID:24252636

VAGUS NERVE STIMULATION REGULATES HEMOSTASIS IN SWINE

PubMed Central

Czura, Christopher J.; Schultz, Arthur; Kaipel, Martin; Khadem, Anna; Huston, Jared M.; Pavlov, Valentin A.; Redl, Heinz; Tracey, Kevin J.

2010-01-01

The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical stimulation of the vagus nerve suppresses pro-inflammatory cytokine release in response to endotoxin, I/R injury, and hypovolemic shock and protects against lethal hypotension. To determine the effect of vagus nerve stimulation on coagulation pathways, anesthetized pigs were subjected to partial ear resection before and after electrical vagus nerve stimulation. We observed that electrical vagus nerve stimulation significantly decreased bleeding time (pre–electrical vagus nerve stimulation = 1033 ± 210 s versus post–electrical vagus nerve stimulation = 585 ± 111 s; P < 0.05) and total blood loss (pre–electrical vagus nerve stimulation = 48.4 ± 6.8 mL versus post–electrical vagus nerve stimulation = 26.3 ± 6.7 mL; P < 0.05). Reduced bleeding time after vagus nerve stimulation was independent of changes in heart rate or blood pressure and correlated with increased thrombin/antithrombin III complex generation in shed blood. These data indicate that electrical stimulation of the vagus nerve attenuates peripheral hemorrhage in a porcine model of soft tissue injury and that this protective effect is associated with increased coagulation factor activity. PMID:19953009

Stereological analysis of sciatic nerve in chickens following neonatal pinealectomy: an experimental study

PubMed Central

2010-01-01

Background Although the injury to the peripheral nervous system is a common clinical problem, understanding of the role of melatonin in nerve degeneration and regeneration is incomplete. Methods The current study investigated the effects of neonatal pinealectomy on the sciatic nerve microarchitecture in the chicken. The chickens were divided into two equal groups: unpinealectomized controls and pinealectomized chickens. At the end of the study, biochemical examination of 10 sciatic nerve samples from both groups was performed and a quantitative stereological evaluation of 10 animals in each group was performed. The results were compared using Mann-Whitney test. Results In this study, the results of axon number and thickness of the myelin sheath of a nerve fiber in newly hatched pinealectomy group were higher than those in control group. Similarly, surgical pinealectomy group had significantly larger axonal cross-sectional area than the control group (p < 0.05). In addition, the average hydroxyproline content of the nerve tissue in neonatal pinealectomy group was higher than those found in control group. Our results suggest that melatonin may play a role on the morphologic features of the peripheral nerve tissue and that melatonin deficiency might be a pathophysiological mechanism in some degenerative diseases of peripheral nerves. The changes demonstrated by quantitative morphometric methods and biochemical analysis has been interpreted as a reflection of the effects of melatonin upon nerve tissue. Conclusion In the light of these results from present animal study, changes in sciatic nerve morphometry may be indicative of neuroprotective feature of melatonin, but this suggestion need to be validated in the human setting. PMID:20409336

The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

PubMed

Gravvanis, A I; Lavdas, A A; Papalois, A; Tsoutsos, D A; Matsas, R

2007-01-01

The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

Assessing sudomotor impairment in patients with peripheral neuropathy: Comparison between electrochemical skin conductance and skin biopsy.

PubMed

Duchesne, Mathilde; Richard, Laurence; Vallat, Jean-Michel; Magy, Laurent

2018-04-27

Sudoscan provides a rapid assessment of sudomotor function based on the measurement of electrochemical skin conductance (ESC), which is thought to be proportional to small nerve fibres innervating the sweat glands. However, the relationship between ESC and small nerve fibre density on skin biopsy remains unclear. In a retrospective single-centre study, we compared ESC measurements with autonomic sweat gland nerve fibre density (SGNFD) and somatic intraepidermal nerve fibre density (IENFD) in patients with polyneuropathy. 63 patients were included (mean age: 60.6 ± 13.3 years). ESC was more strongly correlated with SGNFD (r = 0.49; p = 0.0005) than with IENFD (r = 0.42; p = 0.0005). Foot ESC was lower in patients with abnormal SGNFD (1.0 ± 0.3 µS/kg versus 0.7 ± 0.4 µS/kg; p = 0.0419) or abnormal IENFD (1.1 ± 0.3 µS/kg versus 0.8 ± 0.3 µS/kg; p = 0.0425). ESC measurement is a novel method of potential value for assessing sudomotor function. More studies are required to define its place beside ancient well-established techniques. The weak correlation of ESC with skin biopsy results suggests that mechanisms other than the loss of innervating fibres may be responsible for sweat gland dysfunction in polyneuropathies. Copyright © 2018. Published by Elsevier B.V.

Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

PubMed

Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

2016-05-01

Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced peripheral nerve regeneration by the combination of a polycaprolactone tubular prosthesis and a scaffold of collagen with supramolecular organization

PubMed Central

Maturana, Luiz G; Pierucci, Amauri; Simões, Gustavo F; Vidigal, Mateus; Duek, Eliana A R; Vidal, Benedicto C; Oliveira, Alexandre L R

2013-01-01

The purpose of this study was to investigate the influence of implanting collagen with a supramolecular organization on peripheral nerve regeneration, using the sciatic nerve tubulization technique. For this purpose, adult female Sprague Dawley rats were divided into five groups: (1) TP – sciatic nerve repaired with empty polyethylene tubular prothesis (n = 10), (2) TPCL – nerve repair with empty polycaprolactone (PCL) tubing (n = 8), (3) TPCLF – repair with PCL tubing filled with an implant of collagen with a supramolecular organization (n = 10), (4) AG – animals that received a peripheral nerve autograft (n = 8), and (5) Normal nerves (n = 8). The results were assessed by quantification of the regenerated fibers, nerve morphometry, and transmission electron microscopy, 60 days after surgery. Immunohistochemistry and polarization microscopy were also used to analyze the regenerated nerve structure and cellular elements. The results showed that the AG group presented a larger number of regenerated axons. However, the TPCL and TPCLF groups presented more compact regenerated fibers with a morphometric profile closer to normal, both at the tube midpoint and 2 mm distal to the prosthesis. These findings were reinforced by polarization microscopy, which indicated a better collagen/axons suprastructural organization in the TPCLF derived samples. In addition, the immunohistochemical results obtained using the antibody anti-p75NTR as a Schwann cell reactivity marker demonstrated that the Schwann cells were more reactive during the regenerative process in the TPCLF group as compared to the TPCL group and the normal sciatic nerve. Altogether, the results of this study indicated that the implant of collagen with a supramolecular organization positively influenced and stimulated the regeneration process through the nerve gap, resulting in the formation of a better morphologically arranged tissue. PMID:24381812

The Effectiveness of Aerobic Exercise in Improving Peripheral Nerve Functions in Type 2 Diabetes Mellitus: An Evidence Based Case Report.

PubMed

Mirtha, Listya Tresnanti; Permatahati, Viandini

2018-01-01

peripheral neuropathy is known as one of most common complication in diabetes mellitus type 2 patient. This complication is caused by uncontrolled condition of blood glucose level in long periode. Regular physical activity in moderate to high intensity is beneficial in management of diabetes mellitus. This report aimed to know the effectiveness of aerobic exercise in causing improved peripheral functions in type 2 diabetes mellitus. literature searching using several related keywords in Medline®, Pubmed®, and Cochrane library, following inclusion and exclusion criteria. Dixit et al suggested that a heart rate intensity of 40-60% aerobic exercise of 30-45 min duration per session for eight weeks suggest an important impact in controlling diabetic peripheral neuropathy. Kluding PM et al suggested that significantly improved selected measures of peripheral nerve function ("worst" pain levels and MNSI score), glycemic control (HbA1c), and resting heart rate. the studies showed significant benefit of aerobic exercise, despite the short duration of exercise being used as intervention towards improvement in peripheral nerve function. However, further studies with large samples and longer duration of intervention are needed to confirm the finding.

A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration

PubMed Central

He, Xuelian; Zhang, Liguo; Queme, Luis F; Liu, Xuezhao; Lu, Andrew; Waclaw, Ronald R; Dong, Xinran; Zhou, Wenhao; Kidd, Grahame; Yoon, Sung-Ok; Buonanno, Andres; Rubin, Joshua B; Xin, Mei; Nave, Klaus-Armin; Trapp, Bruce D; Jankowski, Michael P; Lu, Q Richard

2018-01-01

Deficits in Schwann cell–mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice. HDAC3 antagonizes the myelinogenic neuregulin–PI3K–AKT signaling axis. Moreover, genome-wide profiling analyses revealed that HDAC3 represses promyelinating programs through epigenetic silencing while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include the HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann cell–specific deletion of either Hdac3 or Tead4 in mice resulted in an elevation of myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3–TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair. PMID:29431744

Hibernating myocardium results in partial sympathetic denervation and nerve sprouting.

PubMed

Fernandez, Stanley F; Ovchinnikov, Vladislav; Canty, John M; Fallavollita, James A

2013-01-15

Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (-32%, P < 0.001), norepinephrine uptake transport protein (-25%, P = 0.01), and tissue norepinephrine content (-45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors.

Hibernating myocardium results in partial sympathetic denervation and nerve sprouting

PubMed Central

Fernandez, Stanley F.; Ovchinnikov, Vladislav; Canty, John M.

2013-01-01

Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (−32%, P < 0.001), norepinephrine uptake transport protein (−25%, P = 0.01), and tissue norepinephrine content (−45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors. PMID:23125211

Schwannomas of the foot and ankle: a technical report.

PubMed

Kellner, Christopher P; Sussman, Eric; Bar-David, Tzvi; Winfree, Christopher J

2014-01-01

The present technical report provides a detailed description of open surgical resection of peripheral nerve sheath tumors in the foot and ankle. We present 3 cases to illustrate important differences in the technique based on the presentation, anatomic location, and intraoperative neurophysiologic monitoring findings. It is important for surgeons to understand that surgical excision of many peripheral nerve sheath tumors can be undertaken without en bloc resection of the entire nerve trunk. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

An autopsy case of minamata disease (methylmercury poisoning)--pathological viewpoints of peripheral nerves.

PubMed

Eto, Komyo; Tokunaga, Hidehiro; Nagashima, Kazuo; Takeuchi, Tadao

2002-01-01

The outbreak of methylmercury poisoning in the geographic areas around Minamata Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on earlier reports and extensive pathological studies on autopsied cases at the Kumamoto University School of Medicine, destructive lesions in the anterior portion of the calcarine cortex and depletion predominantly of granular cells in the cerebellar cortex came to be recognized as the hallmark and diagnostic yardstick of methylmercury poisoning in humans. As the number of autopsy cases of Minamata disease increased, it became apparent that the cerebral lesion was not restricted to the calcarine cortex but was relatively widespread. Less severe lesions, believed to be responsible for the motor symptoms of Minamata patients, were often found in the precentral, postcentral, and lateral temporal cortices. These patients also frequently presented with signs of sensory neuropathy affecting the distal extremities. Because of few sufficiently comprehensive studies, peripheral nerve degeneration has not been universally accepted as a cause of the sensory disturbances in Minamata patients. The present paper describes both biopsy and autopsy findings of the peripheral nerves in a male fisherman who died at the age of 64 years and showed the characteristic central nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with electron microscopy performed 1 month prior to his death showed endoneurial fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of Büngner's bands. The spinal cord showed Wallerian degeneration of the fasciculus gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia. These findings support the contention that there is peripheral nerve degeneration in Minamata patients due to toxic injury from methylmercury.

Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats.

PubMed

Jensen, Vivi F H; Molck, Anne-Marie; Soeborg, Henrik; Nowak, Jette; Chapman, Melissa; Lykkesfeldt, Jens; Bogh, Ingrid B

2018-01-01

Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery period in some of the animals. Sciatic, plantar nerves and thigh muscle were examined histopathologically after four or eight weeks of infusion and after the recovery period. IIH resulted in high incidence of axonal degeneration in sciatic nerves and low incidence in plantar nerves indicating proximo-distal progression of the neuropathy. The neuropathy progressed in severity (sciatic nerve) and incidence (sciatic and plantar nerve) with the duration of IIH. The myopathy consisted of groups of angular atrophic myofibres which resembled histopathologic changes classically seen after denervation of skeletal muscle, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses proximo-distally, that severity and incidence increase with duration of the hypoglycaemia and that these changes are partially reversible within four weeks. Furthermore, IIH-induced myopathy is most likely secondary to the neuropathy. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).