Peripheral Nerve Development and the Pathogenesis of Peripheral Neuropathy: the Sorting Point

AbstractImpaired postural control is often observed in response to neurotoxic chemotherapy. However, potential explanatory factors other than chemotherapy-induced peripheral neuropathy (CIPN) have not been adequately considered to date due to primarily cross-sectional study designs. Our objective was to comprehensively analyze postural control during and after neurotoxic chemotherapy, and to identify potential CIPN-independent predictors for its impairment. Postural control and CIPN symptoms (EORTC QLQ-CIPN20) were longitudinally assessed before, during and three weeks after neurotoxic chemotherapy, and in three and six months follow-up examinations (N = 54). The influence of peripheral nerve function as determined by nerve conduction studies (NCS: compound motor action potentials (CMAP) and sensory action potentials (SNAP)), physical activity, and muscle strength on the change in postural control during and after chemotherapy was analyzed by multiple linear regression adjusted for age and body mass index. Postural control, CIPN signs/symptoms, and CMAP/SNAP amplitudes significantly deteriorated during chemotherapy (p < .01). During follow-up, patients recovered from postural instabilities (p < .01), whereas CIPN signs/symptoms and pathologic NCS findings persisted compared to baseline (p < .001). The regression model showed that low CMAP and high SNAP amplitudes at baseline predicted impairment of postural control during but not after chemotherapy. Hence, pre-therapeutically disturbed somatosensory inputs may induce adaptive processes that have compensatory effects and allow recovery of postural control while CIPN signs/symptoms and pathologic peripheral nerve function persist. Baseline NCS findings in cancer patients who receive neurotoxic chemotherapy thus might assist in delineating individual CIPN risk profiles more precisely to which specific exercise intervention programs could be tailor-made.

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Effect of aerobic exercise on peripheral nerve functions of population with diabetic peripheral neuropathy in type 2 diabetes: A single blind, parallel group randomized controlled trial

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2013.12.006 ◽

2014 ◽

Vol 28 (3) ◽

pp. 332-339 ◽

Cited By ~ 50

Author(s):

Snehil Dixit ◽

Arun G. Maiya ◽

B.A. Shastry

Keyword(s):

Type 2 Diabetes ◽

Randomized Controlled Trial ◽

Peripheral Neuropathy ◽

Peripheral Nerve ◽

Diabetic Peripheral Neuropathy ◽

Controlled Trial ◽

Randomized Controlled ◽

Parallel Group ◽

Single Blind

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Peripheral nerve biopsy: Is it still important for the early diagnosis of neural leprosy?

10.5327/1516-3180.410 ◽

2021 ◽

Author(s):

Isabella Sabião Borges ◽

João Victor Aguiar Moreira ◽

Thales Junqueira Oliveira ◽

Maria Fernanda Prado Rosa ◽

Gabriel Nunes Melo Assunção ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Early Diagnosis ◽

Peripheral Nerve ◽

Clinical Evidence ◽

Early Recognition ◽

Diagnostic Errors ◽

Nerve Biopsy ◽

Skin Lesions ◽

National Reference Center ◽

Neural Impairment

Background: The early recognition of neural impairment in leprosy represents a challenge in clinical practice and peripheral nerve biopsy may be required for diagnostic. Objective: Characterize the epidemiological, clinical, electroneuromyographic, laboratory and histopathological aspects of patients undergoing peripheral nerve biopsy during investigation of primary neural leprosy. Methods: 104 patients with peripheral neuropathy, referred to a national reference center leprosy, were biopsied. All patients had clinical evidence of peripheral neuropathy associated with the absence of skin lesions and were being investigated. Results: Of 104 biopsied, leprosy was confirmed in 89.4%. 66 were classified as primary neural leprosy and 27 as neural relapse or reinfection. All cases confirmed presented asymmetric neural impairment with predominance of sensory symptoms (88.2%), followed by muscular weakness and/or amyotrophy in 44.1% and pain in 34.4%. Neural thickening of one or more nerves was observed in 78.5% of the patients. The biopsied nerves were: ulnar (67.8%), superficial fibular (21.5%), sural (8.6%), radial (1.1%) and deep fibular (1.1%). 29% presented histopathological abnormalities and 4.4% acid fast bacilli. Nerve and superjacent skin qPCR were positive in 49.5% and 24.8% of cases, respectively. The patients with multiple mononeuropathy presented higher frequency of neural thickening (p<0.0001) and histopathological abnormalities (p=0.0077), but lower rates of positivity of ELISA anti-PGL-I (p=0.0100), qPCR in the peripheral blood (p=0.0157), and in the slit skin smear (p=0.0032). Conclusions: Peripheral nerve biopsy is an important tool in the investigation of primary neural cases, contributing to the early diagnosis and reducing diagnostic errors and the need for empirical treatment.

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Peripheral Neuropathy and Peripheral Nerve Lesions

Principles and Practice of Geriatric Psychiatry ◽

10.1002/0470846410.ch61 ◽

2003 ◽

pp. 341-344

Author(s):

Janice M. Massey ◽

E. Wayne Massey

Keyword(s):

Peripheral Neuropathy ◽

Peripheral Nerve ◽

Nerve Lesions ◽

Peripheral Nerve Lesions

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

Cellular Physiology and Biochemistry ◽

10.1159/000489373 ◽

2018 ◽

Vol 46 (5) ◽

pp. 1879-1894 ◽

Cited By ~ 13

Author(s):

Wei Tang ◽

Xiangfang Chen ◽

Haoqi Liu ◽

Qian Lv ◽

Junjie Zou ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Rat Model ◽

Peripheral Nerve Injury ◽

Signal Pathway ◽

Inflammatory Factors ◽

Survival Ratio ◽

Nrf2 Expression

Background/Aims: 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. Methods: 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. Results: 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. Conclusions: Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury.

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A Case of Fever and a Wrist Drop

Neuroimmunology ◽

10.1093/med/9780190693190.003.0013 ◽

2018 ◽

pp. 69-74

Author(s):

Aaron E. Miller ◽

Tracy M. DeAngelis ◽

Michelle Fabian ◽

Ilana Katz Sand

Keyword(s):

Nervous System ◽

Gastrointestinal Tract ◽

Peripheral Neuropathy ◽

Peripheral Nerve ◽

Polyarteritis Nodosa ◽

Joint Pain ◽

Immunosuppressive Agents ◽

Nerve Biopsy ◽

Definitive Diagnosis ◽

Wrist Drop

Polyarteritis nodosa (PAN) is a systemic illness that most often involves the skin, kidneys, and gastrointestinal tract, in addition to the peripheral nervous system. It most often affects middle-aged individuals, men more than women. The particular type of peripheral neuropathy is often mononeuropathy or mononeuritis multiplex—a condition in which there is discrete involvement of multiple individual nerves. Definitive diagnosis of the vascular nature of the neuropathy requires peripheral nerve biopsy, which will demonstrate inflammation throughout the walls of small and medium-sized arteries. The CNS is also frequently involved in PAN. Constitutional symptoms, including fever, fatigue, and diffuse muscle and joint pain, are common and raise the suspicion of a systemic illness. Treatment generally involves the use of corticosteroids and immunosuppressive agents such as cyclophosphamide or azathioprine.

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Molecular mechanisms in schwann cell survival and death during peripheral nerve development, injury and disease

Neurotoxicity Research ◽

10.1007/bf03033784 ◽

2005 ◽

Vol 7 (1-2) ◽

pp. 151-167 ◽

Cited By ~ 5

Author(s):

Kristy Boyle ◽

Michael F. Azari ◽

Christos Profyris ◽

Steven Petratos

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Cell Survival ◽

Molecular Mechanisms ◽

Nerve Development

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Accumulation of fructosyl-lysine and advanced glycation end products in the kidney, retina and peripheral nerve of streptozotocin-induced diabetic rats

Biochemical Society Transactions ◽

10.1042/bst0311423 ◽

2003 ◽

Vol 31 (6) ◽

pp. 1423-1425 ◽

Cited By ~ 93

Author(s):

N. Karachalias ◽

R. Babaei-Jadidi ◽

N. Ahmed ◽

P.J. Thornalley

Keyword(s):

Peripheral Neuropathy ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Plasma Protein ◽

Advanced Glycation End Products ◽

Diabetic Rats ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Carboxymethyl Lysine

The accumulation of AGEs (advanced glycation end products) in diabetes mellitus has been implicated in the biochemical dysfunction associated with the chronic development of microvascular complications of diabetes – nephropathy, retinopathy and peripheral neuropathy. We investigated the concentrations of fructosyl-lysine and AGE residues in protein extracts of renal glomeruli, retina, peripheral nerve and plasma protein of streptozotocin-induced diabetic rats and normal healthy controls. Glycation adducts were determined by LC with tandem MS detection. In diabetic rats, the fructosyl-lysine concentration was increased markedly in glomeruli, retina, sciatic nerve and plasma protein. The concentrations of N∊-carboxymethyl-lysine and N∊-carboxyethyl-lysine were increased in glomeruli, sciatic nerve and plasma protein, and N∊-carboxymethyl-lysine also in the retina. Hydroimidazolone AGEs derived from glyoxal, methylglyoxal and 3-deoxylglucosone were major AGEs quantitatively. They were increased in the retina, nerve, glomeruli and plasma protein. AGE accumulation in renal glomeruli, retina, peripheral nerve and plasma proteins is consistent with a role for AGEs in the development of nephropathy, retinopathy and peripheral neuropathy in diabetes. High-dose therapy with thiamine and Benfotiamine suppressed the accumulation of AGEs, and is a novel approach to preventing the development of diabetic complications.

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