Demyelinating Neuropathies

2017 ◽  
Author(s):  
John A. Goodfellow ◽  
Amy I. Davidson ◽  
Hugh J. Willison
Keyword(s):  
Molecular Structure ◽  
Axonal Degeneration ◽  
Pathophysiological Mechanism ◽  
Normal Process ◽  
Nodes Of Ranvier ◽  
Demyelinating Neuropathies ◽  
Distal Axonal Degeneration ◽  
Inherited Neuropathies

Many neuropathies have in common the basic pathophysiological mechanism of demyelination. Our understanding of the normal process of myelination and the molecular structure of myelin, nodes of Ranvier, and internodes has increased in recent years, yielding a greater understanding of the process of demyelination in disease. This chapter focuses on the inherited neuropathies as examples of non-inflammatory demyelinating neuropathies. For these conditions there are ongoing genotype-phenotype correlations and a greater appreciation of the importance of distal axonal degeneration as a consequence of demyelination.

scholarly journals New Evidence for Secondary Axonal Degeneration in Demyelinating Neuropathies

2020 ◽  
pp. 135595
Author(s):  
Kathryn R. Moss ◽  
Taylor S. Bopp ◽  
Anna E. Johnson ◽  
Ahmet Höke
Keyword(s):  
Axonal Degeneration ◽  
Demyelinating Neuropathies ◽  
New Evidence

scholarly journals Cisplatin induced neurotoxicity is mediated by Sarm1 and calpain activation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aysel Cetinkaya-Fisgin ◽  
Xinghua Luan ◽  
Nicole Reed ◽  
Ye Eun Jeong ◽  
Byoung Chol Oh ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Side Effects ◽  
Cancer Cells ◽  
Wallerian Degeneration ◽  
Axonal Degeneration ◽  
Adduct Formation ◽  
Calpain Activation ◽  
Chemotherapy Agent ◽  
Distal Axonal Degeneration ◽  
Calpain Inhibitors

AbstractCisplatin is a commonly used chemotherapy agent with significant dose-limiting neurotoxicity resulting in peripheral neuropathy. Although it is postulated that formation of DNA-platinum adducts is responsible for both its cytotoxicity in cancer cells and side effects in neurons, downstream mechanisms that lead to distal axonal degeneration are unknown. Here we show that activation of calpains is required for both neurotoxicity and formation of DNA-platinum adduct formation in neurons but not in cancer cells. Furthermore, we show that neurotoxicity of cisplatin requires activation of Sarm1, a key regulator of Wallerian degeneration, as mice lacking the Sarm1 gene do not develop peripheral neuropathy as evaluated by both behavioral or pathological measures. These findings indicate that Sarm1 and/or specific calpain inhibitors could be developed to prevent cisplatin induced peripheral neuropathy.

scholarly journals Distal Symmetrical Polyneuropathy in a Dog

1980 ◽  
Vol 17 (4) ◽  
pp. 422-435 ◽  
Author(s):  
K. G. Braund ◽  
P. J. Luttgen ◽  
R. W. Redding ◽  
P. F. Rumph
Keyword(s):  
Central Nervous System ◽  
Cell Proliferation ◽  
Axonal Degeneration ◽  
Neurologic Disease ◽  
Qualitative And Quantitative ◽  
Quantitative Studies ◽  
The Central Nervous System ◽  
Distal Symmetrical Polyneuropathy ◽  
Distal Axonal Degeneration ◽  
Dying Back

A 1.3-year-old Great Dane dog had a chronic progressive neurologic disease clinically expressed as a distal symmetrical polyneuropathy characterized by weakness and bilateral atrophy of bulbar and distal appendicular musculature. Qualitative and quantitative studies showed neurogenic atrophy of muscles below the elbow and stifle. There was Walleriantype degeneration. Schwann cell proliferation and cell bands of Büngner, and marked depletion of medium (5 to 8 μm) to large (9 to 15 μm) diameter myelinated fibers in the distal parts of appendicular and laryngeal nerves. Sensory (saphenous and superficial radial) and autonomic (sympathetic and dorsal vagal trunk) nerves were affected to a lesser degree. A distribution of distal axonal degeneration suggested a dying back process. The disease differed from classical dying back disorders by absence of axonal degeneration in selected pathways of the central nervous system.

scholarly journals Altered interplay between endoplasmic reticulum and mitochondria in Charcot–Marie–Tooth type 2A neuropathy

2019 ◽  
Vol 116 (6) ◽  
pp. 2328-2337 ◽  
Author(s):  
Nathalie Bernard-Marissal ◽  
Gerben van Hameren ◽  
Manisha Juneja ◽  
Christophe Pellegrino ◽  
Lauri Louhivuori ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Axonal Degeneration ◽  
Calcium Handling ◽  
Gene Encoding ◽  
Mitofusin 2 ◽  
Charcot Marie Tooth ◽  
Tooth Type ◽  
Distal Axonal Degeneration

Mutations in theMFN2gene encoding Mitofusin 2 lead to the development of Charcot–Marie–Tooth type 2A (CMT2A), a dominant axonal form of peripheral neuropathy. Mitofusin 2 is localized at both the outer membrane of mitochondria and the endoplasmic reticulum and is particularly enriched at specialized contact regions known as mitochondria-associated membranes (MAM). We observed that expression of MFN2R94Qinduces distal axonal degeneration in the absence of overt neuronal death. The presence of mutant protein leads to reduction in endoplasmic reticulum and mitochondria contacts in CMT2A patient-derived fibroblasts, in primary neurons and in vivo, in motoneurons of a mouse model of CMT2A. These changes are concomitant with endoplasmic reticulum stress, calcium handling defects, and changes in the geometry and axonal transport of mitochondria. Importantly, pharmacological treatments reinforcing endoplasmic reticulum–mitochondria cross-talk, or reducing endoplasmic reticulum stress, restore the mitochondria morphology and prevent axonal degeneration. These results highlight defects in MAM as a cellular mechanism contributing to CMT2A pathology mediated by mutated MFN2.

scholarly journals Polyneuropathy in Young Siberian Huskies Caused by Degenerative and Inflammatory Diseases

2020 ◽  
Vol 57 (5) ◽  
pp. 666-674
Author(s):  
Hanne Jahns ◽  
Karen M. Vernau ◽  
Catherine M. Nolan ◽  
Emma J. O’Neill ◽  
Robert E. Shiel ◽  
...  
Keyword(s):  
Axonal Degeneration ◽  
Inflammatory Diseases ◽  
Age At Onset ◽  
Case Series ◽  
Clinicopathological Characteristics ◽  
Autonomic Nerve ◽  
Laryngeal Paralysis ◽  
Immune Mediated ◽  
Large Fiber ◽  
Inherited Neuropathies

Polyneuropathy is defined as the simultaneous dysfunction of several peripheral nerves. In dogs, a number of breeds are predisposed to a variety of immune-mediated and/or degenerative inherited forms of polyneuropathy, with laryngeal paralysis and/or megaesophagus as important clinical features of many of these conditions. This case series describes degenerative and inflammatory polyneuropathies in 7 young Siberian huskies that were categorized based on clinicopathological characteristics as follows: (1) slowly progressive laryngeal paralysis and megaesophagus caused by primary axonal degeneration with large fiber loss (n = 2); (2) slowly progressive polyneuropathy without megaesophagus or laryngeal paralysis caused by primary axonal degeneration with large fiber loss (n = 2); (3) acute inflammatory demyelinating neuropathy causing sensory, motor and autonomic nerve deficits (n = 2); and (4) ganglioradiculitis (sensory neuronopathy; n = 1). Based on the predominantly young age at onset, slow progression, relatedness of affected dogs, and clinical and pathological similarities with inherited neuropathies reported in other dog breeds, a hereditary basis for the degenerative polyneuropathies in Siberian huskies is suspected. However, 5 different mutations in 3 genes known to cause polyneuropathy in other dog breeds ( NDRG1, ARHGEF10, or RAB3GAP1) were not detected in the affected Siberian huskies suggesting that more genetic variants remain to be identified. This study highlights the varied underlying lesions of polyneuropathies in young Siberian huskies.

scholarly journals Nodopathies of the peripheral nerve: an emerging concept

2015 ◽  
Vol 86 (11) ◽  
pp. 1186-1195 ◽  
Author(s):  
Antonino Uncini ◽  
Satoshi Kuwabara
Keyword(s):  
Peripheral Nerve ◽  
Axonal Degeneration ◽  
Conduction Block ◽  
Good Prognosis ◽  
Apparent Paradox ◽  
Nodal Region ◽  
Demyelinating Neuropathies ◽  
Temporal Dispersion ◽  
Peripheral Nerve Diseases ◽  
Nerve Conduction Block

Peripheral nerve diseases are traditionally classified as demyelinating or axonal. It has been recently proposed that microstructural changes restricted to the nodal/paranodal region may be the key to understanding the pathophysiology of antiganglioside antibody mediated neuropathies. We reviewed neuropathies with different aetiologies (dysimmune, inflammatory, ischaemic, nutritional, toxic) in which evidence from nerve conductions, excitability studies, pathology and animal models, indicate the involvement of the nodal region in the pathogenesis. For these neuropathies, the classification in demyelinating and axonal is inadequate or even misleading, we therefore propose a new category of nodopathy that has the following features: (1) it is characterised by a pathophysiological continuum from transitory nerve conduction block to axonal degeneration; (2) the conduction block may be due to paranodal myelin detachment, node lengthening, dysfunction or disruption of Na+channels, altered homeostasis of water and ions, or abnormal polarisation of the axolemma; (3) the conduction block may be promptly reversible without development of excessive temporal dispersion; (4) axonal degeneration, depending on the specific disorder and its severity, eventually follows the conduction block. The term nodopathy focuses to the site of primary nerve injury, avoids confusion with segmental demyelinating neuropathies and circumvents the apparent paradox that something axonal may be reversible and have a good prognosis.

51-year old man with tingling, burning and progressive limb weakness

2018 ◽  
Vol 18 (5) ◽  
pp. 382-388 ◽  
Author(s):  
Anu Gupta ◽  
Pappula Santhosh Kumar ◽  
Vinod Puri ◽  
Ravindra Kumar Saran ◽  
Poonam Narang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Axonal Degeneration ◽  
Correct Diagnosis ◽  
Common Reason ◽  
Demyelinating Neuropathy ◽  
Limb Weakness ◽  
Immune Mediated ◽  
Demyelinating Neuropathies ◽  
Acquired Demyelinating Neuropathies

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

Dapsone-Induced Distal Axonal Degeneration of the Motor Neurons

Dermatology ◽  
1978 ◽  
Vol 156 (6) ◽  
pp. 321-324 ◽  
Author(s):  
I. Helander ◽  
J. Partanen
Keyword(s):  
Motor Neurons ◽  
Axonal Degeneration ◽  
Distal Axonal Degeneration

scholarly journals Ethylene oxide induces central-peripheral distal axonal degeneration of the lumbar primary neurones in rats.

1985 ◽  
Vol 42 (6) ◽  
pp. 373-379 ◽  
Author(s):  
A Ohnishi ◽  
N Inoue ◽  
T Yamamoto ◽  
Y Murai ◽  
H Hori ◽  
...  
Keyword(s):  
Ethylene Oxide ◽  
Axonal Degeneration ◽  
Distal Axonal Degeneration
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