Axonal neuropathies

The electrophysiological and neuropathological changes are similar to the axonal neuropathy and prominent loss of unmyelinated fibers seen in DSP (Simpson and Tagliati 1995). Although the specific pathological mechanisms of ATN are not fully known, there is abundant indirect evidence of mitochondrial dysfunction as a principal mechanism. Prominent mitochondrial disruption and cristae abnormalities... 

Electrophysiologic studies usually show axonal neuropathy, but in 15%, it is demyelinating (Moulignier et al. 1997). CSF is remarkable for a mild nonspecific lymphocytic pleocytosis, but with markedly raised protein up to 2 g/L (Brew 2003). Nerve biopsy shows marked angiocentric CD8 infiltrates without mural necrosis... 

In axonal neuropathies, the velocity of action potential propagation in surviving axons is well maintained but the number of axons capable of conducting action potentials is diminished. Transcutaneous nerve stimulation and recording, the method routinely used for studying nerve conduction in the clinic, does not permit evaluation of the function of autonomic or unmyelinated sensory axons. These smaller, slow-conducting axons can be analyzed, in research studies, by intraneural recording with needle electrodes. 

Miller-Fisher syndrome, Bickerstaff s brainstem encephalitis Acute motor axonal neuropathy Immunoglobulin light-chain amyloid neuropathy Cryoglobulinemic neuropathy... 

Familial demyelinative/dysmyelinative and axonal neuropathies may also be caused by impaired lysosomal lipid metabolism. Metachromatic leukodystrophy (sulfatide lipidosis) results from mutations of the arylsulfatase A gene, which encodes a lysosomal enzyme required for sulfatide turnover. Myelin is affected in both CNS and PNS, though dysfunction is restricted to the PNS in some patients, and the onset of symptoms can occur at any time between infancy and adulthood. Bone marrow transplantation can slow disease progression and improve nerve conduction velocities [57]. (See in Ch. 41.)... 

Magira, E. E., Papaioakim, M., Nachamkin, I. et al. Differential distribution of HLA-DQP/DRP epitopes in the two forms of Guillain-Barre syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating... 

AMAN acute motor axonal neuropathy CART cocaine- and amphetamine-regulated transcript... 

Davenport JG, Farrell DF, Sumi SM. 1976. Giant axonal neuropathy caused by industrial chemicals Neurofilamentous axonal masses in man. Neurology 26 919-923. 

Among the pathologies associated with RLS, several groups [38, 40] have reported neuropathies and radiculopathies. Evidence of peripheral axonal neuropathy of a mild degree was found in some putative idiopathic RLS patients through electro-physiological (EMG/NCV) and psychophysiological tests, subsequently confirmed by sural nerve biopsy [41], These data have recently been confirmed in 30 % of 22 patients by means of skin biopsy, and related to late onset associated with pain-like symptoms [42],... 

Abbreviations AMAN acute motor axonal neuropathy... 

Kloos L, Sillevis Smitt P, Ang CW, Kruit W, Stoter G. Paraneoplastic ophthalmoplegia and subacute motor axonal neuropathy associated with anti-GQlb antibodies in a patient with malignant melanoma. J Neurol Neurosurg Psychiatry 2003 74(4)507-509. 

The neuron and the Schwann cell are the principal cell types in the PNS. There are great morphological, biochemical, and functional differences between neurons and Schwann cells, and this is reflected in the considerable variation in their vulnerability to toxic injury. Some toxic neuropathies are characterized primarily by injury of the neuron, its axon, or its terminal, as evidenced by the presence of axonal degeneration in peripheral nerve, while other toxic neuropathies are characterized primarily by Schwann cell injury, as evidenced by the presence of demyelination. Those neuropathies characterized by axonal injury are often categorized as axonal neuropathies, whereas those characterized by demyelination are categorized as demyelinating neuropathies. ... 

Yuki N, Ho TW, Tagawa Y Koga M, Li CY, Hirata K, Griffin JW (1999) Autoantibodies to GMlb and GalNAc-GDla Relationship to Campylobacter jejuni infection and acute motor axonal neuropathy in China. J Neurol Sci 164 134—138. 

Figure 20.2. Proposed pathogenesis in acute motor axonal neuropathy (AMAN) In AMAN there is primary axonal injury without T-ceU inflammation and demyelination. Deposition of autoantibodies and complement on the axolemma is followed by structural axonal injury or alteration of axon conduction. Macrophages within the periaxonal space contribute to the axonal damage (B B-cell M< > Macrophage, C5b-9 complement factors).

GoodfeUow JA, Bowes T, Sheikh K, Odaka M, Halstead SK, Humphreys PD, Wagner ER, Yuki N, Furukawa K, Furukawa K, Plomp JJ, Willison HJ (2005) Overexpression of GDla ganghoside sensitizes motor nerve terminals to anti-GDI a antibody-mediated injury in a model of acute motor axonal neuropathy. J Neurosci 25 1620-1628. 

Griffin JW, Li CY, Macko C, Ho TW, Hsieh S-T, Xue P, Wang FA, Comblath DR, McKhann GM, Asbury AK (1996b) Early nodal changes in the acute motor axonal neuropathy pattern of the Guillain-Barre syndrome. J Neurocytol 25 33-51. 

Ho TW, Hsieh ST, Nachamkin I, WiUison HJ, Sheikh K, Kiehl-bauch J, Flanigan K, McArthur JC, Comblath DR, McKhann GM, Griffin JW (1997) Motor nerve terminal degeneration provides a potential mechanism for rapid recovery in acute motor axonal neuropathy after Campylobacter infection (see comments). Neurology 48 717-724. 

Susuki K, Nishknoto Y, Yamada M, Baba M, Ueda S, Hirata K, Yuki N (2003) Acute motor axonal neuropathy rabbit model Immune attack on nerve root axons. Ann Neurol 54 383-388. 

Susuki K, Odaka M, Mori M, Hirata K, Yuki N (2004) Acute motor axonal neuropathy after Mycoplasma infection Evidence of molecular mimicry. Neurology 62 949-956. 

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