Axonal motor neuropathy

A 13-year-old girl with acute intermittent porphyria had several attacks of the disease and developed an acute severe axonal motor neuropathy after taking porphyrinogenic medications, including phenobarbital, for 3 weeks [233 ]. 

Mutant Tbce mice. Progressive motor neuropathy (PMN), an autosomal recessive murine disease, manifests as weakness beginning within a few weeks of birth [14, 136]. These mice are homozygous for a Trp 524 Gly substitution of Tbce (tubulin-specific chaperone E), localized to mouse chromosome 13 [14]. Tbce mRNA is present in neurons in the spinal cord. Degenerative changes are conspicuous in motor axons, and ultrastructural studies of peripheral nerves of PMN mice disclose reduced numbers of microtubules in these axons. Mutations of the highly conserved Trp524 residue, which appears to influence... 

Polyneuropathy with both sensory and motor involvement is much more common among cancer patients than pure SN [83, 110, 111]. SCLC is the most common associated tumor, although other solid tumors may be found [112]. Sensory-motor neuropathy is a quite common paraneoplastic feature in patients with onconeural antibodies, especially Hu and CRMP-5 antibodies. The CRMP-5 antibody is particularly associated with SCLC and thymoma [30]. The CRMP-5 antibody binds to oligodendrocytes as well as to neurons in specific brain regions and the retina and Schwann cells of the peripheral nervous system. In accordance with this, the clinical characteristics are heterogeneous. Many patients exhibit mixed axonal and demye-linating sensory-motor neuropathy, optic neuritis, or cerebellar dysfynction [85, 113], as well as extrapyramidal symptoms (Chapter 5.3). 

The milder axonal polyneuropathy is the most common neurological adverse effect of suramin and causes distal paresthesia, reduced pain and vibration sensation in the feet, weak toe extensors, and absent ankle jerks this neuropathy is largely reversible. Milder neuropathies occurred in 50-70% of patients with plasma concentrations below 300 pg/ml, and severe motor neuropathy was rare in this category of patients. 

Foubert-Samier A, Kazadi A, Rouanet M, Vital A, Lagueny A, Tison F, Meissner W. Axonal sensory motor neuropathy in copper-deficient Wilson s disease. Muscle Nerve 2009 40(2) 294-6. 

Peripheral neuropathy is degeneration of peripheral nerves. Because motor and sensory axons tun in the same nerves, usually both motor and sensory functions are affected in this disease. Neuropathies may be either acute (e.g., Charcot-Marie-Tooth disease) or chronic (e.g., Guillain-Barre syndrome) and are categorized as demyelinating or axonal. 

Other diseases with disruptions in neurofilament organization include diabetic neuropathy and Charcot-Marie-Tooth disease. For these diseases, the disruption of neuro filaments may be a secondary effect as in the case of trembler axons or a direct effect. For example, some forms of Charcot-Marie-Tooth peripheral neuropathy result from mutations in a neurofilament subunit [22, 43]. In most cases, neuronal degeneration is an eventual consequence, but neuronal function may be impaired prior to substantial loss of neurons. Generally, disruptions of neurofilaments have the most severe consequences in large motor neurons, which is consistent with the fact that the largest neurons have the highest levels of neurofilament expression. 

IGF I has recently been the focus of considerable interest due to its actions on motor neurons. It can prevent normal motor neuron cell death during development, reduce the loss of these cells following nerve injury and enhance axonal regeneration. In the adult, injection of IGF I results in sprouting of motor neuron terminals and increases the size of the neuromuscular junction. These and other studies suggest potential therapeutic applications of IGF I in several neurological diseases including amyotrophic lateral sclerosis and peripheral neuropathies. 

Peripheral neuropathies maybe widely disseminated or focal. Patients with disseminated polyneuropathy, whether demyelinative or axonal, usually demonstrate distal sensory and/or motor impairment. Multifocal neuropathy, also referred to as mononeuropathy multiplex, is often a consequence of lesions affecting the vasa nervorum, the blood vessels that supply peripheral nerves. The most common diseases to compromise the vasa nervorum and cause infarction of nerve fascicles are diabetes mellitus and periarteritis nodosa. Other frequent causes of mononeuropathy multiplex include infection (e.g. Lyme disease and leprosy) and multiple compression injury (e.g. bilateral carpal tunnel syndrome). When mononeuropathy... 

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

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... 

The disease models can be grouped into four primary categories (Fig. 20.1). (1) Motor neuron diseases, in which the death of motor neuron somata in the spinal cord results in denervation of the muscles, progressive flaccid paralysis, and usually premature death. In humans, examples of such diseases would include amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). (2) Peripheral neuropathies, in which axonal integrity or conduction is not maintained, resulting in axon degeneration and impaired connectivity of the nervous system and the musculature. 

In combination with counts of ventral roots, femoral axon counts can be used to distinguish peripheral neuropathy from motor neuron death. The nerve has a primarily motor branch that innervates the quadriceps, and a primarily sensory branch that becomes the saphenous nerve more distally (Fig. 20.5). 

Abbreviations AMAN acute motor axonal neuropathy... 

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