Neuronopathy

Megadosage vitamin B6 (pyridoxine) and cisplatin cause sensory neuronopathy. Pyridoxine toxicity, usually the result of inappropriate self-overmedication, kills dorsal root ganglion neurons. Affected individuals become severely ataxic because of loss of proprioceptive afferent input to the cerebellum. A similar syndrome is elicited by cisplatin chemotherapy. Neurotrophin-3 treatment is effective in protecting dorsal root ganglion neurons in experimental animals against these toxins [48,49]. 

Sillevis Smitt, P., Grefkens, J., de Leeuw, B. etal. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. /. Neurol. 249 745-753, 2002. 

Martin, N., Jaubert, J., Gounon, P. et al. A missense mutation in Tbce causes progressive motor neuronopathy in mice. Nat. Genet. 32 443-447, 2002. 

Neuronopathy Nerve cell death MPTP, trimethyltin... 

Neuronopathy. Neuronopathy refers to generalized damage to nerve cells, with the primary damage occurring at the nerve cell body. Axonal and dendritic processes die secondarily in response to loss of the cell body. Like other cells in the body, neurons die by one of two processes distinguished by their morphological and molecular features apoptosis and necrosis. (This division is overly simplistic there is much debate... 

Bommel, H., Xie, G., Rossoll, W., Wiese, S., Jablonka, S., Boehm, T., et al. (2002) Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease. J Cell Biol 159, 563-569. 

The term classical PNS is reserved for the PNS in which the association with cancer is common and includes encephalomyelitis, limbic encephalitis, paraneoplastic cerebellar degeneration, and paraneoplastic opsoclonus myoclonus (OM), as well as sensory neuronopathy (SN), chronic gastrointestinal pseudo-obstruction, Lambert Eaton myasthenic syndrome (LEMS), and dermatomyositis [14]. This chapter does not include dermatomyositis. 

Anti-CRMP5/CV2 CRMP5 Cytoplasm of oligodendrocytes Encephalomyelitis, cerebellar degeneration, LE, chorea, sensory neuronopathy, sensorimotor neuropathy, optic neuritis, gastrointestinal pseudo-obstruction SCLC, thymoma, gynecological tumors... 

Ichimura M, Yamamoto M, Kobayashi Y, Kawakami O, Niimi Y, Hattori N, et al. Tissue distribution of pathological lesions and Hu antigen expression in paraneoplastic sensory neuronopathy. Acta Neuropathol (Berl) 1998 95(6) 641-648. 

Schold SC, Cho ES, Somasundaram M, Posner JB. Subacute motor neuronopathy A remote effect of lymphoma. Ann Neurol 1979 5(3) 271-287. 

Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore) 1992 71(2) 59-72. 

Wanschitz J, Hainfellner JA, Kristoferitsch W, Drlicek M, Budka H. Ganglionitis in paraneoplastic subacute sensory neuronopathy A morphologic study. Neurology 1997 49(4) 1156—1159. 

Dalmau J, Furneaux HM, Cordon-Cardo C, Posner JB. The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. Am J Pathol 1992 141(4) 881—886. 

Dalmau J, Furneaux HM, Rosenblum MK, Graus F, Posner JB. Detection of the anti-Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuronopathy. Neurology 1991 41(11) 1757-1764. 

Hainfellner JA, Kristoferitsch W, Lassmann H, Bernheimer H, Neisser A, Drlicek M, et al. T-cell-mediated ganglionitis associated with acute sensory neuronopathy. Ann Neurol 1996 39(4) 543-547. 

Methylmercury and trimethyltin also produce neuronopathies. Methylmercury inhibits protein synthesis, but experimental evidence suggests that additional or alternative mechanisms must exist to account for the neuronal degeneration. The mechanism of action of trimethyltin is unknown. 

Neurotoxicity Cells of the central nervous system, CNS (brain and spinal cord) and the peripheral nervous system (nerves outside the CNS) Neuronopathies (neuron injury) Axonopathies (axon injury) Demyelination (loss of axon insulation) Interference with neurotransmission... 

McLachlan RS and Brown WF (1995) Pyridoxine dependent epilepsy with iatrogenic sensory neuronopathy. Canadian Journal of Neurological Science 22, 50-1. 

Werler MM, Shapiro S, Mitchell AA (1993) Periconceptional foUc add exposure and risk of occurrent neural tube defects. JAMA 269(10) 1257-1261 Xu Y, Sladky JT, Brown MJ (1989) Dose-dependent expression of neuronopathy after experimental pyridoxine intoxication. Neurology 39(8) 1077-1083... 

The first eategory of neurotoxieants [e.g. doxombicin (England eta/., 1988), MPTP (Langston and Irwin, 1986), and trimethyltin (Bouldin et al, 1981)] results in a neuronopathy or death of a neuron, with subsequent degeneration of its associated axon, dendrites, and myelin sheath when present. 

Neuronopathy Loss of neurons with subsequent degeneration of axons, dendrites, and myelin sheath Doxorubicin MPTP Trimethyltin... 

England, J.D., Asbury, A.K., Rhee, E.K., Sumner, A.J. (1988). Lethal retrograde axoplasmic transport of doxorubicin (adria-mycin) to motor neurons. A toxic motor neuronopathy. Brain 111 (Pt 4) 915-26. 

Extrapyramidal syndrome Cerebellar syndrome, visual dysfunction, encephalopathy, CNS teratogenicity Peripheral neuropathy, encephalopathy Encephalopathy, neuronopathy (trimethyltin) leukoencephalopathy, vacuolar myelinopathy (triethyltin) Peripheral neuropathy, optic neuropathy Peripheral neuropathy Acute, chronic encephalopathy, CNS teratogenicity (fetal alcohol syndrome) Peripheral neuropathy Optical neuropathy... 

Ion channel syndrome (Na+ channels) Encephalopathy, neuronopathy, seizures Neuronopathy... 

Sendtner, M., Schmalbruch, H., Stbckli, K.A., Carroll, P., Kreutzberg, G.W. and Thoenen, H. (1992a) Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358 502-504. 

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