Toxic Neuropathies

Antiretroviral toxic neuropathy Any stage Subacute rarely acute with lactic acidosis Distal sensory loss and neuropathic pain Toxic neuropathy mitochondrial damage... 

The phenotype and clinical presentation of antiretroviral toxic neuropathy (ATN) are similar to those of HIV-associated DSP. However, ATN is more likely to be painful, and has an abrupt onset and rapid progression. The main diagnostic clue is the temporal relationship of peripheral neuropathy to the start of NRTI therapy and stabilization, or at least the partial resolution when therapy is interrupted (Moyle and Sadler 1998). ATN most often develops after a mean of 16 to 20 weeks of treatment, unless there are other conditions that lower the threshold. Symptomatic improvement over weeks to months has been reported in two thirds of patients after discontinuation of the offending drug, but may be preceded by an initial period of worsening symptoms, also known as coasting (Berger et al. 1993). Despite the improvement, most patients do not return to a completely asymptomatic state (Hoke and Comblath 2004). 

Blum AS, Dal Pan GJ et al (1996) Low-dose zalcitabine-related toxic neuropathy frequency, natural history, and risk factors. Neurology 46(4) 999-1003 Bradley WG, Verma A (1996) Painful vascuhtic neuropathy in HlV-1 infection relief of pain with prednisone therapy. Neurology 47(6) 1446-1451 Breen EC (2002) Pro- and anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome. Pharmacol Ther 95(3) 295-304 Bremer J (1990) The role of carnitine in intracellular metabolism. J Clin Chem Clin Biochem 28(5) 297-301... 

Herzberg U, Sagen J (2001) Peripheral nerve exposure to HIV viral envelope protein gpl20 induces neuropathic pain and spinal gliosis. J Neuroimmunol 116(l) 29-39 Herzmann C, Johnson MA et al (2005) Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clin Trials 6(6) 344-350... 

Keswani SC, Chander B et al (2003a) FK506 is neuroprotective in a model of antiretroviral toxic neuropathy. Ann Neurol 53(l) 57-64... 

Youle M, Oslo M (2007) A double-blind, parallel-group, placebo-controUed, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV Med 8(4) 241-250... 

Cavanagh JB, Buxton PH. 1989. Trichloroethylene cranial neuropathy Is it really a toxic neuropathy or does it activate latent herpes virus J Neurol Neurosurg Psychiatry 52 297-303. 

Cisplatin-docetaxel diarrhea, cardiac toxicity, renal toxicity, neuropathy, weakness, hypersensitivity reactions, anemia Infection, thromocytopenia, nausea, vomiting, diarrhea, cardiac, High (day 1 only)... 

Docetaxel asthenia, peripheral neuropathy, alopecia, cardiovascular Fatigue, nausea, vomiting, skin toxicity, neuropathy, anemia, Mild (on administration days... 

Asbury AK. 1979. Pathology of industrial toxic neuropathies. Acta Neurol Scand SuppI 60 52-53. 

It is worth noting that some NNRTl combinations are not recommended in clinical practice. The AZT/d4T combination is antagonistic while a d4T/ddI combination leads to severe toxicity (neuropathy, acidosis and pancreatitis). A TDF/ddI combination with 3TC is associated with poor virologic... 

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. ... 

Detailed studies of the PNS in animal models of toxic neuropathy reveal that in most instances the axonal degeneration initially involves only the distal end of the... 

Among the best studied of these morphologic abnormalities associated with toxic neuropathies are the large masses of neurolilaments that accumulate locally within axons during intoxication with 2,5-hexanedione (2,5-HD) and related y-diketones, as well as with acrylamide, p, 3-iminodipropionitrile (IDPN), and carbon disulfide. 

Umapathi, T., and Chaudhry, V. Toxic neuropathy. Curr. Opin. Neurol. 18, 574-580, 2005. 

Cavanagh, J.B. (1984). Towards the molecular basis of toxic neuropathies. In Recent Advances in Nervous System Toxicology (C.L. Galli et al, eds), pp. 23-42. Plenum Press, New York, NY. 

A review of certain chemicals is essential. Ethylene glycol is an antifreeze used for gasoline engines and may produce somnolence, imreactive pupils, disc swelling, and kidney failure. Systemic lead poisoning produces headaches, coma, cranial nerve palsies, and papilledema. Wood alcohol, or methanol, may produce severe toxic neuropathy and disc edema. Drugs known to produce toxic optic neuropathy include amiodarone (an antiar-rhythmic), quinine, aminoquinolines, ibuprofen, ethambutol, isoniazid, and chloramphenicol. 

Fichtenbaum CJ, Clifford DB, Powderly WG. Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol 1995 10(2) 169-74. 

Berger AR, Schaumburg HH, Schroeder C, et al. (1992) Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy A prospective study of pyridoxine neurotoxicity. Neurology 42(7) 1367-1370. 

Peripheral neuropathy may be the most frequent neurologic disorder associated with HIV infection (Cherry et al., 2005). Its symptoms cause substantial morbidity and discomfort to patients with AIDS. A 30%-35% prevalence of peripheral neuropathy has been documented in patients with HIV infection, but autopsy-based studies have found it in nearly 100% of patients who died of AIDS. The most common peripheral neuropathy associated with HIV occurs in the later stages of HIV disease, usually after the patient has had other AIDS defining illnesses. Symptoms of HIV-associated sensory neuropathies are almost identical to those of other sensory neuropathies. Both distal sensory neuropathy due to HIV infection (seen mainly in late disease) and antiretroxdral toxic neuropathy occur, or sensory neuropathy is caused by a combination of both (Cherry et al., 2005). 

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