Download PDF
Semin Neurol 2005; 25(2): 204-216
DOI: 10.1055/s-2005-871329
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Medication and Toxin-Induced Peripheral Neuropathy

Robert W. Pratt1 , Louis H. Weimer1
  • 1Department of Neurology, The Neurological Institute, New York, New York
Further Information

Publication History

Publication Date:
03 June 2005 (online)

    Permissions and Reprints

ABSTRACT

Medication and toxin-induced neuropathies, although uncommon, are important to identify because of potential reversibility. Numerous medications and toxins are implicated with neuropathy, but objective proof is lacking for many. Chemotherapeutic agents, nucleoside analogs, and other medications and toxins have clear causative links with neuropathy, but many agents have only rare temporal associations. Neuropathies are being recognized from new medications approved for use and other medications, which have expanded indications. Some established associations with neuropathy are less widely known while others are overestimated. Peripheral neuropathy from chronic drug exposure is more problematic to determine. Axonal pathology is most common, but some agents cause demyelination and even conduction block, mimicking immune-mediated neuropathies. Multiple and varied toxic mechanisms are implicated. Neuropathy is a dose-limiting complication of some critical treatments and preventative agents are being actively pursued.

KEYWORDS

Peripheral neuropathy - polyneuropathy - neurotoxicity - coasting - toxic - drug-induced - demyelinating neuropathy - conduction block - chemotherapy

REFERENCES

  • 1 Jain K K. Drug-induced peripheral neuropathies. In: Jain KK Drug-Induced Neurological Disorders. 2nd ed. Seattle; Hogrefe & Huber 2001: 263-294
    Google Scholar
  • 2 Hill A B. The environment and disease: association or causation?.  Proc R Soc Med. 1965;  58 295-300
    PubMedGoogle Scholar
  • 3 Chaudhry V, Chaudhry M, Crawford T O et al.. Toxic neuropathy in patients with pre-existing neuropathy.  Neurology. 2003;  60 337-340
    CrossrefPubMedGoogle Scholar
  • 4 Graf W D, Chance P F, Lensch M W et al.. Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A.  Cancer. 1996;  77 1356-1362
    CrossrefPubMedGoogle Scholar
  • 5 Prezant T R, Agapian J V, Bohlman M C et al.. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.  Nat Genet. 1993;  4 289-294
    CrossrefPubMedGoogle Scholar
  • 6 Wang M S, Fang G, Culver D G et al.. The WldS protein protects against axonal degeneration: a model of gene therapy for peripheral neuropathy.  Ann Neurol. 2001;  50 773-779
    CrossrefPubMedGoogle Scholar
  • 7 Peltier A C, Russell J W. Recent advances in drug-induced neuropathies.  Curr Opin Neurol. 2002;  15 633-638
    CrossrefPubMedGoogle Scholar
  • 8 Dalakas M C. Peripheral neuropathy and antiretroviral drugs.  J Peripher Nerv Syst. 2001;  6 14-20
    PubMedGoogle Scholar
  • 9 Dalakas M C, Semino-Mora C, Leon-Monzon M. Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3′-dideoxycytidine (ddC).  Lab Invest. 2001;  81 1537-1544
    CrossrefPubMedGoogle Scholar
  • 10 Moyle G J, Sadler M. Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management.  Drug Saf. 1998;  19 481-494
    CrossrefPubMedGoogle Scholar
  • 11 Kapoor K, Chandra M, Nag D et al.. Evaluation of metronidazole toxicity: a prospective study.  Int J Clin Pharmacol Res. 1999;  19 83-88
    PubMedGoogle Scholar
  • 12 Rustscheff S, Hulten S. An unexpected and severe neurological disorder with permanent disability acquired during short-course treatment with metronidazole.  Scand J Infect Dis. 2003;  35 279-280
    PubMedGoogle Scholar
  • 13 Navarro J C, Rosales R L, Ordinario A T, Izumo S, Osame M. Acute dapsone-induced peripheral neuropathy.  Muscle Nerve. 1989;  12 604-606
    PubMedGoogle Scholar
  • 14 Koller W C, Gehlmann L K, Malkinson F D, Davis F A. Dapsone-induced peripheral neuropathy.  Arch Neurol. 1977;  34 644-646
    CrossrefPubMedGoogle Scholar
  • 15 Ng T H, Chan Y W, Yu Y L et al.. Encephalopathy and neuropathy following ingestion of a Chinese herbal broth containing podophyllin.  J Neurol Sci. 1991;  101 107-113
    CrossrefPubMedGoogle Scholar
  • 16 Filley C M, Graff-Richard N R, Lacy J R, Heitner M A, Earnest M P. Neurologic manifestations of podophyllin toxicity.  Neurology. 1982;  32 308-311
    PubMedGoogle Scholar
  • 17 Breen R A, Lipman M C, Johnson M A. Increased incidence of peripheral neuropathy with co-administration of stavudine and isoniazid in HIV-infected individuals.  AIDS. 2000;  14 615
    PubMedGoogle Scholar
  • 18 Moosmann B, Behl C. Selenoprotein synthesis and side-effects of statins.  Lancet. 2004;  363 892-894
    CrossrefPubMedGoogle Scholar
  • 19 Jeppesen U, Giast D, Smith T, Sindrup S H. Statins and peripheral neuropathy.  Eur J Clin Pharmacol. 1999;  54 835-838
    CrossrefPubMedGoogle Scholar
  • 20 Gaist D, Garcia Rodriguez L A, Huerta C, Hallas J, Sindrup S H. Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?.  Eur J Clin Pharmacol. 2001;  56 931-933
    CrossrefPubMedGoogle Scholar
  • 21 Gaist D, Jeppesen U, Andersen M, Garcia Rodriguez L A, Hallas J, Sindrup S H. Statins and risk of polyneuropathy: a case-control study.  Neurology. 2002;  58 1333-1337
    CrossrefPubMedGoogle Scholar
  • 22 Charness M E, Morady F, Scheinman M M. Frequent neurologic toxicity associated with amiodarone therapy.  Neurology. 1984;  34 669-671
    CrossrefPubMedGoogle Scholar
  • 23 Santoro L, Barbieri F, Nucciotti R et al.. Amiodarone-induced experimental acute neuropathy in rats.  Muscle Nerve. 1992;  15 788-795
    PubMedGoogle Scholar
  • 24 Fraser A G, McQueen I N, Watt A H, Stephens M R. Peripheral neuropathy during long-term high-dose amiodarone therapy.  J Neurol Neurosurg Psychiatry. 1985;  48 576-578
    CrossrefPubMedGoogle Scholar
  • 25 Windebank A J. Chemotherapeutic neuropathy.  Curr Opin Neurol. 1999;  12 565-571
    CrossrefPubMedGoogle Scholar
  • 26 Quasthoff S, Hartung H P. Chemotherapy-induced peripheral neuropathy.  J Neurol. 2002;  249 9-17
    CrossrefPubMedGoogle Scholar
  • 27 Krarup-Hansen A, Rietz B, Krarup C et al.. Histology and platinum content of sensory ganglia and sural nerves in patients treated with cisplatin and carboplatin: an autopsy study.  Neuropathol Appl Neurobiol. 1999;  25 29-40
    PubMedGoogle Scholar
  • 28 Lehky T J, Leonard G D, Wilson R H et al.. Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy.  Muscle Nerve. 2004;  29 387-392
    CrossrefPubMedGoogle Scholar
  • 29 Weimer L H. Medication-induced peripheral neuropathy.  Curr Neurol Neurosci Rep. 2003;  3 86-92
    PubMedGoogle Scholar
  • 30 Russell J W, Gill J S, Sorenson E J, Schultz D A, Windebank A J. Suramin-induced neuropathy in an animal model.  J Neurol Sci. 2001;  192 71-80
    CrossrefPubMedGoogle Scholar
  • 31 Chaudhry V, Eisenberger M A, Sinibaldi V J, Sheikh K, Griffin J W, Cornblath D R. A prospective study of suramin-induced peripheral neuropathy.  Brain. 1996;  119 2039-2052
    CrossrefPubMedGoogle Scholar
  • 32 Soliven B, Dhand U K, Kobayashi K et al.. Evaluation of neuropathy in patients on suramin treatment.  Muscle Nerve. 1997;  20 83-91
    PubMedGoogle Scholar
  • 33 Gill J S, Windebank A J. Ceramide initiates NFkappaB-mediated caspase activation in neuronal apoptosis.  Neurobiol Dis. 2000;  7 448-461
    CrossrefPubMedGoogle Scholar
  • 34 Dawkins J L, Hulme D J, Brahmbhatt S B, Auer-Grumbach M, Nicholson G A. Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I.  Nat Genet. 2001;  27 309-312
    PubMedGoogle Scholar
  • 35 Richardson P G, Barlogie B, Berenson J et al.. A phase 2 study of bortezomib in relapsed, refractory myeloma.  N Engl J Med. 2003;  348 2609-2617
    CrossrefPubMedGoogle Scholar
  • 36 Kane R C, Bross P F, Farrell A T, Pazdur R. Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy.  Oncologist. 2003;  8 508-513
    CrossrefPubMedGoogle Scholar
  • 37 Davis N B, Taber D A, Ansari R H et al.. Phase II trial of PS-341 in patients with renal cell cancer: a University of Chicago phase II consortium study.  J Clin Oncol. 2004;  22 115-119
    PubMedGoogle Scholar
  • 38 Giannini F, Volpi N, Rossi S, Passero S, Fimiani M, Cerase A. Thalidomide-induced neuropathy: a ganglionopathy?.  Neurology. 2003;  60 877-878
    CrossrefPubMedGoogle Scholar
  • 39 Briani C, Zara G, Rondinone R et al.. Thalidomide neurotoxicity: prospective study in patients with lupus erythematosus.  Neurology. 2004;  62 2288-2290
    PubMedGoogle Scholar
  • 40 Chaudhry V, Cornblath D R, Corse A, Freimer M, Simmons-O'Brien E, Vogelsang G. Thalidomide-induced neuropathy.  Neurology. 2002;  59 1872-1875
    CrossrefPubMedGoogle Scholar
  • 41 Cavaletti G, Beronio A, Reni L et al.. Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study.  Neurology. 2004;  62 2291-2293
    PubMedGoogle Scholar
  • 42 Molloy F M, Floeter M K, Syed N A et al.. Thalidomide neuropathy in patients treated for metastatic prostate cancer.  Muscle Nerve. 2001;  24 1050-1057
    CrossrefPubMedGoogle Scholar
  • 43 Hilkens P H, Verweij J, Stoter G, Vecht C J, van Putten W L, van den Bent M J. Peripheral neurotoxicity induced by docetaxel.  Neurology. 1996;  46 104-108
    PubMedGoogle Scholar
  • 44 van Gerven J M, Moll J W, van den Bent M J et al.. Paclitaxel (Taxol) induces cumulative mild neurotoxicity.  Eur J Cancer. 1994;  30A 1074-1077
    PubMedGoogle Scholar
  • 45 Gedlicka C, Kornek G V, Schmid K, Scheithauer W. Amelioration of docetaxel/cisplatin induced polyneuropathy by alpha-lipoic acid.  Ann Oncol. 2003;  14 339-340
    CrossrefPubMedGoogle Scholar
  • 46 Roberts J A, Jenison E L, Kim K et al.. A randomized, multicenter, double-blind, placebo controlled, dose-finding study of ORG 2766 in the prevention or delay of cisplatin-induced neuropathies in women with ovarian cancer.  Gynecol Oncol. 1997;  67 172-177
    CrossrefPubMedGoogle Scholar
  • 47 Chattopadhyay M, Goss J, Wolfe D et al.. Protective effect of herpes simplex virus-mediated neurotrophin gene transfer in cisplatin neuropathy.  Brain. 2004;  127 929-939
    CrossrefPubMedGoogle Scholar
  • 48 Bonnel R A, Graham D J. Peripheral neuropathy in patients treated with leflunomide.  Clin Pharmacol Ther. 2004;  75 580-585
    CrossrefPubMedGoogle Scholar
  • 49 Carulli M T, Davies U M. Peripheral neuropathy: an unwanted effect of leflunomide?.  Rheumatology (Oxford). 2002;  41 952-953
    CrossrefPubMedGoogle Scholar
  • 50 Bronster D J, Yonover P, Stein J, Scelsa S N, Miller C M, Sheiner P A. Demyelinating sensorimotor polyneuropathy after administration of FK506.  Transplantation. 1995;  59 1066-1068
    PubMedGoogle Scholar
  • 51 Ayres R C, Dousset B, Wixon S, Buckels J A, McMaster P, Mayer A D. Peripheral neurotoxicity with tacrolimus.  Lancet. 1994;  343 862-863
    PubMedGoogle Scholar
  • 52 Soto O, Hedley-Whyte E T. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2003. A 37-year-old man with a history of alcohol and drug abuse and sudden onset of leg weakness.  N Engl J Med. 2003;  349 1656-1663
    CrossrefPubMedGoogle Scholar
  • 53 Kuncl R W, Duncan G, Watson D, Alderson K, Rogawski M A, Peper M. Colchicine myopathy and neuropathy.  N Engl J Med. 1987;  316 1562-1568
    CrossrefPubMedGoogle Scholar
  • 54 Berger A R, Schaumburg H H, Schroeder C, Apfel S, Reynolds R. Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity.  Neurology. 1992;  42 1367-1370
    PubMedGoogle Scholar
  • 55 Albin R L, Albers J W. Long-term follow-up of pyridoxine-induced acute sensory neuropathy-neuronopathy.  Neurology. 1990;  40 1319
    PubMedGoogle Scholar
  • 56 Spruijt L, Naviaux R K, McGowan K A et al.. Nerve conduction changes in patients with mitochondrial diseases treated with dichloroacetate.  Muscle Nerve. 2001;  24 916-924
    PubMedGoogle Scholar
  • 57 Wu P B, Kingery W S, Date E S. An EMG case report of lead neuropathy 19 years after a shotgun injury.  Muscle Nerve. 1995;  18 326-329
    PubMedGoogle Scholar
  • 58 Ratnaike R N. Acute and chronic arsenic toxicity.  Postgrad Med J. 2003;  79 391-396
    CrossrefPubMedGoogle Scholar
  • 59 Davis L E, Standefer J C, Kornfeld M, Abercrombie D M, Butler C. Acute thallium poisoning: toxicological and morphological studies of the nervous system.  Ann Neurol. 1981;  10 38-44
    CrossrefPubMedGoogle Scholar
  • 60 Clarkson T W, Magos L, Myers G J. The toxicology of mercury: current exposures and clinical manifestations.  N Engl J Med. 2003;  349 1731-1737
    CrossrefPubMedGoogle Scholar
  • 61 Monforte R, Estruch R, Valls-Sole J, Nicolas J, Villalta J, Urbano-Marquez A. Autonomic and peripheral neuropathies in patients with chronic alcoholism. A dose-related toxic effect of alcohol.  Arch Neurol. 1995;  52 45-51
    PubMedGoogle Scholar
  • 62 Vittadini G, Buonocore M, Colli G, Terzi M, Fonte R, Biscaldi G. Alcoholic polyneuropathy: a clinical and epidemiological study.  Alcohol Alcohol. 2001;  36 393-400
    PubMedGoogle Scholar
  • 63 Ishibashi S, Yokota T, Shiojiri T et al.. Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?.  J Neurol Neurosurg Psychiatry. 2003;  74 674-676
    CrossrefPubMedGoogle Scholar
  • 64 Behse F, Buchthal F. Alcoholic neuropathy: clinical, electrophysiological, and biopsy findings.  Ann Neurol. 1977;  2 95-110
    CrossrefPubMedGoogle Scholar
  • 65 Koike H, Iijima M, Sugiura M et al.. Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy.  Ann Neurol. 2003;  54 19-29
    CrossrefPubMedGoogle Scholar
  • 66 Jokanovic M, Stukalov P V, Kosanovic M. Organophosphate induced delayed polyneuropathy.  Curr Drug Targets CNS Neurol Disord. 2002;  1 593-602
    PubMedGoogle Scholar
  • 67 Morgan J P, Penovich P. Jamaica ginger paralysis. Forty-seven-year follow-up.  Arch Neurol. 1978;  35 530-532
    PubMedGoogle Scholar
  • 68 Tobe T J, Braam G B, Meulenbelt J, van Dijk G W. Ethylene glycol poisoning mimicking Snow White.  Lancet. 2002;  359 444-445
    PubMedGoogle Scholar
  • 69 Chang A P, England J D, Garcia C A, Sumner A J. Focal conduction block in n-hexane polyneuropathy.  Muscle Nerve. 1998;  21 964-969
    PubMedGoogle Scholar
  • 70 Smith A G, Albers J W. n-Hexane neuropathy due to rubber cement sniffing.  Muscle Nerve. 1997;  20 1445-1450
    CrossrefPubMedGoogle Scholar
  • 71 Kinsella L J, Green R. “Anesthesia paresthetica”: nitrous oxide-induced cobalamin deficiency.  Neurology. 1995;  45 1608-1610
    CrossrefPubMedGoogle Scholar
  • 72 Butera R, Prockop L D, Buonocore M, Locatelli C, Gandini C, Manzo L. Mild ciguatera poisoning: case reports with neurophysiological evaluations.  Muscle Nerve. 2000;  23 1598-1603
    PubMedGoogle Scholar
  • 73 Perez C M, Vasquez P A, Perret C F. Treatment of ciguatera poisoning with gabapentin.  N Engl J Med. 2001;  344 692-693
    CrossrefPubMedGoogle Scholar
  • 74 Pearn J. Neurology of ciguatera.  J Neurol Neurosurg Psychiatry. 2001;  70 4-8
    CrossrefPubMedGoogle Scholar
  • 75 Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy.  Neurology. 2002;  58 873-880
    CrossrefPubMedGoogle Scholar
  • 76 Felz M W, Smith C D, Swift T R. A six-year-old girl with tick paralysis.  N Engl J Med. 2000;  342 90-94
    CrossrefPubMedGoogle Scholar
  • 77 Vedanarayanan V V, Evans O B, Subramony S H. Tick paralysis in children: electrophysiology and possibility of misdiagnosis.  Neurology. 2002;  59 1088-1090
    CrossrefPubMedGoogle Scholar

Louis H WeimerM.D. 

Associate Clinical Professor of Neurology, Department of Neurology, Columbia University College of Physicians & Surgeons

The Neurological Institute, 710 West 168th Street

Unit 55, New York, NY 10032

      >