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Table of Contents
Vol. 22, No. 4, 2003
Issue release date: July–August 2003
Neuroepidemiology 2003;22:217–228
(DOI:10.1159/000070562)

An Evidence-Based Medicine Approach to the Evaluation of the Role of Exogenous Risk Factors in Sporadic Amyotrophic Lateral Sclerosis

Armon C.
Department of Neurology, Loma Linda University School of Medicine, Loma Linda, Calif., USA
email Corresponding Author

Abstract

An evidence-based medicine approach was applied to evaluate analytic studies of exogenous risk factors for amyotrophic lateral sclerosis (ALS) published since 1991. Classification systems for evaluating the literature and for drawing conclusions based on the class of available evidence were developed, modeled on those used by national societies. Considerations regarding the impact on the general public of confirming a role for putative risk factors were made explicit. There was evidence in support of smoking being a probable (‘more likely than not’) risk factor for ALS. Smoking has broad public health impact, no redeeming features, and is a modifiable risk factor. Evidence supported the conclusion that the following were probably not risk factors for ALS: trauma, physical activity, residence in rural areas and alcohol consumption. Evidence-based medicine methodology does not permit calculation of the magnitude of type I or type II errors in drawing these conclusions. New evidence may change these conclusions. Recommendations for future research include: draw on clinical trial methodology in designing future, confirmatory, case-control studies; consider utilizing cohort studies, recognizing the longer timelines for these to come to fruition; accord priority to investigating putative risk factors with greatest public health impact. Advances in study methodology may lead to development of finite research cycles for individual putative risk factors for sporadic ALS.


 goto top of outline Key Words

  • Motor neuron disease
  • Evidence-based medicine
  • Risk factors
  • Amyotrophic lateral sclerosis
  • Case-control studies
  • Cohort studies
  • Mortality studies
  • Occupations

 goto top of outline Abstract

An evidence-based medicine approach was applied to evaluate analytic studies of exogenous risk factors for amyotrophic lateral sclerosis (ALS) published since 1991. Classification systems for evaluating the literature and for drawing conclusions based on the class of available evidence were developed, modeled on those used by national societies. Considerations regarding the impact on the general public of confirming a role for putative risk factors were made explicit. There was evidence in support of smoking being a probable (‘more likely than not’) risk factor for ALS. Smoking has broad public health impact, no redeeming features, and is a modifiable risk factor. Evidence supported the conclusion that the following were probably not risk factors for ALS: trauma, physical activity, residence in rural areas and alcohol consumption. Evidence-based medicine methodology does not permit calculation of the magnitude of type I or type II errors in drawing these conclusions. New evidence may change these conclusions. Recommendations for future research include: draw on clinical trial methodology in designing future, confirmatory, case-control studies; consider utilizing cohort studies, recognizing the longer timelines for these to come to fruition; accord priority to investigating putative risk factors with greatest public health impact. Advances in study methodology may lead to development of finite research cycles for individual putative risk factors for sporadic ALS.

Copyright © 2003 S. Karger AG, Basel


 goto top of outline References
  1. Nelson LM: Epidemiology of ALS. Clin Neurosci 1995/96;3:327–331.
  2. Roman GC: Neuroepidemiology of amyotrophic lateral sclerosis: Clues to aetiology and pathogenesis. J Neurol Neurosurg Psychiatry 1996;61:131–137.
  3. Mitchell JD: Amyotrophic lateral sclerosis: Toxins and environment. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:235–250.
  4. Armon C: Environmental risk factors for amyotrophic lateral sclerosis. Neuroepidemiology 2001;20:2–6.
  5. Noonan CW, Sykes L, Hilsdon R: Motor neuron disease/amyotrophic lateral sclerosis: Preliminary Review of Environmental Risk Factors and Mortality in Bexar County, Texas. Agency for Toxic Substances and Disease Registry (March 5, 2002) http://www.atsdr.cdc.gov/NEWS/als_032002.html
  6. Armon C, Kurland LT: Classic and Western Pacific Amyotrophic Lateral Sclerosis: Epidemiologic comparisons; in Hudson AJ (ed): Amyotrophic Lateral Sclerosis: Concepts in Etiology and Pathogenesis. Toronto, University of Toronto Press, 1990, pp 144–165.
  7. Armon C, Kurland LT, Smith GE, Steele JS: Sporadic and Western Pacific Amyotrophic Lateral Sclerosis: Epidemiologic implications; in Smith RA (ed): Handbook of Amyotrophic Lateral Sclerosis. New York, Dekker, 1992, pp 93–131.
  8. Armon C: Motor neuron disease; in Gorelick PB, Alter M (eds): Handbook of Neuroepidemiology. New York, Dekker, 1994, pp 407–456.
  9. ALSA-Funded Workshop: Meeting Report. Environmental factors and genetic susceptibility in amyotrophic lateral sclerosis. May 29–31, 2002, Keystone, Colo. http://www.alsa.org/research/workshops1.cfm
  10. Kuller LH: Circular epidemiology. Am J Epidemiol 1999;150:897–903.
  11. Hirtz D, Ashwal S, Berg A, Bettis D, Camfield C, Camfield P, Crumrine P, Elterman R, Schneider S, Shinnar S: Practice parameter: Evaluating a first nonfebrile seizure in children. Report of the Quality Standards Subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology 2000;55:616–623.
  12. Lewis DW, Ashwal S, Dahl G, Dorbad D, Hirtz D, Prensky A, Jarjour I: Practice parameter: Evaluation of children and adolescents with recurrent headaches. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2002;59:490–498.
  13. Hill AB: The environment and disease: Association or causation? Proc R Soc Med 1965;58:295–300.
  14. US Department of Health, Education and Welfare: Smoking and health: A report of the Surgeon General. Washington, US Government Printing Office, 1964.
  15. Armon C, Kurland LT, Daube JR, O’Brien PC: Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. Neurology 1991;41:1077–1084.
  16. Chancellor AM, Slattery JM, Fraser H, Warlow CP: Risk factors for motor neuron disease: A case-control study based on patients from the Scottish Motor Neuron Disease Register. J Neurol Neurosurg Psychiatry 1993;56:1200–1206.
  17. Cruz DC, Nelson LM, McGuire V, Longstreth WT Jr: Physical trauma and family history of neurodegenerative diseases in amyotrophic lateral sclerosis: A population-based case-control study. Neuroepidemiology 1999;18:101–110.
  18. Gunnarsson LG, Lindberg G, Soderfeldt B, Axelson O: Amyotrophic lateral sclerosis in Sweden in relation to occupation. Acta Neurol Scand 1991;83:394–398.
  19. Longnecker MP, Kamel F, Umbach DM, Munsat TL, Shefner JM, Lansdell LW, Sandler DP: Dietary intake of calcium, magnesium and antioxidants in relation to risk of amyotrophic lateral sclerosis. Neuroepidemiology 2000;19:210–216.
  20. McGuire V, Longstreth WT Jr, Nelson LM, Koepsell TD, Checkoway H, Morgan MS, van Belle G: Occupational exposures and amyotrophic lateral sclerosis. A population-based case-control study. Am J Epidemiol 1997;145:1076–1088.
  21. Nelson LM, Matkin C, Longstreth WT Jr, McGuire V: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet. Am J Epidemiol 2000;151:164–173.
  22. Schulte PA, Burnett CA, Boeniger MF, Johnson J: Neurodegenerative diseases: Occupational occurrence and potential risk factors, 1982 through 1991. Am J Public Health 1996;86:1281–1288.
  23. Longstreth WT, McGuire V, Koepsell TD, Wang Y, van Belle G: Risk of amyotrophic lateral sclerosis and history of physical activity: A population-based case-control study. Arch Neurol 1998;55:201–206.
  24. Nelson LM, McGuire V, Longstreth WT Jr, Matkin C: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption. Am J Epidemiol 2000;151:156–163.
  25. Kamel F, Umbach DM, Munsat TL, Shefner JM, Sandler DP: Association of cigarette smoking with amyotrophic lateral sclerosis. Neuroepidemiology 1999;18:194–202.
  26. Kamel 2002 Kamel F, Umbach DM, Munsat TL, Shefner JM, Hu H, Sandler DP: Lead exposure and amyotrophic lateral sclerosis. Epidemiology 2002;13:311–319.
  27. Bergomi M, Vinceti M, Nacci G, Pietrini V, Bratter P, Alber D, Ferrari A, Vescovi L, Guidetti D, Sola P, Malagu S, Aramini C, Vivoli G: Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: A population-based case-control study. Environ Res 2002;89:116–123.
  28. McGuire V, Longstreth WT Jr, Koepsell TD, van Belle G: Incidence of amyotrophic lateral sclerosis in three counties in western Washington State. Neurology 1996;47:571–573.
  29. Andrews KW, Savitz DA: Accuracy of industry and occupation on death certificates of electric utility workers: Implications for epidemiologic studies of magnetic fields and cancer. Bioelectromagnetics 1999;20:512–518.
  30. Riggs JE, Schochet S Jr: Rising mortality due to Parkinson’s disease and amyotrophic lateral sclerosis: A manifestation of the competitive nature of human mortality. J Clin Epidemiol 1992;45:1007–1012.
  31. Armon C: ALS: Clinical and epidemiologic clues to pathogenesis; in Neurobiology of ALS. Course Syllabus, 51st Annual Meeting, American Academy of Neurology, 1999.
  32. Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Michalek AM, Laughlin R, Nemoto T, Gillenwater KA, Shields PG: Cigarette smoking, N-acetyltransferase-2 genetic polymorphisms, and breast cancer risk. JAMA 1996;276:1494–1501.
  33. Seljeseth YM, Vollset SE, Tysnes OB: Increasing mortality from amyotrophic lateral sclerosis in Norway? Neurology 2000;55:1262–1266.
  34. Esclaire F, Kisby G, Spencer P, Milne J, Lesort M, Hugon J: The Guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates τ mRNA expression and excitotoxicity. Exp Neurol 1999;155:11–21.
  35. Kisby GE, Kabel H, Hugon J, Spencer P: Damage and repair of nerve cell DNA in toxic stress. Drug Metab Rev 1999;31:589–618.
  36. Schaeffer MC, Rogers QR, Leung PM, Wolfe BM, Strombeck DR: Changes in cerebrospinal fluid and plasma amino acid concentrations with elevated dietary protein concentration in dogs with portocaval shunts. Life Sci 1991;48:2215–2223.

 goto top of outline Author Contacts

Carmel Armon, MD
Department of Neurology, Loma Linda University School of Medicine
11175 Campus Street, CP-11108
Loma Linda, CA 92354 (USA)
Tel. +1 909 5584907, Fax +1 909 5580207, E-Mail res0tna7@verizon.net


 goto top of outline Article Information

Number of Print Pages : 12
Number of Figures : 1, Number of Tables : 3, Number of References : 36


 goto top of outline Publication Details

Neuroepidemiology
Founded 1982 by B.S. Schoenberg, continued by M. Alter (1989–1996)

Vol. 22, No. 4, Year 2003 (Cover Date: July-August 2003)

Journal Editor: G.C. Román, San Antonio, Tex.
ISSN: 0251–5350 (print), 1423–0208 (Online)

For additional information: http://www.karger.com/journals/ned


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

An evidence-based medicine approach was applied to evaluate analytic studies of exogenous risk factors for amyotrophic lateral sclerosis (ALS) published since 1991. Classification systems for evaluating the literature and for drawing conclusions based on the class of available evidence were developed, modeled on those used by national societies. Considerations regarding the impact on the general public of confirming a role for putative risk factors were made explicit. There was evidence in support of smoking being a probable (‘more likely than not’) risk factor for ALS. Smoking has broad public health impact, no redeeming features, and is a modifiable risk factor. Evidence supported the conclusion that the following were probably not risk factors for ALS: trauma, physical activity, residence in rural areas and alcohol consumption. Evidence-based medicine methodology does not permit calculation of the magnitude of type I or type II errors in drawing these conclusions. New evidence may change these conclusions. Recommendations for future research include: draw on clinical trial methodology in designing future, confirmatory, case-control studies; consider utilizing cohort studies, recognizing the longer timelines for these to come to fruition; accord priority to investigating putative risk factors with greatest public health impact. Advances in study methodology may lead to development of finite research cycles for individual putative risk factors for sporadic ALS.



 goto top of outline Author Contacts

Carmel Armon, MD
Department of Neurology, Loma Linda University School of Medicine
11175 Campus Street, CP-11108
Loma Linda, CA 92354 (USA)
Tel. +1 909 5584907, Fax +1 909 5580207, E-Mail res0tna7@verizon.net


 goto top of outline Article Information

Number of Print Pages : 12
Number of Figures : 1, Number of Tables : 3, Number of References : 36


 goto top of outline Publication Details

Neuroepidemiology
Founded 1982 by B.S. Schoenberg, continued by M. Alter (1989–1996)

Vol. 22, No. 4, Year 2003 (Cover Date: July-August 2003)

Journal Editor: G.C. Román, San Antonio, Tex.
ISSN: 0251–5350 (print), 1423–0208 (Online)

For additional information: http://www.karger.com/journals/ned


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Nelson LM: Epidemiology of ALS. Clin Neurosci 1995/96;3:327–331.
  2. Roman GC: Neuroepidemiology of amyotrophic lateral sclerosis: Clues to aetiology and pathogenesis. J Neurol Neurosurg Psychiatry 1996;61:131–137.
  3. Mitchell JD: Amyotrophic lateral sclerosis: Toxins and environment. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:235–250.
  4. Armon C: Environmental risk factors for amyotrophic lateral sclerosis. Neuroepidemiology 2001;20:2–6.
  5. Noonan CW, Sykes L, Hilsdon R: Motor neuron disease/amyotrophic lateral sclerosis: Preliminary Review of Environmental Risk Factors and Mortality in Bexar County, Texas. Agency for Toxic Substances and Disease Registry (March 5, 2002) http://www.atsdr.cdc.gov/NEWS/als_032002.html
  6. Armon C, Kurland LT: Classic and Western Pacific Amyotrophic Lateral Sclerosis: Epidemiologic comparisons; in Hudson AJ (ed): Amyotrophic Lateral Sclerosis: Concepts in Etiology and Pathogenesis. Toronto, University of Toronto Press, 1990, pp 144–165.
  7. Armon C, Kurland LT, Smith GE, Steele JS: Sporadic and Western Pacific Amyotrophic Lateral Sclerosis: Epidemiologic implications; in Smith RA (ed): Handbook of Amyotrophic Lateral Sclerosis. New York, Dekker, 1992, pp 93–131.
  8. Armon C: Motor neuron disease; in Gorelick PB, Alter M (eds): Handbook of Neuroepidemiology. New York, Dekker, 1994, pp 407–456.
  9. ALSA-Funded Workshop: Meeting Report. Environmental factors and genetic susceptibility in amyotrophic lateral sclerosis. May 29–31, 2002, Keystone, Colo. http://www.alsa.org/research/workshops1.cfm
  10. Kuller LH: Circular epidemiology. Am J Epidemiol 1999;150:897–903.
  11. Hirtz D, Ashwal S, Berg A, Bettis D, Camfield C, Camfield P, Crumrine P, Elterman R, Schneider S, Shinnar S: Practice parameter: Evaluating a first nonfebrile seizure in children. Report of the Quality Standards Subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology 2000;55:616–623.
  12. Lewis DW, Ashwal S, Dahl G, Dorbad D, Hirtz D, Prensky A, Jarjour I: Practice parameter: Evaluation of children and adolescents with recurrent headaches. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2002;59:490–498.
  13. Hill AB: The environment and disease: Association or causation? Proc R Soc Med 1965;58:295–300.
  14. US Department of Health, Education and Welfare: Smoking and health: A report of the Surgeon General. Washington, US Government Printing Office, 1964.
  15. Armon C, Kurland LT, Daube JR, O’Brien PC: Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. Neurology 1991;41:1077–1084.
  16. Chancellor AM, Slattery JM, Fraser H, Warlow CP: Risk factors for motor neuron disease: A case-control study based on patients from the Scottish Motor Neuron Disease Register. J Neurol Neurosurg Psychiatry 1993;56:1200–1206.
  17. Cruz DC, Nelson LM, McGuire V, Longstreth WT Jr: Physical trauma and family history of neurodegenerative diseases in amyotrophic lateral sclerosis: A population-based case-control study. Neuroepidemiology 1999;18:101–110.
  18. Gunnarsson LG, Lindberg G, Soderfeldt B, Axelson O: Amyotrophic lateral sclerosis in Sweden in relation to occupation. Acta Neurol Scand 1991;83:394–398.
  19. Longnecker MP, Kamel F, Umbach DM, Munsat TL, Shefner JM, Lansdell LW, Sandler DP: Dietary intake of calcium, magnesium and antioxidants in relation to risk of amyotrophic lateral sclerosis. Neuroepidemiology 2000;19:210–216.
  20. McGuire V, Longstreth WT Jr, Nelson LM, Koepsell TD, Checkoway H, Morgan MS, van Belle G: Occupational exposures and amyotrophic lateral sclerosis. A population-based case-control study. Am J Epidemiol 1997;145:1076–1088.
  21. Nelson LM, Matkin C, Longstreth WT Jr, McGuire V: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet. Am J Epidemiol 2000;151:164–173.
  22. Schulte PA, Burnett CA, Boeniger MF, Johnson J: Neurodegenerative diseases: Occupational occurrence and potential risk factors, 1982 through 1991. Am J Public Health 1996;86:1281–1288.
  23. Longstreth WT, McGuire V, Koepsell TD, Wang Y, van Belle G: Risk of amyotrophic lateral sclerosis and history of physical activity: A population-based case-control study. Arch Neurol 1998;55:201–206.
  24. Nelson LM, McGuire V, Longstreth WT Jr, Matkin C: Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption. Am J Epidemiol 2000;151:156–163.
  25. Kamel F, Umbach DM, Munsat TL, Shefner JM, Sandler DP: Association of cigarette smoking with amyotrophic lateral sclerosis. Neuroepidemiology 1999;18:194–202.
  26. Kamel 2002 Kamel F, Umbach DM, Munsat TL, Shefner JM, Hu H, Sandler DP: Lead exposure and amyotrophic lateral sclerosis. Epidemiology 2002;13:311–319.
  27. Bergomi M, Vinceti M, Nacci G, Pietrini V, Bratter P, Alber D, Ferrari A, Vescovi L, Guidetti D, Sola P, Malagu S, Aramini C, Vivoli G: Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: A population-based case-control study. Environ Res 2002;89:116–123.
  28. McGuire V, Longstreth WT Jr, Koepsell TD, van Belle G: Incidence of amyotrophic lateral sclerosis in three counties in western Washington State. Neurology 1996;47:571–573.
  29. Andrews KW, Savitz DA: Accuracy of industry and occupation on death certificates of electric utility workers: Implications for epidemiologic studies of magnetic fields and cancer. Bioelectromagnetics 1999;20:512–518.
  30. Riggs JE, Schochet S Jr: Rising mortality due to Parkinson’s disease and amyotrophic lateral sclerosis: A manifestation of the competitive nature of human mortality. J Clin Epidemiol 1992;45:1007–1012.
  31. Armon C: ALS: Clinical and epidemiologic clues to pathogenesis; in Neurobiology of ALS. Course Syllabus, 51st Annual Meeting, American Academy of Neurology, 1999.
  32. Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Michalek AM, Laughlin R, Nemoto T, Gillenwater KA, Shields PG: Cigarette smoking, N-acetyltransferase-2 genetic polymorphisms, and breast cancer risk. JAMA 1996;276:1494–1501.
  33. Seljeseth YM, Vollset SE, Tysnes OB: Increasing mortality from amyotrophic lateral sclerosis in Norway? Neurology 2000;55:1262–1266.
  34. Esclaire F, Kisby G, Spencer P, Milne J, Lesort M, Hugon J: The Guam cycad toxin methylazoxymethanol damages neuronal DNA and modulates τ mRNA expression and excitotoxicity. Exp Neurol 1999;155:11–21.
  35. Kisby GE, Kabel H, Hugon J, Spencer P: Damage and repair of nerve cell DNA in toxic stress. Drug Metab Rev 1999;31:589–618.
  36. Schaeffer MC, Rogers QR, Leung PM, Wolfe BM, Strombeck DR: Changes in cerebrospinal fluid and plasma amino acid concentrations with elevated dietary protein concentration in dogs with portocaval shunts. Life Sci 1991;48:2215–2223.