Toxic Disorders and Encephalopathy



The purpose of this chapter is to selectively review the literature on the neuroanatomical, neuropsychological, and emotional/behavioral effects of exposure to three different substances: organic solvents, lead, and carbon monoxide. Recent research regarding each of these substances has provided a window into the mechanisms for changes in behavior and cognition. There are far too many substances known to affect the central nervous system to review them all here. In addition, the volume of literature on each of the substances we discuss is too large for comprehensive review. Rather, our goal is to provide clinicians with a theoretical background of the changes in behavior/emotions and cognition commonly observed with exposure to these substances and to provide guidance for assessing exposed individuals. For each substance, we will review the particulars of exposure and symptom expression, the neurobehavioral symptoms, the neuroimaging changes, and the relationship between these. Based upon these findings, where possible, we will recommend areas to focus on and hypotheses to explore when evaluating patients with such exposures. We will finish up by addressing general themes for the assessment of patients with a history of toxic exposure, including measurement of exposure, determination of effort in medical–legal cases, and collaboration with occupational medicine specialists.


White Matter Single Photon Emission Computerize Tomography Fractional Anisotropy Corpus Callosum Magnetic Resonance Spectroscopy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Baker EL, Fine LJ. Solvent neurotoxicity: the current evidence. J Occup Med. 1986;28:126–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Baker EL. A review of recent research on health effects of human occupational exposure to organic solvents: a critical review. J Occup Med. 1994;36:1079–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Hartman DE. Neuropsychological toxicology: identification and assessment of human neurotoxic syndromes. 2nd ed. Newyork, NY: Springer; 1995.Google Scholar
  4. 4.
    Jin CF, Haut M, Ducatman A. Industrial solvents and psychological effects. Clin Occup Environ Med. 2004;4:597–620.PubMedCrossRefGoogle Scholar
  5. 5.
    Mikkelsen S. Epidemiological update on solvent neurotoxicity. Environ Res. 1997;73:101–12.PubMedCrossRefGoogle Scholar
  6. 6.
    White R, Proctor S. Solvent encephalopathy. In: Parks RW, Zec RF, Wilson RS editors. Neuropsychology of Alzheimer’s disease and other dementias. Oxford, England: Oxford University Press; 1993. pp. 350–74.Google Scholar
  7. 7.
    Meyer-Baron M, Blaszkewicz M, Henke H, Knapp G, Muttray A, Schaper M, van Thriel C. The impact of solvent mixtures on neurobehavioral performance: conclusions from epidemiological data. Neurotoxicology. 2008;29:349–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Hanninen H, Antti-Poika M, Juntenen J, Koskenvuo M. Exposure to organic solvents and neuropsychological dysfunction: a study on monozygotic twins. Br J Ind Med. 1991;48:18–25.PubMedGoogle Scholar
  9. 9.
    Akila R, Muller K, Kaukianinen A, Sainio M. Memory performance profile in occupational chronic solvent encephalopathy suggests working memory dysfunction. J Clin Exp Neuropsychol. 2006;28:1307–26.PubMedCrossRefGoogle Scholar
  10. 10.
    Morrow LA. Cueing attention: Disruptions following organic solvent exposure. Neuropsychology. 1994;8:471–6.CrossRefGoogle Scholar
  11. 11.
    Morrow L, Robin N, Hodgson MJ, Kamis H. Assessment of attention and memory efficiency in persons with solvent neurotoxicity. Neuropsychologia. 1992;30:911–22.PubMedCrossRefGoogle Scholar
  12. 12.
    Morrow L, Muldoon SB, Sandstrom DJ. Neuropsychological sequelae associated with occupational and environmental exposure to chemicals. In: Tarter R, Butters M, Beers S, editors. Medical neuropsychology: the impact of disease on behavior. 2nd ed. New York, NY: Kluwer Academic/Plenum Publishers; 2001a. pp. 199–245.Google Scholar
  13. 13.
    Morrow LA, Steinhauer SR, Condray R, Hodgson M. Neuropsychological performance of journeymen painters under acute solvent exposure and exposure-free conditions. J Int Neuropsychol Soc. 1997;3:269–75.PubMedGoogle Scholar
  14. 14.
    Morrow LA, Ryan CM, Hodgson MJ, Robin N. Risk factors associated with persistence of neuropsychological deficits in persons with organic solvent exposure. J Nerv Ment Dis. 1991;179:540–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Nilson LN, Sallsten G, Hagber S, Backman L, Barregard L. Influence of solvent exposure and aging on cognitive functioning: an 18 year follow up of formerly exposed layers and their controls. Occup Environ Med. 2002;59:49–57.PubMedCrossRefGoogle Scholar
  16. 16.
    Nilson LN, Backman L, Sallsten G, Hagberg S, Barregard L. Dose-related cognitive deficits among floor layers with previous heavy exposure to solvents. Arch Environ Health. 2003;58:208–17.PubMedCrossRefGoogle Scholar
  17. 17.
    Condray R, Morrow LA, Steinhauer SR, Hodgson M, Kelley M. Mood and behavioral symptoms in individuals with chronic solvent exposure. Psychiatry Res. 2000;97:191–206.PubMedCrossRefGoogle Scholar
  18. 18.
    Haut MW, Kuwabara H, Ducatman AM, Hatfield G, Parsons MW, Scott A, Parsons E, Morrow LA. Corpus callosum volume in railroad workers with chronic exposure to solvents. J Occup Environ Med. 2006;48:615–24.PubMedCrossRefGoogle Scholar
  19. 19.
    Morrow LA, Ryan CM, Goldstein G, Hodgson MJ. A distinct pattern of personality disturbance following exposure to mixtures of organic solvents. J Occup Med. 1989;31:743–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Morrow LA, Gibson C, Bagovich GR, Stein L, Condray R, Scott A. Increased incidence of anxiety and depressive disorders in persons with organic solvent exposure. Psychosom Med. 2000;62:746–50.PubMedGoogle Scholar
  21. 21.
    Aydin K, Sencer S, Demir T, Ogel K, Tunaci A, Minareci O. Cranial MR findings in chronic toluene abuse by inhalation. Am J Neuroradiol. 2002;23:1173–9.PubMedGoogle Scholar
  22. 22.
    Rosenberg NL, Kleinschmidt-DeMasters BK, Davis KA, Creisback JN, Hormes JT, Filley CM. Toluene abuse causes diffuse central nervous system white matter changes. Ann Neurol. 1988;23:611–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Unger E, Alexander A, Fritz T, Dreisback J. Toluene abuse: physical basis for hypointensity of the basal-ganglia on T2-weighted MR images. Radiology. 1994;193:473–6.PubMedGoogle Scholar
  24. 24.
    Alkan A, Kutlu R, Hallac T, Sigirci A, Emul M, Pala N, Altinok T, Aslan M, Sarac K, Ozcan C. Occupational prolonged organic solvent exposure in shoemakers: brain MR spectroscopy findings. Magn Reson Imaging. 2004;22:707–13.PubMedCrossRefGoogle Scholar
  25. 25.
    Haut MW, Leach S, Kuwabara H, Whyte S, Callahan T, Ducatman A, Lombardo LJ, Gupta N. Verbal working memory and solvent exposure: a positron emission tomography study. Neuropsychology. 2000;14:551–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Visser I, Lavini C, Booij J, Reneman L, Majoie C, de Boer AG, Wekking EM, de Joode EA, van der Lann G, van Dijk FJ, Schene AH, Den Heeten GJ. Cerebral impairment in chronic solvent-induced encephalopathy. Ann Neurol. 2008;63:572–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Shih RA, Hu H, Weiskopf MG, Schwartz BS. Cumulative lead dose and cognitive function in adults: a review of the studies that measure both blood and bone lead. Environ Health Perspect. 2007;115:483–92.PubMedCrossRefGoogle Scholar
  28. 28.
    Balbus-Kornfeld JM, Stewart W, Bolla KI, Schwartz BS. Cumulative exposure to inorganic lead and neurobehavioural test performance in adults: An epidemiological review. Occup Environ Med. 1995;52:2–12.PubMedCrossRefGoogle Scholar
  29. 29.
    Goodman M, LaVerda N, Clarke C, Foster ED, Iannuzzi J, Mandel J. Neurobehavioural testing in workers occupationally exposed to lead: Systematic review and meta-analysis of publications. Occup Environ Med. 2002;59:217–23.PubMedCrossRefGoogle Scholar
  30. 30.
    Meyer-Baron M, Seeber A. A meta-analysis for neurobehavioural results due to occupational lead exposure with blood lead concentrations <70 microg/100 ml. Arch Toxicol. 2000;73:510–18.PubMedCrossRefGoogle Scholar
  31. 31.
    Stewart WF, Schwartz BS. Effects of lead on the adult brain: A 15-year exploration. Am J Ind Med. 2007;50:729–39.PubMedCrossRefGoogle Scholar
  32. 32.
    Bleecker ML, Ford DP, Celio MA, Vaughan CG, Lindgren KN. Impact of cognitive reserve on the relationship of lead exposure and neurobehavioral performance. Neurology. 2007;69(5):470–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Lindgren KN, Masten VL, Tiburzi MJ, Ford DP, Bleecker ML. The factor structure of the profile of mood states (poms) and its relationship to occupational lead exposure. J Occup Environ Med. 1999;41:3–10.PubMedCrossRefGoogle Scholar
  34. 34.
    Rhodes D, Spiro A 3rd, Aro A, Hu H. Relationship of bone and blood lead levels to psychiatric symptoms: The normative aging study. J Occup Environ Med. 2003;45:1144–51.PubMedCrossRefGoogle Scholar
  35. 35.
    Stewart WF, Schwartz BS, Davatzikos C, Shen D, Liu D, Wu X, et al. Past adult lead exposure is linked to neurodegeneration measured by brain mri. Neurology. 2006;66(10):1476–84.PubMedCrossRefGoogle Scholar
  36. 36.
    Weisskopf MG, Hu H, Mulkern RV, White R, Aro A, Oliveira S, et al. Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning. Environ Health Perspect. 2004;112:620–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Weisskopf MG, Hu H, Sparrow D, Lenkinski RE, Wright RO. Proton magnetic resonance spectroscopic evidence of glial effects of cumulative lead exposure in the adult human hippocampus. Environ Health Perspect. 2007;115:519–23.PubMedCrossRefGoogle Scholar
  38. 38.
    Caffo B, Chen S, Stewart W, Bolla K, Yousem D, Davatzikos C, et al. Are brain volumes based on magnetic resonance imaging mediators of the associations of cumulative lead dose with cognitive function? Am J Epidemiol. 2008;167:429–37.PubMedCrossRefGoogle Scholar
  39. 39.
    Schwartz BS, Chen S, Caffo B, Stewart WF, Bolla KI, Yousem D, et al. Relations of brain volumes with cognitive function in males 45 years and older with past lead exposure. Neuroimage. 2007;37:633–41.PubMedCrossRefGoogle Scholar
  40. 40.
    Center for Disease Control. Unintential non-fire-related carbon monoxide exposures: United States, 2001–2003. MMWR Morb Mortal Wkly. 2005;54:36–9.Google Scholar
  41. 41.
    Centers of Disease Control. Carbond monoxide related deaths: United States 1999–2004. MMWR Morb Mortal Wkly. 2007;56:1309–12.Google Scholar
  42. 42.
    Gale SD, Hopkins RO, Weaver LK, Bigler ED, Booth EJ, Blatter DD. MRI, quantitative MRI, SPECT, and neuropsychological findings following carbon monoxide poisoning. Brain Inj. 1999;13:229–43.PubMedCrossRefGoogle Scholar
  43. 43.
    Prockop LD. Carbon monoxide brain toxicity: clinical, magnetic rsonance imaging, magnetic resonance spectroscopy, and neuropsychological effects in 9 people. J Neuroimaging. 2005;15:144–9.PubMedGoogle Scholar
  44. 44.
    Wolfe SJ, Lavonas EJ, Sloan EP, Jagoda AS. Clinical policy: Critical issues in the management of adult patients presenting to the emergency department with acute carbon monoxide poisoning. Ann Emerg Med. 2008;51:138–52.CrossRefGoogle Scholar
  45. 45.
    Hopkins RO, Woon FLM. Neuroimaging, cognitive, and neurobehavioral outcomes following carbon monoxide poisoning. Behav Cogn Neurosci Rev. 2006;5:141–56.PubMedCrossRefGoogle Scholar
  46. 46.
    Dunham MD, Johnstone B. Variablity of neuropsychological deficits associated with carbon monoxide poisoning: four case reports. Brain Inj. 1999;11:917–25.Google Scholar
  47. 47.
    Kesler SR, Hopkins RO, Weaver LK, Blatter DD, Edge-Booth H, Bigler ED. Verbal memory deficits associated with fornix atrophy in carbon monoxide poisoning. J Int Neuropsychol Soc. 2001;7:640–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Porter SS, Hopkins RO, Weaver LK, Bigler ED, Blatter DD. Corpus callosum atrophy and neuropsychological outcome following carbon monoxide poisoning. Arch Clin Neuropsychol. 2002;17:195–204.PubMedGoogle Scholar
  49. 49.
    Weaver LK, Hopkins RO, Chan KJ, Churchill S, Elliott CG, Clemmer TP, Orme JF Jr., Thomas FO, Morris AH. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002;347:1057–67.PubMedCrossRefGoogle Scholar
  50. 50.
    Parkinson RB, Hopkins RO, Cleavinger HB, Weaver LK, Victoroff J, Foley JF, Bigler ED. White matter hyperintensities and neuropsychological outcome following carbon monoxide poisoning. Neurology. 2002;58:1525–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Wilson BA. Cognitive functioning of adult survivors of cerebral hypoxia. Brain Inj. 1996;10:863–74.PubMedCrossRefGoogle Scholar
  52. 52.
    Myers RAM, DeFazio A, Kelly MP. Chronic carbon monoxide exposure: A clinical syndrome detected by neuropsychological tests. J Clin Psychol. 1998;54:555–67.PubMedCrossRefGoogle Scholar
  53. 53.
    Bourgeois JA. Amnesia after carbon monoxide poisoning. Am J Psychiatry. 2000;157:1884–5.PubMedCrossRefGoogle Scholar
  54. 54.
    Sohn YH, Jeong Y, Kim HS, Im JH, Kim JS. The brain lesion responsible for parkinsonism after carbon monoxide poisoning. Arch Neurol. 2000;57:1214–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Cocito L, Biagioli M, Fontana P, Inglese ML, Pizzorno M, Spigno F, Volpe S. Cognitive recovery after delayed crbon monoxide encephalopathy. Clin Neurol Neurosurg. 2005;107:347–50.PubMedCrossRefGoogle Scholar
  56. 56.
    Jasper BW, Hopkins RO, Duker HV, Waver LK. Affective outcome following carbon monoxide poisoning: a prospective longitudinal study. Cogn Behav Neurol. 2005;18:127–34.PubMedCrossRefGoogle Scholar
  57. 57.
    Choi IS. Parkinsonism after carbon monoxide poisoning. Eur Neurol. 2002;48:30–3.PubMedCrossRefGoogle Scholar
  58. 58.
    Min SK. A brain syndrome associated with delayed neuropsychiatric sequelae following acute carbon monoxide intoxication. Acta Psychiatr Scand. 1986;73:80–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Lo CP, Chen SY, Lee KW, Chen WL, Chen CY, Hsueh CJ, Huang GS. Brain injury after acute carbon monoxide poisoning: early and late complications. Am J Roentgenol. 2007;189:W205–11.CrossRefGoogle Scholar
  60. 60.
    O’Donnell P, Buxton PJ, Pitkin A, Jarvis LJ. The magnetic rsonance imaging appearances of the brain in acute carbon monoxide poisoning. Clin Radiol. 2000;55:273–80.PubMedCrossRefGoogle Scholar
  61. 61.
    Gottfried JA, Chatterjee A. Carbon monoxide-mediated hippocampal injury. Neurology. 2001;57:17.PubMedCrossRefGoogle Scholar
  62. 62.
    Pulsipher DT, Hopkins RO, Weaver LK. Basal ganglia volumes following CO poisoning: a prospective longitudinal study. Undersea Hyperb Med. 2006;33:245–56.PubMedGoogle Scholar
  63. 63.
    Chu K, Jung KH, Kim HJ, Jeong SW, Kang DW, Roh JK. Diffusion-weighted MRI and 99mTc-HMPAO SPECT in delayed relapsing type of carbon monoxide poisoning: evidence of delayed cytotoxic edema. Eur Neurol. 2004;51:98–103.PubMedCrossRefGoogle Scholar
  64. 64.
    Lo CP, Chen SY, Chou MC, Wang CY, Lee KW, Hsueh CJ, Chen CY, Huang KL, Huang GS. Diffusion-tensor MR imaging for evaluation of the efficacy of hyperbaric oxygen therapy in patients with delayed neuropsychiatric syndrome cause by carbon monoxide inhalation. Eur J Neurol. 2007;14:777–82.PubMedCrossRefGoogle Scholar
  65. 65.
    Jang JY, Lee SY, Kim J, Park JB, Lee KJ, Chung HK. Application of biological monitoring to the quantitative exposure assessment for neuropsychological effect by chronic exposure to organic solvents. Int Arch Occup Environ Health. 1999;72:107–14.PubMedCrossRefGoogle Scholar
  66. 66.
    Bianchini KJ, Houston RJ, Greve KW, Irvin TR, Black FW, Swift DA, Tamimie RJ. Malingered neurocognitive dysfunction in neurotoxic exposure: an application of the slick criteria. J Occup Environ Med. 2003;45:1087–99.PubMedCrossRefGoogle Scholar
  67. 67.
    Van Hout MSE, Schmand B, Wekking EM, Hageman G, Deelman BG. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy. Neurotoxicology. 2003;24:547–51.PubMedCrossRefGoogle Scholar
  68. 68.
    Morrow LA, Stein L, Bagovich G, Condray R, Scott A. Neuropsychological assessment, depression and past exposure to organic solvents. Appl Neuropsychol. 2001b;8:65–73.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Departments of Behavioral Medicine and Psychiatry, Neurology, and RadiologyWest Virginia University School of MedicineMorgantownUSA
  2. 2.Department of Behavioral Medicine and PsychiatryWest Virginia University School of MedicineMorgantownUSA

Personalised recommendations