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Occupational Chronic Solvent Encephalopathy in Finland 1995 2007 Petra Keski-Säntti Petra Keski-Säntti During recent decades, the number of solvent-exposed workers Occupational chronic solvent and solvent exposure in many work tasks has diminished. This Occupational chronic solvent encephalopathy in Finland 1995–2007: incidence and diagnostic methods has led to a decrease in the number of occupational chronic encephalopathy in Finland 1995–2007: solvent encephalopathy (CSE) patients, but still every year reveals new cases. incidence and diagnostic methods This book presents the incidence of CSE in Finland during 1995–2007 and the work tasks and solvent exposure related to CSE. It also presents the findings in brain magnetic resonance imaging, electroencephalography, and event-related potentials and discusses their diagnostic value in CSE. Orders: Finnish Institute of Occupational Health Topeliuksenkatu 41 a A FI-00250 Helsinki Finland Fax +358-9 477 5071 E-mail [email protected] www.ttl.fi/bookstore ISBN 978-952-261-082-9 (paperback) 978-952-261-083-6 (PDF) ISSN-L 1237-6183 ISSN 1237-6183 94 Cover picture: People and Work Suomen kuvapalvelu / Science foto library Research Reports 94 People and Work Editor in chief Harri Vainio Scientific editors Raoul Grönqvist Irja Kandolin Timo Kauppinen Kari Kurppa Anneli Leppänen Hannu Rintamäki Riitta Sauni Editor Virve Mertanen Address Finnish Institute of Occupational Health Topeliuksenkatu 41 a A FI-00250 Helsinki Tel. +358- 30 4741 Fax +358-9 477 5071 www.ttl.fi Cover design Tiina Vaahtera Cover Picture Suomen kuvapalvelu / Science foto library ISBN 978-952-261-082-9 (paperback) 978-952-261-083-6 (PDF) ISSN-L 1237-6183 ISSN 1237-6183 Press Tampereen Yliopistopaino Oy – Juvenes Print, Tampere 2011 Occupational chronic solvent encephalopathy in Finland 1995–2007: incidence and diagnostic methods Petra Keski-Säntti People and Work Research Reports 94 Finnish Institute of Occupational Health Helsinki, Finland ACADEMIC DISSERTATION To be publicly discussed, by permission of the Faculty of Medicine of the University of Helsinki, in auditorium 2, Meilahti Hospital, Haartmaninkatu 4, Helsinki, on May 27th, 2011, at 12 noon. Supervisor Docent Markku Sainio Finnish Institute of Occupational Health Department of Occupational Medicine, Brain and Work Research Centre Helsinki, Finland Reviewers Professor Matti Hillbom Department of Neurology, University of Oulu Oulu, Finland Docent Ville Jäntti Department of Biomedical Engineering Tampere University of Technology Tampere, Finland and Department of Clinical Neurophysiology Seinäjoki Central Hospital Seinäjoki, Finland Opponent Professor Juhani Juntunen Etera Mutual Pension Insurance Company Helsinki, Finland CONTENTS LIST OF ORIGINAL ARTICLES .......................................... 5 ABBREVIATIONS............................................................ 6 ABSTRACT .................................................................... 8 TIIVISTELMÄ (SUMMARY IN FINNISH) .............................. 10 1. INTRODUCTION ......................................................... 12 2. REVIEW OF THE LITERATURE ....................................... 15 2.1 Organic solvents .................................................. 15 2.1.1 Classifi cation ............................................... 15 2.1.2 Occupational use ......................................... 16 2.1.3 Solvent abuse ............................................. 16 2.1.4 Pharmacokinetics ........................................ 18 2.2 Neurotoxicity of solvents incentral nervous system .... 19 2.2.1 Neuroanatomical changes ............................. 20 2.2.2 Neurochemical changes ................................ 21 2.2.3 Neurophysiological changes .......................... 24 2.2.4 Solvent effects on cognitive functions ............. 27 2.3 Occupational chronic solvent encephalopathy ........... 31 2.3.1 Epidemiology .............................................. 31 2.3.2 Diagnostic criteria ........................................ 32 2.3.3 Diagnostic procedure ................................... 31 2.3.4 Assessment of exposure ............................... 34 2.3.5 Symptoms and clinical signs .......................... 35 2.3.6 Diagnostic methods ..................................... 35 2.3.7 Differential diagnoses ................................... 40 3. AIMS OF THE STUDY .................................................. 42 4. MATERIALS AND METHODS ......................................... 43 4.1 Patients and controls ............................................ 43 4.2 Assessment of depression ..................................... 48 4.3 Cognitive parameters ............................................ 48 4.4 Assessment of exposure ........................................ 48 4.5 Assessment of incidence ....................................... 50 3 CONTENTS 4.6 Magnetic resonance imaging .................................. 50 4.7 Electroencephalography ........................................ 51 4.8 Auditory event-related potentials ............................ 53 4.9 Multimodal event-related potentials ........................ 54 4.10 Statistical methods .............................................. 57 5. RESULTS ................................................................... 59 5.1 Cases with suspected chronic solvent encephalopathy .. 59 5.2 Cases with chronic solvent encephalopathy .............. 61 5.3 Incidence of chronic solvent encephalopathy ............ 63 5.4 Exposure-work of the chronic solvent encephalopathy cases .................................................................. 65 5.5 Solvent exposure of the chronic solvent encephalopathy cases .................................................................. 66 5.6 Magnetic resonance imaging .................................. 69 5.7 Quantitative electroencephalography ...................... 72 5.8 Auditory event-related potentials ............................ 72 5.9 Multimodal event-related potentials ........................ 73 6. DISCUSSION ............................................................. 78 6.1 Referred and diagnosed chronic solvent encephalopathy cases .................................................................. 78 6.2 Magnetic resonance imaging .................................. 83 6.3 Quantitative electroencephalography ...................... 84 6.4 Event-related potentials ........................................ 86 6.5 Strengths and limitations of the study ..................... 91 7. CONCLUSIONS ........................................................... 94 ACKNOWLEDGEMENTS ................................................... 95 REFERENCES ................................................................ 97 ORIGINAL ARTICLES (I–V) .............................................. 115 4 LIST OF ORIGINAL ARTICLES I Keski-Säntti P, Kaukiainen A, Hyvärinen HK, Sainio M. Occu- pational chronic solvent encephalopathy in Finland 1995–2007: incidence and exposure. Int.Arch.Occup.Environ.Health 2010 Aug;83(6):703–712. II Keski-Säntti P, Mäntylä R, Lamminen A, Hyvärinen HK, Sainio M. Magnetic resonance imaging in occupational chronic solvent encephalopathy. Int.Arch.Occup.Environ.Health 2009 Apr;82(5):595–602. III Keski-Säntti P, Kovala T, Holm A, Hyvärinen HK, Sainio M. Quantitative EEG in occupational chronic solvent encephalopa- thy. Hum.Exp.Toxicol. 2008 Apr;27(4):315–320. IV Keski-Säntti P, Holm A, Akila R, Tuisku K, Kovala T, Sainio M. P300 of auditory event-related potentials in occupation- al chronic solvent encephalopathy. Neurotoxicology. 2007 Nov;28(6):1230–6. Epub 2007 Aug 10. V Keski-Säntti P, Palmu K, Pitkonen M, Liljander S, Partanen JV, Akila R, Sainio M, Holm A. Multimodal event-related potentials in chronic solvent encephalopathy (submitted). 5 ABBREVIATIONS BAEP Brainstem auditory-evoked potentials CANTAB Cambridge neuropsychological test automated battery CNS Central nervous system CSE Chronic solvent encephalopathy CT Computerized tomography CYP Cytochrome P DA Dopamine DEPS Depression scale DEY Duration of exposure in years DTI Diff usion tensor imaging DSM-IV Diagnostic and statistical manual for mental disorders, fourth edition EEG Electroencephalography ERP Event-related potentials FINJEM Finnish job-exposure matrix FIOH Finnish Institute of Occupational Health Fz Electrode location on the frontal midline in electroencephalography GABA Gamma-aminobutyric acid GST Glutathione S-transferase MRI Magnetic resonance imaging MRS Magnetic resonance spectroscopy NAA N-acetylaspartate NMDA N-methyl-D-aspartic acid OEL Occupational exposure limit OELY Occupational exposure limit years OHS Occupational health services 6 ABBREVIATIONS PET Positron emission tomography Pz Electrode location on the parietal midline in electroencephalography QEEG Quantitative electroencephalography SEP Somatosensory evoked potential SPECT Single photon emission computed tomography VEP Visual evoked potential WHO World Health Organization WCST Wisconsin card sorting test 7 ABSTRACT Background Th e occurrence of occupational chronic solvent encepha- lopathy (CSE) seems to decrease, but still every year reveals new cases. To prevent CSE and early retirement of solvent-exposed workers, actions should focus on early CSE detection and diagnosis. Identifying the work tasks and solvent exposure associated with high risk for CSE is crucial. Methods Clinical and exposure data of all the 128 cases diagnosed with CSE as an occupational disease in Finland during 1995–2007 was col- lected from the patient records at the Finnish Institute of Occupational Health (FIOH) in
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