Gert van der Laan

Parkinsonism, pyramidal signs, polyneuropathy, and cognitive decline after long-term occupational solvent exposure.

Abstract It is well known that exposure to manganese, solvents, or carbon monoxide in an occupational setting may lead to central nervous system damage and parkinsonism. The most important solvents in this respect are methanol, toluene, carbon disulfide, and n-hexane. We describe three patients who had been exposed to various solvents for more than 20 years (25, 34, and 46 years). They presented with parkinsonism, pyramidal signs, mild cognitive decline, and unresponsiveness to levodopa. Two patients had a predominantly axonal and sensory polyneuropathy of the lower legs with fasciculations in one of them. Parkinsonian features were progressive, even after the patients had stopped work. We present clinical data, neuropsychological findings, and results of brain computed tomography or magnetic resonance imaging, electroneuromyography, evoked potentials, single photon emission computed tomography, and positron-emission tomography. There is growing evidence that various organic solvents give rise to a parkinsonism syndrome with pyramidal features in susceptible individuals.

The course of chronic solvent induced encephalopathy: A systematic review

BACKGROUND Worldwide millions of workers are exposed to organic solvents. Long term exposure leads in some workers to the development of Chronic Solvent induced Encephalopathy (CSE). The first reports about CSE came from the European Nordic countries in the 1970s. In spite of decades of experience with this disease, little is known about the course and prognostic factors of CSE. OBJECTIVE To provide an overview of the evidence about the course and prognostic factors of CSE. METHODS A systematic review was conducted. Databases PubMed, PsycINFO (1970-2008) and EMBASE (1980-2008) were searched with the search strategy: solvent AND follow up AND (encephalopathy OR chronic intoxication). Inclusion criteria were: written in English, study population of CSE patients, follow-up time of at least 1 year. Included articles were assessed on methodological quality. RESULTS Sixty unique articles were retrieved of which sixteen met the inclusion criteria. Data extraction provided information about domains of neurology, neuropsychology, physical and mental health perceptions, and social consequences. In a number of studies no significant changes, and in other studies improvement of functioning could be measured. Prognostic factors resulting from included studies were summarized for each domain indicating a potential positive influence of younger age and lower exposure variables. DISCUSSION Due to the large heterogeneity of methodology no levels of evidence could be obtained. This review shows that there is a need for future research that addresses a variety of domains of functioning, hopefully resulting in an overall prognostic model for CSE. CONCLUSION Studies in this review are in agreement about CSE being a non-progressive disease in which no severe deterioration of functioning occurs after diagnosis. In a number of studies no significant changes, and in other studies improvement of functioning could be measured. Presumably cessation of exposure might be one of the causal factors for the non-progressive character of the disease as has been found. Future studies are needed to clarify the role of various prognostic factors on the course of CSE.

Cerebral impairment in chronic solvent-induced encephalopathy

Worldwide, many workers experience occupational exposure to organic solvents, which may induce chronic solvent‐induced encephalopathy (CSE). Disturbances within the frontostriatothalamic (FST) circuitry might explain the symptomatology of CSE. We tested the hypothesis of FST circuitry abnormalities in CSE, as well as associations with performance of psychomotor speed, attention, and solvent exposure. To detect preclinical, solvent‐related effects, we also studied the FST circuitry in solvent‐exposed, but asymptomatic workers.

Chronic solvent-induced encephalopathy: European consensus of neuropsychological characteristics, assessment, and guidelines for diagnostics

INTRODUCTION The presence of neuropsychological impairment is a hallmark of chronic solvent-induced encephalopathy (CSE), and using clinical neuropsychological procedures to generate a valid assessment of the condition is crucial for its diagnosis. The goals of this consensus document are to provide updated knowledge of the neuropsychological characteristics of CSE and to provide internationally acceptable guidelines for using neuropsychological assessments in the process of diagnosing patients who are suspected of having CSE. MATERIALS AND METHODS A European working group that was composed of experts in the field of the clinical diagnosis of CSE met at several round-table meetings and prepared this report. The first section of the consensus paper addresses a review of the relevant literature that was published between 1985 and March 2012. The second section addresses recommendations for the clinical neuropsychological assessment of patients who are suspected of having CSE. RESULTS The literature review indicates that the most common neuropsychological impairments in CSE patients are within the domains of attention, particularly the speed of information processing, memory, and motor performance. It appears that the influence of CSE on memory processes mainly involves immediate recall and generally involves verbal, visual and visuospatial material. In the second section, six recommendations are presented regarding important functional domains for the neuropsychological diagnostic process of CSE that relate to the evaluation of neuropsychological impairment, the assessment and evaluation of symptoms, differential diagnostic considerations, the reliability and validity of neuropsychological test results, and the retesting of patients. DISCUSSION AND CONCLUSIONS These recommendations will contribute to the improvement of the process for accurately diagnosing CSE, better counselling for CSE patients, the comparability of epidemiological data between countries, and finally, by raising awareness, these recommendations will contribute to combating the adverse health effects of occupational exposure to solvents.

Chronic glomerulonephritis and organic solvents

SummaryFifty patients with histologically confirmed chronic glomerulonephritis (34 males, 16 females, average age 42 years) and 50 control patients, age and sex-matched, with a variety of internal diseases, were selected. Both cases and controls completed an extensive questionnaire and additional information was sampled by means of a personal interview, especially concerning the exposure to organic solvents. In contrast to three other recently published case-control studies, no difference in exposure between cases and controls was found in our study. A relative risk of 1.1 with an upper 95% confidence limit of 2.7 was calculated. It is suggested that one particular solvent, contaminant, or additive present, which is less used in the Amsterdam region than in other areas, may explain the discrepancy with previous studies.

Prevalence of psychiatric disorders in patients with chronic solvent induced encephalopathy (CSE).

INTRODUCTION Long term occupational exposure to organic solvents may induce chronic solvent-induced encephalopathy (CSE), characterized by mild to severe cognitive impairment, generally seen as the key diagnostic feature. Psychiatric disorders are often diagnosed in subjects with CSE, but were never studied in more detail. This study was designed to establish the prevalence rates of DSM IV mood, anxiety, and alcohol and substance related disorders in patients with CSE. MATERIALS AND METHODS In CSE, n=203 (consecutively recruited between 2002 and 2005), defined according to the criteria of the World Health Organisation (WHO), one month prevalence rates of DSM IV mood, anxiety, and life time alcohol/substance related disorders were assessed using the Structured Clinical Interview for DSM IV disorders (SCID). These prevalences were compared with those from an age and gender matched community sample (n=3212) while controlling for insufficient neuropsychological test effort. RESULTS In CSE, prevalence rates for major depressive disorder (n=36, relative risk (RR)=7.4), dysthymia (n=15, RR=6.0), panic disorders (n=18, RR=7.1), agoraphobia (n=7, RR=5.5) and generalized anxiety disorder (n=19, RR=15.8) were increased. Reduced prevalence rates were found for alcohol related disorders (n=21, RR=0.3). Insufficient neuropsychological test effort was not associated with increased prevalence rates of DSM IV disorders in subjects suspected of CSE. DISCUSSION AND CONCLUSIONS In conclusion, in this first large scale study in patients with CSE, prevalence rates of DSM IV mood and anxiety disorders were elevated as compared with those in the general community, while the prevalence rates of alcohol related disorders were reduced. Further study must determine whether CSE, and mood and anxiety disorders, share a same, solvent induced, neurobiological pathway, supporting the use of a more inclusive diagnostic approach. Additionally, randomised controlled trials are needed for the urgent issue of how to treat mood and anxiety disorders in CSE patients effectively.

Chronic Solvent induced Encephalopathy: A step forward

Irreversible brain effects known as Chronic Solvent induced Encephalopathy (CSE) may result from long-term occupational exposure to organic solvents. It took many years before CSE with cognitive and mental adverse effects, which are difficult to diagnose objectively, was recognized as an occupational disease. Evidence for chronic brain adverse effects related to occupational solvent exposure began to emerge in the early 1960s when the Finnish neuropsychologist Helena Hänninen published a case series of carbon disulfide intoxication in rubber manufacturing (Hänninen, 1964). She proposed this ‘‘psycho-organic syndrome’’ or ‘‘organic solvent syndrome’’ as a new occupational disease. In the 1970s, there was growing awareness, especially in the Nordic countries, that there was a pattern in symptoms and complaints reported by workers related to long-term solvent exposure. And for clinical purposes, diagnostic criteria for occupational CSE were established in 1978 (Juntunen, 1978). A consensus classification system for the character and severity of CSE was developed by working groups of World Health Organization (WHO, 1985) and a workshop in Raleigh-Durham, NC USA (Baker and Seppäläinen, 1986). Both systems describe three types of CSE with the latter making distinctions between personality/behavioral complaints (type 2a) and cognitive impairments (type 2b) and In 1997, the diagnostic criteria for CSE appeared on the Information notices on occupational diseases in the European Commission (European Communities, 1997, 2009), and also the paper by White and Proctor (1997) spread knowledge about CSE to a wider clinical community. However, still no uniform criteria are in use to characterize CSE in epidemiological studies or in patient evaluation (van der Hoek et al., 2000, 2001). Since then numerous epidemiological and cross-sectional studies have shown that long-term occupational exposure to various organic solvents associate to irreversible damage to the CNS (Mikkelsen, 1997; Kaukiainen et al., 2009a) including impairment in neuropsychological performance (Meyer-Baron et al., 2008; Visser et al., 2008). There are many different solvents with different constituent substances that could lead to different mechanisms of action and to different functional effects (Ridgway et al., 2003). For several single solvents structural neurotoxicity was confirmed in animal (Korbo et al., 1996; Nielsen et al., 2006) and in vitro data (McDermott et al., 2007). Myelin, with high lipid content, is suggested to be the target of solvents’ lipophilic effects and neurotoxicity. A recent overview about neuronal effects in abusers exposed to extreme high solvent concentrations showed severe brain dysfunction and diffuse structural damage in

Leren van gevallen

TBV 21 / nr 8 / oktober 2013 Eén goed beschreven casus van een beroepsziekte kan het achterliggend probleem van de ar beidsomstandigheden of specifieke individuele gevoeligheid helder maken. Je kunt het de ‘vergrootglasfunctie van casuïstiek’ noemen. Zo’n sig nalering van een beroepsziekte is dan een trigger voor preventie. De meeste beroepsziekten zijn aan het licht gekomen na zorgvuldige observaties van clinici of bedrijfsartsen. De ‘disease first-benadering’ zou je het kunnen noemen, met daarop volgend verder vaak epidemiologisch onderzoek om omvang en aard te preciseren. ‘Your case might be the first one’ formuleren de Engelsen het zo mooi.

Time trends and blind spots: what employers, employees and policy-makers want to know about occupational diseases

Abstract Occupational illnesses and accidents impose a heavy burden on both workers and employers and represent enormous economic costs. This burden could be substantially reduced through preventive measures. This paper reports on a Dutch survey to investigate what information employers, employees, policy-makers and other stakeholders need to prevent occupational diseases and how these information needs can best be met. Our survey consisted of two rounds of interviews. In the first round, we interviewed 11 key stakeholders from employers organisations, employees organisations, the Dutch government and labour inspectorate, the EU authorities and the Dutch Society of Occupational Physicians. In the second, we asked 14 disease registration experts to comment on the results of the first round and to give their opinion on what they thought was the best way of meeting stakeholders information needs. Between them, the experts represented six European countries. From the first round of interviews, we deduced five categories of information that stakeholders need: time trends of occupational diseases for setting policy priorities cases of new occupational diseases for early preventive action disease patterns in specific occupational groups for focused prevention measures consequences of occupational diseases and resulting measures for policy evaluation purposes blind spots to reveal areas where more investigation is needed. The interviews with experts revealed that it is wise to rely on several instruments and findings to meet the comprehensive information needs of stakeholders, such as sentinel surveillance, epidemiological studies and case tracing. In addition, the experts indicated that linking registration to prevention requires closer communication between providers of occupational disease statistics and stakeholders.

Solvent-induced encephalopathy in the Netherlands and Finland

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