EUGLOREH project
THE STATUS OF HEALTH IN THE EUROPEAN UNION:
TOWARDS A HEALTHIER EUROPE

FULL REPORT

PART II - HEALTH CONDITIONS

5. HEALTH IMPACTS OF NON COMMUNICABLE DISEASES AND RELATED TIME-TRENDS

5.5. Mental and brain diseases and disorders

5.5.3. OTHER DISEASES

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5.5.3. OTHER DISEASES

 

Acronyms

 

CGD

Corticobasal Ganglionic Degeneration

EBC

European Brain Council

GP

General practitioner

HY

Hoehn & Yahr scale

ILSA

Italian Longitudinal Study on Ageing

MSA

Multiple System Atrophy

PD

Parkinson’s disease

PSP

Progressive Supranuclear Palsy

SMR

Standardized Mortality Ratio

 

5.5.3.1. Eating Disorders

 

5.5.3.1.1. Introduction

 

Eating disorders are a serious and complex problem as defined by the World Health Organization (WHO) that stated : “[…] eating disorders are now seen in developing as well as developed countries and may even manifest themselves in the face of apparent starvation. It is believed that a contribution in the rise of eating disorders is the exposure to Western media and its influence on desirable body characteristics” (WHO, 2003).

Eating disorders such as anorexia and bulimia occupying during adolescence and early adulthood are characterised by an unhealthy relationship with food, abnormal weight loss, difficulties in controlling the weight, and abnormal attitudes (Berkman et al, 2007). An anorectic or bulimic person experiences herself/himself as fat. Normally, people have between 15 and 18 percent body fat, but not less than 10 percent body fat as it is significant for eating disordered persons (National Centre for Eating Disorders, 2008). Eating disorders are more common in adolescents and females (Levey, 2006). Levey (2006) notes that more than 90% of sick people are female; nonetheless, 10% of cases occur in male. Both anorexia and bulimia begin mostly in adolescence in the age of 13 to 18; however, several cases appear in childhood as well as in adulthood (Levey, 2006).

Anorexia as “appetite loss of nervous originsshows beside an avoidance of highly-caloric food, self-induced vomiting, drug abuse and excessive exercise a mortality rate of 5,6% per decade (Misra et al, 2004; Gupta, 1995). Anorexia is a psychological illness that has an impact on mental and physical health, and is therefore classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSMR-IV) which uses clusters of symptoms to diagnose anorexia. A person is sick, if the body weight is less than 85% of the expected weight. Diseased people are afraid to gain weight or becoming fat, they have additionally a wrong body image as well as amenorrhoea (The Cleveland Clinic Foundation, ).

Bulimia has a similar description in the DSMR-IV classification. People with bulimia pass through episodes of binge eating and assume themselves to be obese. Additionally, they need compensatory strategies to cope their problems, and their self-evaluation is over influenced by body shape and weight. Finally, ill people do not exclusively suffer from disturbance during episodes of anorexia (The Cleveland Clinic Foundation, 2003b).

 

5.5.3.1.2. Data sources

 

 

Qualitative methods for measuring eating disorders

 

Qualitative studies with a small sample size allow a well-grounded insight into a person or a group of persons, but forbid conclusions on population level. Several population groups can be used as sample group (students in high school or college, or athletes), and researches have to decide which group is the best to identify those with an eating disorder (Alexander and Rigby, in press). Mostly, qualitative studies are cross-sectional studies and therefore are not able to identify time trends and changes over time. Several measurement methods survey qualitative data, in doing so the Eating Disorder Examination Questionnaire (EDE-Q) is one example. The EDE-Q is a self-report questionnaire which is widely instituted in psychiatry and behavioural science to appreciate key attitudes as well as behavioural features (Luce et al, 2008). Finally, qualitative data and qualitative measurement methods do not allow representative conclusions about prevalence and incidence.   

 

Literature reviews

 

It is difficult to measure incidence and prevalence. One method, which is able to provide a satisfying data basis, is a systematic review of literature that can base on medline and/or other accessible national or international published data source or reference list of articles (Berkman et al, 2007; Hoek and van Hoeken, 2003).

 

Reviewed articles and studies by Hoek and van Hoeken (2003) for several Western and northern European countries (Sweden, United Kingdom, Scotland and Wales, Switzerland, Netherlands) emphasise the upward trend in incidence of anorexia since the 1950s, whereas the highest and linear increase among 15-24-year-old females was noticed from 1935 to 1989

 

It should be emphasised that the evidence level for reviewed studies is predominantly moderate and barely sufficient yet (Berkman et al, 2007). Alexander and Rigby (in press) noticed data inconsistencies among research studies and surveys concerning generalisation, research design, sample size, and a different use of measurement methods. Therefore, data resulted from literature reviews should be carefully used to compare data and the state-of-art between countries.  

 

Quantitative measurement

 

On national level, limited data are mostly available from hospital registers and practitioners. Hospital registers and information from practitioners, however, consist of data for persons with a diagnosed eating disorder and do not provide information (prevalence and incidence) about the whole risk group (Alexander and Rigby, in press). Because of it, these data sources are unlikely to indicate the complete prevalence and incidence of eating disorders. Some national data are surveyed in certain European countries, but a European Union-wide data analysis and comparison of data is currently not available. In that fact, there is really a paucity of data on national as well as at European/international level (Alexander et al, in press).

 

HBSC (Health Behaviour in School Aged Children) and is a cross-national research study carried out by the WHO Regional Office for Europe and was realised for the sixth time in 2001/2002 (WHO, 2004). A lot of European Union (EU) Member States, non-EU Member States as well as the USA and Canada participated (Finland, Norway, Austria, Belgium (French), Hungary, Israel, Scotland, Spain, Sweden, Switzerland, Wales, Denmark, Canada, Latvia, Poland, Belgium (Flemish), Czech Republic, Estonia, France, Germany, Greenland, Lithuania, Russia, Slovak Republic, England, Greece, Portugal, Republic of Ireland, USA, Macedonia, Netherlands, Italy, Croatia, Malta, Slovenia and Ukraine).

 

The more recent project Challenges and Findings in Measuring the Behavioural Determinants of Obesity in Children in Europe; Volume 2: Available Health Information on Behavioural Determinants of Obesity in Children in Europewritten by Alexander et al (in press) deals with eating disorders and therefore collected data in participated European countries. The overview in table 5.5.3.1.2.1 illustrates the limited number of data, surveys and treatments being available. It becomes obvious that in some countries data were measured within national surveys, whereas for other countries data do not exist allowing statements about prevalence and incidence of anorexia and bulimia. The European project provides information about anorexia and bulimia for various countries including 23 EU and non-EU countries (Austria, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Italy, Liechtenstein, Lithuania, Luxembourg, Macedonia, The Netherlands, Norway, Poland, Romania, Slovenia, Sweden and Turkey). The EU27 Member States as well as EU Candidate States (Croatia, Macedonia, Turkey) and Norway participated in the project.

 

Table 5.5.3.1.1 Overview of data availability in Europe

 

 

Country / Measure

Availability of data item?

 

          Yes                    No

Comments

Austria

 

X

In Austria there are no representative epidemiological studies which inform about frequencies of Bulimia and Anorexia Nervosa. Austrian health statistics which inform about eating disorders are limited to the rate of stationary hospitalisation. However, estimates are available (for example, within the eating disorder campaign of the office of Vienna’s Commissioner for Women’s Health).

Bulgaria

 

X

 

Croatia

 

X

There is no national study on bulimia and anorexia nervosa but some data are available in the frame of systematic preventive health examinations of school children and unpublished data from the National Health Survey.

Cyprus

 

X

 

Czech Republic

X

 

Mental anorexia is recorded by pediatricians with respect to the region where the pediatricians practicing, not according to the place of residence of the patient. Two age categories are observed 0 to 14 years and 15 to 19 years. The source of this information is recorded in the so-called "Report of the pediatrician".

Denmark

 

X

 

Estonia

 

X

There are no representative data about prevalence of Bulimia and Anorexia Nervosa. Health care providers report treatment attendance data (number of children for both diagnoses separately in age group 0-14).

Finland

 

X

 

France

 

X

 

Germany

 

X

There are no representative data about the prevalence of Bulimia and Anorexia Nervosa available so far. Results of regional or clinical studies are partly very different regarding the sampling design and the use of diagnostic instruments.

Greece

 

X

National statistics are not available. The Center for Health and Prevention in Adolescence and the 1st Pediatrics Clinic of the University of Athens has some data on anorexia and bulimia 

Italy

X

 

National epidemiologic data on anorexia and bulimia are available at the “ABA” (Anorexia and bulimia association)

Liechtenstein

 

X

 

Lithuania

 

X

In Lithuania national statistics on Bulimia and Anorexia Nervosa are not available. There are no representative epidemiological studies about prevalence of eating disorders. However, some data are available in Health Insurance Centre (treatment attendance data) and in specialized Center for Eating Disorders in Vilnius (www.valgymosutrikimai.lt)

Luxembourg

 

X

 

Macedonia

 

X

 

The Netherlands

 

X

Several centres and universities perform research in the field of eating disorders. For example, the NIVEL institute performs research on the incidence and prevalence of eating disorders in the practice of general practitioners

Poland

 

X

In Poland there are not any reliable epidemiological data concerning prevalence of bulimia and anorexia nervosa. However there are data related to the hospitalization dynamics in patients with eating disorders, territorial diversity and its determinants.

Romania

X

 

At national level data about the general morbidity and mortality for nutrition endocrines and metabolic diseases and mental disorders are collected. The data collection starts from county level; the data are generally presented in published Yearly Statistical Book.

Slovenia

 

X

In Slovenia there exist no extra national study on bulimia and anorexia nervosa but some data are available in the frame of systematic preventive health examinations of school children.

Sweden

 

X

 

Turkey

 

X

 

 

Table 5.5.3.1.2.1: Available data about anorexia and bulimia in European countries

(taken from: Alexander, Rigby, Frazzica, Sjöström, Hillger, Neumann, Kirch : Challenges and Findings in Measuring the Behavioural Determinants of Obesity in Children in Europe; Volume 2: Available Health Information on Behavioural Determinants of Obesity in Children in Europe)

 

A third European study titled Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA started in 2005, ends in 2008) aims at understanding and enhancing nutritional and lifestyle habits of adolescents in Europe, and tries to get a better identification of adolescents at risk of eating disorders (Austrian Council Presidency, 2008). The expected results shall illustrate dietary habits/nutritional status, the amount of physical activity as well as the prevalence of particular high priority health problems of European adolescents between 13 and 16 years of age (3000 adolescents). Findings are assessed through cross-sectional studies accomplished in different countries (10 EU Member States: Austria, Belgium, France, Germany, Greece, Hungary, Italy, Spain, Sweden, and United Kingdom). Furthermore, a Lifestyle Education Programme will be developed and tested improving eating and lifestyle habits of this subpopulation group, and last but not least a number of healthy foods will be developed and marketing strategies will be identified. However, results are not published yet (De Henauw et al, 2007).   

 

 

5.5.3.1.3. Data description and analysis

 

Reviewed articles and studies by Hoek and van Hoeken (2003) for several Western and northern European countries (Sweden, United Kingdom, Scotland and Wales, Switzerland, Netherlands) emphasise the upward trend in the incidence of anorexia since the 1950s, whereas the highest and linear increase among 15-24-year-old females was noticed from 1935 to 1989. Also the incidence rate among 10-14-year-old females has risen since the 1950s although, the incidence rate for women and men older than 25 remains low (Hoek and van Hoeken, 2003). An average prevalence rate of 0.3% for young females in Western Europe and the United States was noticed. The prevalence rate for bulimia is 1% for 15-24-year-old females. 0.1% of young men are bulimic although the number is rising (Hoek and van Hoeken, 2003). Time trends in incidence reveal that bulimia affects 30 per 100.000 females, whereby the incidence rate has remained relatively constant until 1990 (Hoek and van Hoeken, 2003). Hoek and van Hoeken (2003) reported a significant and threshold increase in bulimia for 10-39-year-old women during 1988-1993. The highest risk group (i.e., 2024-year-old females) shows an incidence rate of 81,1 per 100.000 (Hoek and van Hoeken, 2003).

The HBSC (Health Behaviour in School Aged Children) survey showed that 22% of boys and 38% of girls are dissatisfied with their body (adolescents with overweight are included). Additionally, 36% of girls and 22% of boys feel dissatisfied with their weight. Girlsdissatisfaction increases with age: 28% for 11-year-olds, 37% for 13-year-olds and 42% for 15-year-olds. 18% of girls diet or control their weight and the number of girls increases with age: from 12% for 11-year-olds to 23% for 15-year-olds. Adolescents show gender differences in dissatisfaction with body weight, dieting and weight control, with a higher level for girls (18%) than for boys (8%). Again, dissatisfaction increases with age: 12% for 11-year-olds, 23% for 15-year-olds. The correlation between dissatisfaction with body size and dieting and weight control behaviour is not clear, because the results estimate that 18% of girls control their weight but 36% feel dissatisfied with their weight. Once again, the level increases with age (WHO, 2004).

Berkman et al (2007) reviewed various surveys, which were published from 1980 to 2005 and explain the results for some European countries (Sweden, United Kingdom, Germany, Norway and Denmark). Thus, data from 62 articles (out of 32 separate studies) were reviewed. The review analysed indicators such as mortality (death, suicide), diagnostic, personality disorders, biomarkers, substance abuse and eating-related outcomes for men and women separately and represents an overview on the availability of data as well as about lack of data. From this survey, it appears that several studies were follow-up measurements of 5 or 10 years allowing conclusions about changes in incidence, prevalence and progress. With this regard, a prospective cohort study with a 5 year follow-up for Goteborg shows that 50% of anorectic persons recovered.

 

5.5.3.1.4. Risk factors and vulnerable population groups

 

Eating disorders are rare in population and affect particularly adolescents and young women (Gupta, 1995). Young girls and boys follow the social-cultural trend to be thin. Children, adolescents and early adults are a particularly vulnerable subpopulation group, because they are easy to influence. Especially during puberty, adolescents try to find their place in society and community. Instead of circulating reliable information about eating, body weight and weight loss, various magazines and television programmes frequently promote too small body weight and thinness and demonstrate how to lose weight and body fat.

The likelihood of an individual eating disorder depends on risk factors as well as on individual resources (Berkman et al, 2007). Social pressure to be thin, fitter and look aesthetically better are critically important risk factors influencing personal health and may contribute to fall ill. Eating disorders are not only influenced by social factors; actually anorexia and bulimia are caused by several conditions including psychological factors, interpersonal factors, social factors as well as biological factors. In other words, eating disorders are caused by an environment where it is easy to become anorectic or bulimic (NEDA, 2004):

·       Psychological factors: low self-esteem, feelings of inadequacy or lack of control in life, depression, anxiety, anger, or loneliness;

·       Interpersonal factors: trouble with family and personal relationships, difficulty in expressing emotions and feelings, being teased or ridiculed, physical or sexual abuse;

·       Social Factors: cultural pressure that glorifythinness” and the “perfect body”; and

·       Biological factors: chemicals in the brain that control hunger, appetite, and digestion; genetic factor.

 

As a result, ill people commonly experience difficulties which they try to cope with extreme dieting, physical activity, drug abuse (laxatives, diuretics, enemas or other medications) and self-induced vomiting to gain control over events and emotions; thereby, unhealthy behaviour may cause diseases such as osteoporosis, osteoarthritis, orthopaedic injuries and stress fractures, ruptured oesophagus, high blood pressure, type 2 diabetes, menstrual dysfunction, amenorrhea and potential infertility (Gupta, 1995). Therefore, an early diagnosis and the access to treatments are necessary to enable adolescents to have a normal and well-ordered life and development.

The influence of media and internet in adolescence (pro-eating disorder websites and professional websites) has been highlighted as a possible source of information on diet and weight loss (Harper et al, 2008). Websites publishing well-grounded and professional information are helpful; however, adolescents dissatisfied with their body tend to pick up information on websites promoting eating disorders. Generally, pro-eating disorder websites may affect body image and eating disturbance more negatively than professional websites (Harper et al, 2008). This emphasises the need for more professional websites.

5.5.3.1.5. Control tools and policies

 

The WHO Regional Office for Europe implemented a strategy for health in childhood and adolescence for 36 Member States in the WHO European Region. The strategy aims at assisting the States in formulating policies and programmes. The WHO Regional Office for Europe points out main factors to guarantee a successful implementation of policy and intervention (WHO, 2005):

·          provide accurate and reliable information;

·          policy without implementation is meaningless;

·          involve children in designing and implementing programmes and policies;

·          develop clear and ambiguous policy goals and programme objectives;

·          integrate educational approach in a wide set of initiatives using full set of policy instruments available to decision-makers;

·          imply important health sector, coordinate work across ministries; and

·          take into account culture, attitudes and beliefs of children;

 

5.5.3.1.6. Future developments

 

Due to the fact that eating disorders are an increasing problem in Western and European countries, actions and initiatives are absolutely essential. In this regard, the beginning of implementation strategies is a task of utmost importance for national and international public health and policy. In most cases, actions and programmes concern mental health and do not focus on eating disorders. National and international school nutrition policy as well as implementiable programmes shall take into account the current research, theories and practice. Furthermore, policy makers should regularly review the effectiveness of programmes and activities, in order to guarantee that programmes and activities follow specified guidelines.

Further efforts are needed to regularly update data regarding eating disorders. Routinely analysed data are of particular importance, as they can identify time trends and changes over time. Longitudinal studies and population statistics give well-grounded information on prevalence, incidence and progress of anorexia and bulimia. Routinely analysed data are essential for policy making and actions, whilst study results should strongly influence the political work at national and international level.

Effective prevention is beneficial in reducing the number of eating disorders and therefore needs to be integrated in people’s life in order to influence lifestyle and also promote healthy life as well as lifestyle changes. It is well-known that primary and secondary prevention are cost-saving and in the interest of all of us, particularly of families and children. Prevention can be named as a strategy with long-term benefits for individuals, health systems and society. For example, nutrition education programmes as much as school-based intervention and prevention activities play an important role in promoting healthy lifelong eating and in informing parents, educators, health care providers, children and adolescents about: what are eating disorders, how to prevent and medicate anorexia and bulimia. Therefore, governments are obliged to look for support and should also fund and coordinate education prevention programmes.

Parents themselves play an important role in eating disorder prevention. They should take into account certain behavioural rules: prohibit teasing about body shape and size; emphasize fitness; praise children for who they are; encourage healthy eating; dont forbid certain foods; make mealtime pleasant; get help when appropriate; if a child is bound and determined to diet, get a physician involved to supervise the effort; promote physical activity; talk to your children about the normal body changes expected at puberty; inoculate kids against media manipulation (Anorexia Nervosa and Related Eating Disorders Inc, 2005).

In the future, the European Commission should support activities to measure disordered eating in Europe and should, moreover, implement a comparable health monitoring system at European Union level. We must bear in mind that national and international health monitoring systems and health promotion systems are of utmost importance.

 

5.5.3.1.7. References

Alexander D, Rigby M, (in press, due January 2009): Challenges and Findings in Measuring the Behavioural Determinants of Obesity in Children in Europe; Volume 1: The Public Health Challenge of Measuring the Nutritional and Physical activity Behaviour of Children and Adolescents, in press.

Alexander D, Rigby M, Frazzica R.G, Sjöström M, Hillger C, Neumann G, Kirch W (in press, due January 2009): Challenges and Findings in Measuring the Behavioural Determinants of Obesity in Children in Europe; Volume 2: Available Health Information on Behavioural Determinants of Obesity in Children in Europe, in press

Anorexia Nervosa and Related Eating Disorders Inc. (2005): Eating disorders prevention: parents are key players [http://www.anred.com/prev.html] (article online, accessed on 19 March 2008).

Austrian Council Presidency (2008): Showcases Healthy lifestyle in Europe by nutrition in 13-16 years adolescents across Europe. Available at: http://cordis.europa.eu/austria/showcases11_en.html (article online, accessed on 19 March 2008).

Berkman, N. D.; Lohr, K. N.; Bulik, C. M. (2007): Outcomes of Eating Disorders: A Systematic review of the Literature. International Journal of Eating Disorders 40:4 293-309.

De Henauw S , Gottrand F , De Bourdeaudhuij I, Gonzalez-Gross M, Leclercq C, Kafatos A, Molnar D, Marcos A, Castillo M, Dallongeville J, Gilbert CC, Bergman P, Widhalm K, Manios Y, Breidenasse C, Kersting M, Moreno LA, on behalf of the HELENA Study Group (2007): Nutritional status and lifestyles of adolescents from a public health perspective. The HELENA ProjectHealthy Lifestyle in Europe by Nutrition in Adolescence. Journal of Public Health 15:187197. Available at: http://www.springerlink.com/content/u1707h13166u0h9w/fulltext.pdf (article online, accessed on 19 March 2008).

Gupta M A (1995): Concerns About Aging and a Drive for Thinness: A Factor in the biospychosocial Model of Eating Disorders?. International Journal of Eating Disorders, Vol. 18, No. 4, 351-357.

Harper K, Sperry S, Thompson JK (2008): Viewership of Pro-Eating Disorder Websites: Association with Body Image and Eating Disturbance. International Journal of Eating Disorder 41:1 92-95.

Hoek H W, van Hoeken D, (2003): Review of the Prevalence and Incidence of Eating Disorders. Published online in Wiley InterScience DOI: 10.1002/eat.1022.

Levey R (2006): Anorexia Nervosa. eMedicine. Available at: [http://www.emedicine.com/med/topic144.htm] (article online, accessed on 19 February 2008).

Luce KH, Crowther JH, Pole M, (2008): Eating Disorder Examination Questionaire (EDE-Q) Norms for Undergraduate Woman. International Journal of Eating Disorder 00:0 000-000 2008-DOI 10.1002/eat.

Misra M, Aggarwal A Miller, K.K, Almazan, C, Worley, M,. Soyka, L.A, Herzog, D.B, Klibanski, A. (2004): Effects of Anorexia Nervosa on Clinical, Hematologic, Biochemical, and Bone Density Parameters in Community-Dwelling Adolescent Girls. PEDIATRICS Vol. 114 No. 6, 1574-1583.

NEDA (National Eating Disorders Association) (2004): What Causes Eating Disorders? Available at: http://www.nationaleatingdisorders.org/nedaDir/files/documents/handouts/WhatCaus.pdf (article online, accessed on 19 March 2008).

National Centre for Eating Disorders (2008). Available at: http://www.eating-disorders.org.uk/ (article online, accessed on 14 February 2008).

The Cleveland Clinic Foundation (2003a): DSMR-IV classification. Anorexia. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/psychiatry/eating/table1.htm (article online, accessed on 12 March 2007).

The Cleveland Clinic Foundation (2003b): DSMR-IV classification. Bulimia. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/psychiatry/eating/table2.htm (article online, accessed on 12 March 2007).

World Health Organization (WHO) (2003): Eating disorders. National Library for Health Mental Health Specialist Library [http://www.library.nhs.uk/SpecialistLibrarySearch/Download.aspx?resID=79106] (article online, accessed on 19 March 2008).

World Health Organization (2004): Health Policy for Children and Adolescents, No. 4; Young people’s health in context. Health Behaviour in School-aged Children (HBSC) study: international report from the 2001/2002 survey, chapter 3, 110-129. WHO Library Cataloguing in Publication Date. Currie CR, Morgan A, Smith R, Settertobulte W, Samdal O, Barnekow Rasmussen V, eds. Available at: http://www.hbsc.org/downloads/IntReport04/Part4&5.pdf (article online, accessed on 19 March 2008).

World Health Organization (WHO) (2005): The European Health Report 2005Part 3 Child an adolescent health and development. WHO Library Cataloguing-in-Publication Data. WHO Regional Office for Europe.

 

5.5.3.1.8 Acronyms

 

DSMR-IV classification

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition

ECED

European Council on Eating Disorders

EDE-Q

Eating Disorder Examination Questionnaire

EU

European Union

EUFIC

The European Food Information Council

HBSC

Health Behaviour in School Aged Children

HELENA

Healthy Lifestyle in Europe by Nutrition in Adolescence

WHO

World Health Organization

WHO Regional Office for Europe

World Health Organization Regional Office for Europe

 


 

5.5.3.2. Schizophrenia and disorders of the schizophrenia spectrum

 

5.5.3.2.1. Introduction

 

Schizophrenia (ICD-10/F20) is a relapsing mental disorder frequently leading to severe disability with disease onset usually in early adulthood. The clinical picture includes a range of distinctive symptoms such as delusions, hallucinations, behavioural dysfunction and cognitive deficits as for instance  disorganized thinking. Disorders of the schizophrenia spectrum are coded F21-F29.

Schizophrenia is a long-lasting disorder with an early start, and thus a major contributor to DALYs (Disability Adjusted Life Years) and YLDs (Years Lived with Disability). People with schizophrenia spectrum disorders have a high level of excess mortality due to treatable physical disorders. There is a huge gap between the need for treatment of schizophrenia and access or utilization of treatment which is connected with the stigma related to schizophrenia.

Prevalence and Incidence

According to a systematic review (Saha et al, 2005) of prevalence data evaluated in 188 epidemiological studies the median point prevalence was 4.6 per 1000, period prevalence 3.3 per 1000, lifetime prevalence 4.0 per 1000 and lifetime morbid risk 7.2 per 1000, respectively. Based on combined estimates there was no significant gender difference, as well as no effect of urban, rural, and mixed habitation area. However, the prevalence was significantly increased for migrants compared to native-born individuals (ratio 1.84), and lower in the least developed countries. Although there was the long-term persistent belief that schizophrenia occurs in about 1% of the population, independent of gender (with the exception of an earlier age of first onset in males) and place of living and that it remains stable over time, there is new evidence of a substantial difference between the incidence in male and female populations (male:female ratio = 1.4); moreover, not only migrants but also people born in urban areas show a higher incidence. The data on fluctuation across time are controversial and demand further evaluation (McGrath, 2006).

According to the fact sheet of the WHO Mental Health Report, 7 per 1000 suffer from schizophrenia in the WHO European Region (WHO, 2001a). With regards to the population of the EU27 countries (495 128 529 inhabitants, status on February 22, 2008) the calculated prevalence of schizophrenia should be 3 465 899 (http://epp.eurostat.ec.europa.eu). Since relapses are frequent, schizophrenia is associated with repeated hospital stays and accounts for a remarkable percentage of all permanently disabled people especially in younger ages, and an increased death rate from natural and unnatural causes (premature deaths). About 10 percent of affected people commit suicide. Thus, suicide accounts for 28% of the excess mortality and is the largest single cause contributing to the increased death rate. The other main causes of mortality are due to the high psychiatric and somatic co-morbidity (predominantly addiction and the metabolic syndrome) (Brown et al, 1997; Saha et al, 2007).

AetiologySymptomsCourse of disease

The aetiology is only partly elucidated. There is evidence for a multi-factorial pathogenesis including genetic deviations and functional disturbances of the brain. Therefore, and due to the multitude of clinical disease course types, one should rather speak of the “group of schizophrenias” instead of “schizophrenia”. The first onset of this disorder occurs predominantly in late adolescence and early adulthood preceded by a prodromal period of up to 5 years characterized by unspecific symptoms. The course of the disease is quite variable; about one quarter of the patients exhibits only one acute schizophrenic episode, an additional third shows a chronic progressive course, the majority has recurrent acute episodes (relapses) typically characterized by exacerbation of psychosis and need of rehospitalisation, and with more or less residual symptoms in the phases between the recurrent acute episodes (Marneros et al, 1991). This can lead to significant impairment in psychosocial functioning, in particular in maintaining social contacts and functioning in the workplace.

Treatment and treatment gaps

During the past decades, there have been significant advances in the treatment of schizophrenia. Medications (antipsychotics) improve symptoms, while structured psychosocial treatments allow a remarkable fraction of severely ill people to live successfully in the community and improve their social functioning. Unfortunately, a significant percentage of people with schizophrenia are not receiving appropriate care according to evidence based knowledge (Lehman et al, 1998). According to calculated estimates based on the lifetime prevalence rate, the service utilization rates as reported in community-based psychiatric epidemiology studies, and the population size aged > 15 , the regional treatment gap (median untreated rate = remaining untreated or not adequately treated although effective treatments exist) for schizophrenia and non-affective psychosis accounts for 32.2% world wide, of which 17.8% in the WHO European Region (Kohn et al, 2004). Evidence indicates that there is considerably more unmet need for psychotherapeutic than pharmacological treatments (Lehman et al, 2003). Apart from the inadequacy or unavailability of treatment, people with schizophrenia sometimes do not get the help needed because they do not seek it, fearing the stigma associated with mental illness and especially with schizophrenia (Wrigley et al, 2005). The quality of psychiatric care differs between European countries. Institutional care still dominates in the European Region; in a quarter of the EU countries recently studied, community based mental health services were not provided (WHO, 2005b)

Burden of disease

Compared to other psychiatric disorders the greatest amount of expenditures of the health care system is due to schizophrenia which affords relatively long stays in hospital during the acute episode and frequent re-hospitalisation. The economic burden caused by schizophrenia exceeds the direct treatment costs due to remarkable unemployment rates and disability pensions, as well as increased reliance on social care and welfare support (Andlin-Sobocki et al, 2005).

Schizophrenia belongs to the ten leading causes of disability adjusted life years for the 15 to 44  age group, and it ranks third on the list of leading causes of years lived with disability (WHO, 2001b).

 

5.5.3.2.2. Data Sources

 

There are no comprehensive national or European data available focusing on the prevalence and incidence of schizophrenia as a single diagnosis. Available data summarize prevalence and incidence rates for mental disorders as a whole. The calculated estimates for schizophrenia in the majority of epidemiological studies are based on a consistent morbidity risk over the life span of 1% of the population.

 

In  most studies incidence rates are based on data of first admission to or first contact with psychiatric services of patients with the diagnosis of schizophrenia; patients not receiving specialized psychiatric care (none at all or treated by general practitioners) are only included in few studies. With regard to lacking national registries for psychiatric disorders in most of the European countries, the first admission data may underestimate the need for care in schizophrenia and the burden of the disease. In addition – even in times of international classification systems – the divergent criteria used to identify persons with schizophrenia may still be an important source of variation in incidence and prevalence data (Lange et al, 2002). A certain degree of reluctance in diagnosing schizophreniaespecially in non-psychiatric services – with respect to the stigmatizing label of this diagnosis, as well as an unknown percentage of individuals remaining undiagnosed and untreated may further influence the reliability of incidence rates. The renaming of “Schizophrenia” to “Integration Disorder” in Japan led to an increased rate of diagnosis (Sato, 2006).

 

The data concerning morbidity rates (European Hospital Morbidity Database HMDB) with respect to hospital admissions due to ICD-10/F20, i.e. the chapter including schizophrenia, are not complete for all EU25/EU27 countries, not even the EU15.  Although most WHO-data are based on diagnosis according to ICD10 classification (the majority of data is derived from the year 2005), data from countries like France and Germany are classified according to ISHMT (International shortlist for hospital morbidity tabulation). The WHO data cover more European countries but also not all of the EU27countries (Estonia, Greece, Malta, and Sweden are missing). It summarizes, however, the ICD-10 diagnoses F20F29 based on different diagnostic classification levels. Data provided by EUROSTAT on discharges, admission rates and lengths of hospital stays show deviations from the data published by the WHO which we are not able to explain. All available data do not take into account the differences in the national healthcare systems. Hence, the broad range of days in hospital for example may in part be the consequence of the differences between European mental health care systems.

 

Statistics based only on hospital morbidity data yet underestimate the actual prevalence of schizophrenia since about 80% of patients are treated in settings outside the hospital.

 

Data on the outpatient sector and on rehabilitation are not covered in the European databases. With regard to the trend towards community based care, the lack of respective data means a relevant gap of information on the care of patients with schizophrenia.

 

Inter-country comparison data on mortality for selected causes of death are not even available for all EU15 countries. WHO mortality rates are available for schizophrenia (ICD-10/F20). They are listed in the European Detailed Mortality Database (DMDE) but are not differentiated according to natural and unnatural deaths, and no definition is given for a deathcaused” by schizophrenia. Other data sources like EUROSTAT do not provide data restricted to schizophrenia (ICD-10/F20) but focus on an even broader diagnostic groups of psychiatric disorders. In general, the quality of cause-of-death information is questionable since the accuracy of national statistics, as well as the coding quality, are inconsistent. Schizophrenia itself is no fatal disease although it is associated with an increased mortality mainly caused by co-morbid disorders and suicide (Saha et al, 2007). Databases on suicides do not allow for relating the deaths to underlying conditions like schizophrenia. Therefore, these mortality data have to be interpreted with care.

 

The main group of substances applied for treating schizophrenia and relapse prevention are antipsychotics. In general there are little accurate comparative data on prescribing patterns and respective prescription data do not reflect the actual use in patients with schizophrenia since these drugs are applied also to treat other disorders, and limited data are available on antipsychotic medication applied during hospital stays.

 

WHO-data on the intensity of use of pharmaceuticals are principally based on defined daily doses or DDD, and a comparative standard is emerging based on DDD per 1000 inhabitants per day. Compilation, publication and coverage across Europe is however patchy. Another data source is IMS Health, a commercial organization monitoring prescriptions in order to deliver marketing information for the pharmaceutical industry. The IMS-data document standard dosage units (SU) that are not directly convertible into DDD. With regard to the spectrum of the use of antipsychotics (not limited to schizophrenia) numbers should be regarded as indicative, detailed interpretation would be subject of many qualifications. Prescription data from Germany from the 12-months period between July 2002 and June 2003 substantiate that only 30% of the antipsychotics were prescribed to treat patients with schizophrenia (IMS 2003).

 

 

Health indicators usually used have limited relevance for psychiatric conditions or at least do not reflect the complex aspects of the disease burden. Hence the data presented are supplemented by data from the literature.

 

Unless otherwise noted, the source of data is the European Health for all Database (HFA-DB) of the WHO Regional Office for Europe. Other data and information are referenced accordingly.

 

 

5.5.3.2.3. Data description and analysis

 

Data usually representing the burden of disease are death rates due to the diagnosis of interest, hospital admission rates as indicators for prevalence - as well as information on the length of hospital stays and on disability adjusted life-years (DALYs). In addition, we report information on co-morbidity and the stigma associated with schizophrenia, on treatment gaps and costs to cover at least the main aspects of the schizophrenia burden.

Prevalence and Incidence

Figure 5.5.3.2.1. Estimated prevalence of psychotic disorders in EUGLOREH Countries.

The likelihood that individuals experience an onset of schizophrenia during their lifetime is about seven per 1 000 people. The latest available most comprehensive review on prevalence data identified a median point prevalence of 4.6 per 1 000, 3.3 for period prevalence, 4.0 for lifetime prevalence and 7.2 for lifetime morbidity risk (Saha et al, 2005). These findings are reported equally in the 2001 WHO report and the 1996 Burden of disease study – although not congruent with estimates usually reported in textbooks - and e.g. in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) where the value noted for lifetime prevalence is 0.5 to 1.0%.

Worldwide, between 16 and 42 per 100 000 population experience a new onset of schizophrenia per year; thus the incidence rate is 0.016 to 0.042% with a broad variation across studies and countries (WHO, 1997). Recent international literature emphasises the need for research on long-term neglected country or cultural specific differences in prevalence and in certain incidence figures (gender, migrants, urbanicity). Hence, detailed data are not yet available. Factors that may influence the prevalence, such as recovery, suicide or other forms of early mortality, also need to be re-evaluated. In this context, the definition of recovery versus persistence of the disease and how these factors can be operationalised, also need to be addressed.

Incidence data are usually estimates based on first treatment/admission data due to the diagnosis of interest. These estimates have to be interpreted with care taking into account the treatment gap, the evidence for coding bias and the lack of psychiatric case registries in most of the European countries.. Efforts to optimize delivery of data and establish a more reliable database are very important in order to create a firm basis for decisions and strategies regarding mental health policy.

Mortality

The crude F20-death rates per 100 000 inhabitants would allow a comparison between European countries. Available data from the European Detailed Mortality Database show very high rates in Hungary and especially in Finland, while for Finnish women schizophrenia seems to be more often a fatal diagnosis. In order to further evaluate regional differences, we looked for the absolute number of deaths in selected countries with respect to age categories. These data show a peak in the 3034 age group and again between 45 and 49 years of age with a continuous increase from 54 years on in Hungary, while in France the first peak is at 40 to 44 with a plateau at 50 to 59. As already mentioned above, mortality data seem to be quite questionable but these examples might illustrate the problem of missing reliable data although there is evidence for a substantially increased death rate of people suffering from schizophrenia.

There is a substantial difference between reported death rates in statistics and expected mortality rates according to literature.

The projected mortality rates for schizophrenia according to the updated estimates of the Global burden of disease study (Mathers and Loncar, 2006) describe a positive trend in the years to come. This is in contrast with the increasing schizophrenia-attributed mortality rates stated in literature (Saha, 2007).

People with schizophrenia are at an increased mortality risk compared to the general community and have a lower life expectancy. Despite improvements in drug therapy and in mental health services, this mortality gap has even worsened during recent decades as demonstrated in a recently published systematic review. Based on population-based studies reporting primary data on deaths, the standardized mortality ratio (SMR) for people with schizophrenia was elevated by a factor of 2.5 (median value). Suicide was associated with the highest SMR of 12.86. The authors found that the SMRs for all-cause mortality had significantly increased over time (Saha et al, 2007). A recent epidemiological study in Sweden evaluated that the higher mortality rate (23.0% vs. 11.2%) was mainly the result of injuries from accidents and poisonings and cardiovascular disease. Mortality due to cardiovascular disease was more pronounced in middle age (Fors et al, 2007).

Thus, mortality increasing factors such as lifestyle issuesreduced physical activity, increased rate of smoking, etc. –, the high rate of cardiovascular and metabolic co-morbidities and the high percentage of co-morbid addictive disorders should all be addressed in future programmes to reduce the mortality of people with schizophrenia.

In addition, the metabolic side-effects of some of the second generation antipsychotics have to be re-examined in order to identify their contribution to the mortality rate (Saha, 2007).

The mortality data attributed to the group of schizophrenias as reported in the WHO statistics need further clarification. The cause of death assignment does not allow differentiation according to natural and unnatural deaths. Death rates caused by schizophrenia vary widely between countries and this cannot only be due to differences in psychiatric care, actually it is more likely that they express differences in the cause of deaths assignment.

Lifetime suicide rates for schizophrenia of 10% are widely cited. More recently, published estimates of lifetime suicide prevalence in schizophrenia are contradictory: While Palmer et al quote “that 4.9% of schizophrenics will commit suicide during their lifetime, usually near illness onset” (Palmer et al, 2005), a comparison of suicide rates from the pre-community care era and in the years 19941998 (based on cohorts of the North West Wales historical database) performed by Healy and co-workers found a significant increase in the more recent years possibly mediated by deinstitutionalization and other factors (Healy et al, 2006).

Currently available statistical suicide data - if not based on psychiatric registries -do not provide information on underlying illnesses. Thus, there are no reliable data on suicides in the context of schizophrenia.

All these factors underline the need of evaluating detailed mortality data with a more distinct cause of deaths assignment.

In addition, there is a need to identify drugs that may have favourable effects on suicidality.

Hospital-Morbidity

Admission rates according to EDMD show some extremely different values for certain countries, which cannot be due to higher incidence or prevalence rates in these countries. Some countries are missing in figure 5.5.3.3.2 due to lacking ICD-10 documentation. Even if discharge dates were taken into account, there would be no considerable differences. This points to the necessity of a more consistent data collection and documentation.

Figure 5.5.3.2.2. Inter-country comparison of hospital age standardized in-patient admission rates per 1000; Main diagnosis: Schizophrenia ICD-10 codes: F20.

Figure 5.5.3.2.3. Admission rates trend over time

The trend over time of admission rates reflects the tendency of deinstitutionalization, although in some countries the rate still remains high.

Figure 5.5.3.2.4. Average length of stay - trend over time

Available data on inter-country comparisons of hospital in-patient admission rates, average length of stay and number of day-cases vary widely. In addition, data coded according to ICD-10/F20 are only available for a very limited number of EU-countries. Considering in-patients per 1,000 populations (see Figure 5.5.3.3.2), the value reported from Finland of about 20.506 is more than 100 fold higher than the value reported for Norway (0.0164). On the other hand, data from the Nordic Medical Statistical Committee (NOMESCO, 2007) indicate that there is no substantial difference in discharge rates from psychiatric hospitals between Finland and Norway. Although in some cases variations like this might in part be due to differences in the mental health care systems, the extent of variation is due to differences in the national health information systems and deficiencies in international health information systems.

Not even accurate hospital morbidity data alone provide a comprehensive picture of the complex aspects of schizophrenia and their impact on the individual and on society. It is indispensable to supplement morbidity databases with data on outpatient care.

Disability adjusted life-years

In 2005, neuropsychiatric conditions were the second most frequent cause of disability adjusted life years (DALYs) in the WHO European Region according to the Global Burden of Disease estimates, amounting to one fifth of DALYs due to health conditions (WHO, 2007). In terms of years lived with disability (YLD), the portion is even higheri.e. more than two fifths. According to the most recent data, neuropsychiatric conditions now rank first in most European countries. With regards to single neuropsychiatric conditions, four of the top 15 contributors to DALYs in Europe are neuropsychiatric disorders (depression in third place, alcohol use disorders sixth rank, self inflicted injuries eleventh, and dementia fourteenth). In terms of YLDs, schizophrenia is ranking 11th and accounts for 2.3% of the years lived with disability (unipolar depressive disorder ranks 1st and accounts for 13.7% of YLDs, followed by alcohol use disorder accounting for 6.2% YLDs).

Table 5.5.3.2.1. DALYs due to schizophrenia

DALY rates for schizophrenia are especially important since the first onset occurs predominantly in young ages, the time when education is ongoing or the person starts a professional career. This is reflected by the high schizophrenia DALY rates estimated from data of 2002 for the year 2005: In the WHO European Region the 1529 age group has the highest values of schizophrenia-associated DALYs616544 for males and 579006 for females (Mathers et al, 2006).

Deficits in social abilities often lead to restrictions or even incapability to participate in the work life. Therefore, schizophrenia carries with it massive human and economic disability costs. Substantially reducing these impairments in social functioning is one of the major challenges of new therapeutic strategies and the development of innovative drugs.

The social situationliving and performance of social roles – is an important outcome measure for people with schizophrenia. Longitudinal research has shown that antipsychotics effectively prevent relapses. But this is not necessarily linked to an improvement of the social situation. What really matters is how people live, if they are able to establish social relationships, to live with a partner etc. Therefore, social outcome should be given more prominence in research and practice (Priebe, 2007). The importance of social outcome is also reflected in the quality of life assessment which differs significantly between physicians and patients.

There is also a need to develop strategies to prevent disability including the development of new drugs, since prevention will hopefully be far more successful than attempts to rehabilitate individuals after a long and debilitating disease course.

Co-morbidity

People with schizophrenia are significantly more likely to have one or more co-morbid physical or psychiatric conditions compared to controls. Co-morbidity has been shown to be an indicator for a more severe disease course and poorer outcome. Physical co-morbidity accounts for 60% of premature deaths not related to suicide. According to a recent review of the literature on physical illness and schizophrenia, people with schizophrenia have a higher prevalence of HIV infections and hepatitis, osteoporosis, altered pain sensitivity, sexual dysfunction, obstetric complications, cardiovascular diseases, overweight, diabetes, dental problems, and polydipsia than the general population (Leucht et al, 2007).

Available statistics do not cover this important aspect of morbidity.

Table 5.5.3.2.2. Prevalence and adjusted odds ratios for main medical conditions in women and men with schizophrenia compared to controls.

Schizophrenia is associated to co-morbid physical and psychiatric illnesses. With respect to psychiatric diseases, depression and addiction have the most important impact on prognosis. About 50% of the patients with schizophrenia are addicted to alcohol, nicotine or cannabis (Regier et al, 1990). Compared to typical community prevalence rates (25-30%), the rate of nicotine addicts is three times higher (88%; Punnoose and Belgamwar 2006).

The treatment of people with co-morbid addictive disease is a great challenge for therapists, since these patients experience frequent relapses, show poor treatment compliance and are difficult to be treated in a setting tailored to treat people suffering from psychosis. On the other hand, conventional therapeutic settings for detoxification are not adequate for people with schizophrenia. In addition, substance abuse is associated with consecutive somatic diseases of the cardiovascular system (due to the use of nicotine) or the liver (due to alcohol consumption). The underlying causes for this coincidence have not been fully elucidated.

With regards to physical co-morbidities, the greatest amount of available data is on diabetes and the metabolic syndrome. The diabetes prevalence is shown to be about 15% in patients with schizophrenia as compared to 23% in the general population. In the family history of people with schizophrenia there is evidence of an increased frequency of diabetes which may suggest a common pathomechanism (Prince et al, 2007). In addition, people affected by schizophrenia show a much stronger tendency to be obese, i.e. a 1.5 to 4 times increased rate compared to community rates (Coodin, 2001; Silverstone, 1988). Adiposity again represents an important risk factor to develop the metabolic syndrome. Although some second generation antipsychotics are associated with metabolic side effects (Engl et al, 2006) the increased rate in people affected by schizophrenia cannot be exclusively attributed to these substances since abnormalities of glucose regulation were noticed in people with schizophrenia before the use of antipsychotic medication (Holt et al, 2005).

A great deal of co-morbid diseases remains undiagnosed and often inadequately treated. When taking into account the great impact of co-morbidity on outcome, one must be aware that the disease burden due to schizophrenia is underestimated.

Evidence based treatment of schizophrenia and treatment gaps.

Treatment options

The state of the art of the treatment of schizophrenia comprises psycho-pharmacotherapy, psychotherapy and psycho-social therapy. While nearly all people with schizophrenia need antipsychotics not only during the acute episode but also for long-term relapse prevention, many will benefit from psychotherapy, while the majority needs to be supported through psycho-social interventions.

A recently published meta-analysis on the efficacy of psychotherapy for patients with schizophrenia (Pitschel-Walz and Bäuml, 2007) demonstrated beneficial effects for psycho-education, family intervention and cognitive behavioural therapy. For other treatment approaches, the authors found positive trends in efficacy, but due to a paucity of well-controlled randomized studies, a final conclusion could not be drawn.

Psychotic episodes have a devastating impact with respect to morbidity, cost, suffering, and function. Besides optimizing the treatment of patients with schizophrenia, an important issue is represented by early identification and intervention with the goal of preventing morbidity and disability. There is often a long time lag after the onset of symptoms and before schizophrenia is diagnosed and appropriate treatment installed (Häfner et al, 2004). During that time, dire psychosocial consequences of the disease may develop. Besides, delayed treatment is more likely to be associated to compulsory admission to psychiatric hospitals. Therefore, there is an urgent need to identify people at increased risk and to establish optimal intervention measures.

Prodromal state and prevention

People even in an initial prodromal state are already suffering from mental changes, including sub-psychotic symptoms, developing cognitive deficits, decreasing subjective quality of life, substantial loss of occupational and social functioning. Their risk for development of full-blown psychosis is markedly increased (Häfner and Maurer, 2006).

Effective intervention strategies are needed for both, treatment of prodromal syndromes and prevention of psychosis. Based on the limited available data there seems to be evidence that intervention during this phase of the disease is apt to reduce the incidence of first onset of psychosis and can lead to the improvement of symptoms as well as social adjustment. Yet the limited data - although promising - do not allow final conclusions on the preventive effects of such interventions. More conservative opinions concerning early detection and intervention question the validity of prediction criteria and the benefit of early intervention, especially with regards to the underestimated possibility of spontaneous remission of symptoms (Bottlender, 2006).

Although a number of prodromal treatment programmes have been initiated around the world, three early programmes have generated most of the intervention findings to date: Personal Assessment and Crisis Evaluation (PACE) in Australia, and the Prevention through Risk Identification, Management, and Education (PRIME) and Recognition and Prevention (RAP) programmes in the USA. In some European Countries parallel to the establishment of Early Recognition Centres and respective programmes, the European Prediction of Psychosis Study (EPOS) was also initiated. This is the first European prospective trans-national field study of the prodrome and moderating risk/resilience factors of psychosis. As different health systems provide different structures of care, prevention programmes will only be successfully implemented and sustained system-wide if they can be adapted to the system’s special opportunities and needs. EPOS will provide a sound database for a future evidence-based prevention of psychosis. (Klosterkötter et al, 2005; Klosterkötter, 2007).

The gap between need and utilization

According to the 2001 WHO Report, between 36% and 45% of the 6.6 million people in the WHO European Region (7 per 1000) affected by schizophrenia are estimated to be untreated. This may be due to several reasons: lack or misallocation of resources, non-adherence to or inadequate application of guidelines, as well as neglection of certain therapeutic options, non-compliance, etc..

According to a literature review on the treatment gap in mental health care, European data on this topic is limited. Community-based epidemiological surveys on service utilization of adults at age 15 and older covering schizophrenia are available only from Finland, the Netherlands and the UK. The prevalence period for help seeking in these surveys was 12 months (Kohn et al, 2004).

The percentage difference between the number of people needing treatment for schizophrenia and the number of people receiving treatment calculated on service utilization rates in these surveys, population size, and prevalence rates was as follows:

Mini survey                              Finland                        14.3%

NEMESIS                                 Netherlands                53.3%

ONS                                        United Kingdom           15.0%

OPCS                                       United Kingdom           18.0%

 

According to the examination of the extent of the treatment gap in mental health care (people remaining untreated although effective treatments exist), the median treatment gap for schizophrenia (including other non affective-psychoses) was 32.2% (Kohn et al, 2004) worldwide; selected data of studies from Western Europe note 17.8%, while estimates in the WHO Report for Europe 2001 were much higher, namely 36% to 45%. This implies that far too many people with schizophrenia do not receive timely and adequate treatment. This may lead to an increased burden of the disease due to more severe courses of schizophrenia resulting in increased disability rates.

The efficacy-effectiveness gap

Advances in the understanding of schizophrenia and in its treatment have led to the availability of a more complex armamentarium of interventions to be applied on an individual basis. Yet the expansion of knowledge is not adequately translated into practice, thus leading to an “efficacy-effectiveness gap” which is supposed to be the comprehensive description of the gap between what researchers know and what is done in routine care, what psychiatrists do and how well it works (Spollen, 2003).

Domains reflecting this gap are the prescribing practice, the provision of psycho-social treatments in routine care, the standard of guidelines, the degree of adherence to these recommendations and patient’s compliance.

For a multitude of reasons, the routine clinical care of schizophrenia is far behind the current evidence. Closing this gap is essential if people with schizophrenia are to benefit from advances achieved in treatment and basic research. Reasons for this gap might be lack of knowledge, the fact that translation from research into practice is difficult because of differences between the specific circumstances in structured research settings and routine care (patient population, artificial circumstances, resources available, staff knowledge, interventions to enhance compliance, etc.), non-compliance, difficulties in implementing guidelines where available, and lack of resources. Thus , various strategies are required to close the gap.

Unmet needs in psycho-pharmacotherapy and psychosocial interventions

Although there is plenty of evidence that the treatment of schizophrenia should be based on three therapeutic columnsantipsychotic medication, psychotherapy and sociotherapy (Pitschel-Walz, 2007; Vauth, 2006,; Glynn, 2003; Pilling et al, 2002) – with a varying focus during the course of the diseasepractice does not necessarily reflect this approved strategy (Demyttenaere, 2004; Middelboe, 2001).

While pharmacological treatments are extensively studied, there is much to be learned in the everyday use of these treatments, because the study population is usually not representative of routine clinical samples (strict exclusion criteria and study duration limited to some weeks). Thus, clinical trials provide tendencies of efficacy in certain patient groups but give little to no information about individual variability and its effect on treatment. Therefore, there is a need for intervention trials that reflect every day practice, such as CATIE, CUtLASS or EUFEST.

Prescription antipsychotics vary widely in European countries. Finland has by far the highest level of antipsychotic prescriptions per head of population; Germany displaying the next highest use of this drug class (Knapp et al, 2007). According to NOMESCO figures, the DDD sales of antipsychotics in Finland is 50% higher than in Sweden, whereas no IMS-data from Sweden were available. Regarding the prescription of atypical antipsychotics Finland is in the lead, too, while in the UK mostly typical antipsychotics are prescribed, and little to no atypicals. Prevalence estimates on schizophrenia for Finland are contradictory; some findings suggest higher rates compared to many other countries (e.g. Hovatta et al, 1997); more recent evidence suggests a decline in prevalence (e.g. Suvisaari et al, 1999), but even higher estimates cannot account for the extremely unusual high usage of antipsychotics and are probably related to use of antipsychotics for other indications than schizophrenia. Thus, the reasons for this difference should be further evaluated. The United Kingdom has a very low usage of antipsychotics compared to other EU countries.

With regards to the second generation of antipsychotics – “atypical neuroleptics” – the prescribing practice also shows significant differences across European countries. According to IMS-health-data (Intercontinental Marketing Services) based on the 1st quarter of 2004, second generation antipsychotics account for 50% in Great Britain, 43% in Spain, 41% in Finland, 37% in Italy, 35% in Denmark, 34% in Hungary, 26% in Germany, 23% in France, 16% in Czech Republic, and 15% in Poland (Fricke and Pirck, 2004). Differences in usage of second generation antipsychotic drugs recommended by international guidelines may in part be due to health insurance policies but are probably indicators for the gap between guideline evidence and practice. However, in the EU 15 countries there is a consistently increasing trend over time (years 19932002) in prescribing atypicals (Knapp et al, 2007) (Figure 5.5.3.3.5).

Figure 5.5.3.2.5: Prescription of antipsychotics in the year 2002.

The gap between evidence and implementation as well as utilization is especially big for psychosocial treatments. Although there are indications that a number of patients with schizophrenia receive some kind of individual counselling, it is doubtful that many of these therapists are using research-proven models. It is thus indispensable to evaluate barriers of implementation for this kind of interventions and to develop strategies to implement them successfully.

Obviously, there is a widespread practice of focusing on drug therapy and neglecting psychosocial interventions (Lehman and Steinwachs, 2003). The latter is in part reflected in the missing of respective recommendations in guidelines (Table 5.5.3.2.3).

Table 5.5.3.2.3. Psychosocial interventions reflected in European guidelines

Non-compliance

Another key factor responsible for a treatment gap is the non-compliance of people with schizophrenia and their frequent non-adherence to medication. Median non-compliance rates are 50%, thus being similar to other mental illnesses and somatic diseases. The rates vary widely depending on the therapeutic setting, the kind of application of the medication, the assessment methods and the duration of the evaluation; 24 - 88% (Lacro et al, 2002). According to the most recent data evaluated within the EUFEST trial, treatment discontinuation over 12 months in patients with first-episode schizophrenia was significantly greater in patients given a low dose of haloperidol than in those assigned to treatment with second-generation antipsychotic drugs (Kahn et al, 2008). Non-compliance does not necessarily mean “not taking the prescribed medication”, it can also meanChanging the dosage or the medication regimen”; about 30% behave like this. The lack of illness acceptance and insight into the necessity of treatment leads to discontinuation of medication intake with often serious consequences (Byerly et al, 2007). A substantial proportion of relapse is supposed to be due to non-adherence.

Deficits of guidelines and their implementation

Although there are quite a few excellent guidelines on schizophrenia treatment, most of them do not meet current quality standards as assessed by the AGREE (Appraisal Guideline Research and Evaluation Europe) instrument, a rating scale to assess the quality of reporting and of the guideline development process (Leucht et al, 2006; Gaebel et al, 2005; AGREE Collaboration, 2003) – see table 5.5.3.2.4.

Table 5.5.3.2.4. European practice guidelines and their AGREE score

Guidelines are intended to be a synopsis of evidence based knowledge about schizophrenia treatment and to provide an algorithm to help clinicians proceed through the various options in an organized and rational way in order to identify the optimal strategy for the individual patient.

Lack and misallocation of resources

The WHO-Atlas on Mental Health delivers an overview on resources of care available in the EU member states and respective deficits.

Table 5.5.3.2.5. Mental health service in Europe

Not only the lack of resources but also their misallocation may lead to a treatment gap as demonstrated in the WHO-initiated World Mental Health Surveys (WHO, 2004), which were linked to the European Study on Epidemiology of Mental Disorders (ESEMeD) (Demyttenaere et al, 2004). The authors concluded that the findings on unmet needs for treatment among serious cases were not merely a result of limited resources but also of the misallocation of these resources. Although schizophrenia was not explicitly in the focus of this evaluation, the findings might to a certain degree be also valid for schizophrenia.

Adequate numbers of specialized personnel for mental health services are an important resource of a good mental health system. On average, the situation in the WHO European Region is much better than in other regions of the world, but the significant variations between countries arouses concern: the numbers of psychiatrists ranges from 1.8 to 25, of psychiatric nurses from 3 to 104, of psychologists from 0.1 to 96 per 100 000 population (WHO, 2005c). This is also true with regards to community-based care.

The 2001 World Health Report on Mental Health strongly favours the benefits of community-based care delivered close to home and recommends the proper use of a range of services. Several European countries have been leaders in the movement towards effective community-based care. This may be reflected in the fact that Europe has a lower proportion of psychiatric beds in general hospitals (10%) than the world average (16%). However, it may also indicate that many European countries continue to rely on large mental hospitals to provide care for people with the most severe psychiatric disorders.

The extent and quality of mental health care in European countries is characterized by a great degree of variability as highlighted by the current data from the WHO Atlas on mental health resources in the world (WHO, 2001b):

“One third of the European countries do not have specified mental health policies. More than two fifths of them do not have mental health programmes. One fifth does not have a therapeutic drug policy or an essential drug list. One fifth of countries has not made the three essential psychotropic drugs – an antidepressant, an antipsychotic and an antiepilepticavailable in primary care. About a tenth does not have mental health legislation”.

These deficits may in part be the consequence of the limited allocation of the national health budgets to mental disorders: Although mental disorders represent 20% of the disease burden, only 5.7% of the budget is allocated to mental health care. Research is necessary to find out if health expenditures reflect quality of care. However, insufficient treatment is not merely a result of limited resources but also of the misallocation of these resources as demonstrated by the findings of the European Study on Epidemiology of Mental Disorders (ESEMeD) providing information on countries such as Belgium, France, Germany, Italy, The Netherlands, Spain and Ukraine (WHO, 2004). While the need for treatment in cases of severe disorders was not met, many people with subthreshold disorders were treated. A Nordic study on people with schizophrenia living in the community found that, in general, patients reported a need for help from services clearly exceeding the actual amount of help received. The highest proportion for unmet needs was related to social and interpersonal functioning (Middelboe et al, 2001)

Stigma and discrimination

People affected with schizophrenia do not only suffer from psychotic, cognitive or affective symptoms but to a large extent from stigmatization and discrimination. Presumably, the reluctant help seeking behaviour when first symptoms emerge and the delayed treatment even after onset of the first acute psychotic episode are due to the stigma associated to the diagnosis of schizophrenia. An international example for this problem is the Japanese experience with renaming schizophrenia (Sato, 2006). A pilot study recently published in Italy (Buizza et al, 2007) evaluated four dimensions of stigma in 428 concrete cases of stigmatization reported by six focus groups (three with people with schizophrenia and three with patientsrelatives) (Figure 5.5.3.3.6). Internalized stigma is related to low self-esteem, hopelessness, and reduced social contacts (Lysaker et al, 2007) – factors associated with a chronic course of disease.

Figure 5.5.3.2.6. Experiences of stigma in Italy

The stigma attached to mental illness is the main obstacle to the provision of care (Sartorius, 2007). Stigma marks those who are ill, their families across generations, institutions that provide treatment, psychotropic drugs and mental health workers. Furthermore, stigma leads to discrimination in the provision of services for physical illness in those who are mentally ill (Fang and Rizzo, 2007).

Schizophrenia especially is associated with a heavy burden of stigmatization because of psychotic symptoms. The main prejudices are that people with schizophrenia are dangerous and that their behaviour is unpredictable.

Research in stigma has also evaluated self-stigmatization in people afflicted by mental disorders: More than 60% abandon from having close personal relationships and from applying for employment, more than 70% resign from doing or looking for something else that is important to them, and nearly 80% believe they should better not talk about their diagnosis (Baumann et al, 2007).

As stated in the EU Green Paper for Mental Health, fighting stigma is one of the main challenges and most urgent tasks in the process of optimizing the situation of mentally ill people and improving mental health care. An evaluation of the effects of the interventions according to the German WPA Program against stigma and discrimination because of schizophrenia provided limited evidence for the efficacy. The authors concluded that further research is needed to separate direct effects from more general influences on social distance (Gaebel et al, 2005).

Direct and indirect costs of schizophrenia

A number of studies have attempted to estimate the aggregated burden of mental illness as a whole, and schizophrenia as a single diagnosis. Economic costs vary by country; this is particularly true for schizophrenia. The direct costs account only for a small part of the expenditures; most of the economic burden is due to DALYs and the respective expenditures for social welfare, disability pensions etc. A comprehensive European database of national statistics on all expenditures caused by schizophrenia is not available. Yet the European Brain Council has evaluated the costs of brain disorders in Europe by an analysis of studies from Italy, Denmark, the Netherlands, Spain, and the United Kingdom. Included in this analysis are psychotic disorders represented mainly by schizophrenia. However, the authors stressed the fact that the costs provided by the countries do not in all cases cover direct and indirect expenditures for all diagnosis (Andlin-Sobocki & Rössler, 2005).

In 2004, the costs for hospital stays due to mental disorders were about 2.5 times as high as for outpatient care (see Table 5.5.3.3.6). Since psychotic disorders account for the highest amount of direct costs, as evaluated by Andlin-Sobocki (Figure 5.5.3.3.7), it can be assumed that a great part of the costs for hospital stays is related to schizophrenia, being a very severe disease which affords long hospital stays and frequent readmissions. This assumption is supported by the most recent data from Sweden: Lindström and co-workers explored the direct and indirect costs in a cohort of patients with schizophrenia over 5 years. They found that the direct costs were dominated by hospitalization; drug costs represented only 7% of the direct costs. Indirect costs represented 43% of total costs within these 5 years (Lindström et al, 2007)

Table 5.5.3.2.6. Expenditures by kind of health care service for year 2002 and 2004 with respect to F20-F29

Figure 5.5.3.2.7. Direct healthcare costs by brain disorder

The most comprehensive evaluation of costs for brain disorders was performed by the European Brain Council (Figure 5.5.3.3.8). Although not all countries in the scope of this evaluation provided detailed data, these findings are a valuable source of information on the amount of mental health expenditure. Families of people affected by mental disorders carry an enormous amount of financial (and psychological) burden. Providers of care are aware of this fact, but when talking about budgets necessary to treat schizophrenia according to the therapeutic state of the art, this factor is not taken into account.

Figure 5.5.3.2.8. Costs per case of schizophrenia in EUGLOREH countries.

Andrews and colleagues evaluated cost-effectiveness of current and optimal treatment for schizophrenia (Andrews et al, 2003). Their findings22% of burden could be averted by optimal treatment compared to 13% with current intervention practice, the number of YLDs averted could be increased by two-thirds – are convincing also with respect to the affordability of optimal treatment within present budgets.

The costs as segmented according to different health care services, reflect the practice of restrictive assignment to outpatient care and rehabilitative measures.

The allocation of budgets needs to be revised with respect to the increasing burden of mental illnesses,. Investments in the reduction of disabilities should be increased. The strategy of financial allocation should be reconsidered with respect to the minimal share of the budget dedicated to rehabilitation.

5.5.3.2.4. Control tools and policies

 

National mental health acts or programmes

Before and after the publication of the Green paper (European Commission, 2005) and the WHO Helsinki Declaration (WHO, 2005d) some helpful material was made available by the WHO and the EU Commission. The papers reflected the efforts to build the basis for a EU strategy to improve mental health in the European Region. Some of these publications are listed here below:

·          WHO Atlas Mental Health, published in 2001Collection of data on the mental health care system. www.who.int/mental_health/media/en/244.pdf

·          Mental Health in Europe 2001 - Country reports from the WHO European Network on Mental Health
www.euro.who.int/document/e76230.pdf

·          Mental health: facing the challenges, building solutions. Report from the WHO European Ministerial Conference 2005
www.euro.who.int/document/E87301.pdf

·          Mental health promotion and mental disorder prevention across

·          European Member States: a collection of country stories (European Commission, 2006a)

·          Mental Health in the EUKey facts, figures and activities http://ec.europa.eu/health/ph_determinants/life_style/mental/docs/background_paper_en.pdf

There are different EU-programmes dealing with mental health. However, there is still no European master-plan resulting from the consultation process on the Green Paper. Instead of further pursuing the Green Paper Process, plans were made to initiate a Europe-wide Mental Health Pact during a EU Health Ministerial conference held in June 2008. This conference in fact resulted in a consolidated version of the Mental Health Pactwww.ec-mental-health-process.net . The Implementation of the pact focuses on four priority themes; a series of respective thematic conferences is scheduled for 2009-2010. Combating stigma and social exclusion is a priority which runs through across all thematic areas and is supposed to be a main focus of research activities.

A most recent publication on the future direction of mental health care was edited in the UK. This might be an initial step towards a concerted EU strategy (Knapp et al, 2007).

Database

Since strategies and decisions should be backed up by reliable data, the improvement of existing databases (WHO/EUROSTAT) with harmonized information according to ICD-10 is most needed. The establishment of a specific database and investments in optimizing statistics are indispensable. With regards to psychiatric illnesses, detailed case registries (which are only available in some European countries such as Belgium, the Netherlands, and Denmark) and the implementation of disease management programmes would cover three main objectives: complete and ameliorate the database, and improve care.

Guidelines

The development of a methodologically sound guideline is a very complex process that requires time and money. Many countries do not have sufficient funding for guideline development. Independent international organisations could contribute to defining a core set of unbiased schizophrenia treatment recommendations. In countries with a shortage of resources, this could be a basis for adaptation to national and economic backgrounds (Gaebel et al, 2005). Another solution, as suggested by Leucht commenting on the survey on schizophrenia practice guidelines, “would be an international joint project with the aim to develop shareable guidelines and thereby save costs(Leucht, 2006).

Fighting stigma

Some countries already have national and international programmes against stigma. Great Britain is very active in establishing national programmes to fight stigma. In Germany, the German Society of Psychiatry, Psychotherapy and Nervous Diseases recently initiated a National Alliance on Mental Health supported by the Ministry of Health. This is meant to continue and enhance the activities of the WPA Open the Doors programme, explicitly designed to develop and create awareness programmes to fight the stigma of mental disorders. Such programmes are, however, in general not focussed on the stigma of schizophrenia.

To date there are few programmes focusing exclusively on schizophrenia: Poland has established the WPA programme to fight stigma associated with schizophreniaOpen the Doors” as did Germany; also Slovakia has a programme against stigmatization known with the name of Open Hearts.

Research in schizophrenia

Networking in research has proved to be a most effective instrument in schizophrenia research e.g. in Germany. Establishing research alliances and networks of excellence on a European level in order to enhance research and gather comparable data on incidence and prevalence rates, risk factors etc is most desirable (Wölwer et al, 2003)

Prevention

The WHO ReportPrevention of Mental Disorders: Effective Interventions and Policy Options” (2005) mentions 7 groups of disorders for which effective prevention programmes can be designed. One of these disorders is schizophrenia. But when talking about prevention of schizophrenia the only option that will be available in some yearstime is the so called indicated prevention that is targeted to people at high risk and emerging prodromal symptoms (Klosterkötter, 2007). Respective programmese.g. Romania has initiated a focused prevention programme on schizophrenia – are under development. Further research to ensure the evidence base for such programmes is necessary. In Germany this issue is one of the research projects of the German Research Network on Schizophrenia.

5.5.3.2.5. Future developments

 

With regards to the enormous social burden it is indispensable

·          to enhance trans-national research in the field of risk assessment, early detection, first-onset schizophrenia, somatic and psychiatric co-morbidity (especially substance misuse), emerging risk factors like migration;

·          to increase research on mental health-care and on health-services in order to optimize statistics and databases, as well as to minimize problems arising at the interface between hospitals and community care;

·          to accelerate knowledge transfer from research into practice;

·          to enhance implementation of evidence based guidelines

·          to promote early detection and early intervention in order to reduce chronic cases and financial burden;

·          to reduce the stigma associated with schizophrenia;

·          to ameliorate the delivery of mental health care by providing area-wide community based care and other resources necessary for the implementation of strategies essential for optimal comprehensive treatment.

There are reasons for being optimistic, especially with regards to achievements and future progress in treatment and in basic research, and given the growing awareness of the relevance of mental illness. There is still plenty to do to reduce the burden caused by schizophrenia for affected people, their families, and society. Therefore it is necessary to:

·          continue to invest into basic and clinical research on schizophrenia at European level covering aetiology and pathogenesis, development and evaluation of psycho-social treatment strategies, and further improvement of drug therapy;

·          ensure the delivery of state-of-the-art treatment in all medical settings;

·          train psychiatrists in prevention, recognition and management of co-morbidities, and overcome barriers towards optimal treatment;

·          overcome stigma;

·          ensure the adequate supply of all necessary mental health services and providers;

·          facilitate re-entry into the working environment and social life in general, as major factors of quality of life.

 

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5.5.3.2.7. Acronyms

 

DALYs

Disability Adjusted Life Years

DDD

Defined Daily Dose

YLDs

Years Lived with Disability

HMDB

European Hospital Morbidity Database

 

 

5.5.3.3. Autism Spectrum Disorder

 

5.5.3.3.1. Introduction

 

Autism Spectrum Disorders (ASD) is a lifelong neuro-developmental disorder due to neurobiological conditions. One of the main difficulties in estimating the prevalence of ASD in a historical perspective, is the fact that our understanding of autism has changed over the past decade. One of the changes has been the appreciation that several closely-related disorders exist; they share the same essential features but differ on specific symptoms, age of onset, or natural history. These disorders mentioned above are now conceptualised as ASDs.

In 1943 Leo Kanner described Infantile Autism as a clinical condition characterised by “a profound lack of affective contact” and “repetitive, ritualistic behaviour, which must be of an elaborate kind”. Frequent changes since Kanner’s first clinical description with the intention to develop a consistent case definition have created a wider and complex group of diseases/conditions known as Autism Spectrum Disorders (ASDs).

ASDs include the classical Autism described by Kanner and other clinical conditions like Asperger’s syndrome, Fragile X Syndrome, Landau-Kleffner Syndrome, Rett syndrome, childhood disintegrative disorder, and PDD-NOS (pervasive developmental disorder not otherwise specified). In the last five years, research has shown that many people with autistic behaviours have related but distinct disorders:

·          Asperger’s Syndrome is characterized by concrete and literal thinking, obsession with certain topics, excellent memories and beingeccentric’. These individuals are considered as highly functioning, are capable of holding a job and of having an independent life.

·          Fragile X Syndrome is a form of mental retardation in which the long arm on the X chromosome is constricted. Approximately 15% of people with Fragile X Syndrome exhibit autistic behaviours. These behaviours include: delay in speech/language, hyperactivity, poor eye contact, and hand-flapping. The majority of these individuals function at a mild to moderate level. As they grow older, their unique physical facial features may become more prominent (e.g., elongated face and ears), and may also develop heart problems.

·          People with Landau-Kleffner Syndrome also exhibit many autistic behaviours, such as social withdrawal, insistence on sameness and language problems. These individuals are often thought of as havingregressiveautism because they appear to be normal until sometime between ages 3 and 7. They often have good language skills in early childhood but gradually lose their ability to talk. They also have abnormal brain wave patterns which can be diagnosed by analyzing their EEG pattern during an extended sleep period.

·          Rett Syndrome is a degenerative disorder which affects mostly females and usually develops between six and eighteen months of age. Some of their characteristic behaviours include: loss of speech, repetitive hand-wringing, body rocking, and social withdrawal. Individuals suffering from this disorder may be severely to profoundly mentally retarded.

·          Williams Syndrome is characterized by several autistic behaviours including: developmental and language delays, sound sensitivity, attention deficits, and social problems. Opposite to many autistic individuals, those with Williams Syndrome are quite sociable and may have heart problems.

·          Childhood disintegrative disorder (CDD) is a condition occurring in 3 to 4 year olds characterized by deterioration, over several months of intellectual, social and language functioning. Also known as disintegrative psychosis or Heller’s syndrome. This rather rare condition was described many years before autism but has only recently been ‘officiallyrecognized. Children with CDD develop a condition which resembles autism but only after a relatively prolonged period of clearly normal development. Although apparently rare the condition has probably been often diagnosed incorrectly. CDD is usually associated to severe mental retardation. There also appears be an increased frequency of EEG abnormalities and seizure disorder.

·          Pervasive Developmental Disorder, Not Otherwise Specified (PDD-NOS) is a ‘sub thresholdcondition in which some - but not all - features of autism are explicitly identified. PDD-NOS is often incorrectly referred to simply as ‘PDD’. The term PDD refers to the class of conditions to which autism belongs. PDD is not itself a diagnosis, while PDD-NOS is a diagnosis. The term PDD-NOS; also referred to as ‘atypical personality development’, ‘atypical PDD’ or ‘atypical autism’, is included in DSM-IV to encompass cases where there is marked impairment of social interaction, communication, and/or stereotyped behaviour patterns or interest, but when full features for autism or other explicitly defined PDD are not met.

 

5.5.3.3.2. Data sources

 

Autism Spectrum Disorders seem to be on the increase as evidenced by several authors. However, there is no Europe-wide information on the prevalence. Difficulties such as lack of consistency in diagnosis, lack of agreement on case definition and differences in case finding methods have contributed to this. Equally, in Europe, the social and economic burden of ASD has not been adequately recorded, as epidemiological figures are unreliable and inconsistent.

 

There are no available comparable data on morbidity in ASD in Europe. Controversy exists in the management of the disorder and cannot be entered into within the context of this report

 

An epidemiological survey conducted by Fombonne mentions epilepsy as the most frequent co-morbid condition followed by hearing or visual impairments, cerebral palsy, Downs Syndrome, tuberous sclerosis and Fragile X Syndrome, among others (Fombonne, 2005).

 

It is not possible to comment on the current health service usage per Member State in ASD as the case identification system is very weak and variable from country to country.  It has been observed that there are very wide inequalities in terms of waiting lists for diagnosis, in countries where such services exist, often in the private sector and through ParentsGroups.  This situation is profoundly felt in other countries where very few or no diagnostic services for ASD exist

 

Although a higher mortality risk has been observed in autism compared with the general population, as far as we are aware no deaths have been directly attributed to any of the conditions included in the ICD-10 code. Elevated death rates are due to several causes, including seizures, accidents and respiratory diseases among people with severe learning disability (Sanchéz-Valle et al, 2007).

 

 

 

5.5.3.3.3. Data description and analysis

 

Cross-sectional studies suggest that the evidence supporting an increasing rate of autism in the UK and the US has gathered strength. Although both the nomenclature and the criteria used to define autism have changed over the years, these changes are not so great as to prevent comparative analysis and do not explain major differences in reported prevalence over time. The major source of variability in reported autism rates comes from incomplete ascertainment in young age cohorts, which limits the ability to detect an underlying and rising secular trend. Reviews that have downplayed the rising trend have overemphasized unimportant methodological problems and failed to take into account the most relevant biases in survey methodologies. Point prevalence comparisons made within and across surveys conducted in specific geographic areas, using year of birth as a reference for trend assessment, provide the best basis for inferring disease frequency trends from multiple surveys

Prevalence rates have been estimated in different European countries but due to the different methodologies and definitions used, it is not possible to make comparisons. A study published in 2004 (Blaxill, 2004) looks at the different surveys carried out worldwide; the outcome suggests a precautionary approach and that the raise in incidence of autism should be a matter of urgent public concern.

In the United States of America, the Centres for Disease Control and Prevention (CDC) carried out a prevalence study in 2002. This study included approximately 10 percent of U.S. eight-year-old children born in 1994 from 14 states. A total of 407,578 children were involved and 2,685 eight-year-olds (65.88 per 10,000) were identified as having an ASD. The data were reported by the Autism and Development Disabilities Monitoring (ADDM) Network. The previous study, developed in 2000, found ASD rates ranged from one in 222 children to one in 101 eight-year old children in the six communities studied. The 2002 study found ASD rates ranging from one in 303 to one in 94 among eight-year old children. The average finding of 6.6 and 6.7 per 1,000 eight-year-olds translates to approximately one in 150 children in these communities. This is consistent with the upper end of prevalence estimates from previously published studies, with some communities having an estimate higher than those previously reported in U.S. studies.

There is still controversy about the plausible interaction between genetic and environmental risk factors for ASD. The study of risk factors has contributed to the prevention of other health problems e.g. cardio-vascular diseases, diabetes and cancer.

In ASD, several conditions have been found to be potential risk factors. Most risk factors have been identified in clinical studies by using different methods and populations. The inconsistent retrieval of data in these studies has made direct comparison of risk factors very difficult. Considering the ongoing collection of ASD data, several of the EU countries have underlined the need for manuals in order to ensure the largest impact of data quality. By following specific manuals, it will be possible to compare data between the EU countrie, and thereby increase the chance of identifying unique and strong risk factors for ASD.

A systematic review of prevalence studies has contributed to explaining some of the influences on variation among prevalence estimates. Over half of the variation among study estimates can be explained by the age of the children screened, the diagnostic criteria used and the studied country. Other important factors were whether the study was in a rural or urban location and whether cases were assessed prospectively or retrospectively. The impact of these known factors on prevalence estimates should now be further investigated as they may be acting as proxies for other influences on prevalence.

It is well accepted in the scientific community that early and intensive education can help children with ASD to develop and learn new skills. Prognosis is greatly improved if a child is placed into an intensive and highly structured educational program by the age of two or three. Earlier identification of children with ASD could increase the effectiveness of their treatment

 

5.5.3.3.4. Control tools and policies

 

On May 9th, 1996, the European Parliament launched an official Declaration in which it urged the Commission to fully support any effort and project to develop the rights of people with autism. Finally, at the beginning of 2006 the EAIS project approved by the Commission the previous year began its work.

The central aim of the EAIS project is to have an agreed information system to record ASD data. This data, recorded in a common format across the EU, will provide the strongest, most robust evidence, available to determine both the prevalence and financial burden of the disease and monitor ongoing trends in these areas.

The project sets out the work being developed towards a final protocol that will enable us to obtain valid information about ASD prevalence in several European countries as well as harmonized methods for planning an ASD prevalence study in Europe. This is a relevant action as currently there is no such existing Europe-wide information and this sort of study requires thorough planning for implementation.

Another aspect of the EAIS project is the study of the Financial Burden of ASD. The economic consequences of Autism in the UK were calculated in a recent report made by one of the project partners, (Knapp et al, 2007). The findings reveal that children with autism cost £2.7 billion (Euros 3.8 billion) annually, yet for adults the figure is £25 billion (Euros 36.2 billion) – i.e. over eight times as much. For adults with autism the highest costs are those generated by health and social care provision (59%), followed by lost employment (36%) and family expenses (5%). These findings give an up-to-date indication of the overall economic cost of autism in the UK.

Since 2005, ASD has been included in both the ‘Rare Diseases’ and ‘Major and Chronic DiseasesTask Forces of the European Commission, and although some conditions or syndromes within the spectrum can be categorised as rare diseases, there is an argument for no longer categorising ASD in this way. Indeed, the public health burden of these disorders is now a considerable one.

The European Network of Surveillance on Risk Factors for Autism and Cerebral Palsy (ENSACP) a co-financed project by the Public Health Executive Agency (PHEA) proposes to construct a preliminary guide that can be used to standardize the collection process of cerebral palsy (CP) and ASD data in the EU. This will be done by comparing datasets from five countries: Sweden, The Netherlands, England, France and Denmark. Risk factors found in more than one of the populations as well as risk factors found to be associated in only one population will both be included in the guide. The reason for including the unique factors in the guide is that the lack of association in other populations can be due to different criteria or methods and not necessarily because of a direct lack of association, and this needs to be tested.

It is important to mention that as of April 2008, the Welsh Assembly Government has been implementing a 10yrASD Strategic Action Plan for Wales’. This all-age government strategy includes the appointment of a national implementation manager; the recruitment of lead co-ordinators for autism in each of Wales22 Local Authorities; extensive training of a range of health, social care and education and commissioning practitioners; awareness-raising work with related areas including mental health, the criminal justice system and the general public. The strategy is being benchmarked and will be monitored by a stakeholder group. Wales is the first European country to have adopted such a policy in support of people affected by ASD.

 

5.5.3.3.5. Future developments

 

Reports of increased prevalence of Autism Spectrum Disorders (ASD) from 4 per 10,000 to 66 per 10000 children in the last 20 years have alerted the scientific community and public health sector. Although both the nomenclature and the classification criteria used to define autism have changed over the years, these changes do not prevent some comparative analysis and do not fully explain the major differences in reported prevalence over time. The methodology to measure prevalence and the case definition of ASD in Europe is still not fully harmonized, while in many of the newer Member States there is very little or no information available on ASD. This situation needs to be addressed and the EAIS project is in the process of developing a protocol for a harmonised ASD information system in Europe.

Tools have been developed for early detection and diagnosis of the disorders, particularly in the United States of America and Great Britain. At European level, however, the early detection and diagnosis of children with autism varies enormously from country to country. Among other factors, this depends on the number of trained personnel and the health services structure and whether or not ASD is actively screened for; in this chapter we have highlighted the fact that attention to ASD is lacking in most Member States.

There is no general policy for education and health services for people and families affected by ASD in Europe. The initiative by the Welsh Assembly to implement a ten-year Strategic Action Plan for ASD is to be applauded and promoted among European countries.

 

5.5.3.3.6. References

 

Blaxill MF (2004): What’s Going On? The Question of Time Trends in Autism. Public Health Reports, Nov-Dec.

Fombonne E (2005): Epidemiology of autistic disorders and other pervasive developmental disorders. Journal of Clinical Psychiatry 2005, 66 (suppl. 10)

Knapp M, Romeo R, Beecham J (2007): The economic consequences of autism in the UK. Foundation for People with Learning Disabilities, London.

Sánchez-Valle E et al (2007): Estimating the Burden of Disease for Autism Spectrum Disorders in Spain in 2003. Journal of Autism and Development Disorders, 10.

 

 

5.5.3.3.7. Acronyms

 

ASD

Autism Spectrum Disorders

CDD

Childhood disintegrative disorder

ENSACP

European Network of Surveillance on Risk Factors for Autism and Cerebral Palsy

PDD

Pervasive Developmental Disorder

NOS

Not Otherwise Specified

PHEA

Public Health Executive Agency

 

5.5.3.4. Epilepsy

 

5.5.3.4.1. Introduction

 

 

Epilepsy is a chronic clinical disorder affecting both sexes and all ages with a worldwide distribution. Epilepsy is a symptom complex arising from a number of disordered brain functions. The cardinal manifestations of epilepsy are the epileptic seizures, which are recurrent paroxysmal episodes of brain dysfunction characterized by stereotyped alterations in behaviour and reflecting the neural mechanisms involved by the epileptic process. Incidence of epilepsy is expected to increase due to the greater longevity of the European population. Epilepsy is linked to educational difficulties, unemployment, socio-economic disadvantage and co-morbidity. Raising of awareness and public education are necessary to diminish the stigma associated with epilepsy

 

While all people with epilepsy experience seizures, not all individuals with seizures have epilepsy. Epileptic seizures may occur in the context of a brain insult (systemic, toxic or metabolic). These events (provoked or acute symptomatic seizures) are simply an acute manifestation of the insult and may not recur when the underlying cause has been removed or the acute phase has elapsed. Epilepsy in remission with treatment is defined by the absence of seizures for at least five years in patients still receiving antiepileptic drugs (AEDs)(Commission, 1993). Epilepsy in remission without treatment (terminal remission) is seizure remission for at least five years in patients off medications at the time of ascertainment (Commission, 1993). These cases add up to the so-called inactive epilepsy. In contrast, epilepsy is the occurrence of two or more unprovoked seizures (Commission, 1993). An unprovoked seizure is a seizure or a flurry of seizures occurring within 24 hours and in absence of precipitating factors. Unprovoked seizures include events occurring in the absence of a recognized etiological or risk factor (idiopathic and cryptogenic seizures), in patients with previous stable (non-progressing) CNS insults (remote symptomatic seizures), or in those with progressive CNS abnormalities such as brain tumours, genetic, metabolic or degenerative conditions (progressive symptomatic seizures). Unprovoked seizures may be single or recurrent. Although all patients with single unprovoked seizures may have “potentialepilepsy, seizure recurrence can be observed only in about one-half of cases (Berg & Shinnar, 1991). The difference between provoked and unprovoked seizures and between isolated and recurrent seizures is relevant to the interpretation of the main epidemiological indexes. Although epilepsy is, by definition, a chronic clinical condition, about two-thirds of patients achieve seizure remission, most of whom immediately after treatment initiation (Forsgren, 2004). Active epilepsy is defined as having at least one seizure in the preceding 5 years regardless of treatment with AEDs (Commission, 1993). Intractable epilepsy still requires a standard definition. In a prospective U.S. cohort of childhood-onset epilepsy (Berg et al, 2001), intractability was intended as failure on two or more antiepileptic drugs and one or more seizures a month over 18 months or longer.

 

5.5.3.4.2. Data sources

 

The patients with epilepsy enrolled in the epidemiological studies should be representative of the general epilepsy population. Thus, multiple sources of cases must be explored to maximize case ascertainment. The large majority of population-based surveys have been conducted on all patients with epilepsy or in patients in different age groups (children, adults, elderly).

The socio-cultural background of the populations at risk may be a strong confounder when different populations are compared. Reference figures from the entire national population have been made available only for some studies.

With few exceptions, in Europe  the information existing on the epidemiology of epilepsy was largely obtained from small or medium-size populations where community-based surveys were conducted (Forsgren et al, 2005).  In these studies, the disease was diagnosed through a careful history, which relies on the attentiveness of the patient and his/her family, on the emotional and social impact of the seizures, and on the capabilities of the available health care facilities. Although a causative agent can be identified in some instances, in the majority of patients with epilepsy no cause can be found and the diagnosis is only descriptive. The differential diagnosis of epilepsy encompasses a number of clinical conditions characterized by transient alteration of consciousness and/or behaviour, which may explain the possibility of false-positive and false-negative diagnoses. These limitations may be a possible explanation of the heterogeneity of the frequency, course and consequences of the disease in Europe and in the rest of the world.

To our knowledge, there are no European national or regional population-based registries.

 

 

5.5.3.4.3. Data description and analysis

 

In Europe, the incidence, prevalence and mortality of epilepsy are fairly homogeneous across countries. The results of surveys reporting rates at variance with those of the majority of reports can be largely explained by suboptimal case ascertainment or by flaws in the study design.

Based on these findings, one expects that, at least in Europe, genetic susceptibility and the distribution of environmental risk factors to be evenly distributed.

 

Incidence of epilepsy and seizures

Thirteen incidence studies carried out in Europe have been identified, mostly from the northern and Western parts of the continent (Table 5.5.3.4.1). The annual incidence of all unprovoked seizures in these studies ranges from 44 to 73 per 100,000, while the incidence of epilepsy ranges from 24 to 57 per 100,000 (Forsgren et al, 2005; Olafsson et al, 2005). The incidence is higher in children and in the elderly (Table 5.5.3.4.2), even with significant changes across studies. This is most probably due to the different populations at risk, the extent of case identification and the study design.

 

Table 5.5.3.4.1. Incidence of epilepsy in Europe

 

Table 5.5.3.4.2. Incidence (per 100,000) of epilepsy in Europe, by age

 

With one exception (Cockerell et al, 1995), the incidence of epilepsy and unprovoked seizures in Europe has been reported to be higher in men than in women, although this finding does not attain statistical significance in the large majority of reports. The different distribution of epilepsy in men and women can be mostly explained by the differing genetic background, the different prevalence of the most common risk factors in the two sexes and the concealment of the disease in women due to socio-cultural reasons.

In incidence studies, the proportion of cases with documented etiology has been reported to vary from 31 to 56% (Forsgren et al, 2005). The differences are mostly explained by the structure of the population at risk, the prevalence of the etiological factors in the local environment, the study design and the extent of the diagnostic ascertainment. Cerebrovascular disorders are the most common etiological factors (14-21%) followed by trauma (2-16%) and neoplasms (6-10%).

There are only few observations on the temporal trends of epilepsy in Europe. No overall trends have been observed. In one study (Cockerell et al, 1995) age-specific incidence rates of epilepsy tended to decrease in the younger age groups and increase in the elderly. These findings are partly in contrast with reports from Italy (Granieri et al, 1983) and Sweden (Blom et al, 1978; Sidenvall et al, 1993), which showed a decrease with time of the incidence of the disease, mostly in children. Although an improvement in perinatal care and the increasing use of prophylactic measures against neurodevelopmental disorders can be likely explanations of the decreasing incidence of epilepsy in children, the introduction of more specific diagnostic tests has perhaps contributed to a decrease of false positive diagnosis.

An increasing incidence of epilepsy in the elderly has been consistently reported in Northern and Southern Europe. This observation can be attributed to the increased life expectancy (followed by an increasing occurrence of age-related epileptogenic conditions such as stroke and degenerative CNS disorders) and to an increased ascertainment of the disease in this age group.

There are only few reports on the incidence of epileptic syndromes in Europe. In Iceland (Olafsson et al, 2005), the incidence of single unprovoked seizures and epilepsy was prospectively studied by applying the ILAE international classification categories (Commission, 1989). Special syndromes (represented by an isolated seizure or status epilepticus) occurred in 41% of cases (incidence 23.5 per 100,000 per year). Undetermined epilepsy (without unequivocal evidence of generalized and focal features) occurred in 15% (8.7 per 100,000 per year), cryptogenic localization-related epilepsy in 16% (8.8 per 100,000 per year), symptomatic localization-related epilepsy in 15% (8.4 per 100,000 per year), and idiopathic generalized epilepsy in 6% (3.4 per 100,000 per year). In Bordeaux, France, the incidence of the most common syndromes was generally lower. The rate was 15.3 per 100,000 for localization-related epilepsies (idiopathic 1.7; symptomatic 13.6), 6.7 per 100,000 for generalized epilepsies (idiopathic 5.6; symptomatic 1.1) and 1.9 per 100,000 for undetermined epilepsies (Loiseau et al, 1990). Some of the differences between the Icelandic and the French study can be mostly explained through accuracy in case ascertainment and selection bias. However, the most remarkable difference was found for undetermined epilepsies, which reflect a more or less stringent application of the ILAE syndromic classification and the limitations of this classification for epidemiological purposes.

 

Prevalence of epilepsy

There are numerous studies on the prevalence of epilepsy in Europe (Forsgren et al, 2005). The overall prevalence of active epilepsy ranges from 3.2 to 7.8 per 1,000 (Table 5.5.3.4.3). The prevalence is lower in infancy and tends to increase thereafter, with the highest rate occurring in the elderly. As with incidence, prevalence of epilepsy tends to prevail in men. However, this finding is not consistent across studies and, with few exceptions, is not statistically significant. In individual studies, the dominance in females and males has been found to shift between age groups. The percentage of cases with documented etiology in prevalence studies has been shown to vary from 25 to 51% (Beghi, 2004). The main etiological factors are virtually the same as those reported in incidence studies (see above).

 

Table 5.5.3.4.3. Prevalence of active epilepsy in Europe

Modified from Forsgren, 2004 and Forsgren et al., 2005

 

Country           

Population     

Design           

No. of cases           

Prevalence ratio (per 1,000)

Reference(s), year

 

Denmark           

All ages          

MR review       

333     

7.6      

Joensen, 1986(*)

Estonia           

Children          

Prospective    

560     

3.6      

Beilmann et al., 1999

Estonia           

Adults 

MR review and examination   

396     

5.3      

Oun et al., 2003(*)

Finland

Adults 

MR review and examination   

1233   

6.3      

Keranen et al., 1989(*)

Finland

Children          

Retrospective/MR review and examination   

329/348           

3.9/3.2

Eriksson and Koivikko, 1997(*)/

Sillanpaa, 1973(*)

Iceland           

All ages          

MR review       

428     

4.8      

Olafsson and Hauser, 1999(*)

Italy    

All ages          

MR review and examination MR review/MR review and Examination/AED consumption door-to-door survey/MR review and examination

278/51

 

199/235

 

81/47  

6.2/5.1

 

3.9/5.2

 

3.3/3.1

Granieri et al., 1989(*)/Maremmani et al., 1991(*)/

Beghi et al., 1991(*)/Giuliani et al., 1992(*)

Rocca et al., 2001(*)/Gallitto et al, 2005

Italy    

Children          

MR review       

?         

4.5 +   

Cavazzuti, 1986(*)

Lithuania

Children          

MR review       

378     

4.3      

Endziniene et al., 1997

Norway           

Children          

MR review and examination   

198     

5.3-

Waaler et al., 2000(*)

Norway           

All ages?         

MR review and GP contacts    

245     

2.3      

Krohn, 1961(*)            

Poland

All ages          

MR review                  

337.8  

           

Zielinski, 1974(*)

Spain  

Children          

Postal/domiciliary questionnaire

62       

3.7Ø      

Ochoa Sangrador and Luaces, 1991(*)

Spain  

Children >10 years and adults

Two-phase across sectional  

405     

4.1      

Luengo et al., 2001(*)

Sweden

Adults 

Multisource medical register review

713     

5.5      

Forsgren, 1992(*)

Sweden

Children          

Questionnaire and GP and P inquiry/MR review?     

155/195           

4.2/3.5

Sidenvall et al., 1996/Bronson, 1970(*)

The Netherlands

Adults and elderly

Door-to-door survey  

43       

7.7      

de la Court et al., 1996(*)

U.K.     

All ages          

GP files           

?         

6.2      

Pond et al., 1960(*)

U.K.     

Children 4-20 years  

MR review       

69       

4.3      

Tidman et al., 2003(*)

+ = 5-14 years     - = 6-12 years MR = Medical record           P = Pediatricians                                                 

  = 6-16 years        Ø = 6-14 years GP = General practitioners  CM = Community members  (*) Reference listed in original source

 

 

Partial seizures are more common than generalized seizures both in children and adults. As shown by Forsgren (2004) in prevalence studies made on adults from industrialized (largely European) countries, partial seizures were reported in 55-60% of cases, generalized seizures in 26-32%, and unclassifiable seizures in 8-17%. The corresponding numbers in children were respectively 36-66%, 30-62%, and 2-4%. The differing proportions of partial and generalized seizures may be largely explained by the different distribution of epilepsy syndromes in children and adults.

In contrast with incidence, the prevalence of epilepsy syndromes has been calculated in several recent reports, all from the Scandinavian and Baltic countries. In a study made on children in Estonia (Beilmann et al, 1999), the prevalence of idiopathic epilepsies was 1.2 per 1,000, while that of cryptogenic epilepsies was 1.0 per 1,000. In another study of childhood epilepsies in Lithuania (Endziniene et al, 1997), localization-related epilepsies were the most common syndromic category (1.5 per 1,000) followed by generalized epilepsies (1.3 per 1,000) and undetermined epilepsies (0.6 per 1,000). Localization-related epilepsies were the predominant syndromic category in 41-54% of cases from Sweden, Finland and Norway, followed by generalized syndromes (37-48%) and unclassified syndromes (5-10%)(Eriksson & Koivikko, 1997; Sidenvall et al, 1993; Waaler et al, 2000). The prevalence of specific syndromes in these countries was as follows: idiopathic partial epilepsy with centro-temporal spikes 5-17%, absence epilepsy 6-8%, juvenile myoclonic epilepsy 1-5%, West syndrome 0.5-8%, and Lennox-Gastaut syndrome 2-6%.

Socio-economic background has been found to affect the frequency of epilepsy reports. In a study made in Wales, U.K., a strong independent correlation was detected between the prevalence of epilepsy and social deprivation, defined by unemployment, no car in the household, overcrowded households or households not occupied by the owner (Morgan et al, 2000).

 

Mortality

The mortality rate due to epilepsy ranges from 1 to 8 per 100,000 population per year, but international vital statistics give annual mortality rates at 1-2 per 100,000 (Massey et al, 1985).

In a population-based cohort of patients with childhood-onset epilepsy followed up for 35 years, a mortality rate of 6.23 per 1,000 person-years was reported (Sillanpaa et al, 1998). In this cohort, the probability of survival at 10, 20 and 40 years after seizure onset was 0.94 (95% CI 0.91-0.97), 0.88 (95% CI 0.84-0.92), and 0.75 (95% CI 0.74-0.86), respectively.

Based on a meta-analysis of studies investigating mortality in the past 100 years, the SMR for epilepsy in Europe was found to range from 1.6 to 9.3 in community-based studies and 1.9-8.7 in institutionalised populations (Shackleton et al, 2002). In prospective and retrospective incidence cohorts, the SMR for epilepsy ranges from 1.6 to 5.3 in children and adults (Jallon, 2004) (Table 5.5.3.4.4). These data are confirmed when limiting the analysis to prospective and retrospective incidence cohorts (Jallon, 2004).

These rates were not significantly different from those of selected populations followed during different periods. The higher SMRs reported by the French and Swiss studies may be partially explained by the inclusion of acute symptomatic seizures.

 

Table 5.5.3.4.4. Community-based studies of mortality in epilepsy

Modified from Shackleton et al, 2002

 

Country

Source

Design

Deaths

SMR

Reference

 

 

 

 

 

 

 

 

 

 

Observed

Expected

 

 

Europe

Insurance policies

Prevalent cohorts

32

12.4

2.6

Preston and Clarke, 1966(*)

France

GP/MF

Incident cohort

149

16.1

9.3

Loiseau et al., 1999

Iceland

GP/MF

Incident cohort

45

28.0

1.6

Olafsson et al., 1998

Poland

Insurance policies

Prevalent cohort

218

121.0

1.8

Zielinski, 1974

Sweden

GP/MF

Incident cohort

39

15.7

2.5

Lindsten et al., 2000

 

Mental institution

Cross-sectional

105

12.0

8.7

Alstrom, 1942(*)

 

NC/EC

Prevalent cohort

160

67.8

2.4

Alstrom, 1950(*)

 

Insurance policies

Prevalent cohort

32

14.6

2.2

Svensson and Astrand, 1976(*)

 

GP/MF

Prevalent and incident cohort

4001

1109.0

3.6

Nilsson et al, 1997

U.K.

GP/MF

Incident cohort

149

58.3

2.6

Lhathoo et al., 2001

                     GP: General practitioner;     MF: Medical facilities;     SMR: Standardized mortality ratio;        (*)Reference listed in original source.

 

 

Aetiology of epilepsy is one of the strongest predictors of mortality in epilepsy. Patients with symptomatic epilepsy have a two- to six-fold mortality risk than the general population. Patients with a CNS lesion presumed to be present at birth have the highest mortality, with a SMR between 7 and 50 (Forsgren, 2004). Remote symptomatic seizures and refractory epilepsy mostly account for the increased mortality in childhood-onset epilepsy. Mortality is greater in men than in women, as shown in most population-based studies. Most studies have also detected an inverse correlation between SMR and age. In neurologically normal children with idiopathic or cryptogenic epilepsy in remission, mortality does not appear to be substantially higher than that of the general population. The highest mortality in children may be thus explained by the rate expected in the general population, which is lower in children, and by the higher proportion of neurodeficits in this age group. In the Finnish cohort of patients with childhood epilepsy followed into adulthood (Sillanpaa et al, 1998), patients not in remission had a 9.3 RR of death (95% CI 3.8-22.7) compared with patients in 5-year remission. There is also an inverse correlation between SMR and duration of epilepsy during the first 10 to 14 years of disease. Generalised tonic-clonic seizures have been associated to an increased mortality in several studies from Europe. In contrast, data regarding the mortality in patients with partial seizures are inconsistent. Status epilepticus is associated to significant mortality. In prospective population-based studies, the CFR reached 39% (Vignatelli et al, 2003). Although the idiosyncratic reactions and the oncogenic potential of AEDs is well-known, drug-related deaths cannot be estimated, as comparative estimates of the rate of occurrence of such deaths per treatment-years are not available.         

Differient mortality rates have been found for different epileptogenic conditions. Accident-related deaths range between 1 and 6% of all deaths, with SMR ranging between 2.4 and 5.6 (Gaitatzis and Sander, 2004). Patients with epilepsy are reported to be at higher risk of suicide than the general population. However, the PMRs range from 0 to 20% and the SMRs from 1 and 5.8. The wide difference in rates may be mostly explained by the small size of the studied populations and the different methods of analysis. Patients with severe epilepsy have a fivefold and patients with temporal lobe epilepsy a 25-fold increased risk of suicide (Barraclough, 1987). Suicide rates may be even higher (SMR 87.5; 95% CI 35-180) in patients with temporal lobe epilepsy undergoing surgical treatment (Harris & Barraclough, 1997). Antipsychotic drug intake was associated with a 4-fold increase in the risk of suicide in a Swedish case-control study (Nilsson et al, 2002), after adjusting for psychiatric illness and alcohol abuse. Psychiatric comorbidity, psychosocial stressors and iatrogenic factors may thus explain the increased risk of suicide in patients with epilepsy. While seizure-related mortality is rare in new onset epilepsy, in patients with chronic epilepsy most deaths appear to be seizure-related (Tomson et al, 2004). In these populations, sudden unexpected death (SUDEP) accounts for 24-67% of all deaths (Pedley and Hauser, 2002). SUDEP is defined as a non-traumatic, unwitnessed death occurring in a previously healthy patient with epilepsy in whom no cause of death is detected even after post-mortem examination. The incidence of SUDEP ranges from 1 per 1,000 in prevalence studies (ODonogue and Sander, 1997) to 3.5 per 1,000 in incidence studies (Nashef et al, 1995). The patient at risk for SUDEP is a young or middle-aged person with chronic refractory epilepsy, generalized tonic-clonic seizures and a complicated and unstable treatment (Jallon, 2004). SUDEP is rare in community-based series of childhood epilepsy (Callenbach et al, 2001). In most cases, SUDEP is triggered by a seizure with seizure-induced cardio-respiratory alterations representing a plausible hypothesis (Nashef et al, 1996).

In patients undergoing epilepsy surgery, the SMR was found to range from 4.5 to 32 (Jallon, 2004). In a population-based study comparing SMR and SUDEP in surgical patients, the SMR (all causes) was 4.9 (95% CI 2.7-8.3) vs. 7.9 (95% CI 2.6-18.4) in non-surgical patients, while the incidence of SUDEP was 2.5 vs. 6.3 per 1,000 (Nilsson et al, 2003). There is some indication that carbamazepine could increase the risk of SUDEP by causing arrhythmia or altering the cardiac autonomic function.

 

Comorbidity

The termcomorbidity” is used here to define the contemporary occurrence of more than one clinical condition in the same person. There are limited European data on the cumulative incidence (Beghi and Cornaggia, 2002) and the prevalence of comorbidity in patients with epilepsy (Gaitatzis et al, 2004). Records were taken of any medical event occurring in a 1-2 year period in a large cohort of children and adults and matched controls enrolled in referral centres from eight European countries (Italy, Germany, Holland, UK, Portugal, Russia, Estonia, and Slovenia) and followed prospectively (Beghi and Cornaggia, 2002). The cumulative probability of illness by 24 months was 86% in patients with epilepsy and 75% in controls (p<0.0001). The cumulative probability of accident was 27 and 17% respectively (p<0.0001). Illnesses and accidents were mostly trivial and 24% were seizure-related. A cross-sectional population-based survey of somatic and psychiatric comorbidity in adults was undertaken in the UK using the General Practice Research Database (Gaitatzis et al, 2004). The ICD-9 coding system was used for disease classification. Patients with and without epilepsy were compared. Several somatic disorders were significantly more common in people with epilepsy than in non-epileptic controls, with differing prevalence ratios (PR) when comparing individuals aged 16 to 64 to those aged 65 or more. Brain tumors, cerebrovascular disorders and Alzheimer’s disease were, in decreasing order, the clinical conditions with PR greater than 10 in patients aged 16-64 and greater than 5 in patients 65+. A greater than two- to six-fold risk of psychiatric comorbidity was found in patients aged 16 to 64, organic psychoses, alcohol dependence and hysteria being the most common conditions. In patients aged 65 or more alcohol dependence was the most common comorbid disorder (PR 6.1) followed by schizophrenia (PR 5.8).

 

Prognosis

Treatment of epilepsy is generally started at the time of diagnosis, which is made when at least two unprovoked seizures have occurred. A population-based study done in the UK on the long-term prognosis of treated epilepsy reported a 69% cumulative 5-year remission rate at 9 years of age (Cockerell et al, 1995). The 5-year remission rate at 10 years was 61% in adults (Lindsen et al, 2001) and the 3 to 5-year remission rate at 12-30 years of age children was 74-78% (Forsgren, 2004). In the Finnish cohort of patients with childhood-onset epilepsy, 64% of cases were in 5-year terminal remission off medications (Sillanpaa et al, 1998).

 

Epilepsy and learning ability

About 25-50% of children with epilepsy experience some degree of educational difficulties (Anonymous, 2003). An old study made on the Isle of Wight found children with epilepsy of average intelligence exhibiting at least 2-year retardation in reading skills (Rutter et al, 1970). A more recent UK study showed 53% of children with epilepsy attending mainstream schools were coping at a below average level and 16% were seriously behind (Thompson, 1995). Studies made in Finland showed that 27% of children with epilepsy did not complete basic or required education (Sillanpaa, 1992). An international cohort study involving Western and Eastern European countries (RESt-1 Group, 2000) showed comparable levels of education in patients with epilepsy and non-epileptic controls. In Italy, a high proportion of teachers was found to be very poorly prepared for having children with epilepsy in their classes (Pazzaglia and Frank-Pazzaglia, 1976). To our knowledge, there is no evidence that epilepsy education of teachers has improved.

 

Epilepsy and employment

People with epilepsy experience difficulties in finding and maintaining regular employment. Unemployment and underemployment rates are generally higher in patients with epilepsy than in the general population (Smeets et al, 2007). However, most studies on epilepsy and employment have been performed in selected clinical samples and differing definitions of employment problems. Social stigma has long been considered an explanation for the under- and unemployment rates and the unnecessary job restrictions adopted in patients with epilepsy. However, recent studies have indicated an improvement of the public attitude towards people with epilepsy (Jacoby et al, 2004). In addition, unemployment rates are fairly low (15%) in adult patients with newly diagnosed idiopathic or remote symptomatic epilepsy from several Western and Eastern European countries (RESt-1 Group, 2000). Higher seizure frequency is associated with higher rates of unemployment (Smeets et al, 2007). Psychosocial factors also tend to affect employment. These include fear and limitations on lifestyle (Fisher, 2000), intelligence, education, personality, age, psychosocial and neuropsychiatric functioning (Batzel et al, 1980; Fraser et al, 1983). Job restrictions are common in European countries, particularly in Central and Eastern Europe, where unemployment rates are even greater than those of Western Europe (Anonymous, 2003). These findings are in contrast with the fairly low accident rates in people with epilepsy (Van den Broek and Beghi, 2004). Intervention studies on epilepsy and vocational rehabilitation are scarce and long-term effects of specific employment programs are virtually unknown (Smeets et al, 2007).

 

Epilepsy and driving

In the European Union, most member states require a two-year seizure-freedom period before granting or renewing a driving license. In contrast, there is a significant variability of exceptions for patients with active epilepsy (seizures during sleep or on awakening, myoclonic jerks, and simple partial seizures)(Table 5.5.3.4.5). The issue of epilepsy and driving varies depending on the patient’s or the health authority’s perspective (Beghi and Sander, 2005). From a patient’s perspective, the risk of seizure-related accidents (rate ratio, RR 1.8)(Vaa, 2005) and the risk of serious accidents (RR 1.4)(Taylor et al, 1996) may be too high. From the health authority perspective, however, the proportion of accidents attributable to epileptic seizures is extremely low, ranging from 0.02 to 0.2% (Black and Lay, 1997; Sheth et al, 2004). In addition, mandatory reporting of epilepsy may have negative implications as it affects the patient-doctor relationship.

 

Table 5.5.3.4.5. National legislations on epilepsy and driving in Europe

 

________________________________________________________________________________

Country           Group        Seizure freedom               Exceptions (ban)

________________________________________________________________________________

Belgium                   I           12 months                           First unprovoked seizure (6 months)

                                                                                    First seizure, idiopathic (3 months)

                                                                                    Seizures not impairing driving (3 months)

                                                                                    Seizures during sleep, with pattern established

                                                                                    by 24 months

                              II          120 months (no AED;           First unprovoked seizure (5 years)

                                          normal EEG)                        First provoked seizure (2 years)

Croatia                    I           24 months                           Ban in people taking drugs contraindicated

                                                                                    with driving

Denmark                 I           12 months                           Seizures during sleep (license valid 1 year;

                                                                                    2 years if seizure freedom >2 years; 5 years

                                                                                    if seizure freedom >4 years)

                                                                                    First unprovoked seizure (6 months)

                              II          60 months (taxi 120;            Must be off AED for 5 years; license valid for

                                          bus 240)                              5 years

Estonia                    I           24 months                                                -

                              II                   -                                Prohibited

Finland                    I           12 months                           First unprovoked seizure with normal

                                                                                    diagnostic tests (3 months)

                                                                                    Sporadic seizures (6 months)

                                                                                    Myoclonias (dose)

                              II                   -                                Prohibited

France                     I           12 months                           Seizures only on awakening

                              II          24-60 months                      No seizures in previous 3 years

Germany                 I           12 months                           Single seizures or occasion-related seizures

                                                                                    (3-6 months)

                                                                                    First seizure, idiopathic (3-6 months)

                                                                                    Treatment stop (ban 3 months)

                              II          60 months (no AED)             First seizure, idiopathic (24 months)

Ireland                    I           12 months                           Seizures during sleep established by 1 year

Italy                        I           24 months                                                -

                              II                -                                   Prohibited

Netherlands             I           12 months                           First unprovoked seizure (6 months)

                                                                                    First unprovoked, idiopathic seizure (3 months)

                                                                                    Sporadic seizures (6 months)

                                                                                    Myoclonias, single partial seizures (3 months)

                                                                                    Treatment stop/change (ban 3 months)

                              II          60 months (no AED;             Untreated first unprovoked seizure and no

                                          no EEG epileptiform              epileptiform EEG (2 years)

                                          activity)

 

 

Norway                   I           12 months                           Drugs stolen or last seizure in particular

                                                                                    circumstances

                              II          120 months (taxi)                                      -

Sweden                   I           24 months                           Single unprovoked seizure

                              II          60 months (taxi)                                       -

Switzerland              I           12 months                                                -

United Kingdom        I           12 months                           Seizures during sleep with pattern established

                                                                                    by 3 years

                              II          120 months (no AED)           Medical examination required

________________________________________________________________________________

I = Non commercial driving;   II = Commercial driving;

AED = Antiepileptic drugs;     EEG = Electroencephalogram.

 

                                         

                                                                                   

5.5.3.4.4. Control tools and policies

 

Disease severity and poor seizure control affect patientseducation, employment, driving and other daily life activities. However, psychosocial factors and stigma have also been considered as discriminating reasons for patients with epilepsy Although one gets the impression of a better attitude of the society towards epilepsy, patients with epilepsy still face relevant problems in having equal opportunities in several aspects of social life. This issue is further complicated by the lack of harmonization of the national regulations across European countries.

The Second European Working Group on Epilepsy and Driving (SEWGED) has been appointed by the Driving License Committee of the EU in 2004. This group, which was represented by a number of experts in the field of epilepsy, collected all the available information on national driving regulations and outlined the main disease characteristics to adapt the present regulations to the different aspects of the spectrum of the disease and achieve harmonization across Europe. On April 27 2005, the SEWGED submitted a report to the EU Driving License Committee.

The Public Education Commission of the IBE produced a policy statement “Towards a universal understanding of epilepsy”. This statement aims at summarizing the current scientific position on epilepsy and recommends a set of core facts that a lay or professional audience could understand (Anonymous, 2003). The ILAE Employment Commission recommends a non-discriminatory policy for hiring people with epilepsy and considers that job restrictions are discriminatory unless based on an individual assessment (Employment Committee of the IBE, 1989). Reports from various European countries indicate that employment training programmes for people with epilepsy achieve better results than state agencies (Anonymous, 2003). The elements of these programmes include neuropsychological assessment, vocational training, interview technique (including disclosure) and specialized placement and post-placement programmes.

Lay associations, which are present in any EU member state, have a fundamental role in promoting education on epilepsy towards patients, their relatives and all potentially involved society members. Epilepsy and any other disabling condition should be part of the educational programs for teachers. Teachers could be very helpful in removing prejudice against epilepsy and stigma.

A number of guidelines and practice parameters regarding the management of epilepsy have been developed in several European countries. These guidelines have been endorsed by national and international scientific associations (ILAE, IBE. Cochrane Collaboration, LICE) or by national bodies aiming at developing evidence-based medicine measures for clinical practice (NICE, www.nice.org.uk; SIGN, www.sign.ac.uk). Although slightly different when addressing specific aspects of the diagnosis and treatment of epilepsy, these instruments can be easily adopted by countries with no access to in-house guidelines and eventually adapted to national or local situations.

Consortia of epilepsy centres and other specialized units have been implemented in some European countries. In Italy, a network of epilepsy centres was founded in the 90s and was helpful in improving the diagnostic and therapeutic capabilities of each individual centre (Osservatorio Regionale per lEpilessia, 1996). On this basis, a more sophisticated web-based network has been recently created in Lombardy aiming at facilitating dissemination and storage of the clinical, laboratory and imaging data of each enrolled patient. Such networks can be easily implemented at national or multinational level and serve as a basis for the initiation of European comprehensive epilepsy programs.

 

5.5.3.4.5. Future developments

 

In the light of the available evidence, there is no need for further studies on the incidence and prevalence of epilepsy in countries with no population-based surveys. Given the homogeneous ethnic substrate of the European population and the consistency of the results of the published reports, similar incidence, prevalence and mortality rates are expected in these countries. However, age-specific incidence rates of epilepsy in the younger and older age groups are based on small samples of patients. For this reason, a study of the geographic and temporal trends of epilepsy in children and in the elderly may be needed.

Multi-national studies should be performed to identify patients with acute symptomatic seizures, single unprovoked seizures and recurrent unprovoked seizures (epilepsy). Cohorts of patients with a first seizure should be prospectively followed to calculate the risk of seizure recurrence and identify patients at high risk of epilepsy.

The variability of the legislations of the EU governments regarding employment and driving in patients with epilepsy and the scarce attention to the heterogeneity of epilepsy syndromes must change. Harmonization of the national directives, to be incorporated into a unique legal compendium, is required. In addition, in line with the recommendations of the SEWGED, different rules should be set depending on the characteristics and the severity of the different syndromic patterns.

 

With reference to the educational issues, children with epilepsy should be admitted into local neighbourhood schools whilst recognizing that, where epilepsy is not a single complication, adequate provision should be made in specialist schools. Issues relating to educating children with epilepsy should be an integral part of initial and in-service teacher-training provision. Liaison between parents, teachers, and professional healthcare workers is essential to the educational provision for children with epilepsy. Increased knowledge about epilepsy amongst school children should be encouraged.

 

Provisions should be made of high standards of care to patients with epilepsy to reduce the risk of seizure recurrence secondary to an incorrect management of the disease. In this regard, the published guidelines on the diagnosis and treatment of epilepsy should be disseminated into each European country and adapted to the local situation. Networks of health care workers (physicians, nurses, psychologists, technicians, physical therapists, etc.) should be implemented to guarantee a comprehensive management of epilepsy in well-defined geographic areas. These networks should include epilepsy centres and centres for the surgery of epilepsy. Using the available web sources, interactions between professional health care workers should be increased to discuss the problems posed by individual patients and exchange information for educational, practical, and research purposes.

 

5.5.3.4.6. References

 

Anonymous (2003): Living with epilepsy. Employment. Epilepsia 44 (suppl 6):49-50.

Barraclough BM (1987): The suicide rate of epilepsy. Acta Psychiatrica Scandinavica 76:339-345.

Batzel LW, Dodrill CB, Fraser RT (1980): Further validation of the WPSI vocational scale: comparisons with other correlates of employment in epilepsy. Epilepsia 21:235-242.

Beghi E, Cornaggia CM, and the RESt-1 Group (2002): Morbidity and accidents in patients with epilepsy: results of a European cohort study. Epilepsia 43:1076-1083.

Beghi E (2004): Aetiology of epilepsy. In: The Treatment of Epilepsy (2nd edition) (Edited by: Shorvon S, Perucca E, Fish D, Dodson E.) Oxford, Blackwell Science; p. 50-63.

Beghi E, Sander JW (2005): Epilepsy and driving. Regulations in the European Union need harmonization as well as greater flexibility. Br Med J 331:60-61.

Beilmann A, Napa A, Soot A, et al (1999): Prevalence of childhood epilepsy in Estonia. Epilepsia 40:1011-1019.

Berg AT, Shinnar S (1991): The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 41:965-972.

Berg AT, Shinnar S, Levy SR, et al (2001): Early development of intractable epilepsy in children: a prospective studyNeurology 56:1445-1452.

Black AB, Lay NY (1997): Epilepsy and driving in South-Australia – an assessment of compulsory notification. Med Law 16:253-267.

Blom S, Heijbel J, Bergfors PG (1978): Incidence of epilepsy in children: a follow-up study three years after the first seizure. Epilepsia 19:343-350.

Callenbach PM, Westendorp RG, Geertz AT, et al (2001): Mortality risk in children with epilepsy: the Dutch study of epilepsy in childhood. Pediatrics 107:1259-1263.

Cockerell OC, Eckle I, Goodridge DM, et al (1995): Epilepsy in a population of 6000 reexamined: secular trends in first attendance rates, prevalence, and prognosis. J Neurol Neurosurg Psychiatry 58:570-576.

Commission on Classification and Terminology of the International League Against Epilepsy (1989): Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 30:389-399.

Commission on Epidemiology and Prognosis, International League Against Epilepsy (1993): Guidelines for epidemiologic studies on epilepsy. Epilepsia 34:592-596.

Employment Committee of the International Bureau for Epilepsy (1989): Employing people with epilepsy: principles for good practice. Epilepsia 30:411-412.

Endziniene M, Pauza V, Miseviciene V (1997): Prevalence of childhood epilepsy in Kaunas, Lithuania. Brain Dev 19:379-387.

Eriksson KJ., Koivikko MJ (1997): Prevalence, classification, and severity of epilepsy and epileptic syndromes in children. Epilepsia 38:1275-1282.

Fisher RS (2000): Epilepsy from the patient’s perspective: review of results of a community-based survey. Epilepsy Behav 1:S9-S14.

Forsgren L, Bucht G, Erksson S, Bergmark L (1996): Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study. Epilepsia 37:224-229.

Forsgren L (2004): Epidemiology and prognosis of epilepsy and its treatment. In: The Treatment of Epilepsy (2nd edition). (Edited by: Shorvon S, Perucca E, Fish D, Dodson E.) Oxford, Blackwell Science; p. 21-42.

Forsgren L, Beghi E, Oun A, Sillanpaa M (2005): The epidemiology of epilepsy in Europe – a systematic review. Eur J Neurol 12:245-253.

Fraser RT, Clemmons D, Trejo W, Temkin NR (1983): Program evaluation in epilepsy rehabilitation. Epilepsia 24:734-746.

Gaitatzis A, Sander JW (2004): The mortality of epilepsy revisited. Epileptic Disord 6:3-13.

Gaitatzis A, Carroll K, Majeed A, Sander JW (2004): The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia 45:1613-1622.

Gallitto G, Serra S, La Spina P, et al (2005): Prevalence and characteristics of epilepsy in the Aeolian islands. Epilepsia 46:1828-1835.

Harris EC, Barraclough B (1997): Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry 170:205-228.

Jacoby A, Gorry J, Gamble C, Baker GA (2004): Public knowledge, private grief: a study of public attitudes to epilepsy in the United Kingdom and implications for stigma. Epilepsia 45:1405-1415.

Jallon P (2004): Mortality in patients with epilepsyCurr Opin Neurol 17:141-146.

Kotsopoulos IAW, van Merode T, Kessels FGH, et al (2002): Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures. Epilepsia 43:1402-1409.

Lindsten H, Nystrom L, Forsgren L (2000): Mortality risk in an adult cohort with a newly diagnosed unprovoked epileptic seizure: a population-based study. Epilepsia 41:1469-1473.

Lhatoo SD, Sander JWAS, Shorvon SD (2001): The dynamics of drug treatment in epilepsy: an observational study in an unselected population based cohort with newly diagnosed epilepsy followed up prospectively over 11-14 years. J Neurol Neurosurg Psychiatry 71:632-637.

Lindsen, H, Stenlund, H, Forsgren L (2001): Remission of seizures in a population-based adult cohort with a newly diagnosed unprovoked epileptic seizure. Epilepsia 42:1025-1030.

Loiseau J, Loiseau P, Guyot M, et al (1990): Survey of seizure disorders in the French Southwest. I. Incidence of epileptic syndromes. Epilepsia 31:391-396.

Loiseau J, Picot MC, Loiseau P (1999): Short-term mortality after a first epileptic seizure: a population-based study. Epilepsia 40:1388-1392.

Massey EW, Schoenberg BS (1985): Mortality from epilepsy. International patterns and changes over time. Neuroepidemiology 4:65-70.

Morgan CL, Ahmed Z, Kerr MP (2000): Social deprivation and prevalence of epilepsy and associated health usage. J Neurol Neurosurg Psychiatry 69:13-17.

Nashef L, Fish DR, Garner S, et al (1995): Sudden death in epilepsy : a study of incidence in a young cohort with epilepsy and learning difficulty. Epilepsia 36:1187-1194.

Nashef L, Walker F, Allen P, et al (1996): Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry 60:297-300.

Nilsson L, Tomson T, Farahmand BY, et al (1997): Cause-specific mortality in epilepsy: a cohort study of more than 9,000 patients once hospitalized for epilepsy. Epilepsia 38:1062-1068.

Nilsson L, Ahlbom A, Farahmand BY, et al (2002): Risk factors for suicide in epilepsy: a case control study. Epilepsia 43:644-651.

Nilsson L, Ahlbom A, Farahmand BY, Tomson T (2003): Mortality in a population-based cohort of epilepsy surgery patients. Epilepsia 44:575-581.

ODonogue MF, Sander JW (1997): The mortality associated with epilepsy, with particular reference to sudden unexpected death: a review. Epilepsia 38(suppl 11):S15-S19.

Olafsson E, Hauser WA, Gudmundsson G (1998): Long-term survival of people with unprovoked seizures: a population-based study. Epilepsia 39:89-92.

Olafsson E, Ludvigsson P, Gudmundsson G, et al (2005): Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol 4:627-634.

Osservatorio Regionale per lEpilessia (1996): ILAE classification of epilepsies:its applicability and practical value of different diagnostic categories. Epilepsia 37:1051-1059.

Pazzaglia P, Frank-Pazzaglia L (1976): Record in grade school of pupils with epilepsy: an epidemiological study. Epilepsia 17:361-366.

Pedley TA, Hauser WA (2002): Sudden death in epilepsy: a wake-up call for management. Lancet 359:1790-1791.

Rutter M, Graham P, Yule W (1970): A neuropsychiatric study in childhood. Clin Dev Med 3:35-36.

Shackleton DP, Westerndorp RGJ, Kastelejin-Nolst Trenite DGA, et al (2002): Survival of patients with epilepsy: an estimate of the mortality risk. Epilepsia 43:445-450.

Sheth SG, Krauss G, Krumholz A. Li G (2004): Mortality in epilepsy: driving fatalities vs other causes of death in patients with epilepsy. Neurology 63:1002-1007.

Sidenvall R, Forsgren L, Blomquist HK, Heijbel J (1993): A community-based prospective incidence study of epileptic seizures in children. Acta Paediatr 82:60-65.

Sidenvall R, Forsgren L, Heijbel J (1996): Prevalence and characteristics of epilepsy in children in Northern Sweden. Seizure 5:139-146.

Sillanpaa M (1992): Epilepsy in children: prevalence, disability and handicap. Epilepsia 33: 441-449.

Sillanpaa M, Jalava M, Kaleva O, Shinnar S (1998): Long-term prognosis of seizures with onset in childhood. New Engl J Med 338:1715-1722.

Smeets VMJ, van Lierop BAG, Vanhoutvin JPG, et al (2007): Epilepsy and employment: literature review. Epilepsy Behav 10:354-362.

Taylor J, Chadwick D, Johnson T (1996): Risk of accidents in drivers with epilepsy. J Neurol Neurosurg Psychiatry 60:621-627.

The RESt-1 Group (2000): Social aspects of epilepsy in the adult in seven European countries. Epilepsia 41:998-1004.

Thompson PJ (1995): The impact of epilepsy on behavior and emotional development. In: Epilepsy in children and adolescents (Edited by: Aldenkamp A, Dreifuss F, Renier O, et al) Boca Raton, FL: CRC Press; p. 239-148.

Tomson T, Beghi E, Sundqvist A, Johannessen SI (2004): Medical risks in epilepsy: a review with focus on physical injuries, mortality, traffic accidents and their prevention. Epilepsy Res 60:1-16.

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Waaler PE, Blom BH, Skeidsvoll H, Mykletun A (2000): Prevalence, classification, and severity of epilepsy in children in Western Norway. Epilepsia 41:802-810.

Zielinski JJ (1974): Epilepsy and mortality rate and cause of death. Epilepsia 15:191-201.

 

5.5.3.4.7. Acronyms

 

AED

Antiepileptic Drug

CFR

Case Fatality Ratio

IBE

International Bureau for Epilepsy

ILAE

International League Against Epilepsy

LICE

Lega Italiana contro lEpilessia

NICE

National Institute for Clinical Excellence

PMR

Proportionate Mortality Ratio

SEWGED

Second European Working Group on Epilepsy and Driving

SIGN

Scottish Intercollegiate Guidelines

SMR

Standardized Mortality Ratio

SUDEP

Sudden Unexplained Death in Epilepsy

 

5.5.3.5 Multiple sclerosis

 

5.5.3.5.1. Introduction

 

Multiple sclerosis (MS) is a chronic progressive potentially highly disabling disorder with considerable social impact and economic consequences despite its relatively limited prevalence. It is the major cause of non-traumatic physical disability in young adults (Sadovnick and Ebers, 1993).

 

MS is an acquired inflammatory and neurodegenerative immuno-mediated disorder of the central nervous system, characterised by inflammation, demyelination and primary or secondary axonal degeneration (Trapp et al, 1998). MS etiology is unknown. The disease shows heterogeneity with respect to its pathogenesis, clinical manifestations, prognosis and pathology (Lucchinetti et al, 1996).

 

MS clinically manifests itself with signs of multiple neurological dysfunctions (e.g., visual and sensory disturbances, limb weakness, gait problems and bladder and bowel symptoms) followed by recovery or by an increasing disability due to irreversible functional disability over time (Ebers, 1998). However, aspecific symptoms such as fatigue (80% patients) can alone interfere with their quality of life and productivity (Freal et al, 1984; Krupp et al, 1988).

 

5.5.3.5.2. Data sources

 

The distribution of MS incidence and prevalence by age, sex, disease course and disability,and that of MS mortality was reviewed for Europe with regards to “European Union (EU) 27”, European Fair Trade Association (EFTA) Countries, and Switzerland, hereafter referred to as Europe. Articles published in the international scientific peer-reviewed literature (Firnhaber and Lauer, 1994; Rosati, 2001; Pugliatti et al, 2002; Pugliatti et al, 2006; Pugliatti and Rosati, in press), World Health Organisation (WHO) and Eurostat sources were used.

 

Large population-based studies (ie, 50 000 pop. and over, registry-based nationwide surveys) available since 1992 were considered, and the most recent data from the largest populations were prioritised.Reliable evidences reported in non-English scientific literature or from local small population surveys were also used when the search on international peer-reviewed literature failed to produce any result for a specific country.

 

Age categorisation for prevalence and incidence differs from studies to studies. For this report, the age classification was chosen based on what has been published elsewhere (Pugliatti et al, 2006).

When feasible, the total prevalence rate was standardized using the 1966 European population, and age-standardised rates were reported.

The distribution of disability (Kurtzke, 1983) was categorised into mild (Expanded Disability Status Scale (EDSS) 0 to 3.5), moderate (4.0 to 6.5) and severe (7.0 to 9.5).

Based on the clinical course, MS is typified as Primary Progressive (PP-MS), Secondary Progressive (SP-MS), Relapsing-Remitting (RR-MS) and Progressive Relapsing (PR-MS). For practical purposes, SP-MS and PR-MS were aggregated into PR-SP-MS. The distribution of the disease course consisted in the three categories: RR-MS, PR-SP-MS and PP-MS.

 

MS case registers in ”Europe

Population-based registries provide relevant information on the epidemiology of MS; some examples follow. The Danish Multiple Sclerosis Registry (DMSR) has collected MS cases since 1948 (www.si-folkesundhed.dk/Forskning/Sygdomme%20og%20tilskadekomst/Sclerose.aspx), and has been updated by prospectively and retrospectively recording information on MS cases from multiple sources, including the National Patient Registry (Koch-Henriksen et al, 2001). The Registry is estimated to be 90% complete, and with a diagnostic validity for definite MS of 94%. It links with Denmark’s Centralised Civil Registry, including the National Registry of Causes of Death, and the Danish Twin Registry. The DMSR has proved to be a valuable tool for multiple assessments of MS epidemiological indices and for studying the natural history of the disease (Koch-Henriksen and Hyllested, 1988; Koch-Henriksen et al, 1992; Brønnum-Hansen et al, 1994; Koch-Henriksen, 1999).

 

The European Database for Multiple Sclerosis (EDMUS) has been available since 1992. It was designed within the European Concerted Action for Multiple Sclerosis funded by the European Commission (Confavreux et al, 1992; Confavreux, 1994; www.edmus.org) as a dataset containing a minimal set of obligatory information serving MS population-based studies and multicenter collaborative research. EDMUS has been relevant in studying the natural history and physiopathology of MS (Confavreux et al, 2000; 2003).

 

The Norwegian National Multiple Sclerosis Registry was established in 2001 at the Norwegian Multiple Sclerosis National Competence Centre, Haukeland University Hospital, Bergen, aimed at collecting clinical and demographic information of all prevalent MS patients in Norway (Myhr et al, 2006; www.helse-bergen.no/avd/ms/msregisteret). In 2007, a biobank unit for collection of biological samples (DNA and serum) from all available MS patients was implemented.

 

In 2001, a nationwide epidemiological MS register was initiated under the auspices of the German MS Society (Flachenecker et al, 2005; www.dmsg.de/multiple-sklerose-news/index.php?anr=1016&kategorie=forschung). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. To date, standardised data sets of ca. 5800 MS patients were recorded from 82 centers (Flachenecker et al, 2007).

 

 

5.5.3.5.3. Data description and analysis

 

Nearly 200 surveys on MS epidemiology published in the past three decades were scrutinized, out of which a third turned out to be informative with regards to disease burden. The most relevant epidemiological patterns of MS distribution in time and space across Europe are summarised here. Tables 5.5.3.5.1-5.5.3.5.4 provide further details as to prevalence distribution by country, gender, age, and incidence distribution by Country, where available.

 

Table 5.5.3.5.1. Prevalence of Multiple Sclerosis in selected EUGLOREH Countries

 

Table 5.5.3.5.2. Prevalence (per 100 000) of Multiple Sclerosis in selected EUGLOREH Contries by gender

 

Table 5.5.3.5.3. Prevalence (per 100 000) of Multiple Sclerosis in selected EUGLOREH Countries, by age (best estimates)

 

Table 5.5.3.5.4. Incidence (per 100 000/year) of Multiple Sclerosis in Europe

 

 

Systematic surveys in the UK for more than 70 years show three main epidemiological trends: a north-to-south gradient: the northeast mainland and the Scottish offshore islands versus southern England and Wales; a markedly increased prevalence up to tenfold in Wales partly related to repeated assessments over time and increased awareness of MS; and the subsequent tendency for the latitudinal gradient to level off. Scotland’s rates are at least twice those of England and Wales and, despite methodological differences, the north-to-south latitudinal gradient of MS prevalence across the UK is unquestionable, with a discrete change in risk at the Scottish border. The MS prevalence in Northern Ireland is comparable with that in Scotland, probably because of the close ethnic origins and genetic composition of the two populations. In Ireland, the prevalence of MS is similar to that in the UK at comparable latitudes.

The MS prevalence in the Nordic countries is notably high, with some heterogeneity in temporal trends and across regions. The higher prevalence rates of MS reported in some regions compared with the respective national means was referred to as the Fennoscandian focus of MS. This extended from western to southeastern Norway, Denmark, southern Sweden, southwestern Finland and back to northeastern Sweden. A correlation with the distribution of environmental exposure specify to what was hypothesized.

Norway has an uneven distribution of prevalence and incidence, with peaks in central areas. Mean annual incidence rates have increased significantly from 3 to 6 per 100 000 per year in the western regions in the past three decades. The clinical phenotypes also appeared to have changed in Norway over time, with increased proportions of RR- versus PP-MS and among women versus men. A fluctuating incidence pattern was reported for Vestfold and for Hordaland County. Native Norwegians in Oslo had a prevalence rate of 136, which was higher than that in the city’s general population. In Hordaland County prevalence was 151 in 2003. In most Nordic counties of Troms and Finnmark, largely populated by Sami, a genetically resistant population, the prevalence increased 3.5-fold to 73 between 1973 and 1993.

Based on a registry system established in the early 1950s, prevalence in Göteborg in southwestern Sweden was 96 in 1988, while the mean annual incidence rate was 2.6 in 197488. Multiple assessments carried out in Västerbotten County in northern Sweden showed an increase of prevalence from 125 in 1990 to 154 in 1997; and a mean annual incidence rate of 5.2 in 198897.

In Finland, regional differences in MS prevalence and incidence have persisted over a 30-year follow-up period, with the highest rates reported in the western region round the town of Seinäjoki, intermediate rates in central Finland and coastal Vaasa and relatively lower rates in Uusimaa in the south. Prevalence increased between 1983 and 1993 in all these districts and in Vaasa, especially among women.

The DMSR provides epidemiological data on MS in Denmark that appear to be consistent with the findings in Norway and Sweden (Brønnum-Hansen et al, 2006) probably indicating a similar genetic and environmental background for susceptibility to MS.

Iceland provides a 50-year observational period in a well-defined and stable population. The threefold increase of MS prevalence up to 119 in 1999 compared with 1950 was related to improved case assessment over time. The MS risk in Iceland is similar to that in the other Scandinavian countries.

The MS prevalence in Germany has been rather homogeneously distributed over time and geography, with prevalence between 83 and 127 (Pugliatti et al, 2006) and an estimated mean annual incidence rate of 4.2 (Lauer, personal data). Similar prevalence rates were found in the Netherlands, Belgium, Slovenia, Switzerland and Austria, in comparable time periods. The geographical distribution of MS prevalence was heterogeneous in Poland, with a peak rate of 110 in the south, in the Czech Republic, with rates up to 160 in three small northern Bohemian districts, and in Hungary, with rates up to 79 in Fejer County.

Based on a nationwide survey, the estimated prevalence in France is 65 per 100 000 (Vukusic et al, 2007), and a northeast-to-southwest gradient of MS distribution in France was shown with both morbidity and mortality studies (Vukusic et al, 2007). Further studies showed that regional differences applied to prevalence but not to incidence rates, indicating a focal distribution of MS in ethnic groups with different susceptibility.

Parallel to improvement of the national health care system, multiple large population-based assessments conducted in northern, eastern and central Spain found prevalence rates of 3258 and mean annual incidence rates from 24 in the 1990s. Prevalence data are in the same range for Portugal.

Several prevalence surveys on MS have been conducted in Italy in the past two decades and some regions have been multiply assessed. The overall prevalence and the reported increase over time in the mainland and in Sicily probably resulted from improved diagnostic accuracy, epidemiological methods, multiple assessments and increased survival. Prevalence and incidence rates in the island of Sardinia were significantly higher than the national mean rates and showed a significantly increasing time trend over the past 30 years. The 4-fold increase in Malta’s prevalence rate since 1978 was explained by the changing population age structure, generally increased life expectancy and previous diagnoses. The genetic influence from northern Africa, an area at low risk for MS, is believed to account for the low absolute MS risk in the Maltese.

Prevalence of 39 and 21 per 100 000 has been reported for Bulgaria and Romania, respectively, with a mean annual incidence of 0.9 for Romania. Prevalence was 39 in Greece and Cyprus (Pugliatti et al, 2006), with a mean annual incidence of 2.4 in Greece. Methodological issues, such as hospital-based study designs and under-reporting, may account for underestimation of rates in these areas.

In brief, prevalence in Europe ranges from approx. 20 to 190 per 100 000. Mean rates are higher in northern countries, maybe also due to a better degree of ascertainment, i.e. for the use of registry systems and repeated assessments over time.

Nevertheless, a certain extent of prevalence heterogeneity is observed within Countries, so the role of environmental factors and their interaction with the population specific genetic susceptibility in increasing MS frequency cannot be ruled out. A tendency for a decreasing variability in prevalence rates among and within Countries has been observed over time, pointing to a widespread improvement of case ascertainment and survey methodology in the same time frame. Prevalence ranges between 11 and 282 per 100 000 in women and between 10 and 123 per 100 000 in men, with female:male ratios between 1.1 and 3.4. Mean total prevalence estimates by age group varied significantly across Countries. The highest prevalence estimates have been reported for the population aged 3549 for all Countries taken into consideration with the exception of the Republic of Ireland, Northern Ireland, Scotland, and Norway, where prevalence was higher in the population aged 5064.

The total annual mean MS incidence in Europe is estimated to be 4 per 100 000, with peaks registered registered in Finland, Scotland, Norway and Sardinia, insular Italy.

 

The distribution of MS in Europe by disease course

 

The reported prevalence-based distribution of disease course is reported in Table 5.5.3.5.5 and Figure 5.5.3.5.1. RR-MS ranged from 24% (The Netherlands) to 88% (Greece) of prevalent cases. The combined proportion of RP-MS and SP-MS ranged from 4% (Sweden) to 50% (Bulgaria), whereas PP-MS ranged from 4% (Austria) to 35% (The Netherlands).

 

Table 5.5.3.5.5. Proportion of Multiple Sclerosis patients by disease course in selected EUGLOREH countries

The distribution of MS in Europe by severity

The prevalence-based distribution of disease severity indicated by means of disability score is shown in Table 5.5.3.5.6 and Figure 5.5.3.5.2. The estimated proportion range for mild MS (EDSS 0-3.5) was 33% (UK) to 80% (Spain), between 13% (Italy) and 48% (UK) for moderate MS (EDSS 4-6.5) and between 5% (Austria) and 39% (The Netherlands) for severe MS (EDSS 7-9.5)

 

Table 5.5.3.5.6. Proportion of Multiple Sclerosis patients by disease severity (EDSS) in selected EUGLOREH countries

 

MS mortality rates and survival time in Europe

Data on MS mortality must be taken cautiously in time series based on ICD (International Classification of Diseases) codes as they may reflect a change in the coding system over time. Also, when MS patients die from other causes or from age-related diseases if they are in the older tier, misclassification, up to 23%, deriving from the assessment through death certificates is likely to occur as MS is not mentioned (Ford et al, 2002).

MS is associated with an elevated risk for death in Europe, with mortality ranging from 0.6 to 1.0 per 100 000 as reported by WHO for 2002 (WHO, 2004a). However, rates up to 3.6 per 100 000 are reported in the scientific literature. An overview of mortality rates in Europe is reported in Table 7 Decreasing trends over time are reported for Denmark, Scotland, The Netherlands, Switzerland, Germany, Austria and Portugal (Pugliatti et al, 2006), increasing trends in Norway, Sweden, Bulgaria and in Italy for women. The highest mortality rates from MS in Austria were observed for the age group 50-69 and with a woman:man ratio of 2.0. In the same study the total median age at death from MS was 59 years between 1990-2001, with a 15-year shorter life expectancy than the general population. Mean survival time after onset range from about 30 to 45.

 

Table 5.5.3.5.7. Mortality (per 100 000) of MS patients in selected EUGLOREH countries

 

The epidemiology of MS in Europe: methodological issues

Despite the wealth of data deriving from systematic epidemiological studies on MS conducted over the past three decades, reliable information on age-specific prevalence rates, on the distribution of prevalent cases by disease severity and course, and on incidence rates lacks for nearly two thirds of all European countries. Redefining the geographical pattern of MS in Europe is a hard task due to: (a) the variability of the surveyed populations with respect to size, age structure, ethnic origin; (b) the capability to detect benign and/or early cases; (c) the different degree of case ascertainment coverage based on geographic and time setting, access to medical care, number of neurologists, availability of new diagnostic procedures, public awareness about MS; (d) the impact of different diagnostic criteria used and the inter-observer variability when comparing incidence and prevalence rates between studies.

A decreasing north-to-south gradient in the distribution of MS prevalence rates across Europe has been observed. Although assessment biases might play a role in such distribution, biological factors, i.e., differences in environmental exposures, and/or different genetic susceptibility underlying such differences cannot be ruled out. Mean rates tend to be higher in countries where the degree of disease investigation is also higher, with better accuracy in survey methodology, and where assessments have been repeatedly conducted over time, often based on nation-wide surveys and registry systems. However, the tendency for a decreased variability in prevalence rates among and within countries over time and a temporal increase of prevalence and incidence rates where multiple assessments have been carried out point to a general improvement in case ascertainment and survey methodology in time.

When multiple regression models were used to predict the degree of MS prevalence according to latitude, a latitudinal gradient was found if crude prevalence rates were considered (Zivadinov et al, 2003). However, for prevalence and incidence rates age-adjusted to the European (and World) population a weak correlation was found. The population age structure is therefore a relevant factor underlying the differences in MS distribution.

A general methodological issue encountered in reviewing the current epidemiology of MS in Europe was categorisation, and a great deal of variability in categorising variables (age group, disease course, disease severity) was observed among studies. As for disease course, due to the remarkable heterogeneity of the course patterns, the cross-sectional nature of the assessment and the study specific purposes, only the proportion of RR-MS and PP-MS is sometimes reported. Disease course categorisation is mostly prevalence-based, virtually leading to misclassification biases with respect to future outcome. This may account for an underestimation of the proportion of progressive courses and severely disabled cases, subsequently underestimating the impact on the global disease socio-economic burden.

 

The socio-economic burden of MS in Europe

 

The disability adjusted life years (DALYs) is one of the most commonly used measures in evaluating the burden of MS in health economics. DALYs are the sum of the present value of future years of lifetime lost due to premature mortality (years of life lost, YLLs) and of lifetime adjusted for the disease severity due to mental and/or physical disability (years of life with disability, YLDs) (Murray and Lopez, 2000; Fox-Rushby and Hanson 2001). The computation of DALYs is therefore based upon epidemiological data, such as prevalence and incidence rates, age at disease onset, life expectancy at disease onset, age at death, degree and duration of disability. The total DALY for MS in Europe is 307 000 years and varies according to mortality strata, being 157 000 in the very-low-child/very-low-adult stratum, 63 000 in the low-child/low-adult and 87 000 in the low-child/high-adult mortality strata respectively (WHO, 2004b). Few studies measuring DALYs have been carried out so far for MS as compared to other neurological disorders. Furthermore, comorbidity in MS and associated symptoms (eg., depression, urinary tract infections) are often overlooked when measuring DALYs in MS.

The general decreasing trend of mortality rates over time reported for many countries and subsequent increased survival time after MS onset will increase the disease burden due to the greater number of YLDs. The majority of those countries with higher life expectancy are found to also have higher MS incidence (WHO, 2004), thus proportional greater burden of disease in the future.

MS social costs are high. Cost data were extrapolated for EU25 and EFTA countries based on a model, using economic indexes adjusting for price level differences in different sectors between countries (Sobocki et al, 2007). Costs, retrospectively assessed, were presented as total annual cost per patient in 2005, total direct costs (healthcare costs [inpatient care, outpatient care, drug costs and tests], non-medical costs [services, and investments] and informal care), indirect costs (production loss due to sick-leave and early retirement), and intangible costs (comparison of patientsHRQoL to that of age- and gender matched general population). The economic burden of MS for the year 2005 was €13 billion, i.e., €27 per European inhabitant. Intangible costs would add an additional8 billion. The cost per MS case in Europe ranges from €10 000 to €54 000, with a mean of €31 000. Direct costs, excluding informal care, amount to 56% of the total cost, and within these, drug costs dominate with €2.5 billion in 2005 (41% of direct costs or 20% of the total costs). Social services only represent 7% of total cost, explaining the intense use of informal care (22% of total costs) to help patients in their activities of daily living.

 

Figure 5.5.3.5.1. Distribution of total cost of MS in Europe (year 2005) by resource use components.

 

Production losses and especially early retirement (indirect costs) represent 22% of the total cost. No reliable estimates of the cost of premature death were found in the literature, and so could not be included in the study estimates.

A patient with mild disability at the EDSS (the greater proportion) costs14 300 per year, €31 200 per year if with moderate disability, and €58 300 per year if with severe disability.

 

5.5.3.5.4. Risk factors

 

MS is a complex multifactorial disorder, in which environmental factors supposedly interact with genetically susceptible individuals (Noseworthy et al, 2000). The most influential risk factor for MS is hypothesised to operate early in life. Later influences may act in determining the risk, either with individual main effect, or primed by early exposures and with reciprocal interaction(s). It is possible that more than one of these effects implies there are strong possibilities that also genes operate in determining MS risk especially at familial level. Major environmental factors, directly or indirectly climate-related, are operative at population level, among which vitamin D status with diet and sun exposure, early life infections including infectious mononucleosis, and lifestyle factors also acting early in life, such as smoking.

 

5.5.3.5.5. Control tools and policies

 

Primary prevention

The importance of environmental factors and their practical relevance for the prevention of MS have not received adequate consideration (Ebers, 2008). Gene-environment interactions should be studied with our advancing understanding of how genes produce specific susceptibility towards the environment. If sunlight or vitamin D are major environmental risk factors, studies of disease should be started although these might have a long-term outcome.

Secondary prevention

 

Diagnostic criteria

 

There are no pathognomonic tests for the diagnosis of MS. Diagnostic criteria require evidence of dissemination of neurologic signs and symptoms in space and time based on historical, clinical and paraclinical evidence. The most widely used criteria in MS epidemiological research over the past two decades were the Poser Committee criteria (Poser et al, 1983), consisting of two large categories for definite and probable MS, and relevant subcategories: clinically definite MS (CDMS), laboratory-supported definite MS (LSDMS), clinically probable MS (CPMS) and laboratory-supported probable MS (LSPMS). In 2001, an international committee of neurologists headed by W. Ian McDonald published the new diagnostic guidelines by incorporating magnetic resonance imaging (MRI), eliminating the category of probable MS and reintroducing that of possible MS (McDonald et al, 2001). According to these new indications, patients can receive a diagnosis of MS or possible MS. Because of the retrospective methods used in MS epidemiological studies and the lack of MRI facilities in some populations, the Poser et al criteria still comprise the most common classification in such surveys. MS is diagnosed more often according to the McDonald et al criteria than to the Poser et al one CDMS (52% vs 38%) (Fangerau et al, 2004).

Lastly, the lack of “attacks” and of recurrent episodes in primary progressive forms, may lead to an underestimation of such forms when the Poser Committee criteria are used (McDonnell and Hawkins, 1998b).

 

Clinical course

 

The clinical course of MS shows heterogeneity among patients and can be rather unpredictable also in the same patient. The following categorisation of MS clinical course has been reported (Lublin and Reingold, 1996): (a) relapsing-remitting MS (RR-MS), a clearly defined disease with relapses with full recovery, or with sequelae upon recovery and periods between relapses characterized by a lack of disease progression, (b) progressive-relapsing MS (PR-MS), progressive disease from onset with clear superimposed relapses - with or without full recovery - and periods between relapses characterized by continuing progression; (c) secondary-progressive MS (SP-MS), initial RR course followed by progression with or without occasional relapses, minor remissions and plateaus; (d) primary-progressive MS (PP-MS), disease with progression from onset with plateaus and temporary minor improvements.

Due to the cross-sectional or historical design of most epidemiological studies on MS, the disease course is often more simply categorised into RR-MS, secondary progressive (SP-MS) and chronic progressive (CP)- or PP-MS (Ebers, 1998) and is based on prevalent cases. It is often unclear whether PR courses are lumped to RR or PP ones.

 

Disability

Several scales have been used to measure disability in MS, aimed at evaluating the efficacy of interventional programs. In MS epidemiological descriptive research, the burden of disability is most frequently presented as Kurtzke’s Expanded Disability Status Score (EDSS) for prevalent cases (Kurtzke, 1983). Disability due to MS can be measured within functional neurological systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, other) by assigning to each of them a score. The distribution of the scores over the functional systems combined with their degree is then assigned to one of the 20 categories (0, 0.5, 1, etc. to 10) which indicate the level of disability. Further lumping is often needed when precise scores cannot be assessed in historical or cross-sectional studies so that EDSS 0 to 3.5 refers to fully ambulatory with the most moderate disability in at least one functional system, 4.0-6.5 refers to fully ambulatory, although relatively severe disability, eventually constant bilateral assistance needed to walk 20 m; 7.0 to 9.5 refers to patients restricted to wheelchairs, confined to bed and totally helpless and 10 is death due to MS.

 

Treatment

There is no cure for MS, but there are drugs able to slow down the underlying pathogenetic process and help control symptoms. Goals for treating MS may include reducing the number of attacks, improving recovery from attacks and halting further progression of the disease. Based on available evidence, early, aggressive treatment is warranted in all patients with MS or at risk of developing MS (eg., ‘clinically isolated syndromes’). Identifying benign cases in the early stages of MS is difficult and there is evidence that treatment with interferon beta has beneficial effects on the central nervous system (CNS) inflammation compared to placebo.

Five disease-modifying therapies for the initial management of MS are available in Europe, i.e., beta-interferons 1a and 1b, glatiramer acetate and natalizumab, a monoclonal antibody against blood-brain barrier constituents. Mitoxantrone is sometimes used for the treatment of worsening forms of RR- MS and SP-MS. Besides the method and frequency of administration of these drugs (injections and up to every day), side effects can interfere as well interferons with the quality of life and productivity of MS patients’ . An understanding of the potential side effects of these drugs is critical for the patients to ensure compliance. Other drugs are used, such as azathioprine, intravenous immunoglobulins (IVIG), cyclophosphamide. A number of drugs are being tested some of which have shown satisfactorily preliminary results: lamotrigine, campath-alemtuzumab, FTY 720-fingolimod, anti IL 2 receptor monoclonal antibody, teriflunomide, daclizumab and cladribine.

Rehabilitation in MS implies comprehensive, multidisciplinary, individualised, coordinated rehabilitation programmes (Miller et al, 2006). Also, home-based care has been shown to be more cost-effective, and achieve important gains in measures of general health, pain, role-emotion, and social function, regardless of functional status.

 

Policies

 

The Framework Directive on Equal Treatment in the Work Place

 

Council Directive 2000/78 EC, prohibits direct and indirect discrimination on the grounds of disability, and introduces the concept of reasonable accommodation whereby the employer is obliged to accommodate the needs of suitably qualified disabled people by adapting premises, work schedules or job descriptions so that they can be employed. The impact of the Directive on EU citizens with multiple sclerosis has not yet been analysed; however, the onset of multiple sclerosis often occurs at the prime of life, when people have significant economic and social responsibilities. A European wide survey and analysis (Sobocki et al, 2007) revealed the positive psychological and physical benefits of job retention that can reduce the progression of the disease, yet many people affected by MS are forced to give up work due to lack of support.

The Framework Directive on equal treatment in the work place is an important basis upon which to challenge this discrimination; the concept of ‘reasonable accommodation’ within the Directive should be interpreted to include flexible working, rest periods, the necessary work adaptations and a social protection safety net to respond effectively to the symptoms of MS and ensure both access and dignity.

Much more focus is required however to ensure that the Directive has the right impact on the relations towards people affected by MS. The Code of Good Practice on MS ( see below) calls for information and awareness-raising programmes for employers, co-workers and for those diagnosed with MS regarding the Directive, its scope and its potential both as an advocacy tool and for seeking individual redress.

A new study on MS and employment in the EU is in its final phases and results will be made available in scientific literature.

Early published studies on MS patients and their employment situation focused on identifying factors that differentiated the employed from the unemployed for predicting which type of individuals were at risk for leaving the workforce. The most important of these early studies (Larocca, 1985) identified disease and demographic characteristics (age, gender, education, disability level) that were directly associated with employment status, but accounted for only 14% of the variation between employed and unemployed individuals with MS. The important conclusion of this report was that most variations seem due not to the severity of the disease or to demographic differences but to pre-morbid personality, coping style, workplace characteristics and social support. With the exception of pre-morbid personality, appropriate interventions can address these other factors in a way that promotes the individual’s ability and desire to stay in the workforce. Keeping people with MS in the workforce can be beneficial for society in general, as well as for the self-esteem and economic security of the individual. Currently, there are no comprehensive data available on the employment situation of people with MS in Europe, but only reports from a few individual countries, with varying study designs that preclude a comparison of results.. The primary objectives of the new study are to generate data that will substantiate national service provision planning and European-level lobbying by:

o         determining the general employment situation in a sample of European countries (i.e. number of unemployed people due to MS, number of people actively seeking employment, number of currently employed people and at/not at risk for job loss);

o         identifying demographic and disease characteristics that differentiate employed from unemployed people with MS;

o         identifying factors that enable employed people with MS to stay in the workforce;

o         assess the impact of a variety of factors that influence a person’s choice/ability to maintain employment. The outcomes of the study will be published on an international, peer-reviewed, scientific journal reporting the results. The report will be used at national level to promote the rights of people with MS to obtain and maintain employment, without discrimination, architectural barriers or other cultural, social, psychological or physical obstacles. The report will also be used to promote, at European Union level, the employment of people with MS to help guarantee appropriate interpretation and application of the EU directive on employment of the disabled throughout the Union.

 

The European Parliament Resolution on the effects of discriminatory treatment towards people with MS in the European Union

In December 2003 the European Parliament adopted unanimously a resolution and report26 concerning the effects of discriminatory treatment towards people with multiple sclerosis within the European Union) based upon a petition submitted by a British person with Multiple Sclerosis, Louise McVay. This report was actively supported by the European Multiple Sclerosis Platform and all EU Multiple Sclerosis Societies. Health Departments in most member states of the Union provided information which was used for the preparation of the report.

The contents of the report, presented by Parliament’s Rapporteur Uma Aaltonen from Finland -herself a person with MS - analysed the experiences of people with MS in Europe. It did so with regard to the type of medical support they were able to obtain from their respective health services, as well as in relation to their social and family environment, and in particular their employment prospects.

Paragraph 1 of the substantive resolution adopted by the Parliament urged the Ministers of Health of the European Union to develop a “Code of Best Practice” for MS patients.

European Code of Good Practice on the Rights and Quality of Life of People Affected by MS

 

The Code was drawn up in spring 2005 as follow up to the above European Parliament Resolution It is targeted towards all stakeholders in the lives of people affected by MS, including policy makers and administrators, the medical profession, the corporate sector, volunteers, families, and of course, the person affected by MS.

The Code is a political instrument that outlines briefly the issues of fundamental importance to people affected by MS. It provides a practical framework that describes in general terms:

·          The optimal approach in relation to treatments, therapies and services, research, employment, and empowerment of people affected by MS;

·          It signposts core consensus documents and materials that are endorsed by both the medical and patient community;

·          It commits national governments and the European Commission to an independent monitoring system that will feed into the open method of coordination on public health.

 

The Code describes good practice in four key areas critical to the health and Quality of Life of People affected by MS.

·          Equal rights and access to treatment, therapies and services in the management of Multiple Sclerosis;

·          A shared agenda in MS research;

·          Employment and Job retention

·          Participation and Empowerment

 

The European Parliament, the European Commission and the German Health Minister Ulla Schmidt, during the German Presidency of the European Union endorsed the EuropeanCode of Good Practice” on Multiple Sclerosis and its reference documents. Implementation of the Code at national level will help overcome the currently unacceptable inequalities in the diagnosis, treatment and care of people with ms within and across the EU Member States.

 

EU Consensus documents and reference papers in the areas of MS referred to in the Code

·          The European Map of Multiple Sclerosis, (www.europeanmapofms.org)

The European Map of MS database provides information and data on the epidemiology of MS and the availability and accessibility of resources for people with MS at country level. The contents of the database can be searched and illustrated through maps, charts or spreadsheets in the data query section. The whole database will be updated every four years. Data will also be collected on an ongoing basis from countries that have not yet submitted data and new data will be collected for new categories and sub categories as and when necessary, for example when a new treatment becomes available.

·         Escalating Immunomodulatory Therapy of MS Consensus Paper

·         Current therapeutic recommendations, from the updated and edited version 2007 (MSTCG, 2007) of the original report 2006 (MSTCG and Rieckmann, 2006)

Recent clinical studies in MS provide new data on the treatment of clinically isolated syndromes, secondary progression, direct comparison of immunomodulatory treatments and dose issues. All these studies have important implications for the optimised care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provided recommendations for the application of immunoprophylatic therapies.

·         Recommendations on Rehabilitation Services for People with Multiple Sclerosis in Europe by the European Multiple Sclerosis Platform and RIMS, Rehabilitation in Multiple Sclerosis (Battaglia et al, 2004).

These recommendations are the result of an intensive collaboration among foremost experts in Multiple Sclerosis Rehabilitation in Europe; their target is to contribute to ensuring Europeans with MS have access to the best possible rehabilitation services at every stage of their illness.

·         Symptomatic Therapies Consensus Paper based on the German MS Society’s reportMehr Lebensqualität, Sympomatische Therapie bei MS”. (Henze et al, 2006).

Although there is a vast amount of scientific literature dealing with symptomatic treatment, high quality studies are still scarce. The MSTCG from Austria, Germany and Switzerland developed and published consensus guidelines based on the available evidence from clinical studies and on expert opinions collected and critically edited by a group of MS neurologists. The Consensus paper includes treatment guidelines for some of the most important MS symptoms such as motor function and coordination, cranial nerves, autonomic nervous system function e.g bladder, bowel and sexual dysfunction, psychiatric and psychological problems, and pan and paroxysmal symptoms.

·         Position Paper Palliative care among people severely affected with multiple sclerosis ( Haffenden et al, 2006).

This position paper based on recent studies underlines the need for patients severely affected by MS in Europe to have access to palliative care assessments and services.

·         National Institute for Clinical Excellence Guideline on MS Services (UK)

The National Institute for Clinical Excellence Guideline on the management of MS provides clear, evidence-based recommendations on managing all aspects of MS and offers a blueprint for service providers and commissioners on the best way to organise complex services.

·         Principles to promote the quality of life of people with MS (Trisolini et al, 2002)

These 10 principles were designed to guide the development and evaluation of services that are provided by governments, for profit or no-profit health and social services providers, employers and other organizations for people with MS.

 

UN Convention on the rights of People with Disabilities

 

There are number of references in the UN Convention on the Rights of Disabled People, which support and reinforce the European Code of Good Practice on the rights and quality of life of people affected by MS. The UN Convention, once ratified, is legally binding and relates to disabled people in general. The Code is not legally binding but is very specific towards the rights and quality of life of people affected by MS, drawing on key policy developments and consensus papers in the field. In this respect, it is clear that these instruments are highly complementary.

Civil Society: the role of organizations International, European and National Level

There are active MS societies in all 27 member states of the EU; together with other societies from the wider part of Europe they constitute the European Multiple Sclerosis Platform (EMSP). EMSP is represented within the European Medical Agency (EMEA), the European Commission’s Health Policy Forum, and is also part of the European PatientsForum and the European Disability Forum. Its parent body at international level, the Multiple Sclerosis International Federation (MSIF) has consultative status within the WHO.

 

5.5.3.5.6. Future developments

 

There is much work to be carried out in order to achieve full and equal participation of people with MS in society. Advances in medical research, the creation of appropriately flexible labour and social policies for people with MS and the creation of an economic environment in which the cost of the disease of MS on the individual and society are some of the issues on which national MS societies campaign tenaciously.

At the MS-ID conference hosted by EMSP in May 2007, it was conveyed that developments are coming on-stream, and have multifaceted implications for the management of the disease. There is no cure for MS, but medicines may slow it down and help control symptoms.

As a way forward in addressing the future, the needs and voices of people with MS must be formally sought. Consultative status for patients on issues such as pricing and reimbursement matters. The professionalisation of the patient’s status (i.e. the strengthening of MS society foothold in the national framework for effecting political change) is bringing with it enhanced possibilities for empowerment and self-advocacy. But emphasis must be placed on harmonising the status and advocacy role of national MS societies in contributing to social policy changes.

The EMSP has recently embarked upon a three year project entitled MS-ID (Multiple SclerosisInformation Dividend) which seeks to enhance equity of treatment, access thereto and quality of services for EU citizens affected by Multiple Sclerosis (MS). It will create a standardised data collection and management system of different national care approaches to MS, which will allow good practice sharing between the EU Member States. The project will contrast and compare current EU member statesnational care approaches towards the diagnosis, treatment and management of MS. More specifically, the project partners will exchange information on: the creation of a defined strategy to analyse and compare MS data; prevalence and epidemiology of multiple sclerosis in Europe; good practice review of MS treatments and therapies, reviewing the social support and benefits of best management of MS. The project will also analyse existing national studies on the economics of (i.e. the cost of illness of) MS.

This project will contribute significantly to the knowledge database available on MS, with the long-term added value of producing annual national reports on the status of MS using the Open Method of Coordination. The results of the project will come on-line during 2008 and 2009, with announcement thereon at a major public meeting in May 2009.

 

5.5.3.5.7. References

 

Bajenaru O, Pascu I (2004): Report of multiple sclerosis centers. Cephalalgia Hungarica 13:68-70.

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