Journal ofNeurology, , and 1993;56:735-738 735

Journal of J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.7.735 on 1 July 1993. Downloaded from NEUROSURGERY & PSYCHIATRY

Editorial

Neuroepidemiology in the United Kingdom

The purpose of this article is to review important studies nite epilepsy diagnosed from their hospital records, near- of the of neurological disease in the United ly 25% concealed the diagnosis when sent a question- Kingdom, and some of the difficulties encountered in naire."1 The insidious nature of many neurological conducting them. We will also explain the background to disorders means that people may not recognise that they two exciting studies in progress. For a review of the basic are affected and so stay away from medical attention. In a methodology of neuropidemiology the reader is referred twin study of MS, siblings of affected patients were con- to a number of seminal articles. 1-5 tacted, and nearly 5% were found on clinical and MRI Two of the key measurements used in descriptive epi- examination to have MS who previously had not suspect- demiology are the prevalence and incidence of a disease.2 ed their diagnosis.'2 There may be a similar undetected The prevalence measures the number of current cases of group of patients with diseases of the basal ganglia, as a disease in a defined population at a given time and shown by studies using positron emission tomography place. The incidence of a disease is the number of new that can demonstrate presymptomatic nigral involvement cases occurring in a defined population for a given time in subjects before the development of Parkinsonism."3 interval, usually one year, and place. The determination Cases will also evade case ascertainment if diagnosis is of incidence or prevalence figures for a particular disease delayed. In one UK study of epilepsy, it took more than requires the precise ascertainment of all cases of the dis- two years for a diagnosis to be reached in more than 25% ease in the target population. It is worth emphasising that of patients,'4 obviously affecting incidence and prevalence incidence and prevalence figures are measures of rates of rates. disease, and therefore the selection and demographic The third problem is that there are so many neurologi- characterisation of the denominator population is impor- cal diseases (indeed there are many more individual dis- tant. The incompleteness of case ascertainment can be a eases listed in the International Classification of Diseases http://jnnp.bmj.com/ major source of error, and this poses problems that than for any other medical speciality'5), and yet they are appear to be more significant in neurological disease in often relatively rare. To arrive at incidence of rare condi- four particular ways. tions, a large population needs to be surveyed, carrying First, to ascertain patients with a specific neurological generally large logistic and financial costs. This partially disorder it is essential to have a clear and rigid diagnostic explains why the last comprehensive study of the inci- definition. This is often lacking in neurology compared dence of all the neurological diseases occurring in a UK with diseases in other specialities, because the diagnosis population was over 26 years ago in Carlisle.'6 on September 29, 2021 by guest. Protected copyright. is often made on clinical grounds alone with a limited Finally, the late development of neurology as a med- number of useful clinical and laboratory diagnostic tests ical speciality has had an important impact on the pattern available. For example, contrast the rigid diagnostic defi- of neurological care, which has itself affected neuroepide- nition laid down by the World Health Organisation for miological research. For instance, the majority of stroke diabetes,6 and the diagnostic criteria for multi-system patients in the UK never come into contact with a neu- atrophy.7 As new technologies become available, howev- rologist, and patients with multiple problems, often the er, more reliable diagnostic definitions should be possible elderly, are usually looked after by general physicians, by incorporating investigations into diagnostic defini- even if there is a neurological component. It is clear tions, as shown by the recent application of MRI in mul- therefore that for valid investigations of common neuro- tiple sclerosis (MS).8 Diagnostic validity also may be logical disorders, patients have to be recruited at popula- poor. For example in one UK study of 19 untreated tion level, and not from the highly selected groups seen patients with clinically diagnosed Parkinson's disease, in neurological clinics. The failure to recognise this led to 20% later turned out on post mortem to have another false ideas about the prognosis of epilepsy.'7 diagnosis.9 Incidence and prevalence studies provide the most Second, is what might be called the "iceberg" effect. important measure of disease burden and give a broad This refers to sub clinical or hidden cases that evade case picture of disease patterns. However, neuroepidemiology ascertainment, and in neuroepidemiology there are sever- is not only concerned with incidence and prevalence fig- al reasons for this. There is a stigma attached to having a ures, and can advance the knowledge of a disease by disease of the nervous system,'0 so that patients may con- determining risk factors, defining prognosis and calculat- ceal their condition. In a field survey of people with defi- ing attack rates, mortality rates, and case fatality rates. 736 Editorial

Such investigations require the assiduous application of population of 300 000 served by 48 practices was J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.7.735 on 1 July 1993. Downloaded from the key epidemiological principles of investigating large produced as part of the Third National Morbidity numbers of people to achieve statistical power, and using Survey, and in a single year 65% of men and 77% of control populations where appropriate. The organisation women saw their family doctor at least once.29 30 The GP needed is often formidable. In the UK, risk factor data is usually the first medical practitioner to see a patient, have recently been obtained on the risk factors for stroke and is the gatekeeper for hospital referral. The GP case in middle aged men,'8 the risk of serious vascular events notes contain a patient's lifetime medical history. Even if after a TIA,"9 and the risk of developing MS in the UK the patient goes straight to hospital (for example, in an West Indian population.20 emergency), the GP is still informed of the contact at dis- The prospective cohort study from the time of diagno- charge or death. If the patient moves to a new area, the sis is the epidemiological gold standard for investigating notes are transferred to the new GP, and the NHS cen- prognosis. The chronic, and fluctuating, nature of many tral register, run by the Office of Population Census and neurological disorders, like MS which is characterised by Surveys (OPCS), is able to track each patient. Everyone remissions and exacerbations which can be decades in the UK has an individual NHS number that can be apart, means that the study must be long term, with facil- monitored in the event of change of address or name. ity for regular, active follow up. A recent study from the Death certification is linked via computer to the NHS North East of Scotland used information from data col- number, and a patient can be flagged so that death lected on patients with prevalent MS since 1970, produc- and/or its certified causes can be available to the ing results on prognostic indicators.2' Nevertheless, to researcher. The GP is responsible for all but emergency date, there have been no large prospective studies of inci- prescribing, and this can assist with case ascertainment, dent cases of MS in this country. The prospective and other health service research, by accessing GP approach has been successfully applied in the UK to surgery prescription data. common disorders such as, epilepsy,22 and cerebrovascu- Demographic data is also readily available in this lar disease,2' and to specific aspects of prognosis, such as country at local or national level. The OPCS provides the risk of relapse of epilepsy following antiepileptic drug regular comprehensive national reports." The Family withdrawal.24 Health Service Authorities are able to supply local There have been few population based investigations demongraphic data, and now, with the trend towards of mortality in the UK. Care should be taken when computerisation, most practices themselves are able to assessing mortality statistics using death certificate data give demographic information on their own lists. which have well-known limitations.25 In chronic neuro- Care has to be exercised if raw GP data are used, how- logical conditions, inaccuracies may be particularly ever, in view of the potential problems of diagnostic prominent as the cause of death is often an intercurrent validity. In one survey of GP diagnosis the range of confi- illness such as bronchopneumonia, and the neurological dence each practitioner has in their own conclusion condition may be omitted from the death certificate. ranged from 15-84%.32 This problem was tackled in the Assessing the contribution of the neurological condition Oxford Community Stroke Project,23 in which each to the cause of death in this situation is highly subjective. patient was seen by a trained neurologist after being diag- Neuroepidemiology in the UK has not been as well nosed by their GP as having a possible stroke. Similarly supported as in the USA, where the National Institute of in the National General Practice Study of Epilepsy, GP Neurological Disorders and Stroke (NINDS) set up pro- assessment was supplemented by hospital follow up data, grammes of research to encourage development in this and then subjected to a diagnostic panel review.22

area. Between 1980 and 1990 there was a 101% increase The benefits of using data from primary care were http://jnnp.bmj.com/ in articles on Neuroepidemiology in the American med- demonstrated by the Third National Morbidity Survey ical press.26 Much of the NINDS funding initially went to mentioned above.'0 More detailed analysis of this has the flagship of epidemiological research in the USA, the been reported and reviewed in this journal,29 and it was Mayo clinics record linkage system in Rochester, found that 9 5% of the population consulted their GP Minnesota.27 This utilises a system where all the popula- about a neurological symptom per year. tion (approximately 90 000) have their medical contacts The specialist neurological services in the UK have recorded on a central data base. This has enabled exten- some characteristics which are also important to consider sive analysis of all the neurological conditions that have in neuroepidemiological research, that confer advantages on September 29, 2021 by guest. Protected copyright. occurred in that community over the last 40 years, and when studying rare diseases. First, the number of neurol- numerous studies have been produced from work using ogists is small and the services highly centralised into a this data. The major drawback to this system is that all few neurological centres. Thus the logistical problems of the information is retrospective and this introduces prob- surveying specialist practice are greatly eased. Whilst lems with diagnositic validity, accuracy of follow up, and patients with common neurological conditions are often completeness of data. Also, only patients attending the not referred to these neurological services, rare diseases clinics linked to the system will be included, and the usually are. The neurologist provides a consulting role for extent to which findings from such a small and homoge- diagnosis rather than long-term follow up, and thus has a nous population can be extrapolated to the general popu- relatively large case register of uncommon diseases. lation is uncertain. The burden of neurological illness in the UK Advantages of the structure of the UK We have summarised the incidence, prevalence, and system for neuroepidemiology mortality data from the most important neuroepidemio- Facets of our health care system makes the UK a poten- logical studies in the UK in table 1. The list is not tially fertile territory for neuroepidemiological research. exhaustive, as many diseases have not been adequately The most important is the general practitioner (GP) pri- studied, but does give an illustration of the relative fre- mary health care system, which is ideally suited to the quency of those diseases that have been surveyed. The surveillance of common diseases. There is high coverage table does not include descriptive categories, such as of the population with over 98% registered with a GP.28 back , headaches, and neurological symptoms with- Information about neurological disorders occurring in a out an underlying cause, that are covered well else- Editorial 737

Table 1 Annual incidence, point prevalence, and annual mortality ratesa has been cogently argued that much of the work carried J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.7.735 on 1 July 1993. Downloaded from ofselected neurological diseases in the UKper 100 000 population. All out by American neurologists could satisfactorily be ages. undertaken by British general practitioners.29 There is, Annual Point Annual however, a pressing need for studies measuring the rela- Disease incidence prevalence mortality rateb tive clinical outcome, cost effectiveness, and quality of Migraine N/A 330016 N/A care in specialist clinics compared with primary care, so Strokec 20023 57030 230 Epilepsyd 3016 200036 3-3 that realistic referral recommendations and therefore Dementia' 18437 8638 62 long-term manpower needs planned. Parkinsonism' 12"6 16039 14 MS 540 1104' 3-2 Brain tumourg a) malignant 9.3"6 2116 11 b) benign 2.816 2816 9 The future MND 2.442 4.643 1-1 We have reviewed the current status of neuroepidemiolo- Huntington's disease N/A 84" 1 1 Guillain-Barre syndrome 1. 145 N/A 0-095 gy in the UK. For common diseases the trend, for good Myasthenia gravis 0-2246 2 347 0-08 epidemiological reasons, has been towards prospective Myotonic dystrophy 1448 7.144 0-13 Muscular dystrophy 1 2"6 1844 0-81 community based studies and away from hospital based Hereditary neuropathy 0.216 1344 0-13 case series, often via information from general practice. N/A indicates no accurate UK data available. In spite of the advantages the UK has to offer neuroepi- aRates given are to nearest two significant digits based on data quoted from demiology, there are still gaps in the overall picture. A references. bMortality data are from OPCS.22 particular need is for an ongoing survey of neurological cIncident figures are for first ever stroke of any aetiology. disease at the population level, similar to the Mayo Clinic dIncident figure excludes isolated seizures, prevalent figures include. 'Figures were calculated by assuming 20% of UK population >65 years old." record linkage system in the USA, yet more firmly popu- 'Incident rates are for Parkinsonism, prevalent rates for idiopathic Parkinson's lation based, and conducted on a prospective basis. A disease. gIncludes primary and secondary tumours. pilot study has started coordinated from the Neuroepidemiology Research Group of the National Hospitals for Neurology and Neurosurgery, and will col- where.29 Many of the incidence figures come from the lect data on all the neurological diseases seen in a popula- large survey in Carlisle.16 Thus some figures are relatively tion of 25 000 served by two GP group practices. This old, but the study still provides some of our most com- system will record all the incident cases seen and will prehensive data. form the basis for prospective studies on all common The findings vary between studies and inconsistencies neurological disorders. If this pilot study is successful arise. For instance the incidence of myotonic dystrophy is then the population base increases to 100 000 from six or unlikely to be greater than its prevalence. Such variation eight group practices. is due to different methodologies and case ascertainment Such an arrangement, however, will be of little benefit accuracy. The figures are in general agreement with those where cases have a low incidence (<1/100 000), or preva- from the USA,33 and any differences are again probably lence, as even large-scale community-based studies will due to differences in study methodologies rather than any ascertain only a small number of cases. Although the intercontinental variation. total burden of rarer disorders is small, the study of such Neuroepidemiological data should be used to inform disorders is still important. Accurate assessments of the health service research about manpower needs. The sec- incidence of some rare diseases are of public health ond table (table 2) is an extrapolation from table 1, and relevance in order to plot their eradication (that is,

shows the number of cases occurring in the population polio), or possible rise (that is, Jacob-Creutzfeldt http://jnnp.bmj.com/ covered by an average consultant neurologist in the UK. disease). The elucidation of the pathophysiology of rare Out of this total burden only a certain percentage is ever diseases will also expand our basic science knowledge seen by a neurologist. Figures from the National base, with potential to help patients affected with more Morbidity Survey give the referral rates for individual common disorders. Patients with rare disorders are more conditions, for example, only 3-5% of patients with difficult to treat because of unfamiliarity with the condi- migraine and 13-7% with epilepsy were referred.29 This tion, lack of basic prognostic data, and inability to carry indicates the huge potential workload that would fall on out controlled clinical trials. The rarity of the condition is the hospital consultant if GP referral patterns change, or of little comfort to either clinician or patient, and on September 29, 2021 by guest. Protected copyright. patient demand increases. In the USA, neuroepidemio- improvement in the care of these rarer disorders is logical evidence has been used to press for a large required. increase in the number of neurologists,34 but in the UK it To address the problem of rare disease case ascertain- ment, the British Neurological Surveillance Unit (BNSU) has been launched. The BNSU will be run by Table 2 Number of cases occurring in the population served by a the Association of British Neurologists (ABN), with the consultant neurologist in the UKa help of the Communicable Disease Surveillance Centre, Disease New cases Prevalent cases the National Hospitals for Neurology and Neurosurgery, and the Institute of Neurology. The aim is to establish a Migraine 9300 Stroke 750 2100 nationwide case ascertainment scheme of rare neurologi- Epilepsy 220 7500 cal diseases, by a system of prospective active surveil- Dementia 680 6000 Parkinsonism 45 600 lance. The system operates by sending every member of MS 19 410 the ABN a blue monthly reporting card which lists the Brain tumour neurolo- a) malignant 35 78 diseases currently being surveyed. The notifying b) benign 10 100 gist has simply to tick a box if he or she has or has not MND 7 17 a case the card. The card is Huntington's disease - 31 seen and then returns report Guillain-Barre syndrome 2 - postcard size and can be sent anonymously in the post as Myasthenia gravis 1 7 an index number on Myotonic dystrophy 52 26 each ABN member is identified by Muscular dystrophy 4 67 the card. Up to nine diseases will be dealt with by the Hereditary neuropathy 1 48 unit at any one time. Any ABN member can submit a aRatio of population to whole time specialist neurologist being 373 000 to 1.49 study which will be vetted by a scientific advisory 738 Editorial

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