1. Population Surveys Scopes, Prevalence, Incidence, Health Registries Ettore Beghi Institute for Pharmacological Research Mario Negri, Milano, Italy

2. SCOPE OF POPULATION SURVEYS Measure prevalenceMeasure prevalence Measure incidenceMeasure incidence Measure mortalityMeasure mortality Identify cases for case-control studiesIdentify cases for case-control studies Identify exposures for cohort studiesIdentify exposures for cohort studies Study familial aggregation/geneticsStudy familial aggregation/genetics Screen candidates for prevention/early treatmentScreen candidates for prevention/early treatment

3. ANATOMY OF A POPULATION SURVEY Definition of the study populationDefinition of the study population Definition of diseaseDefinition of disease Case ascertainment (prevalence, incidence and mortality)Case ascertainment (prevalence, incidence and mortality) Calculation of epidemiological indexesCalculation of epidemiological indexes Distribution by time, place & personDistribution by time, place & person

4. DIAGRAM OF THE IDENTIFICATION OF A DISEASE IN THE GENERAL POPULATION Kurtzke, 1978

5. HOW TO DEFINE A POPULATION Geographic boundaries - Residency - Istituzionalization - MigrationGeographic boundaries - Residency - Istituzionalization - Migration Temporal boundaries - Prevalence period (point, period, lifetime) - Incidence periodTemporal boundaries - Prevalence period (point, period, lifetime) - Incidence period

6. MEASURES OF DISEASE FREQUENCY INCIDENCE: Number of individuals in a population that become ill in a stated period of timeINCIDENCE: Number of individuals in a population that become ill in a stated period of time CUMULATIVE INCIDENCE: Proportion of a fixed population that becomes ill in a stated period of timeCUMULATIVE INCIDENCE: Proportion of a fixed population that becomes ill in a stated period of time PREVALENCE: Proportion of a population affected by a disease at a given point of timePREVALENCE: Proportion of a population affected by a disease at a given point of time MORTALITY: Number of individuals in a population died for a disease in a stated period of timeMORTALITY: Number of individuals in a population died for a disease in a stated period of time

7. PREVALENCE AND INCIDENCE Migratingin Migratingout Recovery Death Incidence Prevalence Prevalence = Incidence x average duration

8. SOURCES OF NEUROLOGICAL DISEASES IN EPIDEMIOLOGICAL STUDIES Hospital records Ambulatory records Electrophysiological (EMG) records General practitioners’ files Disability records Lay associations Tertiary centers Death certificates Diagnosis related groups (DRGs) Disease registries

9. MIGRAINE IS A HETEROGENEOUS AND ILL-DEFINED CLINICAL CONDITION Intensity, duration, frequency and characteristics of attacks tend to vary in the general population In each patient, symptoms may vary with time Many individuals may have different types of headache Many individuals do not consult their doctor for headache

10. MIGRAINE WITHOUT AURA (IHS, 1988) A. At least 5 attacks with criteria B-D B. Attacks lasting 4-72 hr (no or poor treatment) C. Headache with at least two features: - Unilateral - Pulsating - Moderate or severe D. At least one among: - Nausea and/or vomiting - Photophobia and/or phonophobia E. At least one of the following: - Other disturbances excluded by hx and examination - Other disturbances excluded by diagnostic tests - Other disturbances, but migraine attacks verified

11. CHANGE IN THE PREVALENCE OF MIGRAINE WHEN VARYING THE NUMBER OF IHS DIAGNOSTIC CRITERIA Merikangas et al, 1990

12. EPILEPSY AND EPILEPTIC SEIZURES EPILEPSY = Clinical condition characterized by repeated unprovoked seizuresEPILEPSY = Clinical condition characterized by repeated unprovoked seizures UNPROVOKED SEIZURE = Seizure occurring in the absence of known precipitants; it may occur at the presence of a non-recent CNS injuryUNPROVOKED SEIZURE = Seizure occurring in the absence of known precipitants; it may occur at the presence of a non-recent CNS injury ACUTE SYMPTOMATIC SEIZURE = Seizure occurring in close temporal relationship with an acute CNS insultACUTE SYMPTOMATIC SEIZURE = Seizure occurring in close temporal relationship with an acute CNS insult

13. EPILEPSY, ACTIVE & IN REMISSION Definitions ACTIVE EPILEPSY: epilepsy currently being treated or whose most recent seizure has occurred (usually) within the past two to five years (Thurman et al, Epilepsia, 2011)ACTIVE EPILEPSY: epilepsy currently being treated or whose most recent seizure has occurred (usually) within the past two to five years (Thurman et al, Epilepsia, 2011) EPILEPSY IN TERMINAL REMISSION: absence of seizures for 2 or 5 years without AEDsEPILEPSY IN TERMINAL REMISSION: absence of seizures for 2 or 5 years without AEDs

14. ACUTE SYMPTOMATIC SEIZURES Interval from precipitating factor CNS InsultTiming of occurrence Stroke, head trauma, cerebral anoxia1 week Cerebral infectionPositive clinical/laboratory findings Brain abscess, cerebral tuberculomaDuring treatment HIV infectionAcute infection/metabolic disturb Arterovenous malformationAcute hemorrhage Multiple sclerosisWithin 7 days of relapse Autoimmune diseasesSymptoms/signs of activation Neurodegenerative disordersNone identified Epidemiology Task Force, Epilepsia 2009

15. EPIDEMIOLOGICAL INDEXES OF EPILEPSY IN INDUSTRIALIZED COUNTRIES Incidence Epilepsy29-53 100,000/yr Epilepsy+single seizures73-86 Acute sympt seizures20-30 Status epilepticus10-40Incidence Epilepsy29-53 100,000/yr Epilepsy+single seizures73-86 Acute sympt seizures20-30 Status epilepticus10-40 Cumulative incidence1-3%Cumulative incidence1-3% Prevalence Active epilepsy5-8 x1,000 Lifetime15-50Prevalence Active epilepsy5-8 x1,000 Lifetime15-50 Mortality1-4 x100,000/yrMortality1-4 x100,000/yr SMR2-3SMR2-3

16. DeCarli, Lancet Neurol 2003: 2:15

17. PREVALENCE OF COGNITIVE IMPAIRMENT ACCORDING TO CLINICAL DEFINITION DeCarli, Lancet Neurol 2003: 2:15

18. PROBLEMS REGARDING THE DIAGNOSIS OF POLYNEUROPATHY The majority of the available data comes from clinical series The diagnosis of polyneuropathy is based on clinical and elettrophysiological features Polyneuropathy includes a wide spectrum of disorders ranging from symptomatic clinical conditions to subclinical variants Diagnosis should be confirmed by a neurologist

19. Polyneuropathy in the Elderly Principal Symptoms Muscle cramps Restless legs syndrome Burning feet Muscle pain Problems with handling objects Impairment of standing and gait ‘Glove’ and ‘stocking’ paresthesiae

20. POLYNEUROPATHY IN THE ELDERLY Validity of the screening questions Monticelli et al, Neuroepidemiology 1993

21. POLYNEUROPATHY IN THE ELDERLY Inter-rater agreement (kappa statistic) POLYNEUROPATHY IN THE ELDERLY Inter-rater agreement (kappa statistic) Monticelli et al, Neuroepidemiology 1993

22. EL ESCORIAL CRITERIA FOR THE DIAGNOSIS OF ALS Based on the topographical location of upper (UMN) and lower motor neuron (LMN) signs in 4 CNS regions, progression of these signs, and absence of other diseases Degree of diagnostic certainty (definite, probable, possible, suspected ALS) based on a different combination of UMN and LMN signs Brooks, 1994

23. EL ESCORIAL CRITERIA FOR THE DIAGNOSIS OF ALS DEFINITE ALS - LMN and UMN signs in 3 spinal regions - LMN and UMN signs in the bulbar region and in 2 spinal regions PROBABLE ALS - LMN and UMN signs in 2 spinal regions POSSIBLE ALS - LMN and UMN signs in 1 region - UMN signs in 2 or more regions - LMN signs rostral to UMN signs SUSPECTED ALS - LMN signs in 2 or more regions Source: J Neurol Sci 1994; 124 (suppl): 96-107

24. DISEASE REGISTRIES Lists of diseases (or disease groups) in well-defined populations Collection of data on disease burden and identification of patients’ cohorts to be followed for specific purposes For rare diseases, registries represent a (re)source for the collection of sizable numbers of cases for focused studies

25. EXPLANATIONS FOR HIGHER AND MORE HOMOGENEOUS RATES IN EUROPEAN REGISTRIES Prospective inception of cases Multiple sources Fairly complete case ascertainment Continuous surveillance Use of the same diagnostic criteria

26. OBJECTIVES OF A POPULATION- BASED REGISTRY Incidence and prevalence of the target condition Temporal and geographic trends of the disease Full clinical spectrum of the disease Clinical and paraclinical markers of the disease Practical management and socio-economic implications of the disease Data banks for clinical/biological material

27. PREREQUISITES FOR THE START OF A REGISTRY Definition of the population at risk Selection of the best source(s) of cases Choice of the correct diagnostic criteria

28. SOURCES OF CASES Hospital records Outpatient records Neurophysiology units’ archives General practitioners’ files Disability records Lay associations’ files ALS centers Death certificates Administrative files (hospital discharge diagnoses)

29. THE EURALS CONSORTIUM Ireland5.0M Ireland5.0M Scotland5.0M Scotland5.0M Lancashire & Cumbria1.8M Lancashire & Cumbria1.8M London2.8M London2.8M Italy (all)8.0M Italy (all)8.0M Belgrade2.0M Belgrade2.0M Madrid1.0M Madrid1.0M Limousin0.7M Limousin0.7M Germany? Germany? Russia? Russia? Israel? Israel? Total >25M Total >25M

32. PRACTICAL RECOMMENDATIONS TO START A POPULATION-BASED REGISTRY Select a well-defined geographic area Identify one or more accessible sources Use valid and reliable diagnostic criteria Set a network of specialists able to trace all cases residing in the area Select a number of core variables to verify the correctness of the diagnosis and define the general profile of the disease Start specific studies only after preparing ad-hoc protocols and case collection forms