Population Population SurveysSurveys

Scopes, Prevalence, Scopes, Prevalence, Incidence, Health Incidence, Health

RegistriesRegistriesEttore BeghiEttore Beghi

Institute for Institute for Pharmacological Research Pharmacological Research Mario Negri, Milano, ItalyMario Negri, Milano, Italy

SCOPE OF POPULATION SCOPE OF POPULATION SURVEYSSURVEYS

• 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 Screen candidates for prevention/early

treatmenttreatment

ANATOMY OF A ANATOMY OF A POPULATION SURVEYPOPULATION SURVEY

• Definition of the study populationDefinition of the study population• Definition of diseaseDefinition of disease• Case ascertainment (prevalence, Case ascertainment (prevalence,

incidence and mortality)incidence and mortality)• Calculation of epidemiological indexesCalculation of epidemiological indexes• Distribution by time, place & person Distribution by time, place & person

DIAGRAM OF THE DIAGRAM OF THE IDENTIFICATION OF A DISEASE IDENTIFICATION OF A DISEASE IN THE GENERAL POPULATIONIN THE GENERAL POPULATION

Kurtzke, 1978Kurtzke, 1978

HOW TO DEFINE A HOW TO DEFINE A POPULATIONPOPULATION

• Geographic boundariesGeographic boundaries- Residency- Residency

- Istituzionalization - Istituzionalization - Migration- Migration

• Temporal boundariesTemporal boundaries- Prevalence period - Prevalence period

(point, (point, period, lifetime)period, lifetime)- Incidence period- Incidence period

MEASURES OF DISEASE MEASURES OF DISEASE FREQUENCYFREQUENCY

• INCIDENCEINCIDENCE: Number of individuals in a : Number of individuals in a population that become ill in a stated population that become ill in a stated period of timeperiod of time

• CUMULATIVE INCIDENCECUMULATIVE INCIDENCE: Proportion of : Proportion of a fixed population that becomes ill in a a fixed population that becomes ill in a stated period of timestated period of time

• PREVALENCEPREVALENCE: Proportion of a population : Proportion of a population affected by a disease at a given point of affected by a disease at a given point of timetime

• MORTALITYMORTALITY: Number of individuals in a : Number of individuals in a population died for a disease in a stated population died for a disease in a stated period of timeperiod of time

PREVALENCE AND PREVALENCE AND INCIDENCEINCIDENCE

MigratingMigratinginin

MigratingMigratingoutout

RecoveryRecoveryDeathDeath

IncidenceIncidence

PrevalenPrevalencece

Prevalence = Incidence Prevalence = Incidence x average durationx average duration

SOURCES OF NEUROLOGICAL SOURCES OF NEUROLOGICAL DISEASES IN DISEASES IN

EPIDEMIOLOGICAL STUDIES 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

MIGRAINE IS A HETEROGENEOUS MIGRAINE IS A HETEROGENEOUS AND ILL-DEFINED CLINICAL AND ILL-DEFINED CLINICAL

CONDITIONCONDITION• 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

MIGRAINE WITHOUT MIGRAINE WITHOUT AURA (IHS, 1988)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

CHANGE IN THE PREVALENCE OF CHANGE IN THE PREVALENCE OF MIGRAINE WHEN VARYING THE MIGRAINE WHEN VARYING THE

NUMBER OF IHS DIAGNOSTIC CRITERIANUMBER OF IHS DIAGNOSTIC CRITERIA

0

5

10

15

20

25

Prevalence (%)

Moderate 2/4C,1/2DSevere 2/4C,1/2DModerate 3/4C,1/2DSevere 3/4C,1/2DModerate 2/4C,2/2DSevere 2/4C,2/2DModerate 3/4C,2/2DSevere 3/4C,2/2D

Merikangas et al, Merikangas et al, 19901990

EPILEPSY AND EPILEPSY AND EPILEPTIC EPILEPTIC SEIZURESSEIZURES

• EPILEPSYEPILEPSY = = Clinical condition characterized Clinical condition characterized by repeated unprovoked seizuresby repeated unprovoked seizures

• UNPROVOKED SEIZUREUNPROVOKED SEIZURE = = Seizure occurring Seizure occurring in the absence of known precipitants; it may in the absence of known precipitants; it may occur at the presence of a non-recent CNS occur at the presence of a non-recent CNS injuryinjury

• ACUTE SYMPTOMATIC SEIZURE ACUTE SYMPTOMATIC SEIZURE = Seizure = Seizure occurring in close temporal relationship with occurring in close temporal relationship with an acute CNS insultan acute CNS insult

EPILEPSY, ACTIVE & IN EPILEPSY, ACTIVE & IN REMISSIONREMISSIONDefinitionsDefinitions

• ACTIVE EPILEPSYACTIVE EPILEPSY:: epilepsy epilepsy currently being treated or whose currently being treated or whose most recent seizure has occurred most recent seizure has occurred (usually) within the past two to five (usually) within the past two to five years (years (Thurman et al, Epilepsia, Thurman et al, Epilepsia, 20112011) )

• EPILEPSY IN TERMINAL EPILEPSY IN TERMINAL REMISSIONREMISSION: absence of seizures for : absence of seizures for 2 or 5 years without AEDs 2 or 5 years without AEDs

ACUTE SYMPTOMATIC SEIZURESInterval from precipitating factor

CNS Insult Timing of occurrence

Stroke, head trauma, cerebral anoxia 1 week

Cerebral infection Positive clinical/laboratory findings

Brain abscess, cerebral tuberculoma During treatment

HIV infection Acute infection/metabolic disturb

Arterovenous malformation Acute hemorrhage

Multiple sclerosis Within 7 days of relapse

Autoimmune diseases Symptoms/signs of activation

Neurodegenerative disorders None identified

Epidemiology Task Force, Epilepsia Epidemiology Task Force, Epilepsia 20092009

EPIDEMIOLOGICAL INDEXES EPIDEMIOLOGICAL INDEXES OF EPILEPSY IN OF EPILEPSY IN

INDUSTRIALIZED COUNTRIESINDUSTRIALIZED COUNTRIES• IncidenceIncidence

EpilepsyEpilepsy 29-53 100,000/yr 29-53 100,000/yr Epilepsy+single seizuresEpilepsy+single seizures 73-8673-86

Acute sympt seizuresAcute sympt seizures 20-3020-30Status epilepticusStatus epilepticus 10-4010-40

• Cumulative incidenceCumulative incidence 1-3%1-3%• PrevalencePrevalence

Active epilepsyActive epilepsy 5-8 x1,0005-8 x1,000LifetimeLifetime 15-5015-50

• MortalityMortality 1-4 x100,000/yr 1-4 x100,000/yr • SMRSMR 2-32-3

DeCarli, Lancet DeCarli, Lancet NeurolNeurol2003: 2:152003: 2:15

PREVALENCE OF COGNITIVE IMPAIRMENT ACCORDING TO

CLINICAL DEFINITION

DeCarli, Lancet NeurolDeCarli, Lancet Neurol2003: 2:152003: 2:15

PROBLEMS REGARDING THE PROBLEMS REGARDING THE DIAGNOSIS OF DIAGNOSIS OF

POLYNEUROPATHYPOLYNEUROPATHY

• 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

Polyneuropathy in the Polyneuropathy in the ElderlyElderly

Principal SymptomsPrincipal Symptoms

• Muscle cramps• Restless legs syndrome• Burning feet• Muscle pain• Problems with handling objects• Impairment of standing and gait• ‘Glove’ and ‘stocking’ paresthesiae

POLYNEUROPATHY IN THE POLYNEUROPATHY IN THE ELDERLYELDERLY

Validity of the screening Validity of the screening questionsquestions

Monticelli et al, Neuroepidemiology Monticelli et al, Neuroepidemiology 19931993

POLYNEUROPATHY IN THE POLYNEUROPATHY IN THE ELDERLYELDERLY

Inter-rater agreement (kappa Inter-rater agreement (kappa statistic)statistic)

Monticelli et al, Neuroepidemiology Monticelli et al, Neuroepidemiology 19931993

EL ESCORIAL CRITERIA EL ESCORIAL CRITERIA FOR THE DIAGNOSIS OF FOR THE DIAGNOSIS OF

ALSALS• 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, 1994Brooks, 1994

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 NeurolSource: J NeurolSci 1994; 124 Sci 1994; 124 (suppl): 96-107(suppl): 96-107

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

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

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

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

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)

THE EURALS CONSORTIUM IrelandIreland

5.0M5.0M ScotlandScotland

5.0M5.0M Lancashire & CumbriaLancashire & Cumbria

1.8M1.8M LondonLondon

2.8M2.8M Italy (all)Italy (all)

8.0M8.0M BelgradeBelgrade

2.0M2.0M MadridMadrid

1.0M1.0M LimousinLimousin

0.7M0.7M GermanyGermany ?? RussiaRussia ?? IsraelIsrael ??

Total Total >25M>25M

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