Epidemiologic investigation of ALS and Multiple Sclerosis in Jefferson County, Missouri

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Epidemiologic investigation of ALS and Multiple
Sclerosis in Jefferson County, Missouri

• George Turabelidze, MD, PhD
• Missouri Dept of Health Senior Services

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Background

• Active lead smelter has been in existence in
  Herculaneum, Jefferson County since 1892 it is
  the largest lead smelter in USA
• Residents concerned about the health impact of
  hazardous outputs of the smelter
• Over years residents reported number of people
  with Multiple Sclerosis (MS) and Amyotrophic
  Lateral Sclerosis (ALS) in the area

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Multiple Sclerosis (MS)

• Chronic progressive demyelinating disease of CNS
• Most common disabling neurological disease in
  young people typical age of onset in 20-30s
• No etiologic agent for MS has been identified
  environmental influences in a genetically
  susceptible individuals has been hypothesized
• Prevalence 20 to 236 per 100,000 population
  about 300,000 cases in the US
• Incidence 0.8 to 12.0 per 100,000 population
• F/M ratio is 21 and higher
• More common in Caucasian populations living in
  northern latitudes

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MS Prevalence in World
Source http//www.mult-sclerosis.org/
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Symptoms of MS

• Present in various forms
  some have mostly cognitive changes, while
  others present with prominent ataxia,
  hemiparesis, depression, or visual symptoms
• Patients with MS may present with facial palsies
  or trigeminal neuralgia
• Painful limb syndromes, vertigo, behavioral
  changes, depression, fatigue
• Urinary retention and incontinence
• Sexual dysfunction
• Disease progression continuous or intermittent

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Treatment of MS

• Prevention of relapses or disease progression by
  using immunomodulatory drugs, such as interferon
  beta-1 currently a first-line therapy for MS
• High-dose steroids for the acute attack
• Intravenous immunoglobulin, hormonal treatment,
  bone marrow transplantation, and plasmapheresis
  have been tried
• Treatment of pains, depression, fatigue,
  spasticity, sexual dysfunction
• If untreated, more than 30 of patients with MS
  will develop significant physical disability
  within 20-25 years from onset.

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Amyotrophic Lateral Sclerosis (ALS)

• Also known as Lou Gehrigs disease
• Amyotrophic without muscle nourishment
• Lateral to the side, referring to location of
  damage in the spinal cord
• Sclerosis hardened
• Cause unknown (genetic, environmental,
  infectious, autoimmune)
• Afflicts adults in 40s to 70s
• Nearly 10 of ALS cases are familial transmitted
  in an autosomal dominant fashion.
• Rare disease
• Prevalence 4 to 6 per 100,000 population
• Incidence 0.7 to 2.5 per 100,000 population
• M/F ratio is 1.51 and higher
• Whites/non-whites ratio is 1.61

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ALS primarily involves anterior horn cells in the
spinal cord and cranial motor nerves.
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Symptoms of ALS

• Muscle weakness hands, arms, legs muscles of
  speech, swallowing or breathing
• Muscle twitching, cramping
• Especially muscles in hands, feet
• Impairment of use of arms, legs
• Thick speech, difficulty in projecting voice
• Difficulty in breathing, swallowing
• ALS rarely affects cognitive functions
• Death typically occurs 3-5 yrs after diagnosis
• 10 survive gt10 yrs, e.g., Stephen Hawking, 40
  yrs

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Treatment of ALS

• Medical care is primarily supportive
• Medications may be used to relieve severe
  spasticity
• Riluzole is an FDA-approved medication for
  prolonging tracheostomy-free survival
• No treatment significantly prolongs survival in
  ALS.

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Herculaneum Study Objectives

• To identify all ALS and MS cases in Jefferson
  County through an aggressive case finding and
  ascertainment process
• To determine whether there was evidence of
  increased prevalence of ALS or MS in the County
• To identify whether there was any spatial
  clustering of ALS or MS anywhere in the Jefferson
  County

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Participating Agencies

• Study was conducted by Missouri Department of
  Health Senior Services
• Funding from U.S. Agency for Toxic Substances and
  Disease Registry (ATSDR), Centers for Disease
  Control and Prevention (CDC)
• Assistance provided by academic institutions,
  Jefferson County Health Department

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Study population

• Residents of Jefferson County, Missouri during
  the period of 1998 through 2002
• The county had a mixed suburban and rural
  population of 203,791 (Census 2002 est.)
• - 49.7 were males, 50.3 were females
• - median age of the residents was 34.9 years
• - median household income was 46,338
• - 97.5 of the residents were white non-Hispanic.

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Eligibility Criteria

• Residence in Jefferson County
• Medical visits between January 1, 1998 and
  December 31, 2002
• Confirmed diagnosis of possible, probable, or
  definite ALS or MS by neurologist

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Data sources

• Missouri DHSS
  - hospital inpatient data
  - emergency room
  visits -
  death certificates.
• Outpatient visits to neurologists and primary
  health care providers
• Self-referrals
• Nursing home admissions
• Rehabilitation facilities

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Data sources

• Local newspaper advertisements
• Meetings with community representatives
• Direct mailings to members of the St. Louis
  Regional Chapter of the ALS Association and MS
  Society
• Association newsletters

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Inclusion and exclusion criteria

• ALS revised World Federation of Neurology
  criteria for ALS - the El Escorial criteria
• MS Poser criteria for MS diagnosis
• All cases were assigned to one of five
  categories
  1) definite
  2) probable
  3 )
  possible,
  4) undocumented
  probable/possible 5) not
  MS/ALS.

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Prevalence Estimation

• ALS crude and age-adjusted point prevalence
  estimates of ALS were calculated from those
  patients known to be alive and residing in
  Jefferson County on December 31, 2002.
• MS the crude and age-adjusted period prevalence
  of MS for Jefferson County during January 1, 1998
  through December 31, 2002.
• A Poisson distribution was assumed in calculating
  the 95 confidence intervals (CIs) for the
  prevalence estimates

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Assessment of completeness of case ascertainment

• Capture-recapture method was used for three
  different data sources hospital records,
  outpatient records, and death certificates for
  ALS, and hospital records, outpatient records,
  and self-referral for MS

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Assessment of completeness of case ascertainment

• Three different methods were used to calculate
  case ascertainment completeness and to estimate
  the number of MS and ALS cases that were not
  reported by any of three data sources the
  Petersen and Chapman estimates, the sample
  coverage approach, and log-linear modeling
• Ascertainment-corrected number of MS and ALS
  cases was estimated by adding the estimated
  number of cases missed to the observed number of
  cases.

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Geocoding

• The street address of each ALS and MS case was
  assigned an X and Y coordinate through a
  geocoding process, performed with the Centrus
  Geocoder for ESRI ArcGIS
• The cases were assigned to, and summarized by,
  U.S. Census block groups a block group consists
  of a small group of city blocks, or larger rural
  regions, that include approximately 1,500
  residents on average.

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Spatial Analysis

• Spatial clustering of ALS cases was evaluated
  using a spatial scan statistic performed with the
  software SaTScan
• The analyses were purely spatial with a maximum
  cluster size of 20 of the population
• SatScan method was run with and without
  consideration of the location of the lead smelter
• SaTScan method was performed using census block
  groups.

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Results MS

• Out of 321 potential MS cases, 208 (definite,
  probable, and possible) were included in the
  final dataset
• 168 women and 40 men (F/M ratio 4.21)
• Mean age was 47.3 years (range 25-75)
• Age group with highest prevalence 50-59 years
• Five patients died during the study period
• Estimated completeness of case ascertainment was
  95

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Results MS

• The crude five-year period prevalence of MS was
  105 (95 CI, 91-121) per 100,000
• Age-adjusted to the 2000 US population as
  standard, the period prevalence was 107 (95 CI,
  95 to 119) per 100,000
• No significant clusters were identified by any of
  the four SaTScan tests

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Conclusions MS

• Prevalence of MS in Jefferson County, Missouri,
  appears to be comparable with that seen in other
  areas of similar latitude in the United States
  and other countries
• No spatial clustering of MS was detected in the
  county or around the lead smelter

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Study Limitations MS

• Study was based on prevalent cases rather than
  incident cases clusters based on prevalent cases
  may be influenced by disease survival
• Emigration of persons who have potentially been
  exposed to risk factors for MS could have
  affected our ability to detect clusters
• Study period of 5 years may not be sufficient for
  MS because this disease may have a long induction
  period, resulting in a slow accumulation of cases
  in the study area

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Results ALS

• Out of 58 potential ALS cases, 36 were included
  in the final dataset
• 25 were classified as definite, 5 as
  probable, and 6 as possible cases
• M/F ratio was 2.3 1
• Mean age was 62.1 years (range, 36 to 84)
• 23 patients died during the study period
• Mean survival time from initial diagnosis to
  death was 28 months (range, 1 to 72 months)

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Results ALS

• Crude point prevalence of ALS was 3.9 per 100,000
  population (95 CI, 1.7 to 7.7)
• Age-adjusted prevalence of ALS (using the 2002
  U.S. population as the standard) was 4.2 per
  100,000 (95 CI, 1.9 to 6.6)
• The average annual ALS death rate was to be 2.3
  per 100,000 persons

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Prevalence of ALS in Harris County, Texas in
1980s was (3.0 per 100,000). However, the
estimated case capture rate in the Harris County
study was 69.
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Results ALS

• Case ascertainment of definite and probable
  ALS cases was 100
• One significant cluster (p0.0437) was identified
  around the lead smelter, which included 3
  unrelated ALS cases in 3 block groups expected
  number of ALS cases was 0.47, yielding a
  standardized prevalence ratio of 6.4

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Conclusions ALS

• In Jefferson County, Missouri, the prevalence of
  ALS appears to be comparable to that seen in
  Western European countries in recent years
• A small cluster of ALS cases was found in the
  proximity of a lead smelter

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Study Limitations ALS

• Study was not designed to study risk factors for
  ALS therefore, we cannot evaluate what specific
  factors may be associated with ALS in the area
• Clusters based on prevalent cases may be more
  related to disease survival rather than to the
  development of the disease
• ALS cluster detected in our study was based on
  the small sample of ALS cases emigration of
  persons away from the active lead smelter area
  could have affected the size of the cluster.

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Recommendations

• Establish National ALS Registry such a registry
  could be used to estimate the burden of ALS, and
  to determine temporal trends and geographical
  clustering of ALS
• Outpatient, inpatient and death certificate data
  would provide the basis for a comprehensive ALS
  registry
• Well-designed etiologic studies are needed to
  assess whether living in close proximity to a
  lead smelter may be associated with the
  development of ALS

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Acknowledgement

• The following individuals have made significant
  scientific contributions
• From Missouri Department of Health and Senior
  Services
• Bao-Ping Zhu, MD, MS
• Joseph Weidinger, BS
• Eduardo Simoes, MD (currently no longer with
  DHSS)
• Joseph Malone, MD (currently no longer with DHSS)
• From U.S. Agency for Toxic Substances and Disease
  Registry
• Dhelia Williamson, PhD
• From Washington University School of Medicine
• Mario Schootman, PhD
• From University of Vermont College of Medicine
• Steven Horowitz, MD