“Of MS and Men”Morbidity & Mortality

Outcomes

Mitchell T. Wallin, MD, MPHMitchell T. Wallin, MD, MPHMS Clinic Director MS Clinic Director

Department of Veterans Affairs Medical CenterDepartment of Veterans Affairs Medical CenterWashington, DCWashington, DC

Assistant Professor of NeurologyAssistant Professor of NeurologyGeorgetown University Medical SchoolGeorgetown University Medical School

“Of MS and Men”Morbidity & Mortality Outcomes

I. DefinitionsI. Definitions

II. Morbidity DataII. Morbidity Data

III. Mortality & Survival DataIII. Mortality & Survival Data

IV. ConclusionsIV. Conclusions

Multiple Sclerosis Subtypes(Coyle P, 2002; adapted from Lublin F, et al Neurology 1996)

Secondary Progressive MSvs.

Primary Progressive MS  RR-SP MS PP MS

Age at onset (mean)

30 yrs 40 yrs

Sex ratio (M:F) 2:1 1:1

Race disability progression in AA

disability progression in AA

Onset symptoms

Sensory, visual Paraparesis

“Of MS and Men”Morbidity & Mortality Outcomes

I. DefinitionsI. Definitions

II. Morbidity DataII. Morbidity Data

III. Mortality & Survival DataIII. Mortality & Survival Data

IV. ConclusionsIV. Conclusions

22

Prevalence of Subtypes of MS(N = 3019)

Relapsing-remitting(RR)55%

Secondary-progressive(SP)30%

Primary-progressive

(PP)10%

Progressive-relapsing

(PR)5%

Jacobs et al. Mult Scler. 1999;5:369-376.

Veteran Integrated Service Network (VISN)-5 MS Subtypes

Secondary Progressive(41%)

Relapsing Remitting(47%)

Primary Progressive(6%)

Unknown(6%)

N=218

Veteran Integrated Service Network (VISN)-5 MS Demographic Data

0

20

4060

80

100

120

140160

180

200

Black White Unknown Total

Males

Females

MS Morbidity in the US

Nationwide PrevalenceNationwide Prevalence 58/100,000 population (Baum, 1981)58/100,000 population (Baum, 1981) 102-139/100,000 population (Anderson, 1992)102-139/100,000 population (Anderson, 1992) 85/100,000 population (Noonan, 2002)85/100,000 population (Noonan, 2002)

Olmsted County, MN (Mayr 2003)Olmsted County, MN (Mayr 2003) Raw Incidence: 7.5/100,000 person-yrsRaw Incidence: 7.5/100,000 person-yrs Raw Prevalence: 177/100,000 person-yrs Raw Prevalence: 177/100,000 person-yrs

Estimated prevalence of MS per 100,000 by report in the US NHIS Survey, 1982-1996 (Noonan, 2002)

Estimated number of persons with MS in the US Noonan, 2002

Persons per 100,000 with MSNoonan, 2002

Vietnam and later military service MS cohort Study Population Flow Chart (Wallin, et al 2004)

O ther Fem a les1 6 /9

B lack F em ales1 23 /85

W hite Fem ales6 04 /40 2

O the r M ales3 5 /2 31

B lack M ales4 15 /12 25

W hite M ales3 75 8 /7 42 6

MS CasesAnalyzed

4951

Controls Analyzed

9378

Eligible MS

patients 55345

Eligible Controls10683

394 1305

Adjusted case-control ratios for MS by race and sex at EAD

  WWII-KC Cohort Vietnam and later Cohort

Race-sex category

# of MS cases

Case-control ratio (95% CI)

# of MS cases

Case-control ratio (95% CI)

White female 182 1.86 (1.44 – 2.38)

604 2.85 (2.49-3.25)

Black female 4 1.33 (0.23 – 9.10)

123 2.74 (2.00-3.52)

Other race-female

2 ---- 16 3.37 (1.52-7.56)

White male 4,923 1.04 (0.98 – 1.10)

3,758 0.96 (0.90-1.00)

Black male 177 0.45 (0.38 – 0.54)

415 0.64 (0.57-0.43)

Other race-male

17 0.23 (0.14 – 0.39)

35 0.29 (0.20-0.41)

TOTAL 5,305 1.00 4,951 1.00

Vietnam & Later Service

103

46

55

74

59

56

73

62

62

81

67

83

67

6381

5454

75

83

86

152

138

111

144

160

143 116

141

169

147

216

Case Control Ratios x 100

< 60 61 to 90 91 to 120 121 to 149

>150

81

116

141113

230

126

115

101

80 79

108

110

180

92

107

WWII-KC

61

172

44

61

59

132

52

56

52

74

61

95

6461

4148

50

72

92

198

145

200

131

131

161 211

133

183

138

203

Case Control Ratios x 100

< 60 61 to 90 91 to 120 121 to 149

>150

66

131

117118

118

105

101

116

86109

118

121

127

67

78

129

167

85

94

64

Time from MS onset to EDSS 4.0Confavreux, 2000

Risk of Bone Loss in MenWeinstock-Guttman, 2004

40 male MS patients, mean: EDSS 5.8; Age 51yrs40 male MS patients, mean: EDSS 5.8; Age 51yrs 32 (80%) with reduced bone loss of lumbar spine or femur32 (80%) with reduced bone loss of lumbar spine or femur

17 (43%) had osteopenia17 (43%) had osteopenia 15 (38%) had osteoporosis15 (38%) had osteoporosis

8/38 (21%) with fractures of ribs, vertebrae or extremities8/38 (21%) with fractures of ribs, vertebrae or extremities Risk factors for low bone mineral densityRisk factors for low bone mineral density

Femoral neck: EDSS and BMI Femoral neck: EDSS and BMI Lumbar spine: EDSS Lumbar spine: EDSS

“Of MS and Men”Morbidity & Mortality Outcomes

I. DefinitionsI. Definitions

II. Morbidity DataII. Morbidity Data

III. Mortality & Survival DataIII. Mortality & Survival Data

IV. ConclusionsIV. Conclusions

22

MS Survival

10 years shorter than age-matched general 10 years shorter than age-matched general population (Brpopulation (Brøønnum-Hansen, 2004)nnum-Hansen, 2004)

US Veteran WWII Cohort (Wallin, 2000)US Veteran WWII Cohort (Wallin, 2000) Men: median survival Men: median survival

Black males: 30 yrsBlack males: 30 yrs White males: 34 yrsWhite males: 34 yrs

White women: median survival 43 yrsWhite women: median survival 43 yrs

Secular trend for improved survival over the past Secular trend for improved survival over the past 50 years50 years

Survival in VA MS Cases: Sex/Race

Survival in VA MS Cases: Age at Onset

Survival in VA MS Cases: SES

Risk Factors for MS SurvivalStudy Year of

StudyRegion Total

casesAge at onset

Sex Clincourse

Leibowitz 1967 Israel 266 +/- +  

Visscher 1980 USA 941 + NS  

Phadke 1980 UK 1055 + NS +

Riise 1986 Norway 598 + NS +

Poser 1981 Germany 224/1429 + +  

Wynn 1984 USA 206 + +  

Brønnum-Hansen 1986 Denmark 6727 + +  

Midgard 1991 Norway 251 + NS +

Wallin 1996 USA 2489 + +  

MS Cause-specific mortality

MS as underlying or contributing cause of MS as underlying or contributing cause of death in 47%-83% of cases (Sadovnick, death in 47%-83% of cases (Sadovnick, 1991; Larsen, 1985)1991; Larsen, 1985)

Other causes (BrOther causes (Brøønnum-Hansen, 2004)nnum-Hansen, 2004) Cardiovascular disease: SMR 1.32 (1.22-1.43)Cardiovascular disease: SMR 1.32 (1.22-1.43) Cancer: SMR 0.85 (0.77-0.94)Cancer: SMR 0.85 (0.77-0.94) Suicide/Accidents: 1.42 (1.22-1.64)Suicide/Accidents: 1.42 (1.22-1.64)

Conclusions

Despite a lower prevalence of MS, men are more Despite a lower prevalence of MS, men are more likely to present with the PP subtype and generally likely to present with the PP subtype and generally have increased morbidity and mortality compared have increased morbidity and mortality compared to womento women

Implications for clinical studies Implications for clinical studies Differential pathology by sex Differential pathology by sex Endocrine effects Endocrine effects

More large longitudinal studies needed to evaluate More large longitudinal studies needed to evaluate sex differences in MSsex differences in MS

9

National WWII Memorial