Natural History of ALS among Different Populations in PACTALS Dongsheng Fan Peking University Third Hospital Beijing, China
REVIEW Amyotrophic lateral sclerosis and motor neuron syndromes in Asia N Shahrizaila, 1,2 G Sobue, 3 S Kuwabara, 4 S H Kim, 5 Carol Birks, 6 D S Fan, 7 J S Bae, 8 C J Hu, 9 M Gourie-Devi, 10 Y Noto, 2,11 K Shibuya, 2,4 K J Goh, 1 R Kaji, 12 CP Tsai, 13 L Cui, 14 P Talman, 15 R D Henderson, 16 S Vucic, 17 M C Kiernan 2
Background ALS research largely originate from North America and Europe However, Pan-Asia represents >50% of the world population Pan-Asia represents a diverse population in terms of ethnic, social and cultural backgrounds
Comparisons between Pan-Asia and other regions Mean/median age at onset (years) India 46.2 50 China 49.8 58.7 Japan 58.2 65.4 Australia 58.2 66 North America 54.1 62.8 Europe 57 66.84 0 10 20 30 40 50 60 70 Youngest Eldest
Comparisons between Pan-Asia and other regions M:F ratio Australia 1.2 1.5 Japan 1.37 2.9 China 1.6 1.9 India 3 North America 0.98 2.3 Europe 0.71 2.1 0 0.5 1 1.5 2 2.5 3 Lowest Highest
Comparisons between Pan-Asia and other regions Percentage of bulbar-onset ALS India 6.5 27.1 China 14 34.5 Japan 25.3 30.3 Australia 36.8 North America 16.5 33 Europe 19 39.3 0 5 10 15 20 25 30 35 40 Lowest Highest
Comparisons between Pan-Asia and other regions Mean/median survival (months) Auatralia* 24 73 Japan 48 China 66.6 71 India 114.8 North America 25.2 41.4 Europe 27.5 57.48 0 20 40 60 80 100 120 Shortest Longest *:The difference of survival in Australia was because of different phenotypes
Comparisons between developing and developed Pan-Asia areas Age at onset (years) Developing Asia- Pacific areas 46.2 52.6 Developed Asia- Pacific areas 55.5 66 North America 54.1 62.8 Europe 57 66.84 0 10 20 30 40 50 60 70 Lowest Highest *Developed Asia-Pacific areas include Japan, China Hong Kong, China Taiwan and Australia; Developing Asia-Pacific areas include Mainland China and India
Canada Incidence: 0.91-2.4 M:F 0.98:1 Age at onset: 62.8 Survival: 25.2 months Europe West Incidence: 1.8-2.77 Prevalence: 10.32 M:F 1.1-1.46:1 Age at onset: 63.5-67.8 Survival: 34.8 months Europe North Incidence: 1.06-2.98 Prevalence: 3.1-8.2 M:F 0.71-2.1:1 Age at onset: 57-66.3 Survival: 28.7-33.6 months Mainland China Incidence: NA M:F 1.6-1.83:1 Age at onset: 49.8-52.6 Survival: 71 months USA Incidence: 1.4-4.2 Prevalence: 3.84-5.0 M:F 1.24-2.3:1 Age at onset: 49.7-60.6 Survival: 25-41.4 months Japan Incidence: 0.69-2.50 Prevalence: 2.25-9.9 M:F 1.37-2.9:1 Age at onset: 58.2-65.4 Survival: 48 months Europe South Incidence: 1.4-2.64 Prevalence: 6.0-10.8 M:F 0.88-1.65:1 Age at onset: 57-66.84 Survival: 27.5-57.48 months Taiwan, China Incidence: 0.51 Prevalence: 1.97 M:F 1.65:1 Age at onset: 56.3-56.6 Survival: 66.6 months Hong Kong, China Incidence: 0.3-0.6 Prevalence: 0.95-3 M:F 1.72-1.95:1 Age at onset: 55-58.76 Survival: NA Brazil Incidence: 0.4 Prevalence: 0.9 M:F 1.4-1.7:1 Age at onset: 52-57.2 Survival: 42-49 months Argentina Incidence: 6 (based on OPD attendance) M:F 1.59:1 Age at diagnosis: 55 Survival: NA Australia Incidence: NA M:F 1.2-1.5:1 Age at onset: 58.2-66 Survival: 24-73 months (different phenotypes) Uruguay Incidence: 1.37-1.42 Prevalence: 1.9 M:F 2:1 Age at onset: 58.7 Survival: NA Africa Incidence: NA M:F 1.4-4:1 Age at onset: 50 Survival: 35.2 months India Incidence: 112.6 (based on OPD attendance) M:F 3:1 Age at onset: 46.2 Survival: 114.8 months
Comparisons between developing and developed Pan-Asia areas M:F ratio Developing Asia- Pacific areas 1.6 3 Developed Asia- Pacific areas 1.2 2.9 North America 0.98 2.3 Europe 0.71 2.1 0 0.5 1 1.5 2 2.5 3 Lowest Highest *Developed Asia-Pacific areas include Japan, China Hong Kong, China Taiwan and Australia; Developing Asia-Pacific areas include Mainland China and India
Comparisons between developing and developed Pan-Asia areas Percentage of bulbar-onset ALS Developing Asia- Pacific areas 14 27.1 Developed Asia- Pacific areas 25.3 36.8 North America 16.5 33 Europe 19 39.3 0 5 10 15 20 25 30 35 40 Lowest Highest *Developed Asia-Pacific areas include Japan, China Hong Kong, China Taiwan and Australia; Developing Asia-Pacific areas include Mainland China and India
Comparisons between developing and developed Pan-Asia areas Mean/median Diagnostic delay (months) Developing Asia- Pacific areas 13.8 17.7 Developed Asia- Pacific areas 10 12 North America 6.97 17 Europe 8 15.2 0 2 4 6 8 10 12 14 16 18 20 Shortest Longest *Developed Asia-Pacific areas include Japan, China Hong Kong, China Taiwan and Australia; Developing Asia-Pacific areas include Mainland China and India
Comparisons between developing and developed Pan-Asia areas Mean/median survival (months) Developing Asia- Pacific areas 66.6 114.8 Developed Asia- Pacific areas 24 73 North America 25.2 41.4 Europe 27.5 57.48 0 20 40 60 80 100 120 Shortest Longest *Developed Asia-Pacific areas include Japan, China Hong Kong, China Taiwan and Australia; Developing Asia-Pacific areas include Mainland China and India
Canada Incidence: 0.91-2.4 M:F 0.98:1 Age at onset: 62.8 Survival: 25.2 months Europe West Incidence: 1.8-2.77 Prevalence: 10.32 M:F 1.1-1.46:1 Age at onset: 63.5-67.8 Survival: 34.8 months Europe North Incidence: 1.06-2.98 Prevalence: 3.1-8.2 M:F 0.71-2.1:1 Age at onset: 57-66.3 Survival: 28.7-33.6 months Mainland China Incidence: NA M:F 1.6-1.83:1 Age at onset: 49.8-52.6 Survival: 71 months USA Incidence: 1.4-4.2 Prevalence: 3.84-5.0 M:F 1.24-2.3:1 Age at onset: 49.7-60.6 Survival: 25-41.4 months Japan Incidence: 0.69-2.50 Prevalence: 2.25-9.9 M:F 1.37-2.9:1 Age at onset: 58.2-65.4 Survival: 48 months Europe South Incidence: 1.4-2.64 Prevalence: 6.0-10.8 M:F 0.88-1.65:1 Age at onset: 57-66.84 Survival: 27.5-57.48 months Taiwan, China Incidence: 0.51 Prevalence: 1.97 M:F 1.65:1 Age at onset: 56.3-56.6 Survival: 66.6 months Hong Kong, China Incidence: 0.3-0.6 Prevalence: 0.95-3 M:F 1.72-1.95:1 Age at onset: 55-58.76 Survival: NA Brazil Incidence: 0.4 Prevalence: 0.9 M:F 1.4-1.7:1 Age at onset: 52-57.2 Survival: 42-49 months Argentina Incidence: 6 (based on OPD attendance) M:F 1.59:1 Age at diagnosis: 55 Survival: NA Australia Incidence: NA M:F 1.2-1.5:1 Age at onset: 58.2-66 Survival: 24-73 months (different phenotypes) Uruguay Incidence: 1.37-1.42 Prevalence: 1.9 M:F 2:1 Age at onset: 58.7 Survival: NA Africa Incidence: NA M:F 1.4-4:1 Age at onset: 50 Survival: 35.2 months India Incidence: 112.6 (based on OPD attendance) M:F 3:1 Age at onset: 46.2 Survival: 114.8 months
Advantages for the natural history study of ALS in Pan-Asia 1. A large and growing number of patients 2. Multiple ethnic populations 3. Both developed and developing countries 4. Diverse habits and customs 5. Diverse climate
Aims and Objectives 1. To describe the natural history of ALS in Pan-Asian countries 2. To identify prognostic factors for survival in Pan-Asian countries 3. To compare the natural history, clinical features and prognostic factors both among different Pan-Asian countries and between the Pan-Asian region and other regions 4. To uncover environmental, ethnic, social and cultural factors underlying certain features specific to Pan-Asian ALS patients 5. To accelerate to establish the multicenter database for PACTALS
Brief methodology ALS patients in Pan-Asian countries will be collected with uniform criteria and CRF. ü Make the diagnosis clean (excluded SBMA, other LMNS, ALS-mimic, etc.) ü Various phenotypes of ALS (such as FAS, UNM-D ALS, IBALS, but not Hirayama disease, Madras MND, and ALS- PD-dementia complex) ü Non-motor impairment (including to cognitive, behavioral, even sleeping)
Paresis Death Vacuolation Loss of MN 40d 90d 125d 136d
orexins
Expected outcomes 1. Pan-Asian ALS patients have different natural history, clinical features and prognostic factors compared to European and North American patients. 2. Multiple environmental, ethnic, social and cultural factors account for the heterogeneity within Pan- Asia countries, and these factors may not have been identified in previous studies