Demographic changes in a large motor neuron disease cohort in Portugal: a 27 year experience

Figures & data

Figure 1. MND subgroups’ distribution.

Table 1. Demographic and clinical characteristics of MND patients.

	ALS (n = 1285)	PMA (n = 199)	PLS (n = 52)	Monomelic (n = 14)	p value	Post-hoc comparisons^a
Male (%)	53.9% p = 0.005	73.9% p < 0.001	44.2% p = 0.405	92.9% p = 0.001	<0.001	ALS_PMA, p < 0.001 ALS_ monomelic, p = 0.004 PMA_PLS, p < 0.001
Age at onset, yrs, median [IQR]	63.61 [54.90−71.61]	64.52 [56.16–73.91]	55.61 [47.52-63.85]	55.46 [38.09-56.87]	<0.001	ALS_ monomelic, p = 0.001 ALS_PLS, p < 0.001 PMA_monomelic, p < 0.001 PMA_PLS, p < 0.001
Diagnostic delay, mo, median [IQR]	11.01 [6.37−17.74]	11.07 [5.98–23.06]	28.02 [15.93-55.03]	27.04 [18.96-50]	<0.001	ALS_PLS, p < 0.001 ALS_monomelic, p < 0.001 PMA_PLS, p < 0.001 PMA_monomelic, p < 0.001
Baseline score, median [IQR]	40 [36–43]	41 [36-45]	41 [36-44]	46 [45-47]	<0.001	ALS_PMA p = 0.004 ALS_monomelic, p < 0.001 PLS_monomelic p = 0.001 PMA_monomelic, p < 0.001
Baseline decay, median [IQR]	0.65 [0.35−1.19]	0.49 [0.2–0.89]	0.19 [0.07–0.3]	0.04 [0.03–0.16]	<0.001	monomelic_PMA, p < 0.001 monomelic_ALS, p < 0.001 PLS_PMA, p < 0.001 PLS_ALS, p < 0.001 PMA_ALS, p = 0.001
1Y follow up score, median [IQR]	29 [22–37]	37 [29–43]	38 [32–41]	47 [46–48]	<0.001	ALS_PMA, p < 0.001 ALS_PLS, p < 0.001 ALS_monomelic, p < 0.001 PMA_monomelic, p = 0.006 PLS_monomelic, p = 0.044
1Y follow up decay, median [IQR]	0.83 [0.38−1.29]	0.43 [0.09–0.85]	0.22 [0.07–0.46]	0 [–0.13–0.04]	<0.001	monomelic_PMA, p = 0.016 monomelic_ALS, p < 0.001 PLS_ALS, p < 0.001 PMA_ALS, p < 0.001
NIV rate (%)	61.8%	53.6%	26%	0%	<0.001^b	ALS_PLS, p < 0.001 PMA_PLS, p = 0.001
Time to NIV, mo, median (95% CI)	26.91 (24.9−28.9)	48.26 (33.8−62.7)	–	–	<0.001^b	ALS_PMA, p < 0.001 ALS_PLS, p < 0.001 PMA_PLS, p < 0.001
Survival, median, mo, (95% CI)	38.0 (36.3−39.8)	62.0 (50.7−73.3)	254.5 (−)	–	<0.001^b	ALS_PMA, p < 0.001 ALS_PLS, p < 0.001 PMA_PLS, p < 0.001

^aonly significant results after correction by the Bonferroni adjustment are shown; ^bMonomelic excluded from analysis. Y = year; IQR = 1st and 3rd Interquartile range; NIV- noninvasive ventilation.

Scores are derived from ALSFRS-R scale, baseline decay calculated as 48-observed value/duration in months, and 1Y decay as baseline value - observed value/duration in months.

Bold: p < 0.05, significant differences.

Table 2. Demographic and clinical characteristics of PMA and ALS patients according to the site of onset.

	PMA (n = 199)	s-ALS (n = 808)	b-ALS (n = 374)	ar-ALS (n = 67)	c-ALS (n = 17)	g-ALS (n = 19)	p Value	Post-hoc comparisons^a
Male (%)	73.9% p < 0.001	58.2% p < 0.001	39.0% p < 0.001	83.6% p < 0.001	47.1% p = 0.808	68.4% p = 0.108	<0.001	s-ALS_b-ALS, p < 0.001 s-ALS_ar-ALS, p < 0.001 s-ALS_PMA, p < 0.001 b-ALS_ar-ALS, p < 0.001 b-ALS_PMA, p < 0.001 c-ALS_ar-ALS, p = 0.002
Age at onset, yrs, median [IQR]	64.52 [56.16–73.91]	61.26 [52.31–69.38]	67.3 [59.77–74.53]	69.53 [63.78–73.91]	66.74 [56.85–70.02]	65.39 [59.8–70.88]	<0.001	s-ALS_PMA, p < 0.001 s-ALS_b-ALS, p < 0.001 s-ALS_ar-ALS, p < 0.001
Diagnostic delay, mo, median [IQR]	11.07 [5.98–23.06]	12.02 [6.97–21.03]	9.02 [5.98–12.9]	9.99 [6.8–15.47]	40.02 [12.0–77.96]	6.97 [4.01–12.68]	<0.001	g-ALS_c-ALS, p = 0.001 b-ALS_PMA, p = 0.004 b-ALS_s-ALS, p < 0.001 b-ALS_c-ALS, p < 0.001 ar-ALS_c-ALS, p = 0.003 PMA_c-ALS, p = 0.012 s-ALS_c-ALS, p = 0.024
Baseline score, median [IQR]	41 [36–45]	40 [34–43]	40 [36–43]	39 [34–42]	42 [36–44]	35 [31–42]	0.002	s-ALS_PMA, p = 0.008
Baseline decay, median [IQR]	0.49 [0.2–0.89]	0.59 [0.28–1.15]	0.72 [0.45–1.29]	0.79 [0.49–1.31]	0.14 [0.08–0.62]	1.12 [0.75–1.6]	<0.001	c-ALS_s-ALS, p = 0.010 c-ALS_b-ALS, p < 0.001 c-ALS_ar-ALS, p < 0.001 c-ALS_g-ALS, p < 0.001 PMA_b-ALS, p < 0.001 PMA_ar-ALS, p = 0.002 PMA_g-ALS, p = 0.002 s-ALS_b-ALS, p < 0.001 s-ALS_g-ALS, p = 0.028
1Y follow up score, median [IQR]	37 [29–43]	30 [22–38]	27 [21–34]	29 [26–38]	26 [22–29]	26 [16–34]	<0.001	b-ALS_s-ALS, p = 0.014 b-ALS_PMA, p < 0.001 s-ALS_PMA, p < 0.001
1Y follow up decay, median [IQR]	0.43 [0.09–0.85]	0.75 [0.31–1.17]	1 [0.65–1.52]	0.63 [0.25–1.15]	1.46 [1.21–1.83]	0.99 [0.19–1.48]	<0.001	PMA_s-ALS, p = 0.002 PMA_b-ALS, p < 0.001 PMA_c-ALS, p = 0.019 s-ALS_b-ALS, p < 0.001
NIV rate (%)	53.6%	58.3%	66.2%	85.5%	21.4%	70.6%	<0.001	ar-ALS_s-ALS, p < 0.001 ar-ALS_b-ALS, p < 0.037 ar-ALS_c-ALS, p < 0.001 ar-ALS_ PMA, p < 0.001 c-ALS_b-ALS, p = 0.009
Time to NIV, mo, median (95% CI)	48.26 (33.8–62.7)	33.77 (20.3–37.3)	19.43 (17.4–22.5)	11.99 (10.5–13.4)	–	16.03 (14.1–18.0)	<0.001	ar-ALS_s-ALS, p < 0.001 ar-ALS_b-ALS, p < 0.001 ar-ALS_c-ALS, p < 0.001 ar-ALS_g-ALS, p = 0.021 ar-ALS_ PMA, p < 0.001 b-ALS_s-ALS, p < 0.001 b-ALS_c-ALS, p < 0.001 b-ALS_PMA, p < 0.001 s-ALS_c-ALS, p = 0.008 s-ALS_g-ALS, p = 0.022 s-ALS_ PMA, p = 0.016 c-ALS_g-ALS, p = 0.005 c-ALS_PMA, p = 0.032 g-ALS_PMA, p = 0.002
Survival, median, mo, (95% CI)	62.0 (50.7 − 73.3)	44.95 (41.6 − 48.2)	30.95 (28.9 − 33.0)	31.31 (20.6 − 42.0)	103.3 (32.1 − 174.5)	30.09 (25.4 − 34.8)	<0.001	b-ALS_PMA, p < 0.001 ar-ALS_c-ALS, p < 0.001 ar-ALS_ PMA, p < 0.001 c-ALS_g-ALS, p = 0.001 g-ALS_PMA, p < 0.001

^aonly significant results after correction by the Bonferroni adjustment are shown. For other abbreviations see footnote of Table 1.

Bold: p < 0.05, significant differences.

Figure 2. Kaplan–Meier survival curves stratified by phenotype.

Table 3. Demographic and clinical characteristics of s-ALS, b-ALS and PMA patients according to group period.

		P1: 1994–2002 (n = 236)	n	P2: 2003–2011 (n = 502)	n	P3: 2012–2020 (n = 812)	n	p-value	Post-hoc comparisons^a
Proportion, no (%)	s-ALS	59.3%	140	56.2%	282	47.5%	386	<0.001	P1_P3, p < 0.001 P2_P3, p < 0.001
	b-ALS	26.7%	63	25.9%	130	22.3%	181
	PMA	5.9%	14	8.8%	44	17.4%	141
Male (%)	s-ALS	59.3%	140	61.3%	282	55.4%	386	0.3	–
	b-ALS	44.4%	63	40%	130	36.5%	181	0.52	–
	PMA	78.6%	14	79.5%	44	71.6%	141	0.53	–
Age at onset, yrs, median [IQR]	s-ALS	61.9 [52.1–67.92]	140	60.57 [52.65–69]	277	61.47 [51.96–70.49]	384	0.51	–
	b-ALS	64.2 [59.77–72.65]	63	68.13 [58.74–75.33]	130	67.9 [60.87–74.32]	180	0.42	–
	PMA	54.7 [44.84–69.0]	14	62.74 [56.75–70.63]	44	67.03 [57.14–74.25]	141	0.06	–
Diagnostic delay, mo, median [IQR]	s-ALS	13.22 [7.98–26.12]	140	12.19 [7.62–19.52]	279	11.07 [6.01–20.5]	384	0.02	P1_P3, p = 0.006
	b-ALS	9.4 [5.5–12.48]	63	10.38 [6.64–14.32]	128	8.05 [5.03–11.99]	178	0.01	P2_P3, p = 0.003
	PMA	10.66 [5.95–22.05]	14	14.95 [8.67–31.87]	43	9.99 [5.49–21.98]	140	0.03	P2_P3, p = 0.009
Baseline score, median [IQR]	s-ALS	40 [33–43]	84	40 [35–43]	269	40 [33–43]	374	0.39	–
	b-ALS	40 [34–44]	40	40 [36–43]	125	40 [36–43]	173	0.98	–
	PMA	43 [40–46]	10	42 [37–45]	44	41 [36–44]	136	0.32	–
Baseline decay, median [IQR]	s-ALS	0.56 [0.21–0.86]	84	0.63 [0.3–1.15]	268	0.59 [0.29–1.2]	372	0.29	–
	b-ALS	0.67 [0.46–1.58]	40	0.71 [0.41–1.25]	124	0.8 [0.47–1.22]	171	0.55	–
	PMA	0.43 [0.1–0.74]	10	0.42 [0.13–0.76]	43	0.51 [0.25–1]	136	0.11	–
1Y follow up score, median [IQR]	s-ALS	30 [20–36]	38	32 [23–39]	144	29 [21–37]	162	0.35	–
	b-ALS	31 [19–36]	18	27 [21–33]	52	26 [21–34]	70	0.63	–
	PMA	36 [27–41]	8	37 [31–43]	31	36 [26–43]	66	0.61	–
1Y follow up decay, median [IQR]	s-ALS	0.7 [0.23–1.08]	38	0.69 [0.27–1.15]	144	0.78 [0.38–1.27]	162	0.5	–
	b-ALS	0.8 [0.46–1.13]	18	0.93 [0.69–1.4]	52	1.08 [0.75–1.58]	70	0.12	–
	PMA	0.64 [0.4–0.97]	8	0.29 [0.07–0.82]	31	0.41 [0.09–1]	66	0.59	–
NIV rate (%)	s-ALS	54.8%	124	69.4%	258	51.4%	354	0.005^b	–
	b-ALS	73.7%	57	70.5%	122	60.2%	161	0.659^b	–
	PMA	85.7%	14	79.5%	44	41.8%	134	0.608^b	–
Time to NIV, mo, median (95% CI)	s-ALS	36.9 (25.0–48.7)	122	27.2 (24.2–30.3)	251	38.0 (32.6–43.5)	349	0.05^b	–
	b-ALS	20.8 (10.3–31.3)	54	20.7 (15.9–25.6)	121	19.0 (16.2–21.9)	154	0.200^b	–
	PMA	55.0 (31.4–78.5)	14	33.6 (24.9–42.3)	43	54.0 (32.4–75.7)	130	0.724^b	–
Survival, median, mo, (95% CI)	s-ALS	36.0 (31.3–40.7)	140	49.0 (42.5–55.6)	279	46.5 (42.6–50.3)	384	0.041^b	–
	b-ALS	27.0 (21.9–32.2)	63	31.7 (28.6–34.8)	129	33.0 (30.2–35.8)	178	0.323^b	–
	PMA	75.4 (50.8–100.0)	14	69.6 (46.6–92.5)	43	58.6 (45.8–71.4)	140	0.750^b	–

^aonly significant results after correction by the Bonferroni adjustment are shown.

^bStatistical test done only between P1 and P2. For other abbreviations see footnote of Table 1.

Bold: p < 0.05, significant differences.

Table 4. Multivariate Cox regression model- Independent survival predictors.

		Multivariate analysis (Cox regression)
		HR (95% CI)	p-Value
s-ALS	Age at onset, yrs	1.033 (1.024 − 1.041)	<0.001
	Diagnostic delay, mo	0.98 (0.974 − 0.987)	<0.001
	ALSFRS-R Baseline decay	2.004 (1.818 − 2.21)	<0.001
	1994 - 2003	Reference
	2003-2012	0.565 (0.423 − 0.755)	<0.001
	2012-2021	0.755 (0.569 − 1)	0.05
b-ALS	Age at onset, yrs	1.006 (0.994 − 1.018)	0.354
	Diagnostic delay, mo	0.947 (0.929 − 0.966)	<0.001
	ALSFRS-R Baseline decay	1.639 (1.37 − 1.96)	<0.001
	1994 - 2003	Reference
	2003-2012	1.317 (0.88 − 1.972)	0.181
	2012-2021	1.15 (0.78 − 1.695)	0.48
PMA	Age at onset, yrs	1.027 (1.01 − 1.044)	0.001
	Diagnostic delay, mo	0.983 (0.97 − 0.996)	0.012
	ALSFRS-R Baseline decay	2.52 (2.057 − 3.087)	<0.001
	1994 - 2003	Reference
	2003-2012	0.974 (0.442 − 2.146)	0.948
	2012-2021	0.967 (0.455 − 2.057)	0.931

Bold: p < 0.05, significant differences.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [IA], upon reasonable request.