Prognostic value of motor and extramotor involvement in ALS

Figures & data

Table 1. Definition of the different patient groups in this study.

	Description
ALS-Cn	Cognitively normal patients with ALS.
ALS-Bi	Patients with ALS with behavioral impairment.
ALS-Ci	Patients with ALS with cognitive impairment.
ALS-FTD	Patients with ALS with comorbid frontotemporal dementia.
LMN regions	Number of regions affected with lower motor neuron symptoms, either established clinically or on EMG. 4 regions evaluated are bulbar, cervical, thoracic and lumbosacral.
UMN regions	Number of regions affected with upper motor neuron symptoms, either established. 4 regions evaluated are bulbar, cervical, thoracic and lumbosacral.

Table 2. Demographic data for ALS patients.

	All	ALS-Cn	ALS-Ci/ ALS-Cbi/ ALS-Bi	ALS-FTD	p-Value
Number of patients (%)	179	85 (47.5%)	48 / 14 / 8 (39.1%)	24 (13.4%)
Male (%)	115 (64.2%)	56 (65.9%)	41 (58.6%)	18 (75.0%)	0.414
Age at onset (mean)	62.6 years	59.3 years	64.8 years	68.2 years	0.001
Diagnostic delay (mean)	359.9 days	346.1 days	391.9 days	317.1 days	0.916
Site of onset: bulbar, spinal, thoracic (% per group)	125 spinal (69.8%) 52 bulbar (29.1%) 2 thoracic (1.1%)	67 spinal (78.8%) 17 bulbar (20.0%) 1 thoracic (1.2%)	44 spinal (62.9%) 25 bulbar (35.7%) 1 thoracic (1.4%)	14 spinal (58.3%) 10 bulbar (41.7%)	0.111
ECAS (median)	96.5	110.5	86.4	75.3	0.001
ALSFRS (median, Kruskal Wallis test)	40	41 (IQR 37–44)	40 (IQR 34–44)	35 (IQR 28.5–38.5)	<0.001
C9orf72 status (% per group, chi-square test)	18 (9.8%)	5 (5.7%)	10 (13.9%)	3 (9.8%)	0.379
BMI (mean, t-test)	24.6 (95%CI 24.0–25.2)	24.9 (95%CI 23.9–25.8)	24.7 (95%CI 23.7–25.6)	23.5 (95%CI 22.0–24.9)	0.186

Legend: ALS: Amyotrophic Lateral Sclerosis; ALS-Cn: Cognitive normal; ALS-Ci: Cognitive impaired; ALS-Cbi: cognitive and behavioral impaired; ALS-Bi: behavioral impaired; ALS-FTD: frontotemporal dementia; ECAS: Edinburgh Cognitive and Behavioral ALS Screen. ALSFRS: Amyotrophic Lateral Sclerosis Functional Rating Scale. BMI: Body Mass Index.

Figure 1. Univariate analysis of effect of LMN involvement on survival.

Figure 2. Univariate analysis of effect of UMN involvement on survival.

Figure 3. Univariate analysis of effect of extramotor involvement on survival.

Table 3. Multivariable Cox analysis of effect of ECAS, LMN, age of onset, and diagnostic delay on survival.

	Significance (P value)	Hazard ratio	95% CI
Age of onset	0.001	1.034	1.016–1.052
Diagnostic delay	0.001	0.997	0.996–0.998
ALS-Cn	0.016	—	—
ALS-Ci, ALS-Cbi, ALS-Bi	0.004	1.711	1.187–2.467
ALS-FTD	0.396	1.241	0.753–2.046
LMN 3 or more regions	0.022	—	—
LMN 1 region	0.012	0.524	0.317–0.866
LMN 2 regions	0.115	0.723	0.483–1.083

Legend: ALS-Cn: Cognitive normal; ALS-Ci: Cognitive impaired; ALS-Cbi: cognitive and behavioral impaired; ALS-Bi: behavioral impaired; ALS-FTD: frontotemporal dementia; CI: Confidence Interval; LMN: Lower motor neuron.

Figure 4. Analysis of the combined effect of LMN and extramotor involvement on survival.