Author(s) and year of publication	Follow-up interval (months)	Number of patients/Number or controls	Clinical assessment batteries/Functional rating scales	Imaging data	Main study findings
IMAGING STUDIES
Floeter et al. (15)	6–18	28/28	ALSFRS-R, letter fluency, FBI, MMSE	DWI, structural (T2)	- progression and propagation detected (DTI measures) over 6 months - DTI measures correlated with ALSFRS-R, King's stage and cognitive measures
Kassubek et al. (16)	6	67/31	ALSFRS-R	DTI	- progression detected at group level and 27% of individual patients (DTI measures) - FA correlated with ALSFRS-R
Stampfli et al. (17)	3–6	21/13	ALSFRS-R	T1, DWI	-progression detected (FD values)
Baldaranov et al. (18)	26	6/6	ALSFRS-R	DTI	-progression detected (FA, AD/RD values) and correlated with progression on ALSFRS-R
Bede et al., 2017 (14)	4	32/69	ALSFRS-R	structural,DTI	-progression detected (GM)
de Albuquerque et al. (19)	8	27/27	ALSFRS-R, UMN scale	structural (T1, T2)	- progression detected (AD, MD) - correlation with ALSFRS-R change
Menke et al. (20)	24	16/0	ALSFRS-R, UMN score	T1, DTI, rs-Fmri	- progression detected - correlation with ALSFRS-R decline
Simon et al. (21)	3–6	21/13	ALSFRS-R, MRCSS-LL, MUNE	DTI, structural (T1)	- progression detected (FA values) - correlations with ALSFRS-R change, MUNE, functional disability and strength
Floeter et al. (22)	6	49/28	ALSFRS-R, FBI, MDRS-2, letter fluency, MMSE, D-KEFS	structural (T1)	-progression detected (ventricular volume)
Schulthess et al. (23)	6	135/56	ALSFRS-R	rs-Fmri, DTI	- progression detected (functional connectivity) - correlation with physical disability
McMillan et al. (24)	12	20/25	neuropsychology	structural (T1)	-hypermethylation protective against progression, correlation with protection of some components of neuropsychological assessment
Steinbach et al. (25)	3	16/16	ALSFRS-R, neuropsychology	DTI	-progression detected
Westeneng et al. (26)	5.5	112/60	ALSFRS-R	structural (T1)	- progression detected (volume measures) - correlation with ALSFRS-R
Menke et al. (4)	6	60/36	ALSFRS-R, ACE-R	structural (T1), DTI	-progression detected (GM)
Schuster et al. (27)	3–15	77/60	ALSFRS-R	structural (T1)	-progression detected (cortical thickness)
Stoppel et al. (28)	3	40/42	ALSFRS-R, MRC, neuropsychology	structural, Fmri	- progression detected - correlation with ALSFRS-R and MRC
Verstraete et al. (29)	5.5	24/19	ALSFRS-R	DTI, structural (T1)	- no progression detected - propagation detected
Ignjatovic et al. (30)	6	46/26	ALSFRS-R	structural (T1, T2, FLAIR)	-progression detected (hypointensities in PGGM)
Kwan et al. (31)	1.26–2.08 years	45/19	ALSFRS-R, finger tapping	T1, DTI	-progression detected (cortical thickness, GM volume)
Keil et al. (32)	6	24/24	ALSFRS-R, SF36, FAB, MMSE	DTI, structural (T1, T2)	- progression detected (FA values) - correlations with ALSFRS-R, physical and executive function
Menke et al. (33)	6	24/0	ALSFRS-R	DTI	-progression detected (AD)
Ichikawa et al. (34)	NA	6/NA	NA	NA	-progression detected, correlated to neuropsychology assessment
van der Graaff et al. (35)	NA	48/12	ALSFRS-R, finger tapping	DWI	-progression detected
Zhang et al. (36)	8	17/19	ALSFRS-R	structural (T1), DTI	- progression detected (FA)
Agosta et al. (37)	9	16/10	ALSFRS	structural (T1)	- progression detected (GM)
Agosta et al. (38)	9	17/20	ALSFRS	DWI, structural	- progression detected (cord area, cord average FA)
Avants et al. (39)	5.3	4/4	0	structural (T1)	- progression detected (cortical atrophy)
Lule et al. (40)	6	25/15	ALSFRS-R	Fmri, structural (T1)	- progression detected (activity)
Unrath et al. (41)	6	11/0	ALSFRS	MRS, T1	- progression detected (NAA, NAA/Cr+Cho)
Suhy et al. (42)	Every 3 months	28/12	0	MRS, T1, T2	- progression detected (NAA, Cr, Cho)
Block et al. (43)	24	33/20	0	MRS	- progression detected
Irwin et al. (44)		143/0	MMSE, LGVF	structural VBM	- no progression on MRI reported
Kolind et al. (45)	42	30/12	ALSFRS-R, ACE,	mcDESPOT	- progression detected in PLS only
Verstraete et al. (46)	6	45/25	ALSFRS-R	structural (T1)	- no progression reported
Blain et al. (47)	6–12	23/25	ALSFRS-R, ALSS	structural (T2), DWI	- no significant progression detected (DTI measures)
Rule et al. (48)	3–12	45/17	0	MRS, structural (T1, T2)	- no clear pattern of progressive change over time (NAA rations)
Author(s) and year of publication	Follow-up interval (months)	Total number of patients/Total number of controls	Neurophysiology modality	Target muscle	Key study findings
NEUROPHYSIOLOGY STUDIES
Escorcio-Bezerra et al. (49)	4.3	21/21	MUNIX	tibialis anterior (TA), abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles	- progression detected (mean MUNIX)
de Carvalho et al. (50)	3–6	73/37	FPs, MUPs, fibs-sw, jitter- MU physiology	tibialis anterior	- progression detected
Boekestein et al. (51)	8	18/24	MUNIX, HD-MUNE, CMAP, MUSIX	thenar	- progression detected (MUNE, MUNIX)
Cheah et al. (52)	3	37/0	CMAP, axonal excitability	abductor pollicis brevis	- progression detected (CMAP)
Ahn et al. (53)	NA	135/NA	NA	NA	- asymmetric progression (MUNE)
Cheah et al. (54)	3	58/NA	NI, CMAP	abductor digiti minimi and ulnar nerve	- progression detected (NI)
de Carvalho et al. (55)	6	28/0	NI, CMAP, MUNE	abductor digiti minimi muscles	- progression detected (CSP)
Neuwirth et al. (56)	15	7/8	MUNIX, CMAP,	abductor pollicis brevis (APB), abductor digiti minimi (ADM), abductor halluces brevis (AHB), extensor digitorum brevis (EDB)	- progression detected (MUNIX)
Floyd et al. (57)	18	60/33	TMS, CMCT, MEP	abductor digiti minimi (ADM) and tibialis anterior (TA)	-linear progression detected (TMS threshold, CMCT, TMS amplitude corrected)
Gooch et al. (58)	NA	64/NA-1	TMS, MUNE,	NA	-progression detected (MUNE)
Liu et al. (59)	12	112/12	MUNE, CMAP	Abductor pollicis brevis (APB) and abductor digiti quinti (ADQ)	- progression detected (MUNE), correlated to ALSFRS descent
Albrecht et al. (60)	11.5	10/25	MUNE, S-MUAP	extensor digitorum brevis	- progression detected (MUNE)
Wang et al. (61)	12	20/70	MUNE, SMUP, CMAP, MU loss	thenar	- progression detected - (Thenar MUNE, CMAP)
Chan et al. (62)	24	NA	motor units	thenar	- progression detected
Felice et al. (63)	12	NA	MUNE	thenar	- progression detected (MUNE)
Yuen et al. (64)	6	NA	CMAP, MUNE	abductor digiti minimi	- progression detected (MUNE, fiber density)
Vucic et al. (65)	7–100 days	25/30, 35	cortical and axonal excitability- MEP, CMAP- TMS	abductor pollicus brevis	- aim to determine effect of riluzole
Aggarwal et al. (66)	36	31/57	MUNE	tibialis anterior, abductor pollicis brevis (APB), deltoid, and first dorsal interosseous muscles	- no progression reported
Arasaki et al. (67)	NA	NA	MUNE,	extensor digitorum brevis (EDB)	- no progression reported
de Carvalho et al. (68)	11.6	NA	CMAP, MEP, TMS	NA	- no progression detected
Swash et al. (69)	NA	14/NA	single fiber EMG	NA	- no definite progression detected