Table 3.

ALS motor phenotype classification – examples of assessment

Example	Clinical description	Coded classification
“Classic ALS, bulbar onset”, example #1	History: onset with dysarthria → O1 Follow-up history: progressive dysarthria and, after 10 months from onset, weakness of right arm → PE Investigation: weakness (LMN) and slowed, poorly coordinated voluntary movement (UMN) of the tongue and of right arm → M0	O1, PE, M0
“Classic ALS, bulbar onset”, example #2	History: onset with dysarthria → O1 Follow-up history: progressive dysarthria and, after 14 months from onset, weakness of right arm → PL Investigation: weakness of tongue and of right arm (LMN), discrete UMN symptoms → M2d	O1, PL, M2d
“Progressive bulbar paralysis (PBP)”, example #1	History: onset with dysarthria → O1 Follow-up history: progressive dysarthria and, after 20 months from onset, no limb involvement → PL Investigation: weakness and atrophy (LMN) of tongue; no UMN symptoms → M2p	O1, PL, M2p
“Progressive (pseudo)bulbar paralysis (PBP)”, example #2	History: onset with dysarthria → O1 Follow-up history: progressive dysarthria and, after 8 months from onset, no limb involvement → PN Investigation: slowed, poorly coordinated voluntary movement of the tongue; hyperreflexia of mandibular reflex; palatal spasticity (UMN); discrete wasting and fasciculations of the tongue (LMN) → M1d	O1, PN, M1d
“Classic ALS, arm onset”, example #1	History: onset with weakness of left hand → O2d Follow-up history: progressive weakness of left arm and, after 6 months from onset, dysarthria → PE Investigation: weakness (LMN) and slowed, poorly coordinated voluntary movement (UMN) of the arm and weakness, atrophy of the tongue → M0	O2d, PE, M0
“Classic ALS, arm onset”, example #2	History: onset with weakness of left hand → O2d Follow-up history: progressive weakness of left arm and, after 22 months from onset, dysarthria → PL Investigation: weakness (LMN) and slowed, poorly coordinated voluntary movement (UMN) of the arm and weakness, atrophy of the tongue → M0	O2d, PL, M0
“Classic ALS, arm onset”, example #3	History: onset with weakness of left hand → O2d Follow-up history: progressive weakness of left arm and, after 5 months from onset, weakness of left leg → PE Investigation: weakness and atrophy (LMN) of the left arm and leg; preserved reflexes (discrete UMN) → M2d	O2d, PE, M2d
“Classic ALS, arm onset”, example #4	History: onset with “stiffness” of left hand → O2d Follow-up history: progressive slowed, poorly coordinated voluntary movement of left arm and, after 5 months from onset, “stiffness” of left leg → PE Investigation: slowed, poorly coordinated voluntary movement and hyperreflexia (UMN) of the left arm and leg; discrete atrophy of the left hand and generalized fasciculations (discrete LMN) → M1d	O2d, PE, M1d
“Flail-arm syndrome”, example #1	History: onset with weakness of the proximal right arm → O2p Follow-up history: progressive weakness of the right arm and, after 24 months from onset, weakness of the left shoulder → PL Investigation: weakness and atrophy of bilateral shoulders (LMN), no UMN symptoms; no involvement of head, trunk and legs → M2p	O2p, PL, M2p
“Flail-arm syndrome”, example #2	History: onset with weakness of the proximal right arm → O2p Follow-up history: progressive weakness of the right arm and, after 10 months from onset, weakness of the left shoulder → PN Investigation: weakness and atrophy of bilateral shoulders (LMN), no UMN symptoms; no involvement of head, trunk and legs → M2p	O2p, PN, M2p
“Respiratory ALS”, example #1	History: onset with hypoventilation → O3r Follow-up history: progressive hypoventilation and, after 7 months from onset, weakness of left arm → PE Investigation: weakness and atrophy of the respiratory muscles and the arm (LMN); no UMN symptoms → M2p	O3r, PE, M2p
“Respiratory ALS”, example #2	History: onset with hypoventilation → O3r Follow-up history: progressive hypoventilation and, after 14 months from onset, weakness/instability of the trunk → PL Investigation: weakness and atrophy of the respiratory muscles and the trunk (LMN); no UMN symptoms; no involvement of head, arms and legs → M2p	O3r, PL, M2p
“Dropped head syndrome”	History: onset with weakness/instability of the neck (dropped head) → O3a Follow-up history: progressive weakness/instability of the neck and trunk and, after 6 months from onset, weakness of both arms → PE Investigation: weakness and atrophy of axial muscles and bilateral shoulders (LMN); no UMN symptoms; no involvement of head and legs → M2p	O3a, PE, M2p
“Classic ALS, leg onset”, example #1	History: onset with weakness of right foot → O4d Follow-up history: progressive weakness of right leg and, after 8 months from onset, weakness of left arm → PE Investigation: weakness (LMN) and slowed, poorly coordinated voluntary movement and hyperreflexia (UMN) of left arm and leg; weakness and atrophy of left leg → M0	O4d, PE, M0
“LMN predominant ALS, leg onset”, example #2	History: onset with weakness of left hip muscles → O4p Follow-up history: progressive weakness of left leg and, after 13 months from onset, weakness of right leg and left arm → PL Investigation: weakness and atrophy (LMN) of bilateral legs and left arm; preserved reflexes in wasted muscle of the left hand → M2d	O4p, PL, M2d
“Classic ALS, leg onset”, example #3	History: onset with weakness of right foot → O4d Follow-up history: progressive weakness of right leg and, after 8 months from onset, weakness of left leg → PE Investigation: weakness (LMN) and slowed, poorly coordinated voluntary movement and hyperreflexia (UMN) of the arm; weakness and atrophy of left leg → M0	O4d, PE, M2p
“Flail-leg syndrome”, example #1	History: onset with weakness of left foot → O4d Follow-up history: progressive weakness of left leg and, after 20 months from onset, weakness of right leg → PL Investigation: weakness and atrophy (LMN) of bilateral legs; no UMN symptoms → M2p	O4d, PL, M2p
“Flail-leg syndrome”, example #2	History: onset with weakness of left foot → O4d Follow-up history: progressive weakness of left leg and, after 11 months from onset, weakness of right leg → PN Investigation: weakness and atrophy (LMN) of bilateral legs; preserved reflexes in wasted muscle of the left leg → M2d	O4d, PN, M2d
“pyramidal ALS”, example #1	History: onset with “stiffness” of left hip and leg → O4p Follow-up history: progressive slowed, poorly coordinated voluntary movement of left leg and, after 8 months from onset, “stiffness” of left arm and left leg → PE Investigation: spasticity, and asymmetric, slowed, poorly coordinated voluntary movement and hyperreflexia (UMN) of the left arm and both legs; discrete atrophy of both hand muscles (discrete LMN) → M1d	O4p, PE, M1d
“pyramidal ALS”, example #2	History: onset with dysarthria → O1 Follow-up history: progressive dysarthria and, after 10 months from onset, slowed, poorly coordinated voluntary movement of bilateral arms and legs → PE Investigation: hyperreflexia of mandibular reflex; palatal spasticity, slowed, poorly coordinated voluntary movement of the tongue, arms and legs (UMN); discrete wasting and fasciculations of the tongue and hand muscles; asymmetric, low-grade weakness (MRC grade 4) of hip muscles (discrete LMN) → M1d	O1, PE, M1d
primary lateral sclerosis, (PLS), example #1	History: onset with “stiffness” of both legs → O4d Follow-up history: progressive slowed, poorly coordinated voluntary movement of both legs and, after 20 months from onset, asymmetric “stiffness” of both arms → PL Follow-up investigation (after 48 months from onset): discrete dysarthria; hyperreflexia of mandibular reflex; palatal spasticity; high-grade spasticity, and asymmetric, highly slowed, poorly coordinated voluntary movement and hyperreflexia of all limbs; no LMN symptoms → M1p	O4p, PL, M1p
primary lateral sclerosis, (PLS), example #2	History: onset with dysarthria → O1 Follow-up history: progressive dysarthria and, after 10 months from onset, slowed, poorly coordinated voluntary movement of bilateral arms and legs → PE Follow-up investigation (after 48 months from onset): severe dysarthria; hyperreflexia of mandibular reflex; palatal spasticity; high-grade spasticity, and asymmetric, highly slowed, poorly coordinated voluntary movement and hyperreflexia of all limbs; no LMN symptoms → M1p	O1, PE, M1p
progressive muscle atrophy (PMA), example #1	History: onset with weakness of right foot → O4d Follow-up history: progressive weakness of left leg and, after 14 months from onset, asymmetric weakness of both legs and hands → PL Follow-up investigation (after 48 months from onset): asymmetric weakness and wasting of foot, leg, hip, hand, arm and shoulder muscles; absent reflexes; no UMN symptoms → M2p	O4d, PL, M2p
progressive muscle atrophy (PMA), example #2	History: onset with weakness of right left hand → O2d Follow-up history: progressive weakness of left hand and, after 8 months from onset, asymmetric weakness of both arms, trunk, legs → PE Follow-up investigation (after 14 months from onset): slight dysarthria, atrophy and weakness of the tongue; severe asymmetric weakness and wasting of limbs and trunk muscles; hypoventilation; absent reflexes; no UMN symptoms → M2p	O2d, PE, M2p
“brachial amyotrophic spastic paraparesis variant” of ALS	History: onset with weakness of right left hand → O2d Follow-up history: progressive weakness of left hand and, after 14 months from onset, asymmetric weakness of both hands→ PL Follow-up investigation (after 20 months from onset): slight dysarthria, atrophy and weakness of the tongue; severe asymmetric weakness and wasting of hands and arms; no UMN symptoms of the upper limbs; high-grade spasticity, and asymmetric, highly slowed, poorly coordinated voluntary movement and hyperreflexia of both legs; no LMN symptoms of lower limbs → M3	O2d, PL, M3