Table 1.
Staging anchors for application of the NSD-ISS
| Biologic anchors | Anchors of clinical signs or symptoms (stages 2A and 2B) and functional impairment (stages 3–6)a,b | ||||
|---|---|---|---|---|---|
| Stage | S | Dc | G | Domain | Anchor(s) |
| Stage 0 | - | - | SNCAd | — | — |
| Stage 1A | + | - | ± |
(1) Cognitive (2) Motor (3) Other non-motor |
(1) MDS-UPDRS item 1.1 = 0; and (2a) Does not have subthreshold parkinsonisme; and (2b) is not on PD medicationf; and (3a) Does not have RBD; and (3b) is not hyposmicg |
| Stage 1B | + | + | ± | ||
| Stage 2A | + | - | ± |
(1) Cognitive (2) Motor (3) Other non-motor |
(1) Item 1.1 = 1 AND MoCA ≥ 25; or (2a) Has subthreshold parkinsonisme; or (2b) is on PD medicationf; or (3a) Has RBD; or (3b) is hyposmicg |
| Stage 2B | + | + | ± | ||
| Stage 3 | + | + | ± |
(1) Cognitive (2) Motor |
(1a) Item 1.1 = 1 AND MoCA ≤ 24; or (1b) Item 1.1 = 2 AND MoCA ≥ 25; or (2) MDS-UPDRS-II = 3–13 AND either subthreshold parkinsonisme or PD medicationf |
| Stage 4 | + | + | ± |
(1) Cognitive (2) Motor (3) Other non-motor |
(1a) Item 1.1 = 2 and MoCA ≤ 24; or (1b) item 1.1 = 3 AND MoCA ≥ 25; or (2) MDS-UPDRS-II = 14–26; or (3) MDS-UPDRS-I (excluding item 1.1) = 13–24h |
| Stage 5 | + | + | ± |
(1) Cognitive (2) Motor (3) Other non-motor |
(1a) Item 1.1 = 3 AND MoCA ≤ 24; or (1b) item 1.1 = 4 AND MoCA ≥ 25; or (2) MDS-UPDRS-II = 27–39; or (3) MDS-UPDRS-I (excluding item 1.1) = 25–36 |
| Stage 6 | + | + | ± |
(1) Cognitive (2) Motor (3) Other non-motor |
(1) Item 1.1 = 4 AND MoCA ≤ 24; or (2) MDS-UPDRS-II ≥ 40; or (3) MDS-UPDRS-I (excluding item 1.1) ≥ 37 |
MDS-UPDRS Movement Disorder Society Unified Parkinson’s Disease Rating Scale, MoCA Montreal Cognitive Assessment, NSD neuronal synuclein disease, PD Parkinson’s disease, RBD REM sleep behavior disorder, UPSIT University of Pennsylvania Smell Identification Test.
aPresence of qualifying signs/symptoms in any single domain qualifies for stage 2 but individuals can have combination in all 3 domains.
bPresence of qualifying functional impairment in any single domain qualifies for stage 3-6 but individuals can have combination in all 3 domains.
cD positivity defined as <75% age/sex-expected lowest putamen SBR.
dOnly fully penetrant pathogenic SNCA variants qualify for stage 0.
eSubthreshold parkinsonism defined as MDS-UPDRS-III ≥5 excluding postural and action tremor.
fMedication for treating the symptoms of PD as per MDS-UPDRS item 3a.
gHyposmia defined as UPSIT percentile ≤15 (age and sex adjusted).
hMDS-UPDRS-I (excluding item 1.1) ≥13 is sufficient for stage 4 provided that stage 2 criteria are met.