NfL in MSA, Outcome Measures, UMSARS, MSA-QoL Start
NfL Longitudinal Table (continued)
| study | design | timepoints | matrix / assay | results | correlation / notes |
|---|---|---|---|---|---|
| Palma 2022 (Kaufmann lab) | Interventional (sirolimus/rapamycin), 1-year long study N=12 | Baseline and 12 months | Plasma SIMOA (Kit or homebrew?) |
progressed (>7y), with a very strong correlation, similar to HC, towards the late stages of MSA (rho=0.68, P<0.001, n=20) (Supplementary Fig. 2C). A trial with 28 participants (14 per group) would be able to detect a 30% reduction in annual (12m) NfL level at 80% power (Fig. 3B), js: but we need a slowing-based estimation? email communication: N=12 19.9 (15.3) annualized change (mean (SD)) 23 (10.8) → 42.9 (20.6) | Annual change in UMSARS vs change in NfL (N=12): Total UMSARS (r=0.732, P=0.006) UMSARS-2 (r=0.795, P=0.002) |
| Tokutake et al | Longitudinal sub-study of a cross sectional CSF biomarker study in MSA N=10 | Baseline and 2±1 years | CSF MSD R-PLEX | 14,991 ± 6,481 → 13,058 ± 5,985 감소 trend 네? Longitudinal change -1,933 ± 2844 P=0.16 | Baseline NfL vs change in UMSARS2, N=10 (r=0.8863, P=0.0013) |
| Zhang 2021 | Longitudinal study N=64 Probable MSA with disease duration <3 years | Baseline and 12 months | Plasma SIMOA (Kit or homebrew?) | 9.27 ± 21.88 annualized change (email communication; mean ± SD) 31.64 (13.89) → 41.32 (26.12) (p= 0.01) | Baseline NfL vs baseline UMSARS, N=64 (r=0.381, P<0.001) |
| Petzold 2009 | Longitudinal treatment study N=10 CSF samples for each treatment group Probable MSA, 22.4 mo since diagnosis | Baseline and 12 mo | CSF ELISA | No change over 12 months 1400 → 1200 → 1300 (baseline-6mo-12mo) | Not performed |
| Constantinesu 2010 | Retrospective analysis of data from subject for whom 2 consecutive CSF samples were available N=14 MSA-P N=7 MSA-C | Baseline and 10-12 mo | CSF ELISA (Rosengren 1996) | MSA-P: 995 (250–6030) → 1149 (250–3940) MSA-C: 1210 (740–2332) → 1250 (548–2789) (mean (range)) | Not performed |
NfL Cross-Sectional / Longitudinal CSF and Blood Comparison
| design | study | cohort | assay / results figure | |
|---|---|---|---|---|
| CSF/Blood — Takeda compiled - '20221000 Olga NfL in MSA _longitudinal studies_Oct 2022.pptx' | ||||
| CSF | Cross-sectional | (Bridel, 2019 #1407) |
- Meta-analysis Dear Laura, Just to make sure that this does not fall of your list. We would like to have a kick-off soon. Best, |
Elevated, Nice correlation of NFL between CSF and blood (suppl, eTable2) Fold change (95% CI) compared to HC: 3.63 (2.77-4.75) Yearly increase in CSF NfL in % (95%CI), p-value: -0.68 (-2.03-0.69), ns |
| CSF | longitudinal | From Tokutake, Petzold, Constantinesu, Bride: 뚜렷한 증가/감소 없네, axonal secreton/neuronal loss 가 서로 상쇄하나 보다. 임상에서 slowing 을 보보기는 어렵겠고 pharmadynamic BM 으로서도 어떻게 활용하지 난망인듯? | ||
| Blood | Cross-sectional | {Hansson, 2017 #1691} | Lund (n 5 278) and London (n 5 117) cohorts, and 'early disease cohort' Msa: n of 30+30+? | Simoa — Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p , 0.001) |
| Blood | Cross-sectional | {Ashton, 2021 #1692} | King's College London (n = 805) and the "Swedish BioFINDER study" (n = 1,464, NCT01208675) https://biofinder.se/ .그러나 이중 MSA=29 | |
| blood | longitudinal | {Palleis, 2020 #1693} | N=1 | increase over time, and strong correlation with UMSARS-total (and also with UMSARS-ME) |
Outcome Measures
Unified MSA Rating Scale (UMSARS)
- Unchanged since the original publication by Wenning et al. (2004, PMID: 15452868)
| items | Clinically relevant change | |||
|---|---|---|---|---|
| Historical Review: patient reported | 12 items | Speech, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, walking, falling, orthostatic symptoms, urinary function, sexual function, bowel function | 20181001 TAK-341 IDP page14: 5 (10.4) point difference vs. placebo (Poewe et al. 2015). | |
| Motor Examination Scale: clinician-assessed | 14 items | Facial expression, speech, ocular motor dysfunction, tremor at rest, action tremor, tone, hand alternating movements, finger taps, leg agility, heel-knee-shin test, arising from chair, posture, body sway, gait | ||
| Autonomic Examination | 4 items | Systolic BP, Diastolic BP, HR, orthostatic symptoms | ||
| Global Disability Scale: chore-based disability | 1 item | dependency |
(Palma, 2021 #1633) It is easy to use in clinical practice, with an average time of administration of ~ 15 min to complete four subscales:
Higher scores on the UMSARS indicate more severe disease.
{Wenning, 2013 #1077} n=126,
Progression (6m,12m, 18m, 24m) detailed in table 3 (motor increases 30% at 12m, ie 25.9 (9)→ 33.7 (10)
24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74%(12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. (Autonomic symptom scores progressed throughout the follow-up.)
Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted rapid UMSARS progression.
Sample size
258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor (table3에서 딱 ↑ 30% )examination decline rates at 80% power.
Figure caption (visible footer): Required sample size per group for various effect sizes and different scores. (UMSARS subscales of daily living, ME, motor examination)
Multiple System Atrophy Health-Related Quality of Life (MSA-QoL)
Original
{Schrag, 2007 #1503} , 그런데 questionnaire 자체는 안 구해지네, MDS site 에도 안 보이는 듯?
Example
{Matsushima, 2021 #1389}
MSA (Items That Change Largely in Early-Stage Multiple System Atrophy)
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| top continuation row | header band above Palma 2022 | The very top of the page is a continuation header band continuing from the previous photo; column labels are not visible in this crop. |
| Bridel forest plot fold change | 3.63 (2.77-4.75) | Pulled from the figure footer text; sub-numbers are partially small. |
| London cohort scatter inset | r=0.845, p=0.001 (yellow-highlighted) | Inline scatter plot inset; numeric values are visible in the embedded figure but should be confirmed against the source paper. |
Hansson n 5 278 / n 5 117 | n 5 278, n 5 117 | The character 5 between n and the count is the source’s own use; reads as n = 278 semantically but the visible glyph is 5. |
| Constantinesu vs Constantinescu | Constantinesu 2010 | Surname is visually Constantinesu on this page; standard spelling is Constantinescu. Transcribed as written. |