Key result
Cutaneous phosphorylated-alpha-synuclein scores were significantly higher in pure autonomic failure compared to multiple system atrophy (median 4.5 vs 1, P<0.001).
Why the study?
Atypical presentations of pure autonomic failure (PAF) may lead to diagnostic uncertainty, prompting investigation into whether cutaneous phosphorylated-alpha-synuclein could distinguish PAF from MSA and non-synucleinopathy-related autonomic failure.
Does cutaneous phosphorylated-alpha-synuclein assessment distinguish pure autonomic failure from multiple system atrophy and non-synucleinopathy-related autonomic failure?
Cross-Sectional (n=36)
Does cutaneous phosphorylated-alpha-synuclein assessment distinguish pure autonomic failure from multiple system atrophy and non-synucleinopathy-related autonomic failure?
Absolute Event Rate: 4.5% vs 1%
p-value: p=<0.001
Cutaneous phosphorylated-alpha-synuclein is a highly specific biomarker that can distinguish pure autonomic failure from multiple system atrophy and non-synucleinopathy-related autonomic failure.
May aid PAF vs MSA differentiation in autonomic failure; leaves open prospective validation before clinical adoption.
BACKGROUND: Pure autonomic failure (PAF) presents with progressive autonomic failure without other neurological features. Atypical presentations may lead to diagnostic uncertainty. We studied whether cutaneous phosphorylated-alpha-synuclein (p-syn) could distinguish between PAF, multiple system atrophy (MSA) and non-synucleinopathy-related autonomic failure, and examined its relationship with quantitative markers of cardiovascular autonomic failure. METHODS: All individuals underwent Composite Autonomic Symptom Score-31 autonomic questionnaires, cardiovascular autonomic testing and bilateral distal leg skin biopsies. We noted whether p-syn was present in nerves supplying autonomic adnexa, including sweat glands, blood vessels, arrector pili muscles, and subepidermal fibres, dermal fibres and nerve fascicles (maximum autonomic subscore 3, total p-syn score 6 for each sample, average calculated for both sides). RESULTS: 36 individuals were studied: 11 PAF, 13 MSA and 12 non-synucleinopathy-related autonomic failure. P-syn was present in 22/22 (100%) PAF biopsies, 19/26 (73%) MSA biopsies and 0/22 (0%) non-synucleinopathy biopsies. Mean total p-syn score was significantly higher in PAF compared with MSA (median 4.5 vs 1, p<0.001). Total p-syn score >3 distinguished PAF from MSA with 100% specificity and 82% sensitivity. Autonomic p-syn subscores correlated with orthostatic intolerance ratio on tilt (ρ=0.63, p=0.0004), blood pressure recovery time following Valsalva manoeuvre (r=0.44, p=0.03) and patient-reported orthostatic intolerance (ρ=0.57, p=0.006). CONCLUSION: Cutaneous p-syn was abundant in PAF, a predominantly peripheral alpha-synucleinopathy. It is a promising biomarker to help distinguish between PAF, MSA and non-synucleinopathy-related autonomic failure to aid early diagnosis and recruitment to future clinical trials. P-syn deposition on autonomic nerves may impair control of total peripheral resistance giving rise to symptomatic orthostatic hypotension.
No takes yet. Share an insight, caveat, or question.
Koay et al. (2024) conducted a cross-sectional in Pure autonomic failure (n=36). Cutaneous phosphorylated-alpha-synuclein (p-syn) vs. Multiple system atrophy and non-synucleinopathy-related autonomic failure was evaluated on Mean total p-syn score (p=<0.001). Cutaneous phosphorylated-alpha-synuclein scores were significantly higher in pure autonomic failure compared to multiple system atrophy (median 4.5 vs 1, P<0.001).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: