Skin intraneural phosphorylated α-synuclein is a highly specific biomarker for early Parkinson’s disease
Notice bibliographique
Résumé
The early diagnosis of Parkinson's disease (PD) represents a challenge, and novel accurate biomarkers are therefore needed urgently. Detection of phosphorylated α-synuclein (p-α-syn) in skin nerve fibres has shown promise as such a marker. However, its accuracy for the identification of PD among patients with early signs of parkinsonism has not been explored thoroughly. In this blinded, multicentre, prospective and follow-up study, 151 patients diagnosed with early-stage parkinsonism (<18 months duration) were enrolled at three tertiary movement disorder centres. Clinical scales were performed, and initial diagnoses were reassessed at 18- and 46-month follow-up visits. Skin biopsy, with analysis for neuronal and glial p-α-syn deposits, and olfactory testing were performed at the baseline visit and repeated in 44 patients at the 18-month visit. After the follow-up period, a final diagnosis was reached in 140 patients: PD (n = 101; 67% of all screened patients), tauopathies (n = 22; 15%), multiple system atrophy (n = 5; 3%), vascular parkinsonism (n = 4; 3%), essential tremor (n = 3; 2%), dystonic tremor (n = 2; 1%) and no neurological illness (n = 3, 2%). Eleven patients did not fit any clinical criteria and were therefore classified as undefined. Baseline skin intraneural p-α-syn showed a robust diagnostic accuracy (81% sensitivity and 100% specificity) for identifying PD. Importantly, in 30 of 44 patients not diagnosed with PD until the follow-up, intraneural p-α-syn was already positive at baseline. Moreover, the analyses showed a large degree of consistency over time, in that the same results at baseline and follow-up were obtained in 42 (96%) of the patients tested. Finally, although olfactory testing at baseline showed a more abnormal score in PD compared with the other groups, its predictive accuracy was more modest (72%). In conclusion, given its high sensitivity, specificity and reproducibility, skin intraneural p-α-syn could become a valuable tool for diagnosing PD at early stages, potentially years before the diagnostic criteria are met, and for differentiating PD from atypical parkinsonism. In contrast, olfactory function, although more impaired in PD than in non-PD patients, seems to have only a more limited diagnostic accuracy.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».