Muscle Biopsy Findings in Valosin-Containing Protein Multisystem Proteinopathy.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Schiava Marianela, Parkhurst Yolande, Henderson Matthew, Polvikoski Tuomo, Valtcheva Manouela V, Nishino Ichizo, Inoue Michio, Nishimori Yukako, Saito Yoshihiko, Stojkovic Tanya, Villar-Quiles Rocio N, Romero Norma Beatriz, Evangelista Teresinha, Malfatti Edoardo, Souvannanorath Sarah, Pegoraro Elena, Riguzzi Pietro, Monforte Mauro, Bortolani Sara, Torchia Eleonora, Sabatelli Mario, Tasca Giorgio, Straub Volker, Marini-Bettolo Chiara, Guglieri Michela, Cetin Hakan, Gelpi Ellen, Klotz Sigrid, De Bleecker Jan L, Alonso-Jimenez Alicia, Baets Jonathan, De Ridder Willem, De Jonghe Peter, Claeys Kristl G, Thal Dietmar Rudolf, Bevilacqua Jorge A, Luo Sushan, Zhu Wenhua, Lin Jie, Papadimas George, Papadopoulos Constantinos, Zamba-Papanicolaou Eleni, Xirou Sophia, Pal Endre, Rodolico Carmelo, Kostera-Pruszczyk Anna, Kierdaszuk Biruta, Kaminska Anna, Muelas Nuria, Vilchez Juan Jesus, Domínguez-González Cristina, Hernandez-Lain Aurelio, Alonso-Perez Jorge, Nedkova-Hristova Velina, Aledo Carlos, Oldfors Anders, Badrising Umesh A, Kushlaf Hani, Lloyd Thomas E, Ikenaga Chiseko, Alfano Lindsay N, Quinn Colin C, Walk David, Vorgerd Matthias, Weihl Conrad, Olivé Montse, Diaz-Manera Jordi, VCP International Study Group
Аннотация
METHODS: Muscle biopsy images and data were collected retrospectively from adults (≥18 years) with pathogenic or likely pathogenic VCP variants enrolled in the VCP Multicentre International Study. Biopsy data were standardized using the "Common Data Elements for Muscle Biopsy Reporting." Variations in biopsy findings were analysed by biopsy site, time from disease onset, the four most common VCP variants, and clinical phenotypes.
RESULT: A total of 112 muscle biopsies were included. Most individuals were male (66.0%). The mean age at biopsy was 53.3 years (SD 10.0), with a mean disease duration of 6.5 years (SD 4.5). The most frequent VCP variant was c.464G>A (p.Arg155His) (18.8%). The top clinical phenotypes were isolated myopathy (37.5%), myopathy with Paget disease of bone (17.9%), and myopathy with motor neuron involvement (13.4%). The vastus lateralis was the most common biopsy site (34.8%), and 91% were open biopsies. Histopathologic findings included atrophic fibres (87.5%), rimmed vacuoles (72.3%), endomysial fibrosis (58.0%), and protein aggregates (51.8%), primarily p62 (60.3%) and VCP (36.2%). Degeneration niches with fibrofatty replacement and atrophic fibres were seen in 33.3% of biopsies without frequency differences by clinical phenotypes. There were no differences in biopsy findings among the 4 most common VCP gene variants, except for the absence of degeneration niches in muscle biopsies of 12 patients with c.277C>T (p.Arg93Cys). MRI data from 30 patients showed fat pockets corresponding to these niches and STIR hyperintensity correlated with inflammatory infiltrates in 42.9%. Concordance between clinical phenotype, biopsy, and neurophysiology was observed in only 49.4% of cases, indicating significant heterogeneity.
DISCUSSION: VCP-MSP muscle biopsies consistently show myopathic or mixed patterns with rimmed vacuoles and p62/VCP-positive inclusions, regardless of clinical phenotype, age, or progression. Some lack vacuoles, challenging diagnosis. Discrepancies between clinical, neurophysiology, and biopsy findings should prompt consideration of VCP-MSP to improve detection and management.