Henrike Hanssen1,2, Jannik Prasuhn1,2, Marcus Heldmann1, Cid C Diesta3, Aloysius Domingo2,4, Martin Göttlich1, Anne J Blood5,6,7,8,9,10, Raymond L Rosales11, Roland D G Jamora12, Thomas F Münte1, Christine Klein2, Norbert Brüggemann1,2. 1. Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. 2. Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. 3. Asian Hospital and Medical Center, Filinvest Corporate City, Alabang, Muntinlupa City, the Philippines. 4. Department of Neurology, Massachusetts General Hospital, Boston, MA. 5. Mood and Motor Control Laboratory, Massachusetts General Hospital, Charlestown, MA. 6. Laboratory of Neuroimaging and Genetics, Massachusetts General Hospital, Charlestown, MA. 7. Department of Neurology and Psychiatry, Massachusetts General Hospital, Boston, MA. 8. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA. 9. Division of Child Neurology, Boston Children's Hospital, Boston, MA. 10. Harvard Medical School, Boston, MA. 11. Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, the Philippines. 12. Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, the Philippines.
Abstract
OBJECTIVE: X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease with adult onset dystonia and subsequent parkinsonism. Postmortem and imaging studies revealed remarkable striatal pathology, with a predominant involvement of the striosomal compartment in the early phase. Here, we aimed to disentangle sequential neurodegeneration in the striatum of XDP patients, provide evidence for preferential loss of distinct striatal areas in the early phase, and investigate whether iron accumulation is present. METHODS: We used multimodal structural magnetic resonance imaging (voxel-based morphometry and relaxometry) in 18 male XDP patients carrying a TAF1 mutation and 19 age-matched male controls. RESULTS: Voxel-based relaxometry and morphometry revealed (1) a cluster in the anteromedial putamen showing high iron content and severe atrophy (-55%) and (2) a cluster with reduced relaxation rates as a marker for increased water levels and a lower degree of atrophy (-20%) in the dorsolateral putamen. Iron deposition correlated with the degree of atrophy (ρ = -0.585, p = 0.011) and disease duration (ρ = 0.632, p = 0.005) in the anteromedial putamen. In the dorsolateral putamen, sensorimotor putamen atrophy correlated with disease severity (ρ = -0.649, p = 0.004). INTERPRETATION: This multimodal approach identified a patchy pattern of atrophy within the putamen. Atrophy is advanced and associated with iron accumulation in rostral regions of the striatum, whereas neurodegeneration is moderate and still ongoing in dorsolateral areas. Given the short disease duration and predominant dystonic phenotype, these results are well in line with early and preferential degeneration of striosome-rich striatal areas in XDP. ANN NEUROL 2019;86:517-526.
OBJECTIVE:X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease with adult onset dystonia and subsequent parkinsonism. Postmortem and imaging studies revealed remarkable striatal pathology, with a predominant involvement of the striosomal compartment in the early phase. Here, we aimed to disentangle sequential neurodegeneration in the striatum of XDP patients, provide evidence for preferential loss of distinct striatal areas in the early phase, and investigate whether iron accumulation is present. METHODS: We used multimodal structural magnetic resonance imaging (voxel-based morphometry and relaxometry) in 18 male XDP patients carrying a TAF1 mutation and 19 age-matched male controls. RESULTS: Voxel-based relaxometry and morphometry revealed (1) a cluster in the anteromedial putamen showing high iron content and severe atrophy (-55%) and (2) a cluster with reduced relaxation rates as a marker for increased water levels and a lower degree of atrophy (-20%) in the dorsolateral putamen. Iron deposition correlated with the degree of atrophy (ρ = -0.585, p = 0.011) and disease duration (ρ = 0.632, p = 0.005) in the anteromedial putamen. In the dorsolateral putamen, sensorimotor putamen atrophy correlated with disease severity (ρ = -0.649, p = 0.004). INTERPRETATION: This multimodal approach identified a patchy pattern of atrophy within the putamen. Atrophy is advanced and associated with iron accumulation in rostral regions of the striatum, whereas neurodegeneration is moderate and still ongoing in dorsolateral areas. Given the short disease duration and predominant dystonic phenotype, these results are well in line with early and preferential degeneration of striosome-rich striatal areas in XDP. ANN NEUROL 2019;86:517-526.
Authors: Jamal Al Ali; Christine A Vaine; Shivangi Shah; Lindsey Campion; Ahmad Hakoum; Melanie L Supnet; Patrick Acuña; Gabrielle Aldykiewicz; Trisha Multhaupt-Buell; Niecy G M Ganza; John B B Lagarde; Jan K De Guzman; Criscely Go; Benjamin Currall; Bianca Trombetta; Pia K Webb; Michael Talkowski; Steven E Arnold; Pike S Cheah; Naoto Ito; Nutan Sharma; D Cristopher Bragg; Laurie Ozelius; Xandra O Breakefield Journal: Mov Disord Date: 2020-09-25 Impact factor: 10.338