Norbert Brüggemann1, Marcus Heldmann2, Christine Klein3, Aloysius Domingo3, Dirk Rasche4, Volker Tronnier4, Raymond L Rosales5, Roland Dominic G Jamora6, Lillian V Lee7, Thomas F Münte2. 1. Department of Neurology, University of Lübeck, Lübeck, Germany; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. Electronic address: norbert.brueggemann@neuro.uni-luebeck.de. 2. Department of Neurology, University of Lübeck, Lübeck, Germany. 3. Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. 4. Department of Neurosurgery, University of Lübeck, Lübeck, Germany. 5. XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines. 6. XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines; Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines. 7. XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines.
Abstract
BACKGROUND: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset basal ganglia model disease associated with severe striatal atrophy. Anatomical changes exceeding striatal pathology were not yet described in XDP. The present study aimed to assess the microstructure of white matter tracts in XDP using magnetic resonance tomography. METHODS: Diffusion-weighted imaging was done in 10 XDP patients, aged 42.2 years (SD 8.1), and 14 ethnicity and age-matched controls, aged 40.2 years (SD 6.4). Based on diffusion tensor images, mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated. RESULTS: Except for in the occipital lobe, XDP patients showed generally increased MD values across the entire white matter. FA map analysis identified four significant clusters with controls showing higher FA values than XDP patients. Involved regions included the fornix, anterior thalamic radiation, corticospinal tract, and superior corona radiata bilaterally. In the fornix and the anterior thalamic radiation, the UPDRSIII total score showed a negative correlation with mean FA values at a trend level (tau = -0.40, p = 0.053). Volumetric analysis revealed significant gray matter volume loss of putamen (F(1,19) = 44.2, p < 0.001), caudate nucleus (F(1,19) = 54.3, p < 0.001), and pallidum (F(1,19) = 8.9, p = 0.007). CONCLUSIONS: The present study confirms striatal atrophy in XDP and provides evidence for a strong involvement of the white matter and the pallidum. This calls into question the previously held concept of exclusive striatal atrophy in this unique movement disorder. The spared occipital region may point towards a lack of anatomical connections with the atrophied striatum.
BACKGROUND:X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset basal ganglia model disease associated with severe striatal atrophy. Anatomical changes exceeding striatal pathology were not yet described in XDP. The present study aimed to assess the microstructure of white matter tracts in XDP using magnetic resonance tomography. METHODS: Diffusion-weighted imaging was done in 10 XDP patients, aged 42.2 years (SD 8.1), and 14 ethnicity and age-matched controls, aged 40.2 years (SD 6.4). Based on diffusion tensor images, mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated. RESULTS: Except for in the occipital lobe, XDP patients showed generally increased MD values across the entire white matter. FA map analysis identified four significant clusters with controls showing higher FA values than XDP patients. Involved regions included the fornix, anterior thalamic radiation, corticospinal tract, and superior corona radiata bilaterally. In the fornix and the anterior thalamic radiation, the UPDRSIII total score showed a negative correlation with mean FA values at a trend level (tau = -0.40, p = 0.053). Volumetric analysis revealed significant gray matter volume loss of putamen (F(1,19) = 44.2, p < 0.001), caudate nucleus (F(1,19) = 54.3, p < 0.001), and pallidum (F(1,19) = 8.9, p = 0.007). CONCLUSIONS: The present study confirms striatal atrophy in XDP and provides evidence for a strong involvement of the white matter and the pallidum. This calls into question the previously held concept of exclusive striatal atrophy in this unique movement disorder. The spared occipital region may point towards a lack of anatomical connections with the atrophied striatum.
Authors: Norbert Brüggemann; Aloysius Domingo; Dirk Rasche; Christian K E Moll; Raymond L Rosales; Roland Dominic G Jamora; Henrike Hanssen; Alexander Münchau; Julia Graf; Anne Weissbach; Vera Tadic; Cid C Diesta; Jens Volkmann; Andrea Kühn; Thomas F Münte; Volker Tronnier; Christine Klein Journal: JAMA Neurol Date: 2019-02-01 Impact factor: 18.302
Authors: D Cristopher Bragg; Kotchaphorn Mangkalaphiban; Christine A Vaine; Nichita J Kulkarni; David Shin; Rachita Yadav; Jyotsna Dhakal; Mai-Linh Ton; Anne Cheng; Christopher T Russo; Mark Ang; Patrick Acuña; Criscely Go; Taylor N Franceour; Trisha Multhaupt-Buell; Naoto Ito; Ulrich Müller; William T Hendriks; Xandra O Breakefield; Nutan Sharma; Laurie J Ozelius Journal: Proc Natl Acad Sci U S A Date: 2017-12-11 Impact factor: 11.205
Authors: Anne J Blood; Jeff L Waugh; Thomas F Münte; Marcus Heldmann; Aloysius Domingo; Christine Klein; Hans C Breiter; Lillian V Lee; Raymond L Rosales; Norbert Brüggemann Journal: Neuroimage Clin Date: 2017-10-28 Impact factor: 4.881