Pub Date : 2022-09-01DOI: 10.1136/jnnp-2022-ehdn.91
N. Hobbs, M. Papoutsi, A. Delva, W. Vandenberghe, K. Laere, Mitsuko Nakajima, K. Kinnunen, R. Scahill
{"title":"E15 How useful is neuroimaging in clinical trials of Huntington’s disease? Current opinion from the ehdn imaging working group","authors":"N. Hobbs, M. Papoutsi, A. Delva, W. Vandenberghe, K. Laere, Mitsuko Nakajima, K. Kinnunen, R. Scahill","doi":"10.1136/jnnp-2022-ehdn.91","DOIUrl":"https://doi.org/10.1136/jnnp-2022-ehdn.91","url":null,"abstract":"","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133631426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1136/jnnp-2022-ehdn.82
A. J. Lowe, F. B. Rodrigues, M. Arridge, E. Vita, E. Johnson, R. Scahill, L. Byrne, R. Tortelli, A. Heslegrave, Henrik Zetterberg, E. Wild
{"title":"E05 Longitudinal evaluation of magnetic resonance spectroscopy metabolites as biomarkers in Huntington’s disease","authors":"A. J. Lowe, F. B. Rodrigues, M. Arridge, E. Vita, E. Johnson, R. Scahill, L. Byrne, R. Tortelli, A. Heslegrave, Henrik Zetterberg, E. Wild","doi":"10.1136/jnnp-2022-ehdn.82","DOIUrl":"https://doi.org/10.1136/jnnp-2022-ehdn.82","url":null,"abstract":"","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127119673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1136/jnnp-2022-ehdn.89
Maitrei Kohli, D. Pustina, John H. Warner, Daniel C. Alexander, R. Scahill, S. Tabrizi, P. Wijeratne
{"title":"E13 Predicting Huntington’s disease state using structural MRI: it’s more than just the striatum","authors":"Maitrei Kohli, D. Pustina, John H. Warner, Daniel C. Alexander, R. Scahill, S. Tabrizi, P. Wijeratne","doi":"10.1136/jnnp-2022-ehdn.89","DOIUrl":"https://doi.org/10.1136/jnnp-2022-ehdn.89","url":null,"abstract":"","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134041853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1136/jnnp-2022-ehdn.88
Annabelle Coleman, Mackenzie T Langan, G. Verma, Harry Knights, R. D. Dar Santos, A. Coleman, A. Sturrock, B. Leavitt, S. Tabrizi, R. Scahill, N. Hobbs
{"title":"E12 In vivo investigation of perivascular spaces in Huntington’s disease using T2-W 3T MRI","authors":"Annabelle Coleman, Mackenzie T Langan, G. Verma, Harry Knights, R. D. Dar Santos, A. Coleman, A. Sturrock, B. Leavitt, S. Tabrizi, R. Scahill, N. Hobbs","doi":"10.1136/jnnp-2022-ehdn.88","DOIUrl":"https://doi.org/10.1136/jnnp-2022-ehdn.88","url":null,"abstract":"","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134631837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1136/jnnp-2021-ehdn.43
Carla Guerreiro, L. Guedes, Madalena Rosário, G. Galati, David Berhanu, R. Simões, J. Ferreira, S. Reimão
Background Nigrostriatal dopaminergic neuron degeneration with loss of Substantia Nigra (SN) and Locus Coeruleus (LC) neurons, as well as disruption of iron homeostasis, have been reported in Huntington’s Disease (HD), but literature is still scarce. Recently developed magnetic resonance imaging (MRI) biomarkers, such as neuromelanin-sensitive MRI (NM-MRI) and Nigrosome-1 (N1) visualization on susceptibility-weighted imaging (SWI), permit in vivo evaluation of changes in NM containing neurons of the SN and LC and in iron deposition. Aim The aim of this study was to use these novel MRI methods to further clarify SN and LC involvement in HD, through visual analysis. Methods Cross-sectional comparative study analyzing NM and N1 in HD patients and healthy controls (HC). Visual analysis of the SN and LC NM and of the N1 was performed. Fisher’s exact test was used to compare visual analysis ratings between groups. Additionally, SN NM area was obtained using semi-automatic segmentation and median area was used for non-parametric analysis. Results Twelve HD patients and 13 HC were included. LC and SN NM signal intensity were found to be consistently reduced in HD. Visual and semi-quantitative analysis of the SN-NM area did not show significant differences between the groups. No significant differences were found in the analysis of the N1. Conclusions Reduction of LC and SN NM signal on NM-MRI corroborates previous neuropathological findings suggesting striatonigral dysfunction in symptomatic HD patients. Our results suggest that visual analysis may be useful for the evaluation of NM-MRI and N1 in HD patients in clinical settings.
{"title":"E09 Magnetic resonance imaging visual analysis of neuromelanin and nigrosome-1 for the assessment of striatonigral disfunction in huntington’s disease","authors":"Carla Guerreiro, L. Guedes, Madalena Rosário, G. Galati, David Berhanu, R. Simões, J. Ferreira, S. Reimão","doi":"10.1136/jnnp-2021-ehdn.43","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.43","url":null,"abstract":"Background Nigrostriatal dopaminergic neuron degeneration with loss of Substantia Nigra (SN) and Locus Coeruleus (LC) neurons, as well as disruption of iron homeostasis, have been reported in Huntington’s Disease (HD), but literature is still scarce. Recently developed magnetic resonance imaging (MRI) biomarkers, such as neuromelanin-sensitive MRI (NM-MRI) and Nigrosome-1 (N1) visualization on susceptibility-weighted imaging (SWI), permit in vivo evaluation of changes in NM containing neurons of the SN and LC and in iron deposition. Aim The aim of this study was to use these novel MRI methods to further clarify SN and LC involvement in HD, through visual analysis. Methods Cross-sectional comparative study analyzing NM and N1 in HD patients and healthy controls (HC). Visual analysis of the SN and LC NM and of the N1 was performed. Fisher’s exact test was used to compare visual analysis ratings between groups. Additionally, SN NM area was obtained using semi-automatic segmentation and median area was used for non-parametric analysis. Results Twelve HD patients and 13 HC were included. LC and SN NM signal intensity were found to be consistently reduced in HD. Visual and semi-quantitative analysis of the SN-NM area did not show significant differences between the groups. No significant differences were found in the analysis of the N1. Conclusions Reduction of LC and SN NM signal on NM-MRI corroborates previous neuropathological findings suggesting striatonigral dysfunction in symptomatic HD patients. Our results suggest that visual analysis may be useful for the evaluation of NM-MRI and N1 in HD patients in clinical settings.","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125701672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1136/jnnp-2021-ehdn.42
M. D. Ayllón, C. García-Gorro, S. Martínez-Horta, J. Pérez-Pérez, J. Kulisevsky, N. Rodríguez-Dechicha, I. Vaquer, S. Subirà, M. Calopa, E. Muñoz, P. Santacruz, Jesús Ruiz-Idiago, C. Mareca, R. D. Diego-Balaguer, E. Càmara
Background HD is a suitable model to monitor the whole neurodegeneration process. Huntington’s disease (HD) affects primarily the striatum, but loss of white matter (WM) integrity and iron homeostasis disruption have been also described. These anomalies together with metabolite profiles could unveil the pathophysiologic mechanisms involved. Aims To assess the temporal and spatial progression of neurodegeneration on both anterior thalamic radiations (ATR). Methods Thirty-one HD gene carriers and twenty-four controls underwent neuropsychological evaluation and were scanned at 3T-MRI unit. A multimodal study was conducted to measure relaxometry, diffusivity and spectroscopy as proxies of iron, WM microstructure and metabolite composition, respectively. Three statistical approaches (average, segmental, along-the-tract) were performed, with MANOVA and post-hoc Tukey test to evaluate differences among groups and Pearson test to assess correlations. Results ATR disintegration began in premanifest individuals and progressed in extent and severity in manifest patients. WM damage was more extensive in the right ATR that could translate a higher vulnerability and showed a spatial gradient from subcortical to deep WM in favour of the dying-back hypothesis. Iron was increased in the left ATR in premanifest individuals that might uncover a dysregulated myelination or an abnormal ferritin accumulation. NAA and creatine decreased exclusively in manifest patients suggesting neuronal loss and mitochondrial dysfunction. Furthermore, imaging parameters could be used as biomarkers given their links with clinical scores. Conclusions The complex neurodegeneration pattern of ATR in HD can help to understand the pathophysiological mechanisms underlying HD progression. The multimodal approach and along-the-tract analysis allow for a more comprehensive evaluation of neurodegeneration.
{"title":"E08 Tracking the neurodegeneration pattern of the anterior thalamic radiations in HD: a focus on brain iron, white matter integrity and metabolites","authors":"M. D. Ayllón, C. García-Gorro, S. Martínez-Horta, J. Pérez-Pérez, J. Kulisevsky, N. Rodríguez-Dechicha, I. Vaquer, S. Subirà, M. Calopa, E. Muñoz, P. Santacruz, Jesús Ruiz-Idiago, C. Mareca, R. D. Diego-Balaguer, E. Càmara","doi":"10.1136/jnnp-2021-ehdn.42","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.42","url":null,"abstract":"Background HD is a suitable model to monitor the whole neurodegeneration process. Huntington’s disease (HD) affects primarily the striatum, but loss of white matter (WM) integrity and iron homeostasis disruption have been also described. These anomalies together with metabolite profiles could unveil the pathophysiologic mechanisms involved. Aims To assess the temporal and spatial progression of neurodegeneration on both anterior thalamic radiations (ATR). Methods Thirty-one HD gene carriers and twenty-four controls underwent neuropsychological evaluation and were scanned at 3T-MRI unit. A multimodal study was conducted to measure relaxometry, diffusivity and spectroscopy as proxies of iron, WM microstructure and metabolite composition, respectively. Three statistical approaches (average, segmental, along-the-tract) were performed, with MANOVA and post-hoc Tukey test to evaluate differences among groups and Pearson test to assess correlations. Results ATR disintegration began in premanifest individuals and progressed in extent and severity in manifest patients. WM damage was more extensive in the right ATR that could translate a higher vulnerability and showed a spatial gradient from subcortical to deep WM in favour of the dying-back hypothesis. Iron was increased in the left ATR in premanifest individuals that might uncover a dysregulated myelination or an abnormal ferritin accumulation. NAA and creatine decreased exclusively in manifest patients suggesting neuronal loss and mitochondrial dysfunction. Furthermore, imaging parameters could be used as biomarkers given their links with clinical scores. Conclusions The complex neurodegeneration pattern of ATR in HD can help to understand the pathophysiological mechanisms underlying HD progression. The multimodal approach and along-the-tract analysis allow for a more comprehensive evaluation of neurodegeneration.","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115685481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1136/jnnp-2021-ehdn.37
M. Caligiuri, P. Vizza, P. Veltri, F. Cicone, Paolo Barberio, G. Cascini, E. Scaricamazza, Sabrina Maffi, S. Migliore, F. Squitieri, U. Sabatini
Background Juvenile-onset Huntington’s disease (joHD, neurological onset ≤20 years) is a rare HD variant associated with large CAG repeat-size alleles (>60), showing different clinical features from adulthood HD. Aims The aim of this study is twofold: i) To evaluate multimodal hybrid PET-MRI data fusion for characterizing joHD longitudinal brain changes; ii) to identify potential markers of disease progression, which might be useful in future trials to test disease-modifying drugs. Methods A 20-year-old female with stage-2 joHD, 62 CAG repeats and onset at 16 years, underwent 3T [18F]fluorodeoxyglucose (FDG) PET-MRI at two timepoints (Oct 2019, UHDRS-motor score=45 units and Feb 2021, UHDRS-motor score=53 units). The protocol included the simultaneous acquisition of FDG-PET, T1-weighted and resting-state functional MRI (rs-fMRI). Voxel-wise percentage changes at follow-up relative to baseline status were calculated on (i) grey matter (GM) density, (ii) FDG-PET uptake, (iii) rs-fMRI regional homogeneity (ReHo), and (iv) rs-fMRI amplitude of low frequency fluctuation (fALFF). Results Whole-brain GM density decreased by 31.9±21.1%. FDG uptake increased in the frontoparietal network (approx. 20%), while decreasing in the remaining regions, including the thalamus. ReHo and fALFF followed the pattern of PET changes, also highlighting increased functional connectivity in the frontal cortex opposed to decreased connectivity in posterior regions. Conclusion Hybrid PET/MRI is an emerging technique that allows individually-tailored evaluation of brain changes. Preliminary results are promising and showed rapid structural and metabolic changes in an adult patient with stage 2 joHD, resembling the trajectories reported in the literature in advanced adult HD patients, and involving specific regions thought to be key hubs affected by this disease.
{"title":"E02 Longitudinal hybrid PET/MRI in juvenile-onset huntington disease (joHD)","authors":"M. Caligiuri, P. Vizza, P. Veltri, F. Cicone, Paolo Barberio, G. Cascini, E. Scaricamazza, Sabrina Maffi, S. Migliore, F. Squitieri, U. Sabatini","doi":"10.1136/jnnp-2021-ehdn.37","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.37","url":null,"abstract":"Background Juvenile-onset Huntington’s disease (joHD, neurological onset ≤20 years) is a rare HD variant associated with large CAG repeat-size alleles (>60), showing different clinical features from adulthood HD. Aims The aim of this study is twofold: i) To evaluate multimodal hybrid PET-MRI data fusion for characterizing joHD longitudinal brain changes; ii) to identify potential markers of disease progression, which might be useful in future trials to test disease-modifying drugs. Methods A 20-year-old female with stage-2 joHD, 62 CAG repeats and onset at 16 years, underwent 3T [18F]fluorodeoxyglucose (FDG) PET-MRI at two timepoints (Oct 2019, UHDRS-motor score=45 units and Feb 2021, UHDRS-motor score=53 units). The protocol included the simultaneous acquisition of FDG-PET, T1-weighted and resting-state functional MRI (rs-fMRI). Voxel-wise percentage changes at follow-up relative to baseline status were calculated on (i) grey matter (GM) density, (ii) FDG-PET uptake, (iii) rs-fMRI regional homogeneity (ReHo), and (iv) rs-fMRI amplitude of low frequency fluctuation (fALFF). Results Whole-brain GM density decreased by 31.9±21.1%. FDG uptake increased in the frontoparietal network (approx. 20%), while decreasing in the remaining regions, including the thalamus. ReHo and fALFF followed the pattern of PET changes, also highlighting increased functional connectivity in the frontal cortex opposed to decreased connectivity in posterior regions. Conclusion Hybrid PET/MRI is an emerging technique that allows individually-tailored evaluation of brain changes. Preliminary results are promising and showed rapid structural and metabolic changes in an adult patient with stage 2 joHD, resembling the trajectories reported in the literature in advanced adult HD patients, and involving specific regions thought to be key hubs affected by this disease.","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"149 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133049867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1136/jnnp-2021-ehdn.40
C. Casella, Maxime Chamberland, P. L. Laguna, G. Parker, A. Rosser, E. Coulthard, H. Rickards, Derek K. Jones, C. Metzler-Baddeley
Background White matter (WM) impairments precede striatal atrophy and motor symptoms in Huntington’s disease (HD) but their aetiology remains unknown. Aims We exploited ultra-strong gradient MRI to disentangle the contribution of changes in axon microstructure versus changes in myelin to WM pathology in HD. Methods We assessed apparent myelin [with the magnetization transfer ratio (MTR)], and axon density [with the restricted volume fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED)] in premanifest HD patients and age- and sex-matched controls. Group differences in diffusion tensor MRI measures were also assessed. We investigated region-specific changes across the corpus callosum (CC) with tractometry and brain-wise WM microstructure abnormalities with tract-based cluster analysis (TBCA). Behavioural measures were included to explore disease-associated brain-function relationships. Results We detected lower apparent myelin in the posterior CC of patients (tractometry: p = 0.0343; TBCA: p = 0.030), and higher apparent myelin in the anterior CC (tractometry: p = 0.016). A positive association between apparent myelin and mutation size in patients (all p-values Conclusions We provide novel in vivo evidence for myelin-based WM alterations as an early feature of human HD. Critical pathogenic events were present in mutation carriers prior to clinical onset, emphasising the importance of understanding the mechanisms underlying early WM abnormalities for the discovery of new therapeutic approaches.
背景:亨廷顿舞蹈病(HD)患者纹状体萎缩和运动症状之前存在白质(WM)损伤，但其病因尚不清楚。目的:利用超强梯度MRI分析轴突微结构变化和髓磷脂变化对HD WM病理的影响。方法:我们评估了前期HD患者和年龄、性别匹配的对照组的表观髓磷脂(用磁化传递比(MTR))和轴突密度(用限制体积分数(FR)从复合阻碍和限制扩散模型(魔)中获得)。还评估了弥散张量MRI测量的组间差异。我们利用束测法研究了胼胝体(CC)的区域特异性变化，并利用基于束的聚类分析(TBCA)研究了脑内WM微观结构异常。包括行为测量来探索疾病相关的脑功能关系。结果我们在患者CC后部检测到较低的表观髓磷脂(tractometry: p = 0.0343;TBCA: p = 0.030)， CC前部明显高髓磷脂(束量计:p = 0.016)。结论:我们提供了新的体内证据，证明髓磷脂为基础的WM改变是人类HD的早期特征。关键的致病事件在临床发病之前就存在于突变携带者中，这强调了了解早期WM异常的机制对于发现新的治疗方法的重要性。
{"title":"E05 Mutation-related apparent myelin, not axon density, drives white matter pathology in premanifest huntington’s disease: evidence from in vivo ultra-strong gradient MRI","authors":"C. Casella, Maxime Chamberland, P. L. Laguna, G. Parker, A. Rosser, E. Coulthard, H. Rickards, Derek K. Jones, C. Metzler-Baddeley","doi":"10.1136/jnnp-2021-ehdn.40","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.40","url":null,"abstract":"Background White matter (WM) impairments precede striatal atrophy and motor symptoms in Huntington’s disease (HD) but their aetiology remains unknown. Aims We exploited ultra-strong gradient MRI to disentangle the contribution of changes in axon microstructure versus changes in myelin to WM pathology in HD. Methods We assessed apparent myelin [with the magnetization transfer ratio (MTR)], and axon density [with the restricted volume fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED)] in premanifest HD patients and age- and sex-matched controls. Group differences in diffusion tensor MRI measures were also assessed. We investigated region-specific changes across the corpus callosum (CC) with tractometry and brain-wise WM microstructure abnormalities with tract-based cluster analysis (TBCA). Behavioural measures were included to explore disease-associated brain-function relationships. Results We detected lower apparent myelin in the posterior CC of patients (tractometry: p = 0.0343; TBCA: p = 0.030), and higher apparent myelin in the anterior CC (tractometry: p = 0.016). A positive association between apparent myelin and mutation size in patients (all p-values Conclusions We provide novel in vivo evidence for myelin-based WM alterations as an early feature of human HD. Critical pathogenic events were present in mutation carriers prior to clinical onset, emphasising the importance of understanding the mechanisms underlying early WM abnormalities for the discovery of new therapeutic approaches.","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124961150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1136/jnnp-2021-ehdn.36
A. Delva, Laura Michiels, M. Koole, K. V. Laere, W. Vandenberghe
Background Synaptic damage has long been suspected to play a major role in the pathophysiology of Huntington disease (HD), but in vivo evidence in humans is limited. Aim To assess synaptic damage in early stages of HD in vivo. Methods Eighteen HD mutation carriers (7 premanifest, 11 early manifest; 51.4±11.6 years; 6 female) and 15 age- and gender-matched healthy controls (52.3±3.5 years; 4 female) were included. Subjects underwent clinical assessment of motor and non-motor manifestations, MRI, PET with 11C-UCB-J, a radioligand targeting the ubiquitous presynaptic terminal marker SV2A, and 18F-FDG PET. Standardized uptake value ratio -1 images were calculated for 11C-UCB-J with the centrum semiovale as reference region. 18F-FDG PET activity was normalized to the pons. All PET data were corrected for partial volume effects. Results 11C-UCB-J PET showed loss of SV2A binding in the HD group in putamen (-28%, p Conclusion 11C-UCB-J PET revealed extensive loss of SV2A in early HD, suggesting widespread synaptic disconnection. SV2A loss in the striatum correlated with motor and cognitive functioning. 11C-UCB-J PET is more sensitive than 18F-FDG PET for detection of extrAstriatal changes in early HD.
{"title":"E01 Widespread loss of presynaptic terminal marker SV2A in early huntington disease","authors":"A. Delva, Laura Michiels, M. Koole, K. V. Laere, W. Vandenberghe","doi":"10.1136/jnnp-2021-ehdn.36","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.36","url":null,"abstract":"Background Synaptic damage has long been suspected to play a major role in the pathophysiology of Huntington disease (HD), but in vivo evidence in humans is limited. Aim To assess synaptic damage in early stages of HD in vivo. Methods Eighteen HD mutation carriers (7 premanifest, 11 early manifest; 51.4±11.6 years; 6 female) and 15 age- and gender-matched healthy controls (52.3±3.5 years; 4 female) were included. Subjects underwent clinical assessment of motor and non-motor manifestations, MRI, PET with 11C-UCB-J, a radioligand targeting the ubiquitous presynaptic terminal marker SV2A, and 18F-FDG PET. Standardized uptake value ratio -1 images were calculated for 11C-UCB-J with the centrum semiovale as reference region. 18F-FDG PET activity was normalized to the pons. All PET data were corrected for partial volume effects. Results 11C-UCB-J PET showed loss of SV2A binding in the HD group in putamen (-28%, p Conclusion 11C-UCB-J PET revealed extensive loss of SV2A in early HD, suggesting widespread synaptic disconnection. SV2A loss in the striatum correlated with motor and cognitive functioning. 11C-UCB-J PET is more sensitive than 18F-FDG PET for detection of extrAstriatal changes in early HD.","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115322720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1136/jnnp-2021-ehdn.38
Alexandra Moura, Juliette Champaud, R. Scahill, S. Tabrizi, Daniel C. Alexander, P. Wijeratne
{"title":"E03 Uncovering the temporal sequence of regional brain volume and neural connectivity changes in huntington’s disease","authors":"Alexandra Moura, Juliette Champaud, R. Scahill, S. Tabrizi, Daniel C. Alexander, P. Wijeratne","doi":"10.1136/jnnp-2021-ehdn.38","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.38","url":null,"abstract":"","PeriodicalId":205061,"journal":{"name":"E: Imaging","volume":"99 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126330895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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