Morrison Melanie A, Yao Jingwen, Bhalerao Radhika, Jakary Angela, Glueck Julia, Driscoll Theresa, Geschwind Michael D, Nelson Alexandra B, Possin Katherine L, Hess Christopher P, Lupo Janine M
medRxiv. 2025 Jan 15:2025.01.15.25320232. doi: 10.1101/2025.01.15.25320232.
There are no disease modifying therapies for Huntington's disease (HD), a rare but fatal genetic neurodegenerative condition. To develop and test new management strategies, a better understanding of the mechanisms underlying HD progression is needed. Aberrant changes in thalamo-cortical and striato-cerebellar circuitry have been observed in asymptomatic HD, along with transient enlargement of the dentate nucleus.
To evaluate the relationship between thalamo-cerebellar connectivity and HD progression.
Prospective and retrospective.
Patients with HD and healthy controls from a single-center dataset (n=34), and patients from the public TRACK-HD dataset (n=91).
FIELD STRENGTH/SEQUENCE: 3T and 7T.
Thalamo-cerebellar connectivity was compared across patients and controls and related to motor scores and predicted years to symptom onset. Cross-sectional findings were validated within-patient by mapping changes in individual connectivity over time. HD effects on cognitive performance were also explored and related to connectivity.
Kruskal-Wallis with post hoc Dunn's tests and Pearson correlations (p <0.05).
In the 7T cohort, significant premanifest and control group differences in thalamo-dentate connectivity were observed (p <0.05, η =.19-.22), with manifest HD connectivity approaching normative values. Thalamic connectivity with the dentate nucleus and anterior cerebellum also correlated with years to onset (p =0.06, r=0.42, p <0.05, r=-0.45), together indicating potential transient functional alterations in premanifest HD. Similar patterns were observed between connectivity (thalamus to dentate nucleus and anterior lobe) and cognitive performance scores across all subjects (p<0.05, r =-0.17, r =-0.18). In the premanifest TRACK-HD cohort, connectivity of multiple thalamo-cerebellar connections correlated with years to onset, revealing distinct patterns for patients with low versus high motor scores, again indicative of potential transient alterations. Exploratory non-parametric regression of serial imaging data further supported these findings.
Transient changes in thalamo-cerebellar connectivity are seen in premanifest HD with increasing progression. More studies are needed to validate this potentially useful biomarker.
亨廷顿舞蹈症（HD）是一种罕见但致命的遗传性神经退行性疾病，目前尚无改善病情的疗法。为了开发和测试新的治疗策略，需要更好地了解HD进展的潜在机制。在无症状的HD患者中已观察到丘脑 - 皮质和纹状体 - 小脑神经回路的异常变化，同时齿状核出现短暂性增大。
评估丘脑 - 小脑连接性与HD进展之间的关系。
前瞻性和回顾性研究。
来自单中心数据集的HD患者和健康对照（n = 34），以及来自公共TRACK-HD数据集的患者（n = 91）。
场强/序列：3T和7T。
比较患者和对照之间的丘脑 - 小脑连接性，并将其与运动评分及预测的症状出现年限相关联。通过绘制个体连接性随时间的变化情况，在患者内部验证横断面研究结果。还探讨了HD对认知表现的影响及其与连接性的关系。
采用Kruskal-Wallis检验及事后Dunn检验和Pearson相关性分析（p <0.05）。
在7T队列中，观察到明显的临床前期和对照组在丘脑 - 齿状核连接性方面存在显著差异（p <0.05，η = 0.19 - 0.22），而明显的HD连接性接近正常水平。丘脑与齿状核及小脑前叶的连接性也与发病年限相关（p = 0.06，r = 0.42，p <0.05，r = -0.45），共同表明临床前期HD可能存在潜在的短暂性功能改变。在所有受试者中，连接性（丘脑至齿状核和前叶）与认知表现评分之间也观察到类似模式（p <0.05，r = -0.17，r = -0.18）。在临床前期TRACK-HD队列中，多个丘脑 - 小脑连接的连接性与发病年限相关，揭示了运动评分低和高的患者的不同模式，再次表明可能存在短暂性改变。对系列成像数据的探索性非参数回归进一步支持了这些发现。
在临床前期HD中，随着病情进展可观察到丘脑 - 小脑连接性的短暂变化。需要更多研究来验证这种潜在有用的生物标志物。
