Gaetano Laura, Magnusson Baldur, Kindalova Petya, Tomic Davorka, Silva Diego, Altermatt Anna, Magon Stefano, Müller-Lenke Nicole, Radue Ernst-Wilhelm, Leppert David, Kappos Ludwig, Wuerfel Jens, Häring Dieter A, Sprenger Till
Medical Image Analysis Center, Switzerland.
Novartis Pharma, Switzerland.
Mult Scler J Exp Transl Clin. 2020 Feb 18;6(1):2055217320906844. doi: 10.1177/2055217320906844. eCollection 2020 Jan-Mar.
Lesion location is a prognostic factor of disease progression and disability accrual.
To investigate lesion formation in 11 brain regions, assess correlation between lesion location and physical and cognitive disability measures and investigate treatment effects by region.
In 2355 relapsing-remitting multiple sclerosis patients from the FREEDOMS and FREEDOMS II studies, we extracted T2-weighted lesion number, volume and density for each brain region; we investigated the (Spearman) correlation in lesion formation between brain regions, studied association between location and disability (at baseline and change over 2 years) using linear/logistic regression and assessed the regional effects of fingolimod versus placebo in negative binomial models.
At baseline, the majority of lesions were found in the supratentorial brain. New and enlarging lesions over 24 months developed mainly in the frontal and sublobar regions and were substantially correlated to pre-existing lesions at baseline in the supratentorial brain ( = 0.37-0.52), less so infratentorially ( = -0.04-0.23). High sublobar lesion density was consistently and significantly associated with most disability measures at baseline and worsening of physical disability over 24 months. The treatment effect of fingolimod 0.5 mg was consistent across the investigated areas and tracts.
These results highlight the role of sublobar lesions for the accrual of disability in relapsing-remitting multiple sclerosis.
病灶位置是疾病进展和残疾累积的一个预后因素。
研究11个脑区的病灶形成情况，评估病灶位置与身体和认知残疾指标之间的相关性，并按区域研究治疗效果。
在来自FREEDOMS和FREEDOMS II研究的2355例复发缓解型多发性硬化症患者中，我们提取了每个脑区的T2加权病灶数量、体积和密度；我们研究了脑区之间病灶形成的（斯皮尔曼）相关性，使用线性/逻辑回归研究位置与残疾（基线时以及2年变化情况）之间的关联，并在负二项模型中评估芬戈莫德与安慰剂的区域效应。
在基线时，大多数病灶位于幕上脑区。24个月内新出现和扩大的病灶主要发生在额叶和脑叶下区域，并且与幕上脑区基线时已有的病灶显著相关（ρ = 0.37 - 0.52），幕下相关性较低（ρ = -0.04 - 0.23）。脑叶下病灶高密度与基线时大多数残疾指标以及24个月内身体残疾恶化始终显著相关。0.5毫克芬戈莫德的治疗效果在所有研究区域和神经束中是一致的。
这些结果突出了脑叶下病灶在复发缓解型多发性硬化症残疾累积中的作用。
