Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Curr Opin Neurol. 2014 Jun;27(3):290-9. doi: 10.1097/WCO.0000000000000095.
We summarize MRI measures currently available to assess treatment efficacy and safety in multiple sclerosis (MS) clinical trials and discuss novel metrics that could enter the clinical arena in the near future.
In relapsing remitting MS, MRI measures of disease activity (new T2 and gadolinium-enhancing lesions) provide a good surrogacy of treatment effect on relapse rate and disability progression; however, their value in progressive MS remains elusive. For the progressive disease forms, these measures need to be combined with quantities assessing the extent of irreversible tissue loss, which have already been introduced in some clinical trials (e.g., evolution of active lesions into permanent black holes and brain atrophy). Novel measures (e.g., quantification of gray matter and spinal cord atrophy) have demonstrated a great value in explaining patients' clinical outcome, but still need to be fully validated. Despite showing promise, evaluations of cortical lesions, of microscopic tissue abnormalities, and of functional cortical reorganization are still some way off for monitoring of treatment effects.
Trial outcomes in MS should include measures of inflammation and neurodegeneration, which should be combined according to the disease clinical phenotype, phase of the study, and the supposed mechanism of action of the drug tested.
我们总结了目前可用于评估多发性硬化症（MS）临床试验中治疗效果和安全性的 MRI 测量方法，并讨论了在不久的将来可能进入临床领域的新指标。
在复发缓解型 MS 中，疾病活动的 MRI 测量（新的 T2 和钆增强病变）很好地替代了治疗对复发率和残疾进展的效果；然而，在进展型 MS 中，其价值仍不明确。对于进展性疾病形式，这些测量需要与评估不可逆组织损失程度的数量结合使用，这些已经在一些临床试验中引入（例如，活动病变演变为永久性黑洞和脑萎缩）。新的指标（例如，灰质和脊髓萎缩的定量）在解释患者的临床结果方面显示出了很大的价值，但仍需要充分验证。尽管有希望，但皮质病变、微观组织异常和皮质功能重组的评估距离监测治疗效果还有一定的距离。
MS 的临床试验结果应包括炎症和神经退行性变的测量，这些测量应根据疾病的临床表型、研究阶段以及所测试药物的假定作用机制进行组合。
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