多发性硬化症的诊断与治疗:综述。
Diagnosis and Treatment of Multiple Sclerosis: A Review.
机构信息
Cleveland Clinic Mellen Center, Cleveland, Ohio.
Now with Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.
出版信息
JAMA. 2021 Feb 23;325(8):765-779. doi: 10.1001/jama.2020.26858.
IMPORTANCE
Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS.
OBSERVATIONS
MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid-specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease.
CONCLUSIONS AND RELEVANCE
MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.
重要性
多发性硬化症(MS)是一种中枢神经系统自身免疫介导的神经退行性疾病,其特征是炎症性脱髓鞘伴有轴突横断。在美国,估计有 90 万人患有 MS。MS 通常在年轻人(发病平均年龄为 20-30 岁)中出现,并可导致身体残疾、认知障碍和生活质量下降。本综述总结了目前关于 MS 的诊断和治疗的证据。
观察结果
MS 通常在 20 至 30 岁的年轻人中出现,单侧视神经炎、部分脊髓炎、感觉障碍或脑干综合征(如核间眼肌麻痹)在数天内发展。全球 MS 的患病率为每 10 万人中有 5 至 300 人,在高纬度地区患病率更高。总体预期寿命低于普通人群(75.9 岁与 83.4 岁),MS 更常见于女性(女性与男性的性别比例接近 3:1)。诊断基于体征和症状、影像学发现(例如,磁共振成像 [MRI] T2 病变)和实验室发现(例如,脑脊液特异性寡克隆带)的组合,这些都是 2017 年 McDonald 标准的组成部分。有九类疾病修正治疗(DMT)药物,作用机制和给药途径不同,可用于复发缓解型 MS,定义为发病时有复发,发作之间有稳定的神经功能障碍,和继发性进展型 MS,有活动,定义为在复发过程后出现逐渐增加的神经功能障碍,并伴有持续的炎症活动的证据。这些药物包括干扰素、醋酸格拉替雷、特立氟胺、鞘氨醇 1-磷酸受体调节剂、富马酸、克拉屈滨和 3 种单克隆抗体。还有一种 DMT,奥瑞珠单抗,被批准用于原发性进展型 MS。这些 DMT 可减少临床复发和 MRI 病变(新 T2 病变、钆增强病变)。目前 DMT 的疗效率,通过与安慰剂或活性对照比较,每年复发率的降低来定义,范围为 29%-68%。不良反应包括感染、心动过缓、心脏阻滞、黄斑水肿、输注反应、注射部位反应和继发性自身免疫不良反应,如自身免疫性甲状腺疾病。
结论和相关性
MS 的特征是身体残疾、认知障碍和其他影响生活质量的症状。与安慰剂或活性对照相比,DMT 治疗可将每年的复发率降低 29%至 68%。