Philipps-University, Department of Neurology, Clinical Neuroimmunology Group, Marburg, Germany.
Mult Scler. 2011 Sep;17(9):1060-6. doi: 10.1177/1352458511405088. Epub 2011 May 11.
The objective of this study was to address the differences in onset and disease progression between familial and sporadic multiple sclerosis (MS) and the association within sibling pairs.
Ninety-eight siblings and their controls were included from a database of 763 sporadic MS-patients, randomly pair-matched for age, gender, clinical course, disease duration and treatment. Sixty-eight available siblings completed a prospective six-year follow-up. Outcome parameters included baseline Expanded Disability Status Scale (EDSS), age at onset, mono- or multifocal onset, disease progression and conversion to secondary progression of initially relapsing-remitting MS. For statistical analyses Wilcoxon's signed-rank statistics for categorical differences, t-statistics for continuous variables, McNemar's test for relative frequencies of categories, intra-class correlations for within sibling-pair associations, or Kaplan-Meier analysis for survival analyses were used; all two-sided at the 5% level.
Disease onset was slightly earlier (29.01 vs. 29.44 years, p = 0.0492) and multifocal onset significantly more often (p = 0.0052) in familial than in sporadic MS. Notably, a substantial within sibling-pair correlation for disease progression (rho = 0.40; p = 0.0062) as well as a higher risk for siblings than for controls to convert into secondary progression (0.545 vs. 0.227; p = 0.018) could be observed.
Familial MS differs from sporadic cases with respect to age at onset, multifocal involvement as first clinical event, and conversion into secondary progression. The progression rate of one out of two affected siblings may act as a predictor for the other sib.
本研究旨在探讨家族性和散发性多发性硬化症（MS）之间的发病和疾病进展差异，以及兄弟姐妹之间的相关性。
从 763 例散发性 MS 患者的数据库中纳入了 98 对兄弟姐妹及其对照，按照年龄、性别、临床病程、疾病持续时间和治疗进行了随机配对。68 对可随访的兄弟姐妹完成了为期 6 年的前瞻性随访。主要结局参数包括基线扩展残疾状况量表（EDSS）评分、发病年龄、单灶或多灶发病、疾病进展以及最初缓解-复发型 MS 向继发进展型的转化。对于统计分析，采用 Wilcoxon 符号秩检验进行分类差异，t 检验进行连续变量，McNemar 检验进行分类的相对频率，组内相关系数进行兄弟姐妹对的相关性，Kaplan-Meier 分析进行生存分析；所有检验均为双侧，显著性水平为 5%。
家族性 MS 的发病年龄稍早（29.01 岁 vs. 29.44 岁，p=0.0492），多灶起病更为常见（p=0.0052）。值得注意的是，兄弟姐妹之间的疾病进展具有显著的相关性（rho=0.40；p=0.0062），并且兄弟姐妹比对照组更有可能进展为继发进展（0.545 比 0.227；p=0.018）。
家族性 MS 与散发性病例相比，在发病年龄、首发临床事件多灶性累及以及转化为继发进展方面存在差异。两例受影响的兄弟姐妹中，其中一个的进展速度可能是另一个的预测指标。
