Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Eur J Neurol. 2018 Jan;25(1):142-147. doi: 10.1111/ene.13464. Epub 2017 Oct 19.
To establish and validate diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation.
We developed diagnostic criteria for ALSP based on a recent analysis of the clinical characteristics of ALSP. These criteria provide 'probable' and 'possible' designations for patients who do not have a genetic diagnosis. To verify its sensitivity and specificity, we retrospectively applied our criteria to 83 ALSP cases who had CSF1R mutations (24 of these were analyzed at our institutions and the others were identified from the literature), 53 cases who had CSF1R mutation-negative leukoencephalopathies and 32 cases who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with NOTCH3 mutations.
Among the CSF1R mutation-positive cases, 50 cases (60%) were diagnosed as 'probable' and 32 (39%) were diagnosed as 'possible,' leading to a sensitivity of 99% if calculated as a ratio of the combined number of cases who fulfilled 'probable' or 'possible' to the total number of cases. With regard to specificity, 22 cases (42%) with mutation-negative leukoencephalopathies and 28 (88%) with CADASIL were correctly excluded using these criteria.
These diagnostic criteria are very sensitive for diagnosing ALSP with sufficient specificity for differentiation from CADASIL and moderate specificity for other leukoencephalopathies. Our results suggest that these criteria are useful for the clinical diagnosis of ALSP.
建立并验证因集落刺激因子 1 受体（CSF1R）突变引起的成人发病脑白质病伴轴索性球形细胞和色素性星形细胞增多症（ALSP）的诊断标准。
我们基于最近对 ALSP 临床特征的分析，制定了 ALSP 的诊断标准。这些标准为没有遗传诊断的患者提供了“可能”和“很可能”的诊断。为了验证其敏感性和特异性，我们回顾性地将这些标准应用于 83 例 CSF1R 突变阳性的 ALSP 病例（其中 24 例在我们的机构进行了分析，其余病例从文献中确定）、53 例 CSF1R 突变阴性的脑白质病病例和 32 例 NOTCH3 突变的伴有皮层下梗死和脑白质病的常染色体显性脑动脉病（CADASIL）病例。
在 CSF1R 突变阳性病例中，50 例（60%）被诊断为“可能”，32 例（39%）被诊断为“很可能”，如果按照符合“可能”或“很可能”的病例总数与总病例数的比例计算，敏感性为 99%。特异性方面，使用这些标准正确排除了 22 例（42%）突变阴性的脑白质病病例和 28 例（88%）CADASIL 病例。
这些诊断标准对诊断 ALSP 非常敏感，特异性足以与 CADASIL 区分开来，与其他脑白质病的特异性也较高。我们的研究结果表明，这些标准对于 ALSP 的临床诊断是有用的。
