Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mult Scler Relat Disord. 2019 Jun;31:22-31. doi: 10.1016/j.msard.2019.03.008. Epub 2019 Mar 12.
Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal-dominant white matter disease, typically characterized by juvenile cognitive decline and frontoparietal white matter lesions. A portion of HDLS patients exhibit preferential motor dysfunctions as their initial symptoms, mimicking multiple sclerosis (MS). However, there is no study comparing this phenotype of HDLS and primary progressive multiple sclerosis (PPMS), which greatly resemble each other. This is the first preliminary study to clarify the clinical and neuroimaging features of motor-predominant HDLS, and compare it with PPMS, using cases whose colony stimulating factor 1 receptor (CSF1R) were sequenced.
Clinical and radiological data from Japanese patients at the Department of Neurology, Kyushu University Hospital, Fukuoka, Japan, were evaluated retrospectively and cross-sectionally. Twenty-nine brain and 18 spinal cord magnetic resonance imaging (MRI) scans from four motor-predominant HDLS patients with CSF1R mutations and 15 PPMS patients without CSF1R mutations, were evaluated using an HDLS MRI scoring system.
Two patients with HDLS were initially diagnosed with MS and received immunotherapy. Clinically, motor-predominant HDLS and PPMS patients resembled each other in onset age and disability. However, motor-predominant HDLS patients had a significantly higher frequency of frontal release signs, lower positivity rates of oligoclonal IgG bands (OCB), and lower IgG index values. Total HDLS MRI scores, total white matter lesions (WMLs), and brain atrophy were similar between the diseases. However, motor-predominant HDLS patients had more marked atrophy of the corpus callosum (CC) body, more WMLs in the deep and subcortical regions of the frontoparietal lobes, fewer WMLs in the occipitotemporal periventricular regions, and more restricted diffusivity lesions on MRI than PPMS patients. There was a stronger association between disease duration and CC index in HDLS, suggesting more rapid progression compared with PPMS.
Motor-predominant HDLS has characteristic frequent frontal release signs, normal findings for OCB and the IgG index, severe CC body atrophy, abundant deep and subcortical WMLs in the frontoparietal lobes, subtle occipitotemporal lobe periventricular WMLs, and more restricted diffusivity lesions on MRI. Although the present study was limited by the small number of HDLS cases, we propose that immunotherapy should be avoided in such cases.
遗传性弥漫性脑白质病伴轴索性球体（HDLS）是一种罕见的常染色体显性遗传的脑白质疾病，其特征通常为青少年认知功能下降和额顶叶脑白质病变。一部分 HDLS 患者以运动功能障碍为首发症状，类似于多发性硬化症（MS）。然而，目前尚无研究比较这种以运动障碍为特征的 HDLS 与原发性进展性多发性硬化症（PPMS）之间的差异，尽管这两种疾病的临床表现非常相似。本研究首次采用经集落刺激因子 1 受体（CSF1R）测序的病例，对以运动障碍为特征的 HDLS 的临床和神经影像学特征进行了初步比较研究。
回顾性分析日本九州大学医院神经内科的日本患者的临床和放射学数据，并进行了横断面研究。对四名具有 CSF1R 突变的以运动障碍为特征的 HDLS 患者和十五名无 CSF1R 突变的 PPMS 患者的 29 例脑磁共振成像（MRI）和 18 例脊髓 MRI 进行评估，使用 HDLS MRI 评分系统对 MRI 进行评分。
两名 HDLS 患者最初被诊断为 MS，并接受了免疫治疗。临床方面，以运动障碍为特征的 HDLS 和 PPMS 患者在发病年龄和残疾程度方面相似。然而，以运动障碍为特征的 HDLS 患者的额释放征频率更高，寡克隆 IgG 带（OCB）阳性率更低，IgG 指数值更低。两种疾病的总 HDLS MRI 评分、总脑白质病变（WML）和脑萎缩相似。然而，以运动障碍为特征的 HDLS 患者的胼胝体（CC）体萎缩更明显，额顶叶深部和皮质下 WML 更多，枕颞叶脑室周围 WML 更少，MRI 上弥散受限病变更局限。HDLS 中疾病持续时间与 CC 指数的相关性更强，表明与 PPMS 相比，HDLS 的进展更快。
以运动障碍为特征的 HDLS 具有特征性的频繁额释放征、正常的 OCB 和 IgG 指数、严重的 CC 体萎缩、额顶叶深部和皮质下大量 WML、轻微的枕颞叶脑室周围 WML 和 MRI 上更局限的弥散受限病变。虽然本研究受到 HDLS 病例数量较少的限制，但我们建议避免对这些病例进行免疫治疗。
