Department of Neurology, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan; Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano 396-8555, Japan.
Department of Neurology, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan.
J Neurol Sci. 2024 Nov 15;466:123229. doi: 10.1016/j.jns.2024.123229. Epub 2024 Sep 12.
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) has recently been known as HTRA1-related cerebral small-vessel disease (CSVD), it is caused by variants in HTRA1. Recently, it has been reported to develop in heterozygotes with some variants of the gene. Multiple prospective studies have reported that the frequency of heterozygous HTRA1 variants developing CSVD is 2 - 6.5 % in CARASIL. Heterozygous variant cases lack unique clinical features, have an older age of onset, and are difficult to detect. Characteristic findings are required to identify such cases.
Magnetic resonance imaging (MRI) images of cases that experienced cerebral infarction and carried heterozygous variants in HTRA1 were reviewed.
Four cases of heterozygous HTRA1-related CSVD in two families (Family 1: c.754G > A, p.A252T; three males. Family 2: c.497G > T, p.R166L, one female). In all cases, white matter lesions with lacunar infarcts were observed in the periventricular and basal ganglia, external capsule, and brainstem. Moreover, T2 star weighted image (T2WI) low presented dot-like lesions were present along the surface of the brainstem, which have only been reported in one homozygous case. Susceptibility-weighted imaging (SWI) was performed in two cases, and the dot-like lesions on T2WI resembled a pearly tiara along the surface of the brainstem.
Brainstem surface on T2*WI low showed dot-like lesions, which are not generally observed in patients with stroke and can be characteristic of HTRA1-CSVD associated with heterozygous variant. The pathology requires further investigation for diagnosis.
脑常染色体隐性动脉病伴皮质下梗死和脑白质病（CARASIL）最近被认为是 HTRA1 相关的脑小血管病（CSVD），由 HTRA1 中的变异引起。最近有报道称，携带该基因某些变异的杂合子也会发生这种疾病。多项前瞻性研究报告称，CARASIL 中 CSVD 发生的杂合 HTRA1 变异频率为 2-6.5%。杂合变异病例缺乏独特的临床特征，发病年龄较大，且难以检测。需要有特征性的发现来识别这些病例。
对经历脑梗死并携带 HTRA1 杂合变异的病例的磁共振成像（MRI）图像进行了回顾。
两个家族的 4 例杂合 HTRA1 相关 CSVD 病例（家族 1：c.754G>A，p.A252T；3 名男性。家族 2：c.497G>T，p.R166L，1 名女性）。所有病例均观察到脑室周围和基底节、外囊和脑干的伴有腔隙性梗死的白质病变。此外，在脑干表面还存在 T2 星加权像（T2WI）低信号的点状病变，这些病变仅在 1 例纯合子病例中报道过。对 2 例进行了磁敏感加权成像（SWI）检查，T2WI 上的点状病变在脑干表面呈珍珠状冠状。
T2*WI 低信号的脑干表面出现点状病变，这在一般的脑卒中患者中并不常见，可能是 HTRA1-CSVD 相关杂合变异的特征。该病理学需要进一步研究以明确诊断。
