双语病例—— CADASIL

翻译老师：凌一童     山东省日照市人民医院

审校老师：姜春雷   青岛市第九人民医院

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History and CT images

History: A 45-year-old woman presented to the emergency department with dysarthria and without any other neurological deficit. She previously experienced symptoms of COVID-19, such as fever, persistent cough, tiredness, and generalized myalgia, and had been self-isolating for the past 14 days. However, at the time of presentation, she was asymptomatic for COVID-19.

A brain CT scan was performed. Axial noncontrast images are provided.

病史和CT图像

病史：一名45岁的女性因构音障碍到急诊科就诊，没有任何其它神经功能症状。之前她经历过发烧、持续性咳嗽、乏力和全身性肌痛等covid-19的症状，并在过去的14天里一直自我隔离。本次就诊，COVID-19感染的症状已消失。

完善头颅CT检查。下图为轴位平扫图像。

MR images

Brain MR imaging was performed to evaluate hypodensities seen on CT.

MR图像

行头颅MR检查以评估在CT上看到的低密度影。

Additional images

MRI revealed acute infarcts involving bilateral centrum semiovale and corona radiata. Widespread confluent bilateral subcortical and periventricular white-matter hyperintensities were seen, with prominent involvement of the anterior temporal lobe. Chronic lacunar infarcts were also seen in the right centrum semiovale and left basal ganglia.

Eight days after the initial episode, the patient complained of new acute confusion. Brain MRI with contrast was performed; axial diffusion-weighted images are provided below.

附加图像

MRI显示双侧半卵圆中心和放射冠区的急性梗死，可见广泛的双侧皮质下及脑室周围白质高信号，颞叶前部受累明显，右侧半卵圆中心和左侧基底节区可见陈旧腔隙性脑梗死。

第一次发病后第8天，患者突发急性意识障碍。行头颅MRI，轴位扩散加权像如下。

Findings and diagnosis

Findings

· Multiple acute lacunar infarcts involving bilateral centrum semiovale and corona radiata; rapid interval progression of infarcts

· Anterior temporal lobe-predominant white-matter disease

· Few chronic lacunar infarcts

Differential diagnosis

· Acute stroke as direct manifestation of COVID-19

· Acute disseminated encephalomyelitis (ADEM)

· Vasculitis related to COVID-19 infection

· Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

结果和诊断

结果：

·多发急性腔隙性脑梗死，累及双侧半卵圆中心和放射冠区，梗死快速并间断发作。

·以颞叶前部为主的脑白质疾病。

·少量陈旧腔隙性脑梗死。

鉴别诊断：

· 以急性脑卒中为直接表现的COVID-19感染

· 急性播散性脑脊髓炎 (ADEM)

· 与 COVID-19 感染相关的血管炎

· 伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病 (CADASIL)

Diagnosis: CADASIL

Treatment

Considering the rapid interval progression of infarcts, a provisional diagnosis of central nervous system vasculitis or CADASIL triggered by COVID-19 was made. The patient was treated with methylprednisolone 500 mg for three days, followed by prednisolone 40 mg once a day for four weeks. Symptoms improved and the patient was discharged. A follow-up MRI after seven weeks showed no new infarcts. Genetic investigations showed a pathogenic NOTCH3 missense variant, diagnostic of CADASIL.

最终诊断：CADASIL

治疗：

考虑到梗死进展迅速并间断发作，初步诊断为COVID-19感染引发的中枢神经系统血管炎或CADASIL。给予甲强龙500mg/qd连续3天，后改为强的松40mg/qd连续4周。患者症状好转后出院。7周后复查头颅MRI未见新发梗死灶。基因检查显示这是一种致病性NOTCH3变异，诊断为CADASIL。

Discussion

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

CADASIL is the most frequent single-gene disorder of small cerebral arteries, resulting from NOTCH3 mutations, which are more commonly expressed in vascular smooth muscle cells, causing deposition of granular and osmiophilic substances within the vascular smooth muscle cell membrane. This gradually leads to fibrosis and small infarcts in the white matter, deep grey matter, and pons.

The diagnosis of CADASIL is based on imaging features and laboratory examinations. The classic diagnostic features include leukoaraiosis predominantly involving anterior parts of the temporal white matter; the periventricular, posterior temporal white matter; and multiple, bilateral small infarcts involving the deep white matter, basal ganglia, thalamus, and pons. Electron microscopic examination of vascular smooth muscle in the brain, skeletal muscle, peripheral nerves, and skin can demonstrate granular and osmiophilic substance layers. Diagnosis of CADASIL is confirmed by detecting NOTCH3 mutations by DNA analysis.

诊断

伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病 (CADASIL)

CADASIL是脑小血管病最常见的单基因疾病，由NOTCH3突变引起，NOTCH3突变多在血管平滑肌细胞中表达，导致血管平滑肌细胞膜内嗜锇颗粒物质沉积，可逐渐导致脑白质、深部灰质和桥脑的纤维化和小梗死。

CADASIL的诊断基于影像学特征和实验室检查。经典的诊断特征包括脑白质疏松症，主要累及颞叶前部、脑室周围、颞后部白质，多发双侧小梗死病灶可累及深部白质、基底节、丘脑、脑桥。

血管平滑肌、骨骼肌、周围神经和皮肤的电子显微镜检查可显示嗜锇颗粒物质沉积。CADASIL的诊断可通过DNA分析检测NOTCH3突变来确诊。

Learning points

1. The case illustrates the importance of identifying the pattern of involvement to arrive at the diagnosis of CADASIL, in contrast to other neurological manifestations of COVID-19.

2. The association of CADASIL exacerbation by COVID-19 reinforces the pathophysiology related to endothelial injury behind the cerebrovascular disease precipitated by COVID-19, which also can be a potential infectious trigger here in precipitating the disease.

3. This case sheds light on the postinfectious neurological presentation in COVID-19, which could be due to the inflammatory response. This raises the concern for identifying such patients and advocates early use of anti-inflammatory agents for improved outcome.

4. Timely diagnosis and appropriate management of the condition can improve the long-term outcome of the patients.

学习要点

1. 与COVID-19的其他神经系统表现相比，该病例说明了辨别病变受累模式对诊断CADASIL的重要性。

2 . COVID-19致使CADASIL恶化，可加强脑血管病后内皮损伤的病理生理过程，这也可能是诱发该疾病的潜在感染诱因。

3. 该病例揭示了COVID-19感染后的神经系统表现，可能是由于炎症反应所致。这引起了对鉴别此类患者的关注，并提倡尽早使用抗炎药以改善预后。

4. 及时的诊断和适当的治疗可以改善患者的长期预后。