婴幼儿克拉伯病(0-12 个月)、病情发展和临床试验的推荐终点。

IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2024-11-05 DOI:10.1002/acn3.52114
Melissa R Greco, Mabel A Lopez, Maria L Beltran-Quintero, Ecenur Tuc Bengur, Michele D Poe, Maria L Escolar
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引用次数: 0

摘要

目的:克拉伯病是由于缺乏半乳糖脑苷脂酶,导致脱髓鞘引起的进行性神经变性。本研究的目的是记录新分类的婴儿型发病者(0-12 个月)的疾病进展情况。我们评估了造血干细胞移植(HSCT)的结果,并描述了有意义的临床终点:2000年至2022年期间,我们对婴幼儿克拉伯病患者进行了前瞻性评估。所有患者都接受了全面的标准化方案治疗。分析采用了描述性统计和卡普兰-梅耶生存曲线:结果:共纳入137名患有婴儿克拉伯病的儿童(68名男性和69名女性)。在137名患儿中,96名未接受治疗,41名接受了造血干细胞移植。23名无症状,18名有症状。最初的症状包括易怒、发育迟缓或丧失里程碑、喂养困难、痉挛和反流,平均存活时间为2.2天。两组患者的神经传导研究、听觉脑干反应和脑部核磁共振成像均明显异常。移植时的年龄以及体征和症状决定了功能性结果。有症状和无症状的移植患者半乳糖脑苷脂酶升高,精神氨酸降低,但未达到正常范围。无症状移植患者的中位生存期为5年,而无症状患者的中位生存期延长至15.5年:解读:12 个月前发病的婴儿克拉伯病进展迅速。除非及时进行造血干细胞移植,否则会造成不可逆的脑损伤。造血干细胞移植并不能阻止周围神经疾病的进展。这项研究可用于监测患者病情和评估未来疗法的效果。
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Infantile Krabbe disease (0-12 months), progression, and recommended endpoints for clinical trials.

Objective: Krabbe disease is due to deficiency of galactocerebrosidase, resulting in progressive neurodegeneration due to demyelination. The purpose of this study is to document disease progression in the newly classified infantile-onset (0-12 months). We evaluated the outcomes of hematopoietic stem cell transplantation (HSCT) and described meaningful clinical endpoints.

Methods: Patients with infantile Krabbe disease were prospectively evaluated between 2000 and 2022. All patients underwent comprehensive and standardized protocols. Descriptive statistics and Kaplan-Meier survival curves were used for analysis.

Results: One hundred and thirty-seven children with infantile Krabbe disease were included (68 males and 69 females). Of the 137, 96 were not treated and 41 underwent hematopoietic stem cell transplantation. Twenty-three were asymptomatic and 18 symptomatic. Initial symptoms included irritability, developmental delay or loss of milestones, feeding difficulties, spasticity, and reflux with an average survival of 2.2. Abnormalities in nerve conduction studies, auditory brainstem responses, and brain MRIs were evident in both groups of patients. Age at transplantation and signs and symptoms determined functional outcomes. Symptomatic and asymptomatic transplanted patients showed an increase in galactocerebrosidase and a decrease in psychosine, but did not reach the normal range. The median survival for transplanted symptomatic patients was 5 years while asymptomatic was extended to 15.5 years.

Interpretation: Infantile Krabbe disease with onset before 12 months is rapidly progressive. Irreversible brain damage occurs unless timely HSCT is performed. HSCT does not prevent the progression of peripheral nerve disease. This study can be used to monitor patients and evaluate the effects of future therapies.

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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
期刊最新文献
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