Clinical characteristics and multimodal imaging can help diagnosing and treating mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-02 DOI:10.1002/epd2.20261

Petia S. Dimova, Dimitar Metodiev, Tihomir Todorov, Albena Todorova, Kaloyan Gabrovski, Peter Karazapryanov, Marin Penkov, Yuri Todorov, Yoana Milenova, Denitza Stoyanova, Krassimir Minkin

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引用次数: 0

Abstract

Objective

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently described, histopathologically and molecularly defined (SLC35A2-mutated) type of cortical malformation. Although increasingly recognized, the diagnosis of MOGHE remains a challenge. We present the characteristics of the first six patients diagnosed in Bulgaria, with the aim to facilitate identification, proper presurgical evaluation, and surgical treatment approach in this disease.

Methods

Revision of histopathological specimens of 202 patients operated on for drug-resistant focal epilepsy identified four cases with MOGHE. Another two were suggested, based on clinical characteristics and subsequently, were histologically confirmed. Sanger SLC35A2 sequencing on paraffin-embedded or fresh-frozen brain tissue was performed. Analysis of seizure types, neuropsychological profiles, electroencephalographic (EEG), imaging features and epilepsy surgery outcomes was done.

Results

Three out of the six cases (50%) harbored pathogenic SLC35A2 mutations. One patient had a heterozygous somatic variant with uncertain significance. Clinical characteristics included epilepsy onset in infancy (in 100% under 3 years of age), multiple seizure types, and moderate or severe intellectual/developmental delay. Epileptic spasms with hypsarrhythmia on EEG were the initial seizure type in five patients. The subsequent seizure types resembled those in Lennox–Gastaut syndrome. The majority of the patients (n = 4) presented prominent and persisting autistic features. Magnetic resonance imaging (MRI) showed multilobar (n = 6) and bilateral (n = 3) lesions, affecting the frontal lobes (n = 5; bilaterally in three) and characterized by increased signal on T2/fluid-attenuated inversion recovery (FLAIR). Voxel-based morphometric MRI post-processing and positron emission tomography helped determining the localization and extent of the lesions and presumed epileptogenic zones. After surgery, four patients (66.7%) were seizure-free ≥2 years. Interestingly, all seizure-free patients carried somatic SLC35A2-alterations.

Significance

Epileptic spasms, early prominent neuropsychological disturbances, MRI-T2/FLAIR hyperintense lesions with cortico-subcortical blurring, frequently multilobar and especially frontal, can preoperatively help to suspect MOGHE. Epilepsy surgery is still the only successful treatment option in MOGHE.

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临床特征和多模态成像有助于诊断和治疗伴有少突胶质增生和癫痫的轻度皮质发育畸形。

目的：轻度皮质发育畸形伴少突胶质增生和癫痫（MOGHE）是最近描述的一种组织病理学和分子学定义（SLC35A2突变）的皮质畸形类型。尽管越来越多的人认识到这一点，但 MOGHE 的诊断仍然是一项挑战。我们介绍了在保加利亚确诊的首批六名患者的特征，旨在促进该疾病的鉴别、正确的术前评估和手术治疗方法：方法：对 202 例因耐药局灶性癫痫而接受手术的患者的组织病理学标本进行复查，发现四例患者患有 MOGHE。方法：对 202 例因耐药局灶性癫痫而接受手术的患者的组织病理标本进行复查，发现 4 例患者患有 MOGHE，其中 2 例是根据临床特征推测的，随后经组织学证实。对石蜡包埋或新鲜冷冻的脑组织进行了 Sanger SLC35A2 测序。对癫痫发作类型、神经心理学特征、脑电图（EEG）、影像学特征和癫痫手术结果进行了分析：结果：6例患者中有3例（50%）携带致病性SLC35A2突变。结果：6例患者中有3例（50%）存在致病性SLC35A2突变，1例患者存在意义不明的杂合体细胞变异。临床特征包括婴儿期发病（100%在3岁以下）、多种发作类型、中度或重度智力/发育迟缓。在五名患者中，最初的癫痫发作类型是癫痫痉挛，伴有脑电图低节律。随后的癫痫发作类型与伦诺克斯-加斯科特综合征相似。大多数患者（4 人）表现出明显且持续的自闭症特征。磁共振成像（MRI）显示多叶（6例）和双侧（3例）病变，影响额叶（5例；3例为双侧），特征为T2/流体增强反转恢复（FLAIR）信号增强。基于体素的形态计量磁共振成像后处理和正电子发射断层扫描有助于确定病灶的定位和范围以及推测的致痫区。手术后，四名患者（66.7%）在≥2 年的时间里没有癫痫发作。有趣的是，所有无癫痫发作的患者均携带体细胞 SLC35A2-畸变：意义：癫痫痉挛、早期突出的神经心理障碍、MRI-T2/FLAIR高强化病变伴皮质-皮质下模糊，常为多叶，尤其是额叶，有助于术前怀疑 MOGHE。癫痫手术仍是治疗 MOGHE 的唯一成功方法。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.