Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.
Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.
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DOI：
10.5334/tohm.747
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hassan A
中科院分区：
文献类型：
--
作者：
Hassan A
发作性共济失调（EA）是一组罕见的常染色体显性遗传性疾病的表现，其特征是小脑功能障碍的反复发作。EA 1和EA 2是最常见的，由KCNA 1和CACNA 1A突变引起。EA 3 -8在罕见家系中有报道。基因检测的进展扩大了KCNA 1和CACNA 1A表型，并检测到EA作为其他几种遗传疾病的不寻常表现。此外，EA和模仿障碍还有各种次要原因。总之，这些可能会给神经科医生带来诊断挑战。2022年10月，对“发作性共济失调”和“阵发性共济失调”进行了系统性文献综述，仅限于过去10年的出版物，重点关注最近的临床进展。总结了临床、遗传和治疗特征。EA 1和EA 2表型进一步扩大。特别是，EA 2可能伴有其他具有慢性神经精神特征的儿童期阵发性疾病。EA 2的新治疗方法包括dalfampridine和fampridine，以及4-氨基吡啶和乙酰唑胺。最近有EA 9 -10的提案。EA也可能由与慢性共济失调（SCA-14、SCA-27、SCA-42、AOA 2、CAPOS）、癫痫综合征（KCNA 2、SCN 2A、PRRT 2）、GLUT-1、线粒体疾病（PDHA 1、PDHX、AC 0 2）、代谢紊乱（枫糖浆尿病、Hartnup病、I型瓜氨酸血症、硫胺素和生物素代谢缺陷）等相关的基因突变引起。继发性EA比原发性EA更常见（血管性、炎症性、毒性代谢性）。EA可能被误诊为偏头痛、外周前庭障碍、焦虑和功能性症状。原发性和继发性EA通常是可以治疗的，这应该促使寻找原因。EA可能被忽视或误诊的原因有很多，包括表型-基因型变异性和原发性和继发性病因之间的临床重叠。EA是高度可治疗的，因此在阵发性疾病的鉴别诊断中考虑它是很重要的。经典的EA 1和EA 2表型提示单基因检测和治疗途径。对于非典型表型，下一代基因检测可以帮助诊断和指导治疗。更新的分类系统EA进行了讨论，这可能有助于诊断和管理。
Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in KCNA1 and CACNA1A. EA3–8 are reported in rare families. Advances in genetic testing have broadened the KCNA1 and CACNA1A phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists. A systematic literature review was performed in October 2022 for ‘episodic ataxia’ and ‘paroxysmal ataxia’, restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized. EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9–10. EA may also be caused by gene mutations associated with chronic ataxias (SCA-14, SCA-27, SCA-42, AOA2, CAPOS), epilepsy syndromes (KCNA2, SCN2A, PRRT2), GLUT-1, mitochondrial disorders (PDHA1, PDHX, ACO2), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause. EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.
影响因子：
5.6
作者：
Maksemous N;Smith RA;Sutherland HG;Sampaio H;Griffiths LR
通讯作者：
Griffiths LR
影响因子：
6
作者：
De Michele G;Galatolo D;Galosi S;Mignarri A;Silvestri G;Casali C;Leuzzi V;Ricca I;Barghigiani M;Tessa A;Cioffi E;Caputi C;Riso V;Dotti MT;Saccà F;De Michele G;Cocozza S;Filla A;Santorelli FM
通讯作者：
Santorelli FM
影响因子：
6
作者：
Indelicato E;Unterberger I;Nachbauer W;Eigentler A;Amprosi M;Zeiner F;Haberlandt E;Kaml M;Gizewski E;Boesch S
通讯作者：
Boesch S