A 2020 centenary perspective on neuromuscular disorders.
A 2020 centenary perspective on neuromuscular disorders.
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2020 年神经肌肉疾病百年展望。
DOI：
10.1136/jnnp-2020-324327
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Feldman,Eva
中科院分区：
文献类型：
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作者：
Goutman,StephenA;Callaghan,BrianChristopher;Feldman,Eva
神经外科和精神病学 (JNNP) 发表了一个复发性肥厚性神经炎病例，1 详细描述了一名可能患有遗传性神经病的患者的临床病程。虽然这篇文章在 1921 年还不为人知，但它预示了遗传学将在未来 100 年改变神经肌肉疾病的病程中发挥关键作用。事实上，98 年后 JNNP 发表了一篇关于复杂遗传性疾病中周围神经病变的综述。 2 作为一组疾病，神经肌肉疾病包括影响肌肉、神经肌肉接头、周围神经、神经根和运动神经元的疾病。在每个地点，基因改变都可能导致严重的疾病，导致携带突变的人出现轻度至重度残疾。过去 100 年来，我们对神经肌肉疾病遗传病因学的理解取得了显着的进展。当 JNNP 首次开始发表文章时，DNA 结构尚不清楚，而今天我们拥有有效的基因靶向疗法，可以改变多种神经肌肉疾病的病程。一年前，我们面临的挑战是思考过去 100 年来“神经病学最重要或最具变革性的发展”，以及鉴于其广泛的范围，JNNP 如何为这一成就做出贡献。 3 令我们惊讶的是，神经肌肉疾病的提名没有进入最终名单。 4 因此，我们希望提出神经肌肉疾病的提名。本次提名引用的所有文章均发表在 JNNP 上。我们认为，神经肌肉疾病的亚专业引领神经病学界取得了过去 100 年来最重要的成就：发现了以前无法治疗的神经肌肉疾病的遗传病因，并将这些发现转化为治疗方法。描述、破译、检测那么我们是如何到达这里的呢？毫不夸张地说，就是站在巨人的肩膀上。我们依靠先行者的奉献精神来描述和详细描述这一保护伞下的疾病。他们的详细描述，例如 Anita Harding 和 Peter (PK) Thomas 描述肯尼迪病和遗传性神经病的描述，5 6 帮助我们理解了同一疾病的变异性。只有通过了解表型，无论是基于病史、检查还是病理学，才能将患有相同疾病的患者分为共同的实体。这些广泛的分组变得很重要，因为它们提供了改变疾病的其他特征的线索。例如，考虑脊髓性肌萎缩症（SMA）。 1 型 SMA 儿童与 2 型 SMA 儿童在运动神经元存活蛋白 (SMN) 中具有相同的基因突变，但 SMN2 基因的表达决定了疾病表型。从早期发病到晚期发病的广泛表型是治疗开发的基石。 7 这些早期先驱坚定地对一系列体征和症状进行了分类，并且是在计算机化疾病登记之前的时代这样做的，他们是
Neurosurgery and Psychiatry (JNNP) published a case of recurrent hypertrophic neuritis, 1 which detailed the clinical course of a patient with a likely inherited neuropathy. Although unknown in 1921, this article foreshadowed the critical role that genetics would play in altering the course of neuromuscular diseases in the next 100 years. In fact, 98 years later JNNP published a review on peripheral neuropathy in complex inherited diseases. 2 As a group of disorders, neuromuscular diseases include entities that affect muscle, the neuromuscular junction, peripheral nerves, nerve roots and motor neurons. At each location, genetic alterations can result in severe disease, resulting in mild-to-severe disability for those carrying mutations. The progress made in our understanding of the genetic aetiology of neuromuscular diseases in the last 100 years is remarkable. When JNNP first began publishing articles the structure of DNA was unknown, and today we have effective gene-targeted therapies that alter the course of multiple neuromuscular diseases. One year ago, we were challenged to consider the ‘most important or transformative development in neurology’in the past 100 years and how JNNP contributed to this achievement given its broad scope. 3 To our surprise, no nomination for neuromuscular disorders made the final list. 4 Therefore, we wish to put forth a nomination for neuromuscular disorders. All articles cited for this nomination are published in JNNP. We contend the subspeciality of neuromuscular disorders leads the neurologic community in the most important achievements in the last 100 years: discovering the genetic aetiology of previously untreatable neuromuscular disorders and turning these discoveries into therapies. describe, decipher, detectSo how did we get here? Quite literally by standing on the shoulders of giants. We have relied on the dedication of pioneers that have come before us to describe and detail the diseases under this umbrella. Their detailed descriptions, such as those by Anita Harding and Peter (PK) Thomas describing Kennedy’s disease and inherited neuropathies, 5 6 have helped shape our understanding of variability within the same diseases. It is only by understanding phenotypes, whether they be based on history, examination or pathology, that patients with the same disease can be grouped into common entities. These broad groupings then become important as they provide clues to additional features that alter disease. For example, consider spinal muscular atrophy (SMA). Children with SMA type 1 have the same genetic mutation in survival motor neuron protein (SMN) as children with SMA type 2, but the expression of the SMN2 gene determines disease phenotype. The wide range of phenotypes from early to later onset serve as the cornerstone for therapeutic development. 7 These early pioneers that steadfastly catalogued the range of signs and symptoms, and did so in a time prior to computerised disease registries, were