Promoting Research in PLS: Current Knowledge and Future Challenges

原发性侧索硬化症（PLS）是散发性运动神经元病（MND）的一种最罕见的形式， 运动神经元尽管与ALS不同的是，生存不是一个直接的问题，PLS是一个无情的 导致终身、进行性和严重运动功能障碍的疾病。由于其极其罕见，PLS 在很大程度上被忽视，很少在大量患者中进行系统研究。事实上，PLS 病例从未被纳入任何ALS临床试验。此外，目前的诊断标准要求 在PLS可以被诊断之前的3至4年的等待期，这对患者及其家属来说是非常令人沮丧的。 医生总之，我们对PLS的知识基础很有限，系统的研究很少 迄今为了改善这一现实，我们建议召开一次高度科学化的PLS国际会议。 大多数ALS专家认为PLS是理解MND疾病机制的关键， 人症组织委员会由来自不同族裔/种族的3名妇女和3名男子组成， 建议在2019年5月3日和4日举行R13会议，就在AAN年会之前， 费城机场万豪酒店超过35位演讲者和主持人将参加，占30% 妇女、少数民族/种族和11名国际调查员。所有这些人，以某种方式或 另一位是专门从事PLS研究并发表过相关科学论文的专家。会议将包括 关于PLS和MND的临床谱的讨论， 在PLS中普遍存在，电生理学包括皮质过度兴奋，神经影像学变化，遗传学 可以在PLS表型中识别可定义的疾病，生物标志物特别是新兴的 脂质组学和线粒体异常，测量PLS疾病进展，包括潜在的新的 结果测量和PLS的临床试验。由伊恩麦肯齐，医学博士，FRCPC的主题演讲，将在 “关于PLS、ALS和FTD的神经病理学和生物学观点。”将举行一次小组讨论， (1)修订PLS诊断标准，我们的目标是建立实用和有效的标准;（2） 建立国际PLS登记处。PLS登记处将鼓励未来的国际合作 更广泛地接触这种罕见疾病的患者，从而使严格的科学研究成为可能。的 会议形式是创新的，其特点是简短的介绍，将允许广泛的时间，一般 与会者之间的讨论。我们将邀请希望专注于PLS或至少 国防部研究。特别是妇女和少数民族的参与尤为重要，因为该领域缺乏 黑人和西班牙裔代表。我们将发表至少一篇关于新开发的诊断标准的论文。 我们提议的会议将激发PLS的国际合作和有效的未来研究，包括 成功的临床试验。在这次会议之后，PLS将不再被认为是一种被忽视的疾病。

Primary lateral sclerosis (PLS) is the rarest form of sporadic motor neuron disease (MND), affecting only upper motor neurons. Although distinct from ALS in that survival is not an immediate concern, PLS is a relentless disease that causes life-long, progressive and severe motor dysfunction. Due to its extreme rarity, PLS has been largely neglected and seldom investigated systematically in a large number of patients. In fact, PLS cases have never been included in any clinical trials in ALS. In addition, current diagnostic criteria require a waiting period of 3 to 4 years before PLS can be diagnosed, which is extremely frustrating for patients and their physicians. In short, our knowledge base for PLS is largely limited, and systematic research has been scanty to date. To improve upon this reality, we propose to hold a highly scientific, international conference on PLS. Most ALS experts agree that PLS holds a key to understanding the disease mechanisms of MNDs, particularly ALS. The organizing committee, which consists of 3 women and 3 men of diverse ethnic/racial origins, proposes to hold a R13 conference on May 3rd and 4th, 2019, immediately before the AAN annual meeting at the Philadelphia Airport Marriott. More than 35 speakers and moderators will participate, representing 30% women, ethnic/racial minorities, and 11 international investigators. All of these individuals, in one way or another, specialize in PLS and have published related scientific papers. The conference will include discussions on the clinical spectrum of PLS and MNDs that mimic it, cognitive impairment which is prevalent in PLS, electrophysiology including cortical hyperexcitability, neuroimaging changes, genetics that can identify definable diseases among PLS phenotypes, biological biomarkers particularly emerging lipidomics and mitochondrial abnormalities, measuring PLS disease progression including potential new outcome measures, and clinical trials in PLS. The keynote speech by Ian Mackenzie, MD, FRCPC, will be on “Neuropathological and Biological Views on PLS, ALS, and FTD.” A panel discussion will be devoted to (1) Revising PLS Diagnostic Criteria, for which we aim to establish practical and effective criteria and (2) Establishing an International PLS Registry. The PLS Registry will encourage future international collaborations and broader access to patients with this rare disease, thus enabling rigorous scientific investigations. The conference format is innovative, characterized by brief presentations that will allow time for extensive, general discussion among the attendees. We will invite young investigators who wish to specialize in PLS or at least MND research. The inclusion of women and minorities in particular is especially important as the field lacks Black and Hispanic representation. We will publish at least one paper on newly developed diagnostic criteria. Our proposed conference will incite international collaborations and effective future research in PLS, including successful clinical trials. After this conference, PLS will no longer be considered a neglected disease.