Promoting Research in PLS: Current Knowledge and Future Challenges

原发性侧索硬化症是最罕见的散发性运动神经元病(MND)，仅影响上半部 运动神经元。尽管与肌萎缩侧索硬化症的不同之处在于，生存并不是一个紧迫的问题，但PLS是一个无情的 导致终生的、进行性的和严重的运动障碍的疾病。由于其极端稀有，最小二乘法具有 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，偏最小二乘法 病例从未包括在ALS的任何临床试验中。此外，目前的诊断标准要求 等待3至4年才能确诊，这对患者和他们的患者来说是非常沮丧的 医生。简而言之，我们对偏最小二乘问题的知识基础很有限，系统的研究也很少 到目前为止。为了改善这一现实，我们建议举办一次高度科学性的关于最小二乘问题的国际会议。 大多数肌萎缩侧索硬化症专家都认为，PLS是了解MND疾病机制的关键，尤其是 肌萎缩侧索硬化。组委会由3名女性和3名男性组成，他们来自不同的种族/种族， 建议在2019年5月3日和4日举行R13会议，紧接AAN年会之前在 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、少数族裔和11名国际调查人员。所有这些人，在某种程度上或 另一个，专门研究偏最小二乘法，并发表了相关的科学论文。会议将包括 浅谈拟精神分裂症的临床谱系、认知功能障碍 电生理学包括皮质高兴奋性、神经影像改变、遗传学 可以在偏最小二乘表型中识别可定义的疾病，特别是新兴的生物生物标记物 脂质组学和线粒体异常，包括潜在的新的疾病进展的测量 结果指标，以及偏最小二乘法的临床试验。FRCPC医学博士Ian Mackenzie的主旨演讲将在 神经病理学和生物学观点对偏头痛、肌萎缩侧索硬化症和股骨头痉挛的认识。一场小组讨论将致力于 (1)修订偏最小二乘诊断标准，以期制订切实可行的标准；及(2) 建立国际最小二乘注册中心。PLS注册处将鼓励未来的国际合作 以及更广泛地接触这种罕见疾病的患者，从而使严格的科学调查成为可能。这个 会议形式是创新的，特点是简短的演讲，以便有时间进行广泛的、一般性的 与会者之间的讨论。我们将邀请希望专门研究最小二乘的年轻研究人员，或者至少 MND研究。由于该领域缺乏妇女和少数群体的参与，这一点尤为重要 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。 我们提议的会议将促进在最小二乘法领域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.