中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (9): 1881-1882.doi: 10.4103/1673-5374.391184

• 观点:退行性病与再生 • 上一篇    下一篇

原发性侧索硬化：不仅仅是一种上运动神经元疾病

  

  • 出版日期:2024-09-15 发布日期:2024-01-25

Primary lateral sclerosis: more than just an upper motor neuron disease

Ee Ling Tan, Jasmin Lope, Peter Bede*   

  1. Computational Neuroimaging Group (CNG), School of Medicine, Trinity College Dublin, Ireland (Tan EL, Lope J, Bede P) 
    Department of Neurology, St James’s Hospital, Dublin, Ireland (Bede P)
  • Online:2024-09-15 Published:2024-01-25
  • Contact: Peter Bede, MD, PhD, bedep@tcd.ie.
  • Supported by:
    This work was sponsored by the Spastic Paraplegia Foundation (SPF) (to PB). Professor PB is also supported by the Health Research Board (HRB EIA-2017-019 & JPND-Cofund-2-2019-1), the Irish Institute of Clinical Neuroscience (IICN), the EU Joint Programme – Neurodegenerative Disease Research (JPND), the Andrew Lydon Scholarship, The Hayes Family Charitable Fund and the Iris O’Brien Foundation.

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摘要： https://orcid.org/0000-0003-0492-4772 (Peter Bede)

Abstract: Advances in clinical care and recent research achievements: Primary lateral sclerosis (PLS) has traditionally been regarded as a pure upper motor neuron condition, a view perpetuated by most medical textbooks. Recent research has challenged the classical view that only the motor cortex and the descending corticospinal tracts are affected in PLS and the clinical and radiological profile of the condition has now been characterized by more nuanced descriptions. Research in PLS has gained unprecedented momentum in recent years, resulting in the painstaking characterization of disease burden patterns both post mortem and in vivo. Post mortem studies have confirmed distinguishing characteristics between amyotrophic lateral sclerosis (ALS) and PLS cohorts, namely the scarcity of TAR DNA-binding protein 43 pathology in the spinal anterior horns (Mackenzie and Briemberg, 2020). Genetic studies of larger cohorts have helped to delineate PLS from ALS and hereditary spastic paraplegia. While the core imaging signature of PLS is associated with primary motor cortex, corpus callosum and pyramidal tract degeneration (Finegan et al., 2019a), recent imaging studies have demonstrated frontotemporal changes, brainstem-cortex disconnection (Tahedl et al., 2023b), cerebellar involvement (Finegan et al., 2022) and subcortical grey matter degeneration (Finegan et al., 2019b). The pathognomonic clinical features of PLS such as spasticity, bulbar impairment, and pseudobulbar affect (Tahedl et al., 2023a) have been complemented by reports of language deficits, memory impairment, and executive dysfunction (de Vries et al., 2019). Two important practical developments have also taken place. The new consensus diagnostic criteria published in 2020 reduced the minimum symptom duration criterion to diagnose patients with PLS and introduced the categories of “definite” and “probable” PLS. The validity of the new criteria has already been demonstrated by cohorts of “probable” PLS patients harboring clinical and imaging features consistent with PLS and transitioning to “definite” PLS over time (Finegan et al., 2020). Up to recently, the revised ALS functional rating scale was widely administered to cohorts of PLS patients as a composite measure of motor disability. The recent development of the PLS functional rating scale is an important new tool to accurately appraise and monitor PLS-associated disability. Developed by Mitsumoto et al. and published in 2020, this new instrument has excellent intra-rater, inter-rater, and test-retest reliability and is increasingly utilized worldwide. The introduction of the new diagnostic criteria and the development of the PLS-specific functional rating scale have important practical ramifications for an earlier diagnosis and more accurate clinical monitoring. While no disease-modifying treatment has been developed, considerable advances have taken place in the management of common, PLS-associated symptoms such as pseudobulbar affect. The departure from isolated, single-center research efforts, to consortium-lead collaborative initiatives is likely to give PLS research further momentum. Recent research has also contributed to the development of precision clinical, biofluid, and radiological markers, which are indispensable for successful pharmacological trials.