Primary Lateral Sclerosis: Clinical, radiological and molecular features

Rev Neurol (Paris). 2022 Mar;178(3):196-205. doi: 10.1016/j.neurol.2021.04.008. Epub 2021 Jul 6.


Primary Lateral Sclerosis (PLS) is an uncommon motor neuron disorder. Despite the well-recognisable constellation of clinical manifestations, the initial diagnosis can be challenging and therapeutic options are currently limited. There have been no recent clinical trials of disease-modifying therapies dedicated to this patient cohort and awareness of recent research developments is limited. The recent consensus diagnostic criteria introduced the category 'probable' PLS which is likely to curtail the diagnostic journey of patients. Extra-motor clinical manifestations are increasingly recognised, challenging the view of PLS as a 'pure' upper motor neuron condition. The post mortem literature of PLS has been expanded by seminal TDP-43 reports and recent PLS studies increasingly avail of meticulous genetic profiling. Research in PLS has gained unprecedented momentum in recent years generating novel academic insights, which may have important clinical ramifications.

Keywords: Biomarkers; Motor Neuron Disease; Neuroimaging; Primary Lateral Sclerosis.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis* / diagnostic imaging
  • Amyotrophic Lateral Sclerosis* / genetics
  • Consensus
  • Humans
  • Motor Neuron Disease* / diagnostic imaging
  • Motor Neuron Disease* / genetics
  • Motor Neurons / physiology