Amyotrophic lateral sclerosis; clinical features, differential diagnosis and pathology

Michael A. Van Es*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review


Amyotrophic lateral sclerosis (ALS) is a late-onset syndrome characterized by the progressive degeneration of both upper motor neurons (UMN) and lower motor neurons (LMN). ALS forms a clinical continuum with frontotemporal dementia (FTD), in which there are progressive language deficits or behavioral changes. The genetics and pathology underlying both ALS and FTD overlap as well, with cytoplasmatic misvocalization of TDP-43 as the hallmark. ALS is diagnosed by exclusion. Over the years several diagnostic criteria have been proposed, which in essence all require a history of slowly progressive motor symptoms, with UMN and LMN signs on neurological examination, clear spread of symptoms through the body, the exclusion of other disorder that cause similar symptoms and an EMG that it is compatible with LMN loss. ALS is heterogeneous disorder that may present in multitude ways, which makes the diagnosis challenging. Therefore, a systematic approach in the diagnostic process is required in line with the most common presentations. Subsequently, assessing whether there are cognitive and/or behavioral changes within the spectrum of FTD and lastly determining the cause is genetic. This chapter, an outline on how to navigate this 3 step process.

Original languageEnglish
Title of host publicationMotor Neurone Disease
EditorsPamela J. Shaw, Janine Kirby
Number of pages47
ISBN (Print)9780443141164
Publication statusPublished - Jan 2024

Publication series

NameInternational Review of Neurobiology
ISSN (Print)0074-7742
ISSN (Electronic)2162-5514


  • ALS
  • Amyotrophic lateral sclerosis
  • Diagnostic criteria
  • Frontotemporal dementia
  • FTD
  • Genetic testing


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