Patterns of symptom development in patients with motor neuron disease

Renée Walhout, Esther Verstraete, Martijn P Van Den Heuvel, Jan H Veldink, Leonard H Van Den Berg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: To investigate whether symptom development in motor neuron disease (MND) is a random or organized process. Methods: Six hundred patients with amyotrophic lateral sclerosis (ALS), upper motor neuron (UMN) or lower motor neuron (LMN) phenotypes were invited for a questionnaire concerning symptom development. A binomial test was used to examine distribution of symptoms from site of onset. Development of symptoms over time was evaluated by Kaplan-Meier analysis. Results: There were 470 respondents (ALS = 254; LMN = 100; UMN = 116). Subsequent symptoms were more often in the contralateral limb following unilateral limb onset (ALS: arms p = 1.05 × 10 −8 , legs p < 2.86 × 10 −15 ; LMN phenotype: arms p = 6.74 × 10 −9 , legs p = 6.26 × 10 −6 ; UMN phenotype: legs p = 4.07 × 10 −14 ). In patients with limb onset, symptoms occurred significantly faster in the contralateral limb, followed by the other limbs and lastly by the bulbar region. Patterns of non-contiguous symptom development were also reported: leg symptoms followed bulbar onset in 30%, and bulbar symptoms followed leg onset in 11% of ALS patients. Conclusions: Preferred spread of symptoms from one limb to the contralateral limb, and to adjacent sites appears to be a characteristic of MND phenotypes, suggesting that symptom spread is organized, possibly involving axonal connectivity. Non-contiguous symptom development, however, is not uncommon, and may involve other factors.

Original languageEnglish
Pages (from-to)21-28
Number of pages8
JournalAmyotrophic Lateral Sclerosis & Frontotemporal Degeneration
Issue number1-2
Early online date2017
Publication statusPublished - Feb 2018


  • upper motor neuron
  • lower motor neuron
  • symptom development
  • Motor neuron disease
  • amyotrophic lateral sclerosis
  • Humans
  • Middle Aged
  • Kaplan-Meier Estimate
  • Male
  • Disease Progression
  • Young Adult
  • Phenotype
  • Aged, 80 and over
  • Motor Neurons/physiology
  • Adult
  • Female
  • Surveys and Questionnaires
  • Aged
  • Amyotrophic Lateral Sclerosis/diagnosis


Dive into the research topics of 'Patterns of symptom development in patients with motor neuron disease'. Together they form a unique fingerprint.

Cite this