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

doi:10.1080/21678421.2017.1386688

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 Journal › Article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	21-28
Number of pages	8
Journal	Amyotrophic lateral sclerosis and frontotemporal degeneration
Volume	19
Issue number	1-2
DOIs	https://doi.org/10.1080/21678421.2017.1386688
Publication status	Published - 2 Jan 2018
Externally published	Yes

Funding

This study was supported by the ALS Foundation Netherlands, Prinses Beatrix Spierfonds, the European Community’s Health Seventh Framework Programme (grant agreement n° 259867), and the SOPHIA project (funded through the EU Joint Programme – Neurodegenerative Disease Research, JPND). R. Walhout reports no disclosures. E. Verstraete received a consultancy fee from Biogen Idec. MPvdH received a grant from The Netherlands Organization for Health Research and Development (Veni scheme), from the ALS Foundation Netherlands and from MQ. J.H. Veldink reports no disclosures. LHvdB received a grant from The Netherlands Organization for Health Research and Development (Vici scheme), travel grants and consultancy fees from Baxalta; serves on scientific advisory boards for Prinses Beatrix Spierfonds, Thierry Latran Foundation, Cytokinetics and Biogen.

Funders	Funder number
Netherlands Organization for Health Research and Development
Fondation Thierry Latran
EU Joint Programme – Neurodegenerative Disease Research
Cytokinetics
European Commission
Prinses Beatrix Spierfonds
Seventh Framework Programme	259867

Keywords

amyotrophic lateral sclerosis
lower motor neuron
Motor neuron disease
symptom development
upper motor neuron

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title = "Patterns of symptom development in patients with motor neuron disease",

abstract = "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.",

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Patterns of symptom development in patients with motor neuron disease

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