Neuropsychiatric changes precede classic motor symptoms in ALS and do not affect survival

Neurology. 2014 Jan 14;82(2):149-55. doi: 10.1212/WNL.0000000000000023. Epub 2013 Dec 11.


Objectives: To investigate patient susceptibility to neuropsychiatric symptoms in the context of progression of more classic motor symptoms in amyotrophic lateral sclerosis (ALS) and to examine the impact of neuropsychiatric symptoms on survival.

Methods: The study cohort consisted of 219 patients with ALS (limb onset = 159; bulbar onset = 60), with neuropsychiatric symptoms measured using the Motor Neuron Disease Behavioural Scale and more classic ALS symptoms assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. For detection of symptom susceptibility (neuropsychiatric vs classic motor), a Rasch analysis was applied (n = 219). Cox proportional hazard regression models were used for the survival analysis (n = 115 patients), which incorporated neuropsychiatric and classic motor symptoms.

Results: Rasch analysis demonstrated that neuropsychiatric symptoms appeared earlier than classic motor features of ALS. However, differences in neuropsychiatric scores did not affect survival: patients with abnormalities in neuropsychiatric domains did not exhibit a different rate of survival than those without (χ(2), 3.447, p = 0.328, -2 log-likelihood 377.341).

Conclusions: Neuropsychiatric symptoms appear before classic motor features in ALS, which corroborates the notion that ALS and frontotemporal dementia lie on a disease continuum. The early detection of neuropsychiatric symptoms will be critical to inform clinical decisions and alleviate carer burden. Importantly, subtle neuropsychiatric symptoms alone do not affect survival in ALS, which in turn confirms their pervasive nature in ALS.

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / complications*
  • Amyotrophic Lateral Sclerosis / psychology*
  • Cognition / physiology
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mental Disorders / etiology*
  • Mental Disorders / psychology*
  • Middle Aged
  • Movement Disorders / etiology
  • Movement Disorders / physiopathology
  • Neurologic Examination
  • Prognosis
  • Proportional Hazards Models
  • Survival
  • Survival Analysis