Distinct Clinical Features and Outcomes in Motor Neuron Disease Associated with Behavioural Variant Frontotemporal Dementia

Dement Geriatr Cogn Disord. 2018;45(3-4):220-231. doi: 10.1159/000488528. Epub 2018 Jun 8.

Abstract

Aim: To determine the motor phenotype and outcome in a clinically ascertained group of patients with motor neuron disease (MND) and frontotemporal dementia (FTD).

Methods: This is an observational retrospective clinical study of patients fulfilling the clinical criteria for MND-FTD. A contemporary series of patients with amyotrophic lateral sclerosis (ALS) without dementia were included for comparison. Demographic, clinical, genetic, and neuropathological data were collected. A descriptive and comparative data analysis was performed.

Results: We identified 22 patients with MND-FTD. Selective distal upper limb muscle weakness and atrophy with non-significant lower limb weakness during follow-up was the most frequent motor pattern, present in 18 patients - in 15 of them associated with severe dysphagia. Aspiration pneumonia was the most common cause of death (12/19; 63%) despite gastrostomy. One-third of the patients did not develop upper motor neuron dysfunction. When compared to classic ALS without dementia (n = 162), these features were significantly different. A neuro-pathological examination was performed on 7 patients, and it confirmed the presence of MND with TDP43 protein aggregates in all patients.

Conclusions: The MND-FTD patients frequently displayed a distinctive motor pattern characterized by weakness and atrophy in distal upper limb muscles and dysphagia, with no or little spreading to other regions. These features may help to define specific subgroups of patients, which is important with regard to clinical management, outcome, and research.

Keywords: Amyotrophic lateral sclerosis; Clinical aspects; Frontotemporal dementia; Genetics of neurodegenerative diseases; Neuropathology.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / diagnosis
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Amyotrophic Lateral Sclerosis / psychology
  • Behavioral Symptoms / diagnosis
  • DNA-Binding Proteins / genetics*
  • Female
  • Frontotemporal Dementia* / diagnosis
  • Frontotemporal Dementia* / genetics
  • Frontotemporal Dementia* / physiopathology
  • Frontotemporal Dementia* / psychology
  • Humans
  • Male
  • Middle Aged
  • Motor Neuron Disease* / diagnosis
  • Motor Neuron Disease* / genetics
  • Motor Neuron Disease* / physiopathology
  • Motor Neuron Disease* / psychology
  • Muscle Weakness / diagnosis*
  • Outcome Assessment, Health Care
  • Patient Care Management / methods
  • Retrospective Studies
  • Upper Extremity* / pathology
  • Upper Extremity* / physiopathology

Substances

  • DNA-Binding Proteins