Pilar M Ferraro1, Corrado Cabona2, Giuseppe Meo3, Claudia Rolla-Bigliani4, Lucio Castellan4, Matteo Pardini3,5, Matilde Inglese3,5, Claudia Caponnetto3, Luca Roccatagliata4,6. 1. Department of Neuroradiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. PilarMaria.Ferraro@ext.unige.it. 2. Department of Neurophysiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 3. Department of Neurology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 4. Department of Neuroradiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 5. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy. 6. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
Abstract
PURPOSE: The lifetime risk of developing amyotrophic lateral sclerosis (ALS) increases in the elderly, and greater age at symptom onset has been identified as a negative prognostic factor in the disease. However, the underlying neurobiological mechanisms are still poorly investigated. We hypothesized that older age at symptom onset would have been associated with greater extra-motor cortical damage contributing to worse prognosis, so we explored the relationship between age at symptom onset, cortical thinning (CT) distribution, and clinical markers of disease progression. METHODS: We included 26 ALS patients and 29 healthy controls with T1-weighted magnetic resonance imaging (MRI). FreeSurfer 6.0 was used to identify regions of cortical atrophy (CA) in ALS, and to relate age at symptom onset to CT distribution. Linear regression analyses were then used to investigate whether MRI metrics of age-related damage were predictive of clinical progression. MRI results were corrected using the Monte Carlo simulation method, and regression analyses were further corrected for disease duration. RESULTS: ALS patients exhibited significant CA mainly encompassing motor regions, but also involving the cuneus bilaterally and the right superior parietal cortex (p < 0.05). Older age at symptom onset was selectively associated with greater extra-motor (frontotemporal) CT, including pars opercularis bilaterally, left middle temporal, and parahippocampal cortices (p < 0.05), and CT of these regions was predictive of shorter survival (p = 0.004, p = 0.03). CONCLUSION: More severe frontotemporal CT contributes to shorter survival in older ALS patients. These findings have the potential to unravel the neurobiological mechanisms linking older age at symptom onset to worse prognosis in ALS.
PURPOSE: The lifetime risk of developing amyotrophic lateral sclerosis (ALS) increases in the elderly, and greater age at symptom onset has been identified as a negative prognostic factor in the disease. However, the underlying neurobiological mechanisms are still poorly investigated. We hypothesized that older age at symptom onset would have been associated with greater extra-motor cortical damage contributing to worse prognosis, so we explored the relationship between age at symptom onset, cortical thinning (CT) distribution, and clinical markers of disease progression. METHODS: We included 26 ALSpatients and 29 healthy controls with T1-weighted magnetic resonance imaging (MRI). FreeSurfer 6.0 was used to identify regions of cortical atrophy (CA) in ALS, and to relate age at symptom onset to CT distribution. Linear regression analyses were then used to investigate whether MRI metrics of age-related damage were predictive of clinical progression. MRI results were corrected using the Monte Carlo simulation method, and regression analyses were further corrected for disease duration. RESULTS:ALSpatients exhibited significant CA mainly encompassing motor regions, but also involving the cuneus bilaterally and the right superior parietal cortex (p < 0.05). Older age at symptom onset was selectively associated with greater extra-motor (frontotemporal) CT, including pars opercularis bilaterally, left middle temporal, and parahippocampal cortices (p < 0.05), and CT of these regions was predictive of shorter survival (p = 0.004, p = 0.03). CONCLUSION: More severe frontotemporal CT contributes to shorter survival in older ALSpatients. These findings have the potential to unravel the neurobiological mechanisms linking older age at symptom onset to worse prognosis in ALS.
Entities:
Keywords:
Age at onset; Amyotrophic lateral sclerosis; Cortical thinning; Prognosis; Structural magnetic resonance imaging
Authors: Christina Schuster; Elisabeth Kasper; Judith Machts; Daniel Bittner; Jörn Kaufmann; Reiner Benecke; Stefan Teipel; Stefan Vielhaber; Johannes Prudlo Journal: J Neurol Date: 2014-07-15 Impact factor: 4.849