Zhe Long1,2,3, Muireann Irish3,4,5, David Foxe3,4, John R Hodges2,3,5, Olivier Piguet3,4,5, James R Burrell6,7,8,9,10. 1. Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. 2. The University of Sydney, The Faculty of Medicine and Health, Sydney, NSW, Australia. 3. The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia. 4. The University of Sydney, School of Psychology, Sydney, NSW, Australia. 5. ARC Centre of Excellence in Cognition and Its Disorders, Sydney, NSW, Australia. 6. The University of Sydney, The Faculty of Medicine and Health, Sydney, NSW, Australia. james.burrell@sydney.edu.au. 7. The University of Sydney, Faculty of Health Sciences, Sydney, NSW, Australia. james.burrell@sydney.edu.au. 8. The University of Sydney, Concord Medical School, Sydney, NSW, Australia. james.burrell@sydney.edu.au. 9. ARC Centre of Excellence in Cognition and Its Disorders, Sydney, NSW, Australia. james.burrell@sydney.edu.au. 10. Neurosciences 5West, Concord Repatriation General Hospital, Sydney, NSW, 2139, Australia. james.burrell@sydney.edu.au.
Abstract
OBJECTIVE: To comprehensively examine the clinical presentation of patients diagnosed with frontotemporal dementia-motor neuron disease (FTD-MND) compared to FTD subtypes. To clarify the heterogeneity of behavioural and language deficits in FTD-MND using a data-driven approach. METHODS: Patients with FTD-MND (n = 31), behavioural variant FTD (n = 119), non-fluent variant primary progressive aphasia (n = 47), semantic variant primary progressive aphasia (n = 42), and controls (n = 127) underwent comprehensive clinical, cognitive and behavioural assessments. Two-step cluster analysis examined patterns of behavioural and language impairment. Voxel-based morphometry and tract-based spatial statistics were used to investigate differences across the subgroups that emerged from cluster analysis. RESULTS: More than half of FTD-MND patients initially presented with variable combinations of deficits (e.g., mixed behaviour/cognitive, mixed behaviour/cognitive/motor deficits), with 74% of them meeting criteria for FTD-MND within 24 months with a median of 12 months. The frequency and severity of behavioural and language abnormalities in FTD-MND lie between that seen in the three FTD phenotypes. Cluster analysis identified three patterns of behavioural and language impairment in FTD-MND. The three FTD-MND subgroups demonstrated different profiles of white matter tract disruption, but did not differ in age at onset, disease duration or patterns of cortical atrophy. CONCLUSIONS: While highly heterogeneous, in terms of behavioural and language deficits, and disease severity, the presentation of FTD-MND may be distinct to that of FTD. Distinct white matter degeneration patterns may underpin heterogeneous clinical profiles in FTD-MND. FTD presenting with mixed behavioural-language disturbances should be monitored closely for at least 12-24 months for the emergence of MND symptoms/signs.
OBJECTIVE: To comprehensively examine the clinical presentation of patients diagnosed with frontotemporal dementia-motor neuron disease (FTD-MND) compared to FTD subtypes. To clarify the heterogeneity of behavioural and language deficits in FTD-MND using a data-driven approach. METHODS:Patients with FTD-MND (n = 31), behavioural variant FTD (n = 119), non-fluent variant primary progressive aphasia (n = 47), semantic variant primary progressive aphasia (n = 42), and controls (n = 127) underwent comprehensive clinical, cognitive and behavioural assessments. Two-step cluster analysis examined patterns of behavioural and language impairment. Voxel-based morphometry and tract-based spatial statistics were used to investigate differences across the subgroups that emerged from cluster analysis. RESULTS: More than half of FTD-MNDpatients initially presented with variable combinations of deficits (e.g., mixed behaviour/cognitive, mixed behaviour/cognitive/motor deficits), with 74% of them meeting criteria for FTD-MND within 24 months with a median of 12 months. The frequency and severity of behavioural and language abnormalities in FTD-MND lie between that seen in the three FTD phenotypes. Cluster analysis identified three patterns of behavioural and language impairment in FTD-MND. The three FTD-MND subgroups demonstrated different profiles of white matter tract disruption, but did not differ in age at onset, disease duration or patterns of cortical atrophy. CONCLUSIONS: While highly heterogeneous, in terms of behavioural and language deficits, and disease severity, the presentation of FTD-MND may be distinct to that of FTD. Distinct white matter degeneration patterns may underpin heterogeneous clinical profiles in FTD-MND. FTD presenting with mixed behavioural-language disturbances should be monitored closely for at least 12-24 months for the emergence of MND symptoms/signs.
Authors: James R Burrell; Glenda M Halliday; Jillian J Kril; Lars M Ittner; Jürgen Götz; Matthew C Kiernan; John R Hodges Journal: Lancet Date: 2016-03-14 Impact factor: 79.321
Authors: Mamede de Carvalho; Reinhard Dengler; Andrew Eisen; John D England; Ryuji Kaji; Jun Kimura; Kerry Mills; Hiroshi Mitsumoto; Hiroyuki Nodera; Jeremy Shefner; Michael Swash Journal: Clin Neurophysiol Date: 2007-12-27 Impact factor: 3.708
Authors: Rebekah M Ahmed; Emma M Devenney; Cherie Strikwerda-Brown; John R Hodges; Olivier Piguet; Matthew C Kiernan Journal: Neurology Date: 2020-04-10 Impact factor: 9.910