Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration. (21st May 2019)

• Record Type: Journal Article
• Authors: Forrest, Shelley L.; Crockford, Daniel R.; Sizemova, Anastasia; McCann, Heather; Shepherd, Claire E.; McGeachie, Andrew B.; Affleck, Andrew J.; Carew-Jones, Francine; Bartley, Lauren; Kwok, John B.; Kim, Woojin Scott; Jary, Eve; Tan, Rachel H.; McGinley, Ciara V.; Piguet, Olivier; Hodges, John R.; Kril, Jillian J.; Halliday, Glenda M.
• Is Part Of: Neurology. Volume 92:Number 21(2019)
• Publication Date: 2019-05-21
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000007530
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To investigate the prevalence of clinically relevant multiple system atrophy (MSA) and Lewy body disease (LBD) pathologies in a large frontotemporal lobar degeneration (FTLD) cohort to determine if concomitant pathologies underlie the heterogeneity of clinical features. Methods: All prospectively followed FTLD-tau and FTLD-TDP cases held by the Sydney Brain Bank (n = 126) were screened for coexisting MSA and LBD (Braak ≥ stage IV) pathology. Relevant clinical (including family history) and genetic associations were determined. Results: MSA pathology was not identified in this series. Of the FTLD cohort, 9 cases had coexisting LBD ≥ Braak stage IV and were associated with different FTLD subtypes including Pick disease (n = 2), corticobasal degeneration (n = 2), progressive supranuclear palsy (n = 2), and TDP type A (n = 3). All FTLD-TDP cases with coexisting LBD had mutations in progranulin (n = 2) or an abnormal repeat expansion in C9orf72 (n = 1). All FTLD-tau cases with coexisting LBD were sporadic. The H1H1 MAPT haplotype was found in all cases that could be genotyped (n = 6 of 9). Seven cases presented with a predominant dementia disorder, 3 of which developed parkinsonism. Two cases presented with a movement disorder and developed dementia in their disease course. The age at symptom onset (62 ± 11 years) and disease duration (8 ± 5 years) in FTLD cases with coexisting LBD did not differ from pure FTLD or pure LBD cases in the brain bank. Conclusion: Coexisting LBD in FTLD comprises a small proportion of cases but has implications for clinical and neuropathologic diagnoses and the identification of biomarkers.