Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration

Shelley L. Forrest; Daniel R. Crockford; Anastasia Sizemova; Heather McCann; Claire E. Shepherd; Andrew B. McGeachie; Andrew J. Affleck; Francine Carew-Jones; Lauren Bartley; John B. Kwok; Woojin Scott Kim; Eve Jary; Rachel H. Tan; Ciara V. McGinley; Olivier Piguet; John R. Hodges; Jillian J. Kril; Glenda M. Halliday

doi:10.1212/WNL.0000000000007530

Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration

Shelley L. Forrest, Daniel R. Crockford, Anastasia Sizemova, Heather McCann, Claire E. Shepherd, Andrew B. McGeachie, Andrew J. Affleck, Francine Carew-Jones, Lauren Bartley, John B. Kwok, Woojin Scott Kim, Eve Jary, Rachel H. Tan, Ciara V. McGinley, Olivier Piguet, John R. Hodges, Jillian J. Kril, Glenda M. Halliday

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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.

Original language	English
Pages (from-to)	e2472-e2482
Number of pages	11
Journal	Neurology
Volume	92
Issue number	21
DOIs	https://doi.org/10.1212/WNL.0000000000007530
Publication status	Published - 21 May 2019
Externally published	Yes

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Forrest, S. L., Crockford, D. R., Sizemova, A., McCann, H., Shepherd, C. E., McGeachie, A. B., Affleck, A. J., Carew-Jones, F., Bartley, L., Kwok, J. B., Kim, W. S., Jary, E., Tan, R. H., McGinley, C. V., Piguet, O., Hodges, J. R., Kril, J. J., & Halliday, G. M. (2019). Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration. Neurology, 92(21), e2472-e2482. https://doi.org/10.1212/WNL.0000000000007530

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title = "Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration",

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.",

author = "Forrest, {Shelley L.} and Crockford, {Daniel R.} and Anastasia Sizemova and Heather McCann and Shepherd, {Claire E.} and McGeachie, {Andrew B.} and Affleck, {Andrew J.} and Francine Carew-Jones and Lauren Bartley and Kwok, {John B.} and Kim, {Woojin Scott} and Eve Jary and Tan, {Rachel H.} and McGinley, {Ciara V.} and Olivier Piguet and Hodges, {John R.} and Kril, {Jillian J.} and Halliday, {Glenda M.}",

year = "2019",

month = may,

day = "21",

doi = "10.1212/WNL.0000000000007530",

language = "English",

volume = "92",

pages = "e2472--e2482",

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Forrest, SL, Crockford, DR, Sizemova, A, McCann, H, Shepherd, CE, McGeachie, AB, Affleck, AJ, Carew-Jones, F, Bartley, L, Kwok, JB, Kim, WS, Jary, E, Tan, RH, McGinley, CV, Piguet, O, Hodges, JR, Kril, JJ & Halliday, GM 2019, 'Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration', Neurology, vol. 92, no. 21, pp. e2472-e2482. https://doi.org/10.1212/WNL.0000000000007530

TY - JOUR

T1 - Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration

AU - Forrest, Shelley L.

AU - Crockford, Daniel R.

AU - Sizemova, Anastasia

AU - McCann, Heather

AU - Shepherd, Claire E.

AU - McGeachie, Andrew B.

AU - Affleck, Andrew J.

AU - Carew-Jones, Francine

AU - Bartley, Lauren

AU - Kwok, John B.

AU - Kim, Woojin Scott

AU - Jary, Eve

AU - Tan, Rachel H.

AU - McGinley, Ciara V.

AU - Piguet, Olivier

AU - Hodges, John R.

AU - Kril, Jillian J.

AU - Halliday, Glenda M.

PY - 2019/5/21

Y1 - 2019/5/21

N2 - 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.

AB - 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.

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U2 - 10.1212/WNL.0000000000007530

DO - 10.1212/WNL.0000000000007530

M3 - Article

C2 - 31019099

SN - 0028-3878

VL - 92

SP - e2472-e2482

JO - Neurology

JF - Neurology

IS - 21

ER -

Coexisting Lewy body disease and clinical parkinsonism in frontotemporal lobar degeneration

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