Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder

B. F. Boeve, M. H. Silber, T. J. Ferman, S. C. Lin, E. E. Benarroch, A. M. Schmeichel, J. E. Ahlskog, R. J. Caselli, S. Jacobson, M. Sabbagh, C. Adler, B. Woodruff, T. G. Beach, A. Iranzo, E. Gelpi, J. Santamaria, E. Tolosa, C. Singer, D. C. Mash, C. LucaI. Arnulf, C. Duyckaerts, C. H. Schenck, M. W. Mahowald, Y. Dauvilliers, N. R. Graff-Radford, Z. K. Wszolek, J. E. Parisi, Brittany Dugger, M. E. Murray, D. W. Dickson

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

Objective: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. Methods: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. Results: 172 cases were identified, of whom 143 (83%) were men. The mean ± SD age of onset in years for the core features were as follows - RBD, 62 ± 14 (range, 20-93), cognitive impairment (n = 147); 69 ± 10 (range, 22-90), parkinsonism (n = 151); 68 ± 9 (range, 20-92), and autonomic dysfunction (n = 42); 62 ± 12 (range, 23-81). Death age was 75 ± 9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10 ± 12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n = 97), Parkinson's disease with or without mild cognitive impairment or dementia (n = 32), multiple system atrophy (MSA) (n = 19), Alzheimer's disease (AD)(n = 9) and other various disorders including secondary narcolepsy (n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)(n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n = 59), MSA (n = 19), AD (n = 6), progressive supranulear palsy (PSP) (n = 2), other mixed neurodegenerative pathologies (n = 6), NBIA-1/LBD/tauopathy (n = 1), and hypothalamic structural lesions (n = 2). Among the neurodegenerative disorders associated with RBD (n = 170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. Conclusions: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

Original languageEnglish (US)
Pages (from-to)754-762
Number of pages9
JournalSleep Medicine
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Fingerprint

REM Sleep Behavior Disorder
Nervous System Diseases
Lewy Body Disease
Multiple System Atrophy
Parkinsonian Disorders
Pantothenate Kinase-Associated Neurodegeneration
Synucleins
Tauopathies
Narcolepsy
Gene Duplication
North America
Age of Onset
Paralysis
Neurodegenerative Diseases

Keywords

  • Dementia with Lewy bodies
  • Lewy body disease
  • Multiple system atrophy
  • Parasomnia
  • Parkinson's disease
  • REM sleep behavior disorder
  • Synuclein
  • Synucleinopathy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Boeve, B. F., Silber, M. H., Ferman, T. J., Lin, S. C., Benarroch, E. E., Schmeichel, A. M., ... Dickson, D. W. (2013). Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Medicine, 14(8), 754-762. https://doi.org/10.1016/j.sleep.2012.10.015

Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. / Boeve, B. F.; Silber, M. H.; Ferman, T. J.; Lin, S. C.; Benarroch, E. E.; Schmeichel, A. M.; Ahlskog, J. E.; Caselli, R. J.; Jacobson, S.; Sabbagh, M.; Adler, C.; Woodruff, B.; Beach, T. G.; Iranzo, A.; Gelpi, E.; Santamaria, J.; Tolosa, E.; Singer, C.; Mash, D. C.; Luca, C.; Arnulf, I.; Duyckaerts, C.; Schenck, C. H.; Mahowald, M. W.; Dauvilliers, Y.; Graff-Radford, N. R.; Wszolek, Z. K.; Parisi, J. E.; Dugger, Brittany; Murray, M. E.; Dickson, D. W.

In: Sleep Medicine, Vol. 14, No. 8, 01.08.2013, p. 754-762.

Research output: Contribution to journalArticle

Boeve, BF, Silber, MH, Ferman, TJ, Lin, SC, Benarroch, EE, Schmeichel, AM, Ahlskog, JE, Caselli, RJ, Jacobson, S, Sabbagh, M, Adler, C, Woodruff, B, Beach, TG, Iranzo, A, Gelpi, E, Santamaria, J, Tolosa, E, Singer, C, Mash, DC, Luca, C, Arnulf, I, Duyckaerts, C, Schenck, CH, Mahowald, MW, Dauvilliers, Y, Graff-Radford, NR, Wszolek, ZK, Parisi, JE, Dugger, B, Murray, ME & Dickson, DW 2013, 'Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder', Sleep Medicine, vol. 14, no. 8, pp. 754-762. https://doi.org/10.1016/j.sleep.2012.10.015
Boeve, B. F. ; Silber, M. H. ; Ferman, T. J. ; Lin, S. C. ; Benarroch, E. E. ; Schmeichel, A. M. ; Ahlskog, J. E. ; Caselli, R. J. ; Jacobson, S. ; Sabbagh, M. ; Adler, C. ; Woodruff, B. ; Beach, T. G. ; Iranzo, A. ; Gelpi, E. ; Santamaria, J. ; Tolosa, E. ; Singer, C. ; Mash, D. C. ; Luca, C. ; Arnulf, I. ; Duyckaerts, C. ; Schenck, C. H. ; Mahowald, M. W. ; Dauvilliers, Y. ; Graff-Radford, N. R. ; Wszolek, Z. K. ; Parisi, J. E. ; Dugger, Brittany ; Murray, M. E. ; Dickson, D. W. / Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. In: Sleep Medicine. 2013 ; Vol. 14, No. 8. pp. 754-762.
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abstract = "Objective: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. Methods: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. Results: 172 cases were identified, of whom 143 (83{\%}) were men. The mean ± SD age of onset in years for the core features were as follows - RBD, 62 ± 14 (range, 20-93), cognitive impairment (n = 147); 69 ± 10 (range, 22-90), parkinsonism (n = 151); 68 ± 9 (range, 20-92), and autonomic dysfunction (n = 42); 62 ± 12 (range, 23-81). Death age was 75 ± 9 years (range, 24-96). Eighty-two (48{\%}) had RBD confirmed by PSG, 64 (37{\%}) had a classic history of recurrent dream enactment behavior, and 26 (15{\%}) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51{\%}) patients by 10 ± 12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n = 97), Parkinson's disease with or without mild cognitive impairment or dementia (n = 32), multiple system atrophy (MSA) (n = 19), Alzheimer's disease (AD)(n = 9) and other various disorders including secondary narcolepsy (n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)(n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n = 59), MSA (n = 19), AD (n = 6), progressive supranulear palsy (PSP) (n = 2), other mixed neurodegenerative pathologies (n = 6), NBIA-1/LBD/tauopathy (n = 1), and hypothalamic structural lesions (n = 2). Among the neurodegenerative disorders associated with RBD (n = 170), 160 (94{\%}) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. Conclusions: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.",
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author = "Boeve, {B. F.} and Silber, {M. H.} and Ferman, {T. J.} and Lin, {S. C.} and Benarroch, {E. E.} and Schmeichel, {A. M.} and Ahlskog, {J. E.} and Caselli, {R. J.} and S. Jacobson and M. Sabbagh and C. Adler and B. Woodruff and Beach, {T. G.} and A. Iranzo and E. Gelpi and J. Santamaria and E. Tolosa and C. Singer and Mash, {D. C.} and C. Luca and I. Arnulf and C. Duyckaerts and Schenck, {C. H.} and Mahowald, {M. W.} and Y. Dauvilliers and Graff-Radford, {N. R.} and Wszolek, {Z. K.} and Parisi, {J. E.} and Brittany Dugger and Murray, {M. E.} and Dickson, {D. W.}",
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TY - JOUR

T1 - Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder

AU - Boeve, B. F.

AU - Silber, M. H.

AU - Ferman, T. J.

AU - Lin, S. C.

AU - Benarroch, E. E.

AU - Schmeichel, A. M.

AU - Ahlskog, J. E.

AU - Caselli, R. J.

AU - Jacobson, S.

AU - Sabbagh, M.

AU - Adler, C.

AU - Woodruff, B.

AU - Beach, T. G.

AU - Iranzo, A.

AU - Gelpi, E.

AU - Santamaria, J.

AU - Tolosa, E.

AU - Singer, C.

AU - Mash, D. C.

AU - Luca, C.

AU - Arnulf, I.

AU - Duyckaerts, C.

AU - Schenck, C. H.

AU - Mahowald, M. W.

AU - Dauvilliers, Y.

AU - Graff-Radford, N. R.

AU - Wszolek, Z. K.

AU - Parisi, J. E.

AU - Dugger, Brittany

AU - Murray, M. E.

AU - Dickson, D. W.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Objective: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. Methods: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. Results: 172 cases were identified, of whom 143 (83%) were men. The mean ± SD age of onset in years for the core features were as follows - RBD, 62 ± 14 (range, 20-93), cognitive impairment (n = 147); 69 ± 10 (range, 22-90), parkinsonism (n = 151); 68 ± 9 (range, 20-92), and autonomic dysfunction (n = 42); 62 ± 12 (range, 23-81). Death age was 75 ± 9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10 ± 12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n = 97), Parkinson's disease with or without mild cognitive impairment or dementia (n = 32), multiple system atrophy (MSA) (n = 19), Alzheimer's disease (AD)(n = 9) and other various disorders including secondary narcolepsy (n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)(n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n = 59), MSA (n = 19), AD (n = 6), progressive supranulear palsy (PSP) (n = 2), other mixed neurodegenerative pathologies (n = 6), NBIA-1/LBD/tauopathy (n = 1), and hypothalamic structural lesions (n = 2). Among the neurodegenerative disorders associated with RBD (n = 170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. Conclusions: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

AB - Objective: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. Methods: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. Results: 172 cases were identified, of whom 143 (83%) were men. The mean ± SD age of onset in years for the core features were as follows - RBD, 62 ± 14 (range, 20-93), cognitive impairment (n = 147); 69 ± 10 (range, 22-90), parkinsonism (n = 151); 68 ± 9 (range, 20-92), and autonomic dysfunction (n = 42); 62 ± 12 (range, 23-81). Death age was 75 ± 9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10 ± 12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n = 97), Parkinson's disease with or without mild cognitive impairment or dementia (n = 32), multiple system atrophy (MSA) (n = 19), Alzheimer's disease (AD)(n = 9) and other various disorders including secondary narcolepsy (n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)(n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n = 59), MSA (n = 19), AD (n = 6), progressive supranulear palsy (PSP) (n = 2), other mixed neurodegenerative pathologies (n = 6), NBIA-1/LBD/tauopathy (n = 1), and hypothalamic structural lesions (n = 2). Among the neurodegenerative disorders associated with RBD (n = 170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. Conclusions: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

KW - Dementia with Lewy bodies

KW - Lewy body disease

KW - Multiple system atrophy

KW - Parasomnia

KW - Parkinson's disease

KW - REM sleep behavior disorder

KW - Synuclein

KW - Synucleinopathy

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