Skip to main content

AAN.com

Articles

December 1, 1998

Frontotemporal lobar degeneration
A consensus on clinical diagnostic criteria

D. Neary, MD, J. S. Snowden, PhD, L. Gustafson, MD, U. Passant, MD, D. Stuss, PhD, S. Black, MD, M. Freedman, MD, … Show All … , A. Kertesz, MD, P. H. Robert, MD, PhD, M. Albert, PhD, K. Boone, PhD, B. L. Miller, MD, J. Cummings, MD, and D. F. Benson, MDAuthors Info & Affiliations

December 1998 issue

51 (6) 1546-1554

https://doi.org/10.1212/WNL.51.6.1546

Abstract

Objective: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration.

Methods: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members.

Results: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text.

Conclusions: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.

The Lund and Manchester Groups. Consensus Statement. Clinical and neuropathological criteria for fronto-temporal dementia. J Neurol Neurosurg Psychiatry 1994;4:416-418.

2.

Gustafson L. Frontal lobe degeneration of non-Alzheimer type. II. Clinical picture and differential diagnosis. Arch Gerontol Geriatr 1987;6:209-223.

3.

Gustafson L. Clinical picture of frontal lobe degeneration of non-Alzheimer type. Dementia 1993;4:143-148.

4.

Neary D, Snowden JS, Northen B, Goulding PJ. Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry 1988;51:353-361.

5.

Snowden JS, Neary D, Mann DMA. Fronto-temporal lobar degeneration: fronto-temporal dementia, progressive aphasia, semantic dementia. New York: Churchill Livingstone, 1996.

6.

Mesulam M-M. Slowly progressive aphasia without generalized dementia. Ann Neurol 1982;11:592-598.

7.

Delecluse F, Andersen AR, Waldemar G, et al. Cerebral blood flow in progressive aphasia without dementia. Brain 1990;113:1395-1404.

8.

Weintraub S, Rubin NP, Mesulam M-M. Primary progressive aphasia: longitudinal course, neuropsychological profile and language features. Arch Neurol 1990;47:1329-1335.

9.

Snowden JS, Neary D, Mann DMA, Goulding PJ, Testa HJ. Progressive language disorder due to lobar atrophy. Ann Neurol 1992;31:174-183.

10.

Snowden JS, Goulding PJ, Neary D. Semantic dementia: a form of circumscribed atrophy. Behav Neurol 1989;2:167-182.

11.

Hodges JR, Patterson K, Oxbury S, Funnell E. Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy. Brain 1992;115:1783-1806.

12.

Hutton M, Lendon CL, Rizzu P, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998;393:702-705.

13.

Poorkaj P, Bird TD, Wijsman E, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 1998;43:815-825.

14.

Brown J, Ashworth A, Gydesen S, et al. Familial nonspecific dementia maps to chromosome 3. Hum Mol Genet 1995;4:1625-1628.

15.

Gustafson L, Brun A, Ingvar DH. Presenile dementia: clinical symptoms, pathoanatomical findings and cerebral blood flow. In: Meyer JS, Lechner H, Reivich M, eds. Cerebral vascular disease. Amsterdam: Excerpta Medica, 1977:5-9.

16.

Neary D, Snowden JS, Bowen DM, et al. Neuropsychological syndromes in presenile dementia due to cerebral atrophy. J Neurol Neurosurg Psychiatry 1986;49:163-174.

17.

Neary D, Snowden JS, Shields RA, et al. Single photon emission tomography using ^99mTc-HMPAO in the investigation of dementia. J Neurol Neurosurg Psychiatry 1987;50:1101-1109.

18.

Jagust WJ, Reed BR, Seab JP, Kramer JH, Budinger TF. Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia. Am J Physiol Imaging 1989;4:89-96.

19.

Miller BL, Cummings JL, Villanueva-Meyer J, et al. Frontal lobe degeneration: clinical, neuropsychological and SPECT characteristics. Neurology 1991;41:1374-1382.

20.

Gregory CA, Hodges JR. Dementia of frontal type and the focal lobar atrophies. Int Rev Psychiatry 1993;5:397-406.

21.

Donoso A, Lillo R, Quiroz M, Rojas A. Demencias prefrontales: clinica y SPECT en seis casos. Rev Med Chil 1994;122:1408-1412.

22.

Frisoni GB, Pizzolato G, Geroldi C, Rossato A, Bianchetti A, Trabucchi M. Dementia of the frontal type: neuropsychological and [99Tc]-HMPAO SPECT features. J Geriatr Psychiatry Neurol 1995;8:42-48.

23.

Miller BL, Ikonte C, Ponton M, et al. A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations. Neurology 1997;48:937-942.

24.

Assal G, Favre C, Regli F. Aphasie dégénerative. Rev Neurol (Paris) 1985;141:245-247.

25.

Chawluk JB, Mesulam M-M, Hurtig H, et al. Slowly progressive aphasia without generalized dementia: studies with positron emission tomography. Ann Neurol 1986;19:68-74.

26.

Basso A, Capitani E, Laiacona M. Progressive language impairment without dementia: a case with isolated category specific semantic defect. J Neurol Neurosurg Psychiatry 1988;51:1201-1207.

27.

Poeck K, Luzzatti C. Slowly progressive aphasia in three patients. The problem of accompanying neuropsychological deficit. Brain 1988;111:151-168.

28.

Craenhals A, Raison-Van Ruymbeke AM, Rectem D, Seron X, Laterre EC. Is slowly progressive aphasia actually a new clinical entity? Aphasiology 1990;4:485-509.

29.

Kempler D, Metter EJ, Riege WH, Jackson CA, Benson DF, Hanson WR. Slowly progressive aphasia: three cases with language, memory, CT and PET data. J Neurol Neurosurg Psychiatry 1990;53:987-993.

30.

Tyrrell PJ, Warrington EK, Frackowiak RSJ, Rossor MN. Heterogeneity in progressive aphasia due to focal cortical atrophy. A clinical and PET study. Brain 1990;113:1321-1336.

31.

Karbe H, Kertesz A, Polk M. Profiles of language impairment in primary progressive aphasia. Arch Neurol 1993;50:193-201.

32.

Grossman M, Mickanin J, Onishi K, et al. Progressive nonfluent aphasia: language, cognitive and PET measures contrasted with probable Alzheimer's disease. J Cogn Neurosci 1996;8:135-154.

33.

Brun A. Frontal lobe degeneration of non-Alzheimer type. I. Neuropathology. Arch Gerontol Geriatr 1987;6:193-208.

34.

Brun A. Frontal lobe degeneration of non-Alzheimer type revisited. Dementia 1993;4:126-131.

35.

Knopman DS, Mastri AR, Frey WH, Sung JH, Rustan T. Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 1990;40:251-256.

36.

Mann DMA, South PW, Snowden JS, Neary D. Dementia of frontal lobe type; neuropathology and immunohistochemistry. J Neurol Neurosurg Psychiatry 1993;56:605-614.

37.

Mann DMA, South PW. The topographic distribution of brain atrophy in frontal lobe dementia. Acta Neuropathol 1993;85:334-340.

38.

Kirshner HS, Tanridag O, Thurman L, Whetsell WO. Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol 1987;22:527-532.

39.

Graff-Radford NR, Damasio AR, Hyman BT, et al. Progressive aphasia in a patient with Pick's disease: a neuropsychological, radiologic and anatomic study. Neurology 1990;40:620-626.

40.

Neary D, Snowden JS, Mann DMA. The clinical pathological correlates of lobar atrophy. A review. Dementia 1993;4:154-159.

41.

Kertesz A, Hudson L, Mackenzie IRA, Munoz DG. The pathology and nosology of primary progressive aphasia. Neurology 1994;44:2065-2072.

42.

Brion S, Psimaras A, Chevalier JF, Plas J, Masse G, Jatteau O. l'Association maladie de Pick et sclérose latérale amyotrophique. Etude d'un cas anatomo-clinique et revue de la litérature. L'Encephale 1980;6:259-286.

43.

Constantinidis J. Syndrome familial: association de maladie Pick et sclérose latérale amyotrophique. L'Encephale 1987;13:285-293.

44.

Neary D, Snowden JS, Mann DMA, Northern B, Goulding PJ, Mcdermott N. Frontal lobe dementia and motor neuron disease. J Neurol Neurosurg Psychiatry 1990;53:23-32.

45.

Ferrer I, Roig C, Espino A, Peiro G, Matias Guiu X. Dementia of frontal lobe type and motor neuron disease. A Golgi study of the frontal cortex. J Neurol Neurosurg Psychiatry 1991;54:932-934.

46.

Sam M, Gutmann L, Schochet SS, Doshi H. Pick's disease: a case clinically resembling amyotrophic lateral sclerosis. Neurology 1991;41:1831-1833.

47.

Caselli RJ, Windebank AJ, Petersen RC, et al. Rapidly progressive aphasic dementia and motor neuron disease. Ann Neurol 1993;33:200-207.

48.

Lhermitte F. 'Utilization behavior' and its relation to lesions of the frontal lobes. Brain 1983;106:237-255.

Information & Authors

Information

Published In

Neurology^®

Volume 51 • Number 6 • December 1998

Pages: 1546-1554

PubMed: 9855500

Copyright

© 1998.

Publication History

Published online: December 1, 1998

Published in print: December 1998

Permissions

Request permissions for this article.

Request Permissions

Authors

Affiliations & Disclosures

D. Neary, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

J. S. Snowden, PhD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

L. Gustafson, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

U. Passant, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

D. Stuss, PhD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

S. Black, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

M. Freedman, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

A. Kertesz, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

P. H. Robert, MD, PhD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

M. Albert, PhD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

K. Boone, PhD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

B. L. Miller, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

J. Cummings, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

D. F. Benson, MD

From the Manchester Royal Infirmary (Drs. Neary and Snowden), Manchester, UK; the Lund University Hospital (Drs. Gustafson and Passant), Sweden; the Rotman Research Institute (Drs. Stuss, Black, and Freedman) Baycrest Centre for Geriatric Care, Toronto and University of Toronto, Canada; the University of Western Ontario (Dr. Kertesz) London, Canada; the Nice University School of Medicine (Dr. Robert), France; the Massachusetts General Hospital (Dr. Albert), Boston, MA; and the University of California at Los Angeles, School of Medicine (Drs. Boone, Miller, Cummings, and Benson), CA.

View all articles by this author

Notes

Address correspondence and reprint requests to Dr. D. Neary, Department of Neurology, Manchester Royal Infirmary, Manchester M13 9WL, UK.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By

- Kristin Schaffer Mendez,
- Maya L. Henry,
Primary progressive aphasia, Encyclopedia of the Human Brain, (486-500), (2025).https://doi.org/10.1016/B978-0-12-820480-1.00125-X
Crossref
- KXX Yong,
- A Petzold,
- P Foster,
- A Young,
- S Bell,
- Y Bai,
- AP Leff,
- S Crutch,
- JA Greenwood,
The Graded Incomplete Letters Test (GILT): a rapid test to detect cortical visual loss, with UK Biobank implementation, Behavior Research Methods, 56, 7, (7748-7760), (2024).https://doi.org/10.3758/s13428-024-02448-7
Crossref
- Claudia Saraceno,
- Carlo Cervellati,
- Alessandro Trentini,
- Daniela Crescenti,
- Antonio Longobardi,
- Andrea Geviti,
- Natale Salvatore Bonfiglio,
- Sonia Bellini,
- Roland Nicsanu,
- Silvia Fostinelli,
- Gianmarco Mola,
- Raffaella Riccetti,
- Davide Vito Moretti,
- Orazio Zanetti,
- Giuliano Binetti,
- Giovanni Zuliani,
- Roberta Ghidoni,
Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer’s Disease and Frontotemporal Dementia: A Pilot Study, International Journal of Molecular Sciences, 25, 15, (8354), (2024).https://doi.org/10.3390/ijms25158354
Crossref
- Anouk Karcher,
- Rayane Hamza,
- Camille Jantzi,
Case report: Assessing criminal responsibility and recidivism risk in the behavioral variant of frontotemporal dementia, Frontiers in Psychiatry, 15, (2024).https://doi.org/10.3389/fpsyt.2024.1437363
Crossref
- Mirjana Babić Leko,
- Ena Španić Popovački,
- Nanet Willumsen,
- Matea Nikolac Perković,
- Nikolina Pleić,
- Klara Zubčić,
- Lea Langer Horvat,
- Željka Vogrinc,
- Marina Boban,
- Fran Borovečki,
- Tatijana Zemunik,
- Rohan de Silva,
- Goran Šimić,
Further validation of the association between MAPT haplotype-tagging polymorphisms and Alzheimer’s disease: neuropsychological tests, cerebrospinal fluid biomarkers, and APOE genotype, Frontiers in Molecular Neuroscience, 17, (2024).https://doi.org/10.3389/fnmol.2024.1456670
Crossref
- Mohammad Aadil Bhat,
- Suneela Dhaneshwar,
Neurodegenerative Diseases: New Hopes and Perspectives, Current Molecular Medicine, 24, 8, (1004-1032), (2024).https://doi.org/10.2174/1566524023666230907093451
Crossref
- Haitian Nan,
- Yeon-Jeong Kim,
- Min Chu,
- Dan Li,
- Jieying Li,
- Deming Jiang,
- Yiming Wu,
- Toshihisa Ohtsuka,
- Liyong Wu,
Genetic and clinical landscape of Chinese frontotemporal dementia: dominance of TBK1 and OPTN mutations, Alzheimer's Research & Therapy, 16, 1, (2024).https://doi.org/10.1186/s13195-024-01493-w
Crossref
- Shijing Wu,
- Ping Zhan,
- Guojing Wang,
- Xiaohua Yu,
- Hongyun Liu,
- Weidong Wang,
Changes of brain functional network in Alzheimer’s disease and frontotemporal dementia: a graph-theoretic analysis, BMC Neuroscience, 25, 1, (2024).https://doi.org/10.1186/s12868-024-00877-w
Crossref
- Daniele Urso,
- Stefano Giannoni-Luza,
- Stefania Mondello,
- Giancarlo Logroscino,
Accuracy of clinical diagnosis of behavioural variant frontotemporal dementia: a protocol for a systematic review and meta-analysis, BMJ Open, 14, 7, (e081935), (2024).https://doi.org/10.1136/bmjopen-2023-081935
Crossref
- Andrew Kertesz,
- Elizabeth Finger,
- David G. Munoz,
Progress in Primary Progressive Aphasia: A Review, Cognitive and Behavioral Neurology, 37, 1, (3-12), (2024).https://doi.org/10.1097/WNN.0000000000000365
Crossref
See more

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login

Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
[email protected]

We appreciate your patience during this time and apologize for any inconvenience.

View options

PDF and All Supplements

Download PDF and Supplementary Material

Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

advertisement

Open Review Pilot Project

Explore peer reviews, author responses, and editor comments on selected articles.

Learn More

Letters to the Editor

The Letters section represents an opportunity for ongoing author debate and post-publication peer review. View our submission guidelines for Letters to the Editor before submitting your comment.

Submit a Letter for this article

View full text|Download PDF