CLIPPERS and its mimics: Evaluation of new criteria for the diagnosis of CLIPPERS

Guillaume Taieb, Patricia Mulero, Dimitri Psimaras, Bob W. van Oosten, J. rg D. Seebach, Romain Marignier, Fernando Pico, Valérie Rigau, Yuji Ueno, Claire Duflos, Vera Fominykh, Vincent Guiraud, Christine Lebrun-Frénay, Jean-Philippe Camdessanché, Philippe Kerschen, Guido Ahle, Nieves Téllez, Alex Rovira, Khe Hoang-Xuan, Jean Pelletier & 1 others Pierre Labauge

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Methods: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria. Results: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93% and 69%, respectively. Nodular enhancement (≥3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone ≥30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma. Conclusions: Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is ≥30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive.
Original languageEnglish
Pages (from-to)1027-1038
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume90
Issue number9
DOIs
Publication statusPublished - 2019

Cite this

Taieb, Guillaume ; Mulero, Patricia ; Psimaras, Dimitri ; van Oosten, Bob W. ; Seebach, J. rg D. ; Marignier, Romain ; Pico, Fernando ; Rigau, Valérie ; Ueno, Yuji ; Duflos, Claire ; Fominykh, Vera ; Guiraud, Vincent ; Lebrun-Frénay, Christine ; Camdessanché, Jean-Philippe ; Kerschen, Philippe ; Ahle, Guido ; Téllez, Nieves ; Rovira, Alex ; Hoang-Xuan, Khe ; Pelletier, Jean ; Labauge, Pierre. / CLIPPERS and its mimics: Evaluation of new criteria for the diagnosis of CLIPPERS. In: Journal of Neurology, Neurosurgery and Psychiatry. 2019 ; Vol. 90, No. 9. pp. 1027-1038.
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title = "CLIPPERS and its mimics: Evaluation of new criteria for the diagnosis of CLIPPERS",
abstract = "Objective: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Methods: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria. Results: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93{\%} and 69{\%}, respectively. Nodular enhancement (≥3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone ≥30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma. Conclusions: Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is ≥30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive.",
author = "Guillaume Taieb and Patricia Mulero and Dimitri Psimaras and {van Oosten}, {Bob W.} and Seebach, {J. rg D.} and Romain Marignier and Fernando Pico and Val{\'e}rie Rigau and Yuji Ueno and Claire Duflos and Vera Fominykh and Vincent Guiraud and Christine Lebrun-Fr{\'e}nay and Jean-Philippe Camdessanch{\'e} and Philippe Kerschen and Guido Ahle and Nieves T{\'e}llez and Alex Rovira and Khe Hoang-Xuan and Jean Pelletier and Pierre Labauge",
year = "2019",
doi = "10.1136/jnnp-2018-318957",
language = "English",
volume = "90",
pages = "1027--1038",
journal = "Journal of Neurology, Neurosurgery and Psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",
number = "9",

}

Taieb, G, Mulero, P, Psimaras, D, van Oosten, BW, Seebach, JRD, Marignier, R, Pico, F, Rigau, V, Ueno, Y, Duflos, C, Fominykh, V, Guiraud, V, Lebrun-Frénay, C, Camdessanché, J-P, Kerschen, P, Ahle, G, Téllez, N, Rovira, A, Hoang-Xuan, K, Pelletier, J & Labauge, P 2019, 'CLIPPERS and its mimics: Evaluation of new criteria for the diagnosis of CLIPPERS' Journal of Neurology, Neurosurgery and Psychiatry, vol. 90, no. 9, pp. 1027-1038. https://doi.org/10.1136/jnnp-2018-318957

CLIPPERS and its mimics: Evaluation of new criteria for the diagnosis of CLIPPERS. / Taieb, Guillaume; Mulero, Patricia; Psimaras, Dimitri; van Oosten, Bob W.; Seebach, J. rg D.; Marignier, Romain; Pico, Fernando; Rigau, Valérie; Ueno, Yuji; Duflos, Claire; Fominykh, Vera; Guiraud, Vincent; Lebrun-Frénay, Christine; Camdessanché, Jean-Philippe; Kerschen, Philippe; Ahle, Guido; Téllez, Nieves; Rovira, Alex; Hoang-Xuan, Khe; Pelletier, Jean; Labauge, Pierre.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 90, No. 9, 2019, p. 1027-1038.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - CLIPPERS and its mimics: Evaluation of new criteria for the diagnosis of CLIPPERS

AU - Taieb, Guillaume

AU - Mulero, Patricia

AU - Psimaras, Dimitri

AU - van Oosten, Bob W.

AU - Seebach, J. rg D.

AU - Marignier, Romain

AU - Pico, Fernando

AU - Rigau, Valérie

AU - Ueno, Yuji

AU - Duflos, Claire

AU - Fominykh, Vera

AU - Guiraud, Vincent

AU - Lebrun-Frénay, Christine

AU - Camdessanché, Jean-Philippe

AU - Kerschen, Philippe

AU - Ahle, Guido

AU - Téllez, Nieves

AU - Rovira, Alex

AU - Hoang-Xuan, Khe

AU - Pelletier, Jean

AU - Labauge, Pierre

PY - 2019

Y1 - 2019

N2 - Objective: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Methods: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria. Results: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93% and 69%, respectively. Nodular enhancement (≥3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone ≥30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma. Conclusions: Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is ≥30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive.

AB - Objective: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Methods: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria. Results: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93% and 69%, respectively. Nodular enhancement (≥3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone ≥30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma. Conclusions: Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is ≥30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31072955

U2 - 10.1136/jnnp-2018-318957

DO - 10.1136/jnnp-2018-318957

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JF - Journal of Neurology, Neurosurgery and Psychiatry

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