Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)

Sean J Pittock, Jan Debruyne, Karl N. Krecke, Caterina Giannini, Jelle Van Den Ameele, Veerle De Herdt, Andrew McKeon, Robert D. Fealey, Brian G Weinshenker, Allen Jr. Aksamit, Bruce R. Krueger, Elizabeth A. Shuster, B Mark Keegan

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

The classification and pathological mechanisms of many central nervous system inflammatory diseases remain uncertain. In this article we report eight patients with a clinically and radiologically distinct pontine-predominant encephalomyelitis we have named 'chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids' (CLIPPERS). The patients were assessed clinically, radiologically and pathologically at Mayo Clinic, USA and Ghent University Hospital, Belgium from 1999 to 2009. Median follow-up duration from clinical onset was 22 months (range 7-144 months). Patients underwent extensive laboratory (serum and cerebrospinal fluid), radiological and pathological testing (conjunctival, transbronchial and brain biopsies) to search for causes of an inflammatory central nervous system disorder. All eight patients (five female, three male) presented with episodic diplopia or facial paresthesias with subsequent brainstem and occasionally myelopathic symptoms and had a favourable initial response to high dose glucocorticosteroids. All patients had symmetric curvilinear gadolinium enhancement peppering the pons and extending variably into the medulla, brachium pontis, cerebellum, midbrain and occasionally spinal cord. Radiological improvement accompanied clinical response to glucocorticosteroids. Patients routinely worsened following glucocorticosteroid taper and required chronic glucocorticosteroid or other immunosuppressive therapy. Neuropathology of biopsy material from four patients demonstrated white matter perivascular, predominantly T lymphocytic, infiltrate without granulomas, infection, lymphoma or vasculitis. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a definable, chronic inflammatory central nervous system disorder amenable to immunosuppressive treatment. The T cell predominant inflammatory pathology in affected central nervous system lesions and the clinical and radiological response to immunosuppressive therapies is consistent with an immune-mediated process.

Original languageEnglish (US)
Pages (from-to)2626-2634
Number of pages9
JournalBrain
Volume133
Issue number9
DOIs
StatePublished - 2010

Fingerprint

Steroids
Inflammation
Central Nervous System Diseases
Immunosuppressive Agents
Biopsy
Encephalomyelitis
Diplopia
Pons
Paresthesia
Belgium
Gadolinium
Vasculitis
Mesencephalon
Granuloma
Cerebellum
Brain Stem
Cerebrospinal Fluid
Lymphoma
Spinal Cord
Therapeutics

Keywords

  • brain stem
  • encephalitis
  • neuroinflammation

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). / Pittock, Sean J; Debruyne, Jan; Krecke, Karl N.; Giannini, Caterina; Van Den Ameele, Jelle; De Herdt, Veerle; McKeon, Andrew; Fealey, Robert D.; Weinshenker, Brian G; Aksamit, Allen Jr.; Krueger, Bruce R.; Shuster, Elizabeth A.; Keegan, B Mark.

In: Brain, Vol. 133, No. 9, 2010, p. 2626-2634.

Research output: Contribution to journalArticle

Pittock, Sean J ; Debruyne, Jan ; Krecke, Karl N. ; Giannini, Caterina ; Van Den Ameele, Jelle ; De Herdt, Veerle ; McKeon, Andrew ; Fealey, Robert D. ; Weinshenker, Brian G ; Aksamit, Allen Jr. ; Krueger, Bruce R. ; Shuster, Elizabeth A. ; Keegan, B Mark. / Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). In: Brain. 2010 ; Vol. 133, No. 9. pp. 2626-2634.
@article{d23a54fbea514704bf1534d1404bc7f0,
title = "Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)",
abstract = "The classification and pathological mechanisms of many central nervous system inflammatory diseases remain uncertain. In this article we report eight patients with a clinically and radiologically distinct pontine-predominant encephalomyelitis we have named 'chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids' (CLIPPERS). The patients were assessed clinically, radiologically and pathologically at Mayo Clinic, USA and Ghent University Hospital, Belgium from 1999 to 2009. Median follow-up duration from clinical onset was 22 months (range 7-144 months). Patients underwent extensive laboratory (serum and cerebrospinal fluid), radiological and pathological testing (conjunctival, transbronchial and brain biopsies) to search for causes of an inflammatory central nervous system disorder. All eight patients (five female, three male) presented with episodic diplopia or facial paresthesias with subsequent brainstem and occasionally myelopathic symptoms and had a favourable initial response to high dose glucocorticosteroids. All patients had symmetric curvilinear gadolinium enhancement peppering the pons and extending variably into the medulla, brachium pontis, cerebellum, midbrain and occasionally spinal cord. Radiological improvement accompanied clinical response to glucocorticosteroids. Patients routinely worsened following glucocorticosteroid taper and required chronic glucocorticosteroid or other immunosuppressive therapy. Neuropathology of biopsy material from four patients demonstrated white matter perivascular, predominantly T lymphocytic, infiltrate without granulomas, infection, lymphoma or vasculitis. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a definable, chronic inflammatory central nervous system disorder amenable to immunosuppressive treatment. The T cell predominant inflammatory pathology in affected central nervous system lesions and the clinical and radiological response to immunosuppressive therapies is consistent with an immune-mediated process.",
keywords = "brain stem, encephalitis, neuroinflammation",
author = "Pittock, {Sean J} and Jan Debruyne and Krecke, {Karl N.} and Caterina Giannini and {Van Den Ameele}, Jelle and {De Herdt}, Veerle and Andrew McKeon and Fealey, {Robert D.} and Weinshenker, {Brian G} and Aksamit, {Allen Jr.} and Krueger, {Bruce R.} and Shuster, {Elizabeth A.} and Keegan, {B Mark}",
year = "2010",
doi = "10.1093/brain/awq164",
language = "English (US)",
volume = "133",
pages = "2626--2634",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)

AU - Pittock, Sean J

AU - Debruyne, Jan

AU - Krecke, Karl N.

AU - Giannini, Caterina

AU - Van Den Ameele, Jelle

AU - De Herdt, Veerle

AU - McKeon, Andrew

AU - Fealey, Robert D.

AU - Weinshenker, Brian G

AU - Aksamit, Allen Jr.

AU - Krueger, Bruce R.

AU - Shuster, Elizabeth A.

AU - Keegan, B Mark

PY - 2010

Y1 - 2010

N2 - The classification and pathological mechanisms of many central nervous system inflammatory diseases remain uncertain. In this article we report eight patients with a clinically and radiologically distinct pontine-predominant encephalomyelitis we have named 'chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids' (CLIPPERS). The patients were assessed clinically, radiologically and pathologically at Mayo Clinic, USA and Ghent University Hospital, Belgium from 1999 to 2009. Median follow-up duration from clinical onset was 22 months (range 7-144 months). Patients underwent extensive laboratory (serum and cerebrospinal fluid), radiological and pathological testing (conjunctival, transbronchial and brain biopsies) to search for causes of an inflammatory central nervous system disorder. All eight patients (five female, three male) presented with episodic diplopia or facial paresthesias with subsequent brainstem and occasionally myelopathic symptoms and had a favourable initial response to high dose glucocorticosteroids. All patients had symmetric curvilinear gadolinium enhancement peppering the pons and extending variably into the medulla, brachium pontis, cerebellum, midbrain and occasionally spinal cord. Radiological improvement accompanied clinical response to glucocorticosteroids. Patients routinely worsened following glucocorticosteroid taper and required chronic glucocorticosteroid or other immunosuppressive therapy. Neuropathology of biopsy material from four patients demonstrated white matter perivascular, predominantly T lymphocytic, infiltrate without granulomas, infection, lymphoma or vasculitis. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a definable, chronic inflammatory central nervous system disorder amenable to immunosuppressive treatment. The T cell predominant inflammatory pathology in affected central nervous system lesions and the clinical and radiological response to immunosuppressive therapies is consistent with an immune-mediated process.

AB - The classification and pathological mechanisms of many central nervous system inflammatory diseases remain uncertain. In this article we report eight patients with a clinically and radiologically distinct pontine-predominant encephalomyelitis we have named 'chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids' (CLIPPERS). The patients were assessed clinically, radiologically and pathologically at Mayo Clinic, USA and Ghent University Hospital, Belgium from 1999 to 2009. Median follow-up duration from clinical onset was 22 months (range 7-144 months). Patients underwent extensive laboratory (serum and cerebrospinal fluid), radiological and pathological testing (conjunctival, transbronchial and brain biopsies) to search for causes of an inflammatory central nervous system disorder. All eight patients (five female, three male) presented with episodic diplopia or facial paresthesias with subsequent brainstem and occasionally myelopathic symptoms and had a favourable initial response to high dose glucocorticosteroids. All patients had symmetric curvilinear gadolinium enhancement peppering the pons and extending variably into the medulla, brachium pontis, cerebellum, midbrain and occasionally spinal cord. Radiological improvement accompanied clinical response to glucocorticosteroids. Patients routinely worsened following glucocorticosteroid taper and required chronic glucocorticosteroid or other immunosuppressive therapy. Neuropathology of biopsy material from four patients demonstrated white matter perivascular, predominantly T lymphocytic, infiltrate without granulomas, infection, lymphoma or vasculitis. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a definable, chronic inflammatory central nervous system disorder amenable to immunosuppressive treatment. The T cell predominant inflammatory pathology in affected central nervous system lesions and the clinical and radiological response to immunosuppressive therapies is consistent with an immune-mediated process.

KW - brain stem

KW - encephalitis

KW - neuroinflammation

UR - http://www.scopus.com/inward/record.url?scp=77956356555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956356555&partnerID=8YFLogxK

U2 - 10.1093/brain/awq164

DO - 10.1093/brain/awq164

M3 - Article

C2 - 20639547

AN - SCOPUS:77956356555

VL - 133

SP - 2626

EP - 2634

JO - Brain

JF - Brain

SN - 0006-8950

IS - 9

ER -