title: CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders.
abstract: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons. The condition features a combination of clinical symptoms essentially referable to brainstem pathology and a characteristic magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement 'peppering' the pons. The radiological distribution is focused in the pons and adjacent rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla and the midbrain. While the lesion burden with a perivascular pattern is typically most dense in these pontine and peripontine regions, enhancing lesions may additionally extend into the spinal cord and supratentorial structures such as the thalamus, basal ganglia, capsula interna, corpus callosum and the cerebral white matter. Another core feature is clinical and radiological responsiveness to glucocorticosteroid (GCS)-based immunosuppression. As withdrawal of GCS treatment results commonly in disease exacerbation, long-term immunosuppressive therapy appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is challenging, and requires careful exclusion of alternative diagnoses. A specific serum or cerebrospinal fluid (CSF) biomarker for the disorder is currently not known. Pathogenesis of CLIPPERS remains poorly understood, and the nosological position of CLIPPERS has still to be established. Whether CLIPPERS represents an independent, actual new disorder or a syndrome that includes aetiologically heterogeneous diseases and/or their prestages remains a debated and not finally clarified issue. Clinicians and radiologists should be aware of this condition and its differential diagnoses, given that CLIPPERS constitutes a treatable condition and that patients may benefit from an early introduction of GCS ensued by long-term immunosuppression. Based on previous reports in literature - currently encompassing more than 50 reported cases of CLIPPERS - this review addresses clinical features, diagnostic criteria, differential diagnoses and therapeutic management of this peculiar disorder.
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dudesek
authors.forename: F
authors.initials: F
authors.lastname: Rimmele
authors.forename: S
authors.initials: S
authors.lastname: Tesar
authors.forename: S
authors.initials: S
authors.lastname: Kolbaske
authors.forename: P S
authors.initials: PS
authors.lastname: Rommer
authors.forename: R
authors.initials: R
authors.lastname: Benecke
authors.forename: U K
authors.initials: UK
authors.lastname: Zettl
mesh_terms: D002493:Central Nervous System Diseases / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D008279:Magnetic Resonance Imaging; D059906:Neuroimaging; D011149:Pons / Q000473:pathology*; D013256:Steroids / Q000627:therapeutic use*
chemical_list: D013256:Steroids
keywords: CLIPPERS; brainstem; glucocorticosteroids; neuroinflammation; perivascular infiltration
references.citation: Magn Reson Imaging. 2013 Nov;31(9):1640-2
references.pmid: 23969198
references.citation: Brain. 2011 Aug;134(Pt 8):e182; author reply e183
references.pmid: 21303857
references.citation: BMC Neurol. 2013 May 24;13:49
references.pmid: 23706003
references.citation: J Neurol Sci. 2003 May 15;209(1-2):5-11
references.pmid: 12686395
references.citation: J Neurooncol. 2012 Mar;107(1):223-4
references.pmid: 21968945
references.citation: J Neurol Neurosurg Psychiatry. 2009 Oct;80(10):1134-9
references.pmid: 19520698
references.citation: Br J Neurosurg. 2011 Oct;25(5):614-20
references.pmid: 21501048
references.citation: J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):2-3
references.pmid: 22166989
references.citation: Nat Rev Neurol. 2010 Jul;6(7):383-92
references.pmid: 20639914
references.citation: Intern Med. 2001 Jul;40(7):613-9
references.pmid: 11506302
references.citation: Lancet Neurol. 2009 Feb;8(2):192-204
references.pmid: 19161910
references.citation: Neurology. 2011 Sep 6;77(10):e57-8
references.pmid: 21893665
references.citation: Nervenarzt. 2012 Jun;83(6):782-4
references.pmid: 22476512
references.citation: Brain. 2011 Aug;134(Pt 8):2194-6
references.pmid: 21841200
references.citation: Neurology. 2003 Sep 23;61(6):836-8
references.pmid: 14504334
references.citation: Arch Neurol. 2012 Jul;69(7):819-20
references.pmid: 22777258
references.citation: J Neuroimaging. 2013 Apr;23(2):254-5
references.pmid: 21848680
references.citation: Arch Pathol Lab Med. 2012 Jun;136(6):681-5
references.pmid: 22646278
references.citation: JAMA Neurol. 2013 Jul;70(7):915-8
references.pmid: 23649857
references.citation: J Neurol. 2011 Dec;258(12):2140-6
references.pmid: 21556878
references.citation: Arch Neurol. 2008 Jun;65(6):821-4
references.pmid: 18541805
references.citation: Curr Treat Options Neurol. 2013 Apr;15(2):201-9
references.pmid: 23378230
references.citation: Clin Exp Immunol. 2014 Mar;175(3):397-407
references.pmid: 24102425
references.citation: Clin Exp Immunol. 2014 Mar;175(3):373-84
references.pmid: 24001305
references.citation: Brain. 2011 Aug;134(Pt 8):e187
references.pmid: 21653537
references.citation: J Neurol. 2008 May;255(5):674-82
references.pmid: 18274803
references.citation: Arch Neurol. 2012 Jul;69(7):847-55
references.pmid: 22777259
references.citation: J Neurol. 2011 Nov;258(11):2090-2
references.pmid: 21553269
references.citation: Pract Neurol. 2011 Dec;11(6):349-51
references.pmid: 22100944
references.citation: Nervenarzt. 2012 Jun;83(6):775-81
references.pmid: 22215219
references.citation: J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):15-22
references.pmid: 22056964
references.citation: Neurology. 2012 Aug 14;79(7):715-6
references.pmid: 22855867
references.citation: Intern Med. 2012;51(9):1115-9
references.pmid: 22576399
references.citation: Clin Exp Immunol. 2014 Mar;175(3):359-72
references.pmid: 24032475
references.citation: Brain. 2010 Sep;133(9):2626-34
references.pmid: 20639547
references.citation: J Neurol Sci. 2013 Apr 15;327(1-2):61-2
references.pmid: 23453777
references.citation: Brain. 2011 Aug;134(Pt 8):e185; author reply e186
references.pmid: 21389007
references.citation: Curr Neurol Neurosci Rep. 2011 Dec;11(6):543-52
references.pmid: 21956758
references.citation: Brain. 2011 Aug;134(Pt 8):e184; author reply e186
references.pmid: 21385752
references.citation: J Neurol Sci. 2013 Jan 15;324(1-2):183-6
references.pmid: 23149266