CLIPPERSChronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids

CUTTY SARK 1869

3 Neuropathology (DEFINITE) a. Dense lymphocytic inflammation with perivascular predominance

and parenchymal diffuse infiltration; both white matter and grey matter could be

involved (no vasculitic changes)

b.CD3 T cells predominating infiltration (CD4 CD8) with variable macrophages

e.Absence of myelin loss or focal secondary myelin loss.

d. Lack of alternative better explanation for pathological presentation

2 MRI (probable)a. Homogenous, gadolinium enhancing nodules without ring enhancement or

mass effect, predominating in the pons and cerebellum, measuring < 3mm

b. Marked improvement in abnormal gadolinium enhancement with corticosteroid

c. Homogenous T2 signal abnormality, where the degree of T2 does not significantly

exceed the size of the area of post gadolinium enhancement.

d. Spinal cord lesions with similar T2 and gadolinium enhancing lesions as above.

1 Clinical (probable) a. Subacute pontocerebellar dysfunction, with or without other

CNS symptoms such as cognitive dysfunction and myelopathy.

b. CNS symptoms responsive to corticosteroid therapy.

c. Absence of peripheral nervous system disease.

d. Lack of alternative better explanation for clinical presentationW.O.Tobin

Brain 2017

CRITERIA

Clippers Non Clippers : in T2 lesioni

asimmetriche, più estese della assunzione di gad+; presenza di effetto massa,

incompleta risoluzione dopo un breve ciclo di corticosteroidi

FLAIR

CLIPPERS. L’infiammazione

linfocitaria è perivenulare ed

è diffusa, localizzata anche

nella sostanza bianca

apparentemente normale,

parietale ed insulare e nella

root zone dei nervi cranici

CLIPPERS : presentazione «atipica». Gul M. 2015

7 Tesla

Dopo 5 gg

5mp ev

Chronic Lymphocytic Inflammation with

Pontine Perivascular Enhancement

Responsive to Steroids (CLIPPERS) with

Limbic Encephalitis

Otha Y et al., JJIM, 2017

F. 37 aa. Diplopia, disfagia, oftalmoplegia,

paraparesi atassica. Miglioramento dopo 1 mese

di Prednisolone. Ricaduta alla sospensione con

confusione e delirio. > IL6 Liquor

CLIPPERS.

Estensione

talamica e

midollare

Mubasher,

M. 2017

CLIPPERS in Epatite B, Ching-Fu, 2015

Interessamento contemporaneo SNC e infiltrato

linfoistioide perineuraleperiferico (Smith A. 2014)

Nella EBV

CLIPPERS dopo guarigione da HodkingLinfoma di 15 anni prima (Mashima 2015)

However, when the dose of prednisolone was reduced to 10 mg/day at 22 months after the treatment, he started complaining of difficulty in walking and speaking. His neurologicaldeficits and radiological findings improved immediately and CLIPPERS remains well controlled with prednisolone 30 months after the diagnosis.

The Bioptic right FRONTAL lobe specimen: The lymphocytic infiltrates were stained by the markers of CD3 (b), CD4 (c), CD8 (d) and CD20 (e).

“CLIPPERS’ patients should be monitored closely so as not to overlook the coexisting or

subsequent development of CNS lymphoma”. Mashima, 2015

They were all male and aged from 33 to 74 years. First brain biopsy showed reactive T cell lymphocytes

similar to those in our patient. Clinical and radiological responses to corticosteroids were initially favorable.

However, the disease progressed, and a second biopsy was performed at 3–24 months after the first brain

biopsy. Eventually, the diagnosis of B cell lymphoma was made in all four patients. We believe that the

pathogenesis of CLIPPERS is not tightly associated with CNS lymphoma, although there were several

patients with CLIPPERS progressed to CNS lymphoma in the literature

Ortega M. et al. Neurology, 2012.

CLIPPERS in MS after (4 mesi ?) from Natalizumab

withdrawal

Donna 61 aa. MS 1997 -

dopo INF beta 1 IM -> 38

cicli di NATALIZUMAB –>

cessato in Agosto 2010

per JC +

Inizia COPOLIMERO

OTTOBRE 2010 nausea e

atassia – RM negativa –

ciclo 5MP - DICEMBRE

2010 atassia dismetria –

RM e biopsia cerebellare

(infiltrato perivascolare

CD3 – CD5 – qualche

CD19. Liquor JC e EBV -

Controllo RM Gennaio

2011 dopo 1 mese di

Prednisolone – ha poi

proseguito per 8 mesi con

prednisolone 40 mg e poi

Ciclofosfamide ev. Stabile

The Rose ROSSLING’S CHALLENGE

DOPO cortisone Relapse 6 mesi dopo con

Prednisolone 12.5 mg :

LESIONE con effetto

massa e necrosi centrale

-Biopsia : compatibile

con CLIPPERS

Uomo 76 aa : atassia e

disartria subacute.

IgLON5 Positivo siero e

liquor

Risposta al

Prednisolone e

metotrexate

TOBIN REPLY and RECHALLENGE: INITIAL MRI findings best discriminate CLIPPERS from non-CLIPPERS, and the

MRI show gadolinium-enhancing lesions larger than 3 mm. The T2-weighted MRI does not better judge whether the area

of abnormality on T2 exceeded the area of abnormality on post-gadolinium T1 imaging. The follow-up brain MRI

demonstrated a large necrotic lesion within the left cerebellar hemisphere….the lesion does not appear typical of

CLIPPERS…..”anche se la biopsia è largamente consistente – criterio definite”

TOBIN , LUCCHINETTI e PITTOCK….

Incoraggiamo altri centri a segnalarci

avvistamenti - International CLIPPERS

Consortium, multi-centre collaborative effort.

Our case depicts that CLIPPERS cannot be well controlled by a B cell directed approach. This points to a bystander

role of B cells in CLIPPERS and distinguishes it from other inflammatory such as MS. Olmes D.G et al. JNS, 2018