clippers - morecomunicazione.it · 2010 atassia dismetria
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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