PMID- 36451581
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230309
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 29
IP  - 2
DP  - 2023 Feb
TI  - Management approach including pembrolizumab for fingolimod-associated progressive 
      multifocal leukoencephalopathy in a patient with relapsing-remitting multiple 
      sclerosis.
PG  - 301-306
LID - 10.1177/13524585221137279 [doi]
AB  - A 62-year-old man with relapsing-remitting multiple sclerosis developed 
      progressive multifocal leukencephalopathy (PML) after 6 years on fingolimod. The 
      fingolimod was immediately discontinued and preexisting mirtazepine increased. 
      Three weeks later, with brain magnetic resonance imaging (MRI) appearances 
      worsening and cerebrospinal fluid (CSF) JC virus (JCV) titres increasing, 
      maraviroc was introduced. At 6 weeks, subtle punctate contrast enhancement raised 
      the possibility of immune reconstitution inflammatory syndrome (IRIS), followed 
      by a single focal-to-generalised tonic clonic seizure and a further deterioration 
      in clinical disability. Mefloquine was commenced alongside three doses of 
      pembrolizumab administered a month apart. Serial CSF examinations and several 
      imaging modalities including spectroscopy and fused FDG-PET-MRI 
      (18F-fluoro-deoxy-glucose-positron emission tomography-magnetic resonance 
      imaging) were used to help distinguish between PML, PML-IRIS and rebound MS 
      activity and guide optimal management at each stage. A handful of small, 
      enhancing ovoid lesions developed between the first two doses of pembrolizumab, 
      probably representative of a mild rebound phenomenon. A sustained improvement 
      became obvious thereafter with CSF JCV-DNA undetectable 16 weeks following 
      fingolimod withdrawal. To our knowledge, this is the first case of combined 
      therapy and use of pembrolizumab in a fingolimod-associated PML.
FAU - Barritt, Andrew W
AU  - Barritt AW
AUID- ORCID: 0000-0002-9723-6946
AD  - Hurstwood Park Neurological Centre, Haywards Heath, UK/Clinical Imaging Sciences 
      Centre, Brighton and Sussex Medical School, Brighton, UK.
FAU - Das, Esther
AU  - Das E
AD  - Hurstwood Park Neurological Centre, Haywards Heath, UK.
FAU - Morley, Nadine
AU  - Morley N
AD  - Sussex Community NHS Foundation Trust, Brighton, UK.
FAU - Seymour, Matthew
AU  - Seymour M
AD  - Hurstwood Park Neurological Centre, Haywards Heath, UK.
FAU - Saha, Romi
AU  - Saha R
AD  - Hurstwood Park Neurological Centre, Haywards Heath, UK.
FAU - Vera, Jaime
AU  - Vera J
AD  - Hurstwood Park Neurological Centre, Haywards Heath, UK/Department of Global 
      Health and Infection, Brighton and Sussex Medical School, Brighton, UK.
FAU - Vundavalli, Sriram
AU  - Vundavalli S
AD  - Hurstwood Park Neurological Centre, Haywards Heath, UK.
FAU - Dizdarevic, Sabina
AU  - Dizdarevic S
AD  - Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, 
      UK/Department of Nuclear Medicine, Brighton and Sussex University Hospitals NHS 
      Trust, Brighton, UK.
FAU - Nicholas, Richard
AU  - Nicholas R
AD  - Department of Brain Sciences, Imperial College London, London, UK.
FAU - Berger, Joseph R
AU  - Berger JR
AD  - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Fisniku, Leonora K
AU  - Fisniku LK
AD  - Hurstwood Park Neurological Centre, Haywards Heath, UK/Cambridge University 
      Hospitals NHS Foundation Trust, Cambridge, UK.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20221130
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - G926EC510T (Fingolimod Hydrochloride)
RN  - DPT0O3T46P (pembrolizumab)
RN  - 0 (Natalizumab)
SB  - IM
MH  - Male
MH  - Humans
MH  - Middle Aged
MH  - *Leukoencephalopathy, Progressive Multifocal/chemically induced/diagnostic 
      imaging/drug therapy
MH  - Fingolimod Hydrochloride/adverse effects
MH  - *Multiple Sclerosis, Relapsing-Remitting/drug therapy
MH  - *Multiple Sclerosis/drug therapy
MH  - *JC Virus
MH  - Magnetic Resonance Imaging
MH  - Natalizumab/adverse effects
OTO - NOTNLM
OT  - MRI
OT  - Multiple sclerosis
OT  - fingolimod
OT  - pembrolizumab
OT  - progressive multifocal leukencephalopathy
EDAT- 2022/12/02 06:00
MHDA- 2023/02/15 06:00
CRDT- 2022/12/01 01:53
PHST- 2022/12/02 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2022/12/01 01:53 [entrez]
AID - 10.1177/13524585221137279 [doi]
PST - ppublish
SO  - Mult Scler. 2023 Feb;29(2):301-306. doi: 10.1177/13524585221137279. Epub 2022 Nov 
      30.