The utility of FDG-PET imaging in distinguishing PML-IRIS from PML in a patient treated with natalizumab

Baheerathan, Aravindhan; McNamara, Cillian; Kalam, Sabrina; Rane, Neil; Barwick, Tara; Grote, Helen; Nicholas, Richard

doi:10.1212/wnl.0000000000006213

Cited by 3 publications

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“…11 A fused brain FDG-PET-MRI study was undertaken in our patient with a view to help inform the likelihood of either advancing PML or PML-IRIS, reported to associate with either hypo-and hypermetabolism, respectively. 12 It was felt that the relative hypometabolism seen within the established areas of PMLassociated signal change would be less supportive of an ongoing and/or significant PML-IRIS reaction or, indeed, inflammatory relapse activity, whilst acknowledging the undetermined sensitivity of FDG-PET-MRI to confidently rule in or rule out IRIS. In view of the patient's clinical downturn, further encroachment of PML-associated MRI FLAIR signal abnormality and (the so far available) worsening CSF JCV load, use of steroids was not felt ideal at this point -although would have been the authors' treatment of choice if PML-IRIS was strongly suspected.…”

Section: Discussionmentioning

confidence: 99%

Management approach including pembrolizumab for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing-remitting multiple sclerosis

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

Management approach including pembrolizumab for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing-remitting multiple sclerosis

et al. 2022

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“…MRI shows oedematous lesions in the right frontal lobe and corpus callosum (asterisks). labelling 102 and 18 F-fluorodeoxyglucose PET 103 have been proposed as more sensitive tools for imaging of active inflammation.…”

Section: Pathogenesis Of Pmlmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease

2020

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TSPO PET imaging of natalizumab-associated progressive multifocal leukoencephalopathy

Mähler

Schumacher

Kaiser

et al. 2021

Brain

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Progressive multifocal leukoencephalopathy (PML) is a severe infection of the central nervous system caused by the polyomavirus JC (JCV) that can occur in multiple sclerosis (MS) patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not the least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether TSPO positron emission tomography (PET) imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from MS lesions. For this monocenter pilot study we followed 8 patients with natalizumab-associated PML with PET imaging using the TSPO radioligand [18F]GE-180 combined with frequent 3 T MRI imaging. In addition we compared TSPO PET signals in PML lesions with the signal pattern of MS lesions from 17 independent MS patients. We evaluated the standardized uptake value ratio (SUVR) as well as the morphometry of the TSPO uptake for putative PML and MS lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/MS). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogenous distribution in putative MS lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52 months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3-dimensional diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated more than 96% of PML and MS lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active MS lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent MS activity from PML progression.

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The utility of FDG-PET imaging in distinguishing PML-IRIS from PML in a patient treated with natalizumab

Abstract: Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Cited by 3 publications

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Management approach including pembrolizumab for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing-remitting multiple sclerosis

Management approach including pembrolizumab for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing-remitting multiple sclerosis

Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease

TSPO PET imaging of natalizumab-associated progressive multifocal leukoencephalopathy

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