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November 13, 2018; 91 (20) NeuroImages

Imaging microglial activation in tacrolimus-associated CNS vasculitis with translocator protein PET

Christoph Mahler, Marcus Unterrainer, Carolin Muth, Rupert Egensperger, Lena Vomacka, Simon Lindner, Birgit Ertl-Wagner, Maximilian Patzig, Peter Bartenstein, Nathalie Albert, Martin Kerschensteiner, Tania Kümpfel
First published November 12, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006516
Christoph Mahler
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Marcus Unterrainer
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Carolin Muth
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Rupert Egensperger
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Lena Vomacka
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Simon Lindner
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Birgit Ertl-Wagner
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Maximilian Patzig
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Peter Bartenstein
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Nathalie Albert
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Martin Kerschensteiner
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Tania Kümpfel
From the Institute of Clinical Neuroimmunology (C.M., M.K., T.K.) and Departments of Nuclear Medicine (M.U., L.V., S.L., P.B., N.A.), Neurology (C.M.), Radiology (B.E.-W.), and Neuroradiology (M.P.), University Hospital, and Biomedical Center (C.M., M.K., T.K.) and Center for Neuropathology and Prion Research (R.E.), LMU Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.B., M.K.), Germany.
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Full PDF
Citation
Imaging microglial activation in tacrolimus-associated CNS vasculitis with translocator protein PET
Christoph Mahler, Marcus Unterrainer, Carolin Muth, Rupert Egensperger, Lena Vomacka, Simon Lindner, Birgit Ertl-Wagner, Maximilian Patzig, Peter Bartenstein, Nathalie Albert, Martin Kerschensteiner, Tania Kümpfel
Neurology Nov 2018, 91 (20) 936-937; DOI: 10.1212/WNL.0000000000006516

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A 67-year-old man developed gradually worsening left-sided spastic hemiparesis under immunosuppressive therapy with tacrolimus after single lung transplantation. MRI revealed 2 diffusion-restricted, T2-hyperintense lesions without and with partial contrast enhancement, respectively (figure 1). Therefore, differential diagnosis mainly included progressive multifocal leukoencephalopathy, atypical CNS lymphoma, and CNS vasculitis. PET with the novel translocator protein (TSPO) tracer [18F]GE-180 showed high focal tracer uptake in both T2-hyperintense lesions. TSPO is overexpressed in activated micoglia.1 Stereotactic brain biopsy revealed tacrolimus-associated CNS vasculitis with distinct microglia activation, a rarely reported finding2 (figure 2). Our case thus suggests that TSPO PET might be a helpful tool for detection of active CNS inflammation3 in patients with suspected CNS vasculitis.

Figure 1
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Figure 1 MRI and PET

(A) MRI and [18F]GE-180-TSPO-PET reveal a contrast-enhancing lesion in the left gyrus frontalis superior. (B) Periventricular non-contrast-enhancing lesion with focal uptake in PET.

Figure 2
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Figure 2 Brain biopsy demonstrating CNS vasculitis with microglial activation

(A) Lymphocytic infiltration of small-vessel wall (arrow, hematoxylin & eosin staining). (B) Microglial activation in CD3/43 staining. (C) Reactive astrocytes in glial fibrillary acid protein staining. (D) Infiltration of CD3+ T cells. Scale: 100 μm.

Author contributions

Christoph Mahler: study design, data collection, clinical care to the patient, drafting and revising the manuscript. Marcus Unterrainer: study design, acquisition and analysis of PET scans, critical comments during manuscript revision. Carolin Muth: clinical care to the patient. Rupert Egensperger: acquisition and analysis of histopathology images. Lena Vomacka: analysis of PET scans. Simon Lindner: acquisition and analysis of PET scans. Birgit Ertl-Wagner: acquisition and analysis of MRI scans. Maximilian Patzig: acquisition and analysis of MRI scans. Peter Bartenstein: study supervision and analysis of PET scans. Nathalie Albert: study supervision and analysis of PET scans. Martin Kerschensteiner: study supervision and critical comments during manuscript revision. Tania Kümpfel: study supervision and critical comments during manuscript revision.

Study funding

No targeted funding reported.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Footnotes

  • 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.

  • © 2018 American Academy of Neurology

References

  1. 1.↵
    1. Dickens AM,
    2. Vainio S,
    3. Marjamaki P, et al
    . Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. J Nucl Med 2014;55:466–472.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Pizzolato GP,
    2. Sztajzel R,
    3. Burkhardt K,
    4. Megret M,
    5. Borisch B
    . Cerebral vasculitis during FK 506 treatment in a liver transplant patient. Neurology 1998;50:1154–1157.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Unterrainer M,
    2. Mahler C,
    3. Vomacka L, et al
    . TSPO PET with [F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing-remitting multiple sclerosis. Eur J Nucl Med Mol Imaging 2018;45:1423–1431.
    OpenUrl

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