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

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 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 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.

References

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.
OpenUrl Abstract/FREE Full Text
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.
OpenUrl Abstract/FREE Full Text
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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[1] 1.↵
Dickens AM,
Vainio S,
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.
OpenUrl Abstract/FREE Full Text

[2] Dickens AM,

[3] Vainio S,

[4] Marjamaki P, et al

[5] 2.↵
Pizzolato GP,
Sztajzel R,
Burkhardt K,
Megret M,
Borisch B
. Cerebral vasculitis during FK 506 treatment in a liver transplant patient. Neurology 1998;50:1154–1157.
OpenUrl Abstract/FREE Full Text

[6] Pizzolato GP,

[7] Sztajzel R,

[8] Burkhardt K,

[9] Megret M,

[10] Borisch B

[11] 3.↵
Unterrainer M,
Mahler C,
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

[12] Unterrainer M,

[13] Mahler C,

[14] Vomacka L, et al

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