Clinically significant CMV (re)activation during or after radiotherapy/chemotherapy of the brain (original) (raw)

Abstract

Introduction

For both patients with high-grade gliomas and multiple cerebral metastases, radio(chemo)therapy is the standard therapy. Neurological decline during treatment is rarely attributed to infections of the brain but to tumor progression or side effects of radiotherapy.

Case reports

We present 4 cases of cytomegalovirus (CMV) viremia associated with neurological deterioration, which occurred during or shortly after radiotherapy and/or chemotherapy of the brain (brain metastases 2, high-grade glioma 1, carcinoma infiltrating brain 1). In all cases, neurological decline was sudden and unexpected, and causes such as increased intracranial pressure or tumor progression could be excluded radiologically. Treatment with dexamethasone and mannitol had no or only very short-term effects. General infections were either excluded or receding before the neurological symptoms occurred. All patients presented with decreasing levels of thrombocytes. In all cases, CMV (re)activation could be proven using blood test for CMV-DNA. The anti-CMV-IgG status suggested reactivation rather than a primary infection. One patient died within 72 h of onset of the symptoms (results of CMV tests were received postmortem). Diagnosis of 3 patients allowed successful administration of antiviral treatment, which greatly improved the general and neurological conditions of the patients within 48 h.

Discussion

Neurological deterioration during RT is hardly ever attributed to viral infections. These cases suggest that CMV reactivation and subsequent infection might actually be causative and has to be considered and treated.

Conclusion

Further prospective studies verifying and investigating this observation in terms of frequency and clinical relevance seem indicated.

Zusammenfassung

Einleitung

Sowohl für Patienten mit Hirnmetastasen als auch für Patienten mit hochgradigen Gliomen ist eine Radio(chemo)therapie die Therapie der Wahl. Neurologische Verschlechterungen während der Behandlung werden meist einem Tumorprogress oder Nebenwirkungen der Strahlentherapie attribuiert.

Falldarstellungen

Präsentiert werden 4 Fälle von mit einer CMV-Virämie assoziierten neurologischer Verschlechterung, die während bzw. kurz nach Bestrahlung und/oder Chemotherapie des Gehirns auftrat (Hirnmetastasen 2, hochgradiges Gliom 1, zerebral infiltrierendes Karzinom 1): In allen Fällen war die neurologische Verschlechterung unerwartet, und Ursachen wie erhöhter intrakranieller Druck oder Tumorprogress wurden radiologisch ausgeschlossen. Dexamethason und Mannitol hatte keinen dauerhaften Effekt. Allgemeine Infektionen wurden ausgeschlossen oder waren am Abklingen. Bei allen Patienten zeigten sich abnehmende Thrombozytenzahlen, bei allen ließ sich eine CMV-Infektion serologisch nachweisen (Anti-CMV-IgM und/oder CMV-DNA). Der Anti-CMV-IgG-Status wies dabei jeweils auf eine CMV-Reaktivierung hin. Während 2 Patienten innerhalb von 72 h nach Beginn der neurologischen Symptome verstarben (die CMV-Testresultate lagen erst post mortem vor), konnten 3 Patienten antiviral behandelt werden. Ihr Zustand besserte sich innerhalb von 48 h deutlich.

Diskussion

An neurotrope Infektionen wird bei neurologischer Verschlechterung von am Hirn bestrahlten/chemotherapierten Patienten normalerweise nicht gedacht. Die vorgestellten Ergebnisse deuten aber darauf hin, dass eine CMV-Reaktivierung/-Infektion in Betracht gezogen und gegebenenfalls behandelt werden sollte.

Ausblick

Weitere prospektive Studien zur Bestätigung und zur Untersuchung dieser Beobachtung bezüglich Frequenz und klinische Relevanz scheinen angebracht.

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Acknowledgements

We wish to thank the editor and the reviewers for their detailed analysis of our manuscript and their helpful suggestions.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, 91054, Erlangen, Germany
    N. Goerig, S. Semrau, B. Frey, F. Putz, U. S. Gaipl & R. Fietkau
  2. Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    K. Korn, B. Fleckenstein & K. Überla
  3. Institute of Neuroradiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    A. Dörfler

Authors

  1. N. Goerig
  2. S. Semrau
  3. B. Frey
  4. K. Korn
  5. B. Fleckenstein
  6. K. Überla
  7. A. Dörfler
  8. F. Putz
  9. U. S. Gaipl
  10. R. Fietkau

Corresponding author

Correspondence toN. Goerig.

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Conflict of interest

N. Goerig, S. Semrau, B. Frey, K. Korn, B. Fleckenstein, K. Überla, A. Dörfler, F. Putz, U.S. Gaipl, and R. Fietkau state that there are no conflicts of interest.

Ethical standards

The accompanying manuscript does not include studies on humans or animals.

Additional information

The present work was performed in (partial) fulfillment of the requirements for obtaining the degree “Dr. med.” for Nicole Goerig.

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Goerig, N., Semrau, S., Frey, B. et al. Clinically significant CMV (re)activation during or after radiotherapy/chemotherapy of the brain.Strahlenther Onkol 192, 489–497 (2016). https://doi.org/10.1007/s00066-016-0987-7

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