Abstract
Background
Radiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria.
Methods
Patients referred to our center for deterioration in cognitive complaint at least 6 months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded.
Results
Forty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53 Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30 Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL).
Conclusions
RIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.
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Acknowledgements
The authors would like to acknowledge Dr. Loic Feuvret for his work on this paper. He is the radiotherapist that helped to do all the matches between patients MRI and radiotherapy protocol (dedicated to the link between radiotherapy and neurology).
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Authors and Affiliations
Contributions
F. Bompaire: Data acquisition and analysis, data interpretation, manuscript redaction
M. Lahutte: MRI realization and analysis
S. Buffat: MRI analysis
C. Soussain: Study design
A.E. Ardisson: Cognitive evaluation realization and analysis
R. Terziev: MRI analysis
M. Sallansonnet-Froment: Clinical analysis
T. De Greslan: Clinical analysis
S. Edmond: Data collection
M. Saad: Clinical analysis
C. Nioche: MRI post-treatment
T. Durand: Cognitive evaluation analysis
S. Alamowitch: Critical revision of manuscript for intellectual content (vascular aspect)
K Hoang Xuan: Critical revision of manuscript for intellectual content (neuro-oncological aspect)
J.Y. Delattre: Critical revision of manuscript for intellectual content (neuro-oncological aspect)
J.L. Renard: Critical revision of manuscript for intellectual content (neuropsychological aspect)
H. Taillia: Critical revision of manuscript for intellectual content (neuropsychological aspect)
C. Chargari: Critical revision of manuscript for intellectual content (manuscript writing)
D. Psimaras: Study supervision
D. Ricard: Study concept and design, study supervision
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The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
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Keypoints
- Radiation-induced leukopathy (RIL) is attracting growing interest as the number of long-term survivors after brain irradiation increases. Consequences for patients with this condition are potentially severe, with a natural evolution towards dementia and loss of autonomy.
- Oncologists, radiation oncologists, and neurologists are not familiar with this neurological condition. There is an urgent need to describe the condition in order to harmonize the diagnosis, encourage research on physiopathology and treatment, and provide patients with suitable support and care.
- RIL is a diffuse white matter disease triggered by RT. Its incidence is independent of the RT protocol. It shares clinical, neuropsychological, and MRI hallmarks with CSVD spectrum.
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Bompaire, F., Lahutte, M., Buffat, S. et al. New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study. Support Care Cancer 26, 4217–4226 (2018). https://doi.org/10.1007/s00520-018-4296-9
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DOI: https://doi.org/10.1007/s00520-018-4296-9