Flavie Bompaire1, Marion Lahutte2, Stephane Buffat3,4, Carole Soussain5, Anne Emmanuelle Ardisson6, Robert Terziev7, Magali Sallansonnet-Froment6, Thierry De Greslan6, Sébastien Edmond6, Mehdi Saad6,3, Christophe Nioche2, Thomas Durand6,3, Sonia Alamowitch8,9, Khe Hoang Xuan7,9,10,11,12,13, Jean Yves Delattre7,9,10,11,12,13, Jean Luc Renard6, Hervé Taillia6,14, Cyrus Chargari4,14,15,16, Dimitri Psimaras7, Damien Ricard6,3,14. 1. Service de Neurologie, HIA Percy, 101 avenue Henri Barbusse, 92141, Clamart, France. fbompaire@gmail.com. 2. Service de Radiologie, HIA Percy, 101 avenue Henri Barbusse, 92141, Clamart, France. 3. UMR8257 MD4 Cognac G, CNRS, Service de Santé des Armées, Université Paris Descartes, Paris, France. 4. Institut de Recherche Biomédicale des Armées, Place du Général Valérie André, BP 73, 91223, Brétigny-sur-Orge, France. 5. Centre René Huguenin, Service d'Hématologie, 35 rue Dailly, 92210, Saint-Cloud, France. 6. Service de Neurologie, HIA Percy, 101 avenue Henri Barbusse, 92141, Clamart, France. 7. Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Blvd de l'Hôpital, 75013, Paris, France. 8. Stroke Unit, Department of Neurology, Saint Antoine University Hospital, AP-HP, 4 Rue de la Chine, Paris, France. 9. Sorbonne Universités, Paris, France. 10. UPMC Univ Paris 06, Paris, France. 11. UM 75, ICM, 75013, Paris, France. 12. Inserm, U 1127, ICM, Paris, 75013, Paris, France. 13. CNRS, UMR 7225, ICM, Paris, 75013, Paris, France. 14. Ecole du Val de Grâce, 1 place Alphonse Laveran, 75005, Paris, France. 15. Radiotherapy Department, Gustave Roussy Cancer Campus, Villejuif, France. 16. INSERM 1030, Molecular Radiotherapy, Villejuif, France.
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.
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.
Entities:
Keywords:
Cerebral small vessel disease; Dementia; Leukoencephalopathy; Radiation therapy
Authors: Antonio M P Omuro; Leah S Ben-Porat; Katherine S Panageas; Amy K Kim; Denise D Correa; Joachim Yahalom; Lisa M Deangelis; Lauren E Abrey Journal: Arch Neurol Date: 2005-10
Authors: Roshan A Karunamuni; Kevin L Moore; Tyler M Seibert; Nan Li; Nathan S White; Hauke Bartsch; Ruben Carmona; Deborah Marshall; Carrie R McDonald; Nikdokht Farid; Anithapriya Krishnan; Joshua Kuperman; Loren K Mell; James Brewer; Anders M Dale; Vitali Moiseenko; Jona A Hattangadi-Gluth Journal: Radiother Oncol Date: 2016-01-21 Impact factor: 6.280
Authors: F E Froklage; L J Oosterbaan; E M Sizoo; M de Groot; I Bosma; E Sanchez; L Douw; J J Heimans; J C Reijneveld; F J Lagerwaard; J Buter; B M J Uitdehaag; M Klein; T J Postma Journal: J Neurooncol Date: 2013-11-22 Impact factor: 4.130
Authors: Carrie M Carr; John C Benson; David R DeLone; Felix E Diehn; Dong Kun Kim; Kenneth W Merrell; Alex A Nagelschneider; Ajay A Madhavan; Derek R Johnson Journal: Neuroradiology Date: 2021-01-04 Impact factor: 2.804
Authors: J Jacob; L Feuvret; J-M Simon; M Ribeiro; L Nichelli; C Jenny; D Ricard; D Psimaras; K Hoang-Xuan; P Maingon Journal: Neurol Sci Date: 2022-02-11 Impact factor: 3.307