Luisa Chiapparini1, Giulio Cavalli2, Tiziana Langella3, Anna Venerando4, Giacomo De Luca2, Sergio Raspante5,6, Giorgio Marotta7, Bianca Pollo8, Giuseppe Lauria9,10, Maria Giulia Cangi11, Simonetta Gerevini12, Andrea Botturi13, Davide Pareyson14, Lorenzo Dagna2, Ettore Salsano14. 1. Unit of Neuroradiology, IRCCS Foundation "Carlo Besta" Neurological Institute, Via Celoria 11, 20133, Milan, Italy. luisa.chiapparini@istituto-besta.it. 2. Unit of Internal Medicine and Clinical Immunology, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy. 3. Unit of Molecular Neuro-oncology, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy. 4. Unit of Clinical Pathology and Medical Genetics, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy. 5. Unit of Neuroradiology, IRCCS Foundation "Carlo Besta" Neurological Institute, Via Celoria 11, 20133, Milan, Italy. 6. Department of Neuroradiology, Niguarda Hospital, Milan, Italy. 7. Department of Nuclear Medicine, IRCCS Foundation "Ca' Granda" Ospedale Maggiore Policlinico, Milan, Italy. 8. Unit of Neuropathology, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy. 9. Unit of Neuroalgology, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy. 10. Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy. 11. Unit of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy. 12. Unit of Neuroradiology, IRCCS San Raffaele Scientific Institute, Milan, Italy. 13. Unit of Clinical Neuro-oncology, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy. 14. Unit of Neurodegerative and Neurometabolic Rare Diseases, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
Abstract
BACKGROUND: Leukoencephalopathies with prominent involvement of cerebellum and brainstem, henceforward called prominent infratentorial leukoencephalopathies (PILs), encompass a variety of inherited and acquired white matter diseases. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis likely under-diagnosed as cause of adult PIL. METHODS: We reviewed the clinical and laboratory information of ten consecutive sporadic adult patients with PIL of unknown origin, who were investigated for ECD. RESULTS: There were seven males and three females; mean age at clinical onset was 49.6 years (range 38-59); cerebellar ataxia with or without other neurological symptoms was the only or the main clinical manifestation; diabetes insipidus was present in three individuals. Eight patients had white matter focal supratentorial abnormalities, in addition to the infratentorial white matter changes. Six out of eight patients had spinal cord lesions. Thoraco-abdominal CT showed periaortic sheathing in two patients, whole-body FDG-PET revealed increased glucose uptake in the long bones of the legs in five patients, brain FDG-PET showed overt infratentorial hypermetabolism in one patient. In eight patients, ECD was confirmed by bone scintigraphy, pathological data, or both. Two ECD patients treated with vemurafenib showed a marked improvement of neurological symptoms and brain MRI abnormalities at 1 year follow-up. CONCLUSIONS: Symptoms of PIL can be the only clinical manifestation of ECD. Adult patients with PIL of unknown origin should undergo investigations aimed at unveiling ECD, including bone scintigraphy and whole-body FDG-PET. The early diagnosis allows starting disease-modifying therapies of an otherwise life-threatening disease.
BACKGROUND:Leukoencephalopathies with prominent involvement of cerebellum and brainstem, henceforward called prominent infratentorial leukoencephalopathies (PILs), encompass a variety of inherited and acquired white matter diseases. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis likely under-diagnosed as cause of adult PIL. METHODS: We reviewed the clinical and laboratory information of ten consecutive sporadic adult patients with PIL of unknown origin, who were investigated for ECD. RESULTS: There were seven males and three females; mean age at clinical onset was 49.6 years (range 38-59); cerebellar ataxia with or without other neurological symptoms was the only or the main clinical manifestation; diabetes insipidus was present in three individuals. Eight patients had white matter focal supratentorial abnormalities, in addition to the infratentorial white matter changes. Six out of eight patients had spinal cord lesions. Thoraco-abdominal CT showed periaortic sheathing in two patients, whole-body FDG-PET revealed increased glucose uptake in the long bones of the legs in five patients, brain FDG-PET showed overt infratentorial hypermetabolism in one patient. In eight patients, ECD was confirmed by bone scintigraphy, pathological data, or both. Two ECDpatients treated with vemurafenib showed a marked improvement of neurological symptoms and brain MRI abnormalities at 1 year follow-up. CONCLUSIONS: Symptoms of PIL can be the only clinical manifestation of ECD. Adult patients with PIL of unknown origin should undergo investigations aimed at unveiling ECD, including bone scintigraphy and whole-body FDG-PET. The early diagnosis allows starting disease-modifying therapies of an otherwise life-threatening disease.
Entities:
Keywords:
Erdheim–Chester disease; Histiocytosis; Imaging; Leukodystrophy; Leukoencephalopathy; White matter lesion
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