Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim–Chester disease

Luisa Chiapparini, Giulio Cavalli, Tiziana Langella, Anna Venerando, Giacomo de Luca, Sergio Raspante, Giorgio Marotta, Bianca Pollo, Giuseppe Lauria, Maria Giulia Cangi, Simonetta Gerevini, Andrea Botturi, Davide Pareyson, Lorenzo Dagna, Ettore Salsano

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)273-284
Number of pages12
JournalJournal of Neurology
Volume265
Issue number2
DOIs
Publication statusPublished - 2018

Fingerprint

Leukoencephalopathies
Radionuclide Imaging
Non-Langerhans-Cell Histiocytosis
Leg Bones
Cerebellar Ataxia
Diabetes Insipidus
Bone Diseases
Brain
Age of Onset
Cerebellum
Brain Stem
Early Diagnosis
Spinal Cord
Bone and Bones
Glucose

Keywords

  • Erdheim–Chester disease
  • Histiocytosis
  • Imaging
  • Leukodystrophy
  • Leukoencephalopathy
  • White matter lesion

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

@article{095cf6ee61c24d5b99767b0519afb7b1,
title = "Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim–Chester disease",
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.",
keywords = "Erdheim–Chester disease, Histiocytosis, Imaging, Leukodystrophy, Leukoencephalopathy, White matter lesion",
author = "Luisa Chiapparini and Giulio Cavalli and Tiziana Langella and Anna Venerando and {de Luca}, Giacomo and Sergio Raspante and Giorgio Marotta and Bianca Pollo and Giuseppe Lauria and Cangi, {Maria Giulia} and Simonetta Gerevini and Andrea Botturi and Davide Pareyson and Lorenzo Dagna and Ettore Salsano",
year = "2018",
doi = "10.1007/s00415-017-8692-8",
language = "English",
volume = "265",
pages = "273--284",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "Dr. Dietrich Steinkopff Verlag GmbH and Co. KG",
number = "2",

}

TY - JOUR

T1 - Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim–Chester disease

AU - Chiapparini, Luisa

AU - Cavalli, Giulio

AU - Langella, Tiziana

AU - Venerando, Anna

AU - de Luca, Giacomo

AU - Raspante, Sergio

AU - Marotta, Giorgio

AU - Pollo, Bianca

AU - Lauria, Giuseppe

AU - Cangi, Maria Giulia

AU - Gerevini, Simonetta

AU - Botturi, Andrea

AU - Pareyson, Davide

AU - Dagna, Lorenzo

AU - Salsano, Ettore

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Erdheim–Chester disease

KW - Histiocytosis

KW - Imaging

KW - Leukodystrophy

KW - Leukoencephalopathy

KW - White matter lesion

UR - http://www.scopus.com/inward/record.url?scp=85036518387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85036518387&partnerID=8YFLogxK

U2 - 10.1007/s00415-017-8692-8

DO - 10.1007/s00415-017-8692-8

M3 - Article

VL - 265

SP - 273

EP - 284

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

IS - 2

ER -