Central nervous system involvement in Erdheim-Chester disease

Neurology ◽  
2020 ◽  
Vol 95 (20) ◽  
pp. e2746-e2754 ◽  
Author(s):  
Fleur Cohen Aubart ◽  
Ahmed Idbaih ◽  
Damien Galanaud ◽  
Bruno Law-Ye ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Central Nervous System Involvement ◽  
Class Iii ◽  
Cns Involvement ◽  
Erdheim Chester Disease ◽  
Younger Age ◽  
Spine Mri ◽  
Erdheim Chester ◽  
Chester Disease

ObjectiveCNS involvement in Erdheim-Chester disease (ECD) leads to substantial morbidity and mortality. To assess CNS manifestations in a French cohort of 253 patients with ECD, we determined clinical characteristics and outcomes, including those under targeted therapies.MethodsThis was a retrospective longitudinal study. CNS manifestations were determined by clinical examination and brain or spine MRI. Targeted therapy efficacy was assessed using global assessment from a physician and a radiologist. The study was approved by the ethics committee Comité de Protection des Personnes Ile de France III.ResultsNinety-seven of 253 patients (38%) with ECD had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptom onset (mean 50.5 years), as well as with the presence of the BRAFV600E mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than that of patients with ECD without CNS involvement (124 months vs 146 months, p = 0.03). Seventy-four CNS MRIs were centrally reviewed, which showed 3 patterns: tumoral in 66%, pseudo-degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF or MEK inhibitors) was associated with improved symptoms in 43% of patients and MRI improvement in 45%.ConclusionsCNS manifestations are typically associated with poor prognosis in patients with ECD. Three distinct patterns can be recognized: tumoral, pseudodegenerative, and vascular.Classification of evidenceThis study provides Class III evidence that targeted therapy leads to clinical or imaging improvement in almost 50% of patients.

scholarly journals Classification and Prognosis of Central Nervous System Involvement in Erdheim-Chester Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4272-4272
Author(s):  
Fleur Cohen-Aubart ◽  
Ahmed Idbaih ◽  
Damien Galanaud ◽  
Bruno Law-Ye ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapy ◽  
Mapk Pathway ◽  
Central Nervous System Involvement ◽  
Cns Involvement ◽  
Mek Inhibitors ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Background: Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis, characterized by the infiltration of tissues by foamy CD68+CD1a- histiocytes, with 1500 known-cases since 90 years. Mutations activating the MAPK pathway are found in more than 80% of ECD patients, mainly the BRAFV600E in 57 to 70%. Central nervous system (CNS) involvement during ECD lead to significant morbidity and mortality. We assessed CNS manifestations in a French cohort of 253 ECD patients. Since 2012, close to 200 patients worldwide with multi-systemic and refractory ECD (e.g. heart and/or CNS involvements) have benefited from BRAF and MEK inhibitors, which have proven highly beneficial. Methods: CNS manifestations were determined by clinical examination and brain and/or spine magnetic resonance imaging (MRI). Targeted therapy efficacy was assessed using physician and radiologist global assessment. Results: Ninety-seven (38%) among the 253 of the whole cohort of ECD patients had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptoms onset (mean 50.5 years), and also with the presence of the BRAFV600E mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than in ECD patients without CNS involvement (124 months versus 146 months, p=0.03). Seventy-four CNS MRI were centrally reviewed, corresponding to 3 patterns: tumoral in 66%, degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF and/or MEK inhibitors) was associated with improvement of symptoms in 43% of patients, and MRI improvement in 45%. Conclusions: CNS manifestations are typically associated with a poor prognosis in ECD. Three distinct patterns may be recognized: tumoral, degenerative, and vascular. Targeted therapy leads to clinical and/or imaging improvement in almost 50% of patients. OffLabel Disclosure: Targeted therapies such as BRAF inhibitor (vemurafenib) and MEK inhibitor (cobimetinib) are used in severe histiocytosis in EU but are off label

scholarly journals Erdheim-Chester disease: 25-year history with early CNS involvement

2016 ◽  
pp. bcr2016216747 ◽  
Author(s):  
C M Rice ◽  
C A Hall ◽  
P McCoubrie ◽  
S A Renowden ◽  
N Cohen ◽  
...  
Keyword(s):  
Cns Involvement ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Skull Base Manifestations of Erdheim-Chester Disease: A Case Series and Systematic Review

Neurosurgery ◽  
2019 ◽  
Vol 85 (4) ◽  
pp. E693-E701 ◽  
Author(s):  
John P Marinelli ◽  
Pierce A Peters ◽  
Augusto Vaglio ◽  
Jamie J Van Gompel ◽  
John I Lane ◽  
...  
Keyword(s):  
Skull Base ◽  
Central Nervous System Involvement ◽  
Case Series ◽  
Mass Effect ◽  
Female Ratio ◽  
Trigeminal Schwannoma ◽  
Erdheim Chester Disease ◽  
Institutional Review ◽  
Erdheim Chester ◽  
Chester Disease

AbstractBACKGROUNDErdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. Up to 50% of patients develop central nervous system involvement, and a subset of these patients can present with isolated tumor-like masses.OBJECTIVETo describe the skull base manifestations of ECD with an emphasis on aspects most pertinent to surgeons who may be referred such patients for primary evaluation.METHODSScopus, Web of Science, and PubMed were searched from database inception to May 1, 2018 for articles reporting skull base ECD. An institutional retrospective analysis of all patients treated at the authors’ institution since January 1, 1996 was also performed to supplement these data.RESULTSOf 465 retrieved articles, 18 studies totaling 20 patients met inclusion criteria. Institutional review identified an additional 7 patients. Collectively, the median age at diagnosis was 49 yr (interquartile range, 42-58) with a 4:1 male-to-female ratio. Patients frequently presented with diplopia (48%), headache (30%), dysarthria (22%), and vertigo or imbalance (22%), though trigeminal hypesthesia (11%), facial nerve paresis (7%), hearing loss (7%), and trigeminal neuralgia (7%) were also observed. ECD commonly mimicked meningioma (33%), trigeminal schwannoma (8%), neurosarcoidosis (8%), and skull base lymphoma (8%).CONCLUSIONDiscrete skull base lesions frequently mimic more common pathology such as meningioma or cranial nerve schwannomas. Medical therapy comprises the initial treatment for symptomatic skull base disease. Surgical resection is not curative and the utility of surgical intervention is largely limited to biopsy to establish diagnosis and/or surgical debulking to relieve mass effect.

Non-Langerhans cell histiocytosis with isolated CNS involvement: An unusual variant of Erdheim-Chester disease

2010 ◽  
Vol 30 (6) ◽  
pp. 634-647 ◽  
Author(s):  
Alexandria Conley ◽  
Sunil Manjila ◽  
Hui Guan ◽  
Murali Guthikonda ◽  
William J. Kupsky ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Cns Involvement ◽  
Erdheim Chester Disease ◽  
Unusual Variant ◽  
Erdheim Chester ◽  
Chester Disease

scholarly journals Intracranial mass lesions and skin discoloration in the armpits as unusual clues to Erdheim-Chester disease: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pedro Gustavo Barros Rodrigues ◽  
Isabelle de Sousa Pereira ◽  
Valter Barbalho Lima Filho ◽  
Daniel Aguiar Dias ◽  
Paulo Ribeiro Nóbrega ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Skin Lesions ◽  
Neurological Signs ◽  
Intracranial Mass ◽  
Erdheim Chester Disease ◽  
Mass Lesions ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Background Erdheim–Chester disease (ECD) is a non-Langerhans histiocytosis that results in multi-organ disease involving the skin, bones, lungs and kidneys. Central nervous system (CNS) involvement occurs in about 50 % of patients, and diabetes insipidus, visual disturbances, and cerebellar ataxia are the most frequent neurological signs. We report a case of Erdheim-Chester disease with central nervous system involvement in the form of enhancing intracranial mass lesions with massive edema. Case presentation The patient presented with vertigo, ataxia, encephalopathy and pyramidal signs. Diagnosis was suggested by xanthomatous skin lesions and a biopsy was compatible with Erdheim-Chester disease demonstrating xanthogranulomas CD68 positive (clone KP1) and CD1a and S100 negative. Testing for BRAF mutation was negative, which precluded treatment with Vemurafenib. Treatment with steroids and interferon resulted in improvement of neurological signs and regression of edema on MRI. Conclusions The diagnosis of Erdheim-Chester disease should be considered in intracranial mass lesions. Xanthomatous skin lesions are a clue to the diagnosis.

scholarly journals Neuroradiologic manifestations of Erdheim-Chester disease

2018 ◽  
Vol 8 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Natalie E. Parks ◽  
Gaurav Goyal ◽  
Ronald S. Go ◽  
Jay Mandrekar ◽  
W. Oliver Tobin
Keyword(s):  
Spinal Cord ◽  
Diabetes Insipidus ◽  
Brain Mri ◽  
Urine Osmolality ◽  
Erdheim Chester Disease ◽  
Hypothalamic Pituitary Axis ◽  
Spine Mri ◽  
Erdheim Chester ◽  
Chester Disease

BackgroundWe describe the neuroradiologic features of a cohort of patients with Erdheim-Chester disease.MethodsWe assessed patients at Mayo Clinic Rochester between January 1, 1990, and July 31, 2016, with pathologically confirmed Erdheim-Chester disease (n = 53).ResultsNeuroimaging, including head CT (n = 17), brain MRI (n = 39), orbital MRI (n = 15), and spine MRI (n = 16), was available for 42 participants. Median age at diagnosis was 55 years (interquartile range 46–66) with higher male prevalence (33:20). Neurologic symptoms were identified in 47% (25/53); BRAFV600E mutation in 58% (15/26). Median follow-up was 2 years (range 0–20) with 18 patients deceased. Radiologic disease evidence was seen in dura (6/41), brainstem (9/39), cerebellum (8/39), spinal cord (2/16), spinal epidura (2/16), hypothalamic-pituitary axis (17/39), and orbits (13/42). T2 white matter abnormalities (Fazekas score ≥1) were present in 21/34 patients. Diabetes insipidus was present in 30% (16/53); 8 had abnormal hypothalamic–pituitary axis imaging. Radiographic evidence of CNS involvement (i.e., dural, brain, including Fazekas score >1, or spinal cord) occurred in 55% (22/40) and was unassociated with significantly increased mortality.ConclusionsErdheim-Chester disease commonly and variably involves the neuraxis. Patients with suspected Erdheim-Chester disease should undergo MRI brain and spine and screening investigations (serum sodium, serum and urine osmolality) for diabetes insipidus to clarify extent of neurologic disease.

Erdheim-Chester disease

Blood ◽  
2020 ◽  
Vol 135 (16) ◽  
pp. 1311-1318 ◽  
Author(s):  
Julien Haroche ◽  
Fleur Cohen-Aubart ◽  
Zahir Amoura
Keyword(s):  
Mapk Pathway ◽  
Myeloproliferative Neoplasms ◽  
Acquired Resistance ◽  
Central Nervous System Involvement ◽  
Long Bone ◽  
Interferon Α ◽  
Braf Mutations ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Erdheim-Chester disease (ECD) is characterized by the infiltration of tissues by foamy CD68+CD1a− histiocytes, with 1500 known cases since 1930. Mutations activating the MAPK pathway are found in more than 80% of patients with ECD, mainly the BRAFV600E activating mutation in 57% to 70% of cases, followed by MAP2K1 in close to 20%. The discovery of BRAF mutations and of other MAP kinase pathway alterations, as well as the co-occurrence of ECD with LCH in 15% of patients with ECD, led to the 2016 revision of the classification of histiocytoses in which LCH and ECD belong to the “L” group. Both conditions are considered inflammatory myeloid neoplasms. Ten percent of ECD cases are associated with myeloproliferative neoplasms and/or myelodysplastic syndromes. Some of the most striking signs of ECD are the long bone involvement (80%-95%), as well as the hairy kidney appearance on computed tomography scan (63%), the coated aorta (40%), and the right atrium pseudo-tumoral infiltration (36%). Central nervous system involvement is a strong prognostic factor and independent predictor of death. Interferon-α seems to be the best initial treatment of ECD. Since 2012, more than 200 patients worldwide with multisystem or refractory ECD have benefitted from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have an overall, robust, and reproducible efficacy in ECD, with no acquired resistance to date, but their use may be best reserved for the most severe manifestations of the disease, as they may be associated with serious adverse effects and as-yet-unknown long-term consequences.

scholarly journals Vemurafenib as first-line therapy in BRAF-V600E-mutant Erdheim-Chester disease with CNS involvement

2019 ◽  
Vol 12 (11) ◽  
pp. e228280 ◽  
Author(s):  
Gorka Fernández-Eulate ◽  
Amaia Muñoz-Lopetegi ◽  
Irune Ruiz ◽  
Miguel Urtasun
Keyword(s):  
Braf V600e ◽  
Cns Involvement ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Erdheim Chester Disease ◽  
The Central Nervous System ◽  
Prompt Diagnosis ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester disease (ECD) is a rare histiocytosis that may affect the central nervous system (CNS). Infiltration by the disease occurs throughout the neuroaxis, usually involving the dentate nucleus and the pons, manifested as a pyramido-cerebellar syndrome. CNS involvement is an adverse prognostic factor which warrants prompt evaluation and treatment. BRAF mutation occurs in more than half of the cases and has become central in the therapeutic approach. There is rapidly growing evidence that BRAF inhibitors such as vemurafenib or dabrafenib are effective in treating CNS-spread disease. We present a patient with BRAF-V600E-mutant ECD with a classical pyramido-ataxic onset of disease who improved after prompt diagnosis with vemurafenib treatment as first-line therapy.

scholarly journals Erdheim-Chester disease mimicking an intracranial trigeminal schwannoma: case report

2015 ◽  
Vol 15 (5) ◽  
pp. 493-498 ◽  
Author(s):  
Maysam Alimohamadi ◽  
Christian Hartmann ◽  
Vincenzo Paterno ◽  
Madjid Samii
Keyword(s):  
Central Nervous System Involvement ◽  
Multiple Organ ◽  
Imaging Features ◽  
Aged Patients ◽  
Trigeminal Schwannoma ◽  
Erdheim Chester Disease ◽  
Meningeal Involvement ◽  
Organ Systems ◽  
Erdheim Chester ◽  
Chester Disease

Erdheim-Chester disease (ECD) is non-Langerhans histiocytosis that can affect multiple organ systems. It usually affects middle-aged patients, and only a few reports of ECD in children appear in the literature. Central nervous system involvement is a common feature that usually occurs as infiltration of the hypothalamus-pituitary axis, cerebellum, and/or brainstem. Meningeal involvement occurs less commonly. In this article, the authors discuss a rare pediatric case of ECD presenting as an infiltrative mass of the trigeminal nerve and resembling the clinical and imaging features of a trigeminal schwannoma.

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