Tumefactive lesions in retinal vasculopathy with cerebral leucoencephalopathy and systemic manifestations (RVCL-S): a role for neuroinflammation?

Hardy, Todd A.; Young, Stephanie; Sy, Joanne; Colley, Alison; Terwindt, Gisela M.; Ferrari, Michel D.; Hayes, Michael; Hodgkinson, Suzanne

doi:10.1136/jnnp-2017-316142

Cited by 13 publications

(16 citation statements)

References 12 publications

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“…The family history and the multidisciplinary approach (including neurologists, radiologists, ophthalmologists, internists, and geneticists) narrowed the diagnosis to RVCL, and the genetic analysis confirmed a previously described TREX1 mutation1 (variant: CI075707 in HGMDB) in the three clinical cases. The c.703_704insG TREX1 gene mutation has been reported in Caucasian patients from The Netherlands, USA, Australia and Italy 1,3,10,11 . The participants of this study are from a village located in Mexico State, are Mexican Mestizos (parents and grandparents of Mexican origin) and belong to the same family.…”

Section: Discussionmentioning

confidence: 98%

“…However, histologically, the biopsy may be misinterpreted as a neoplasm 10,19 . Hardy et al 11 reported two siblings with RVCL; in one of them demyelinating, tumefactive lesions, cerebral vasculitis and neoplasia were considered as diagnostic possibilities, pointing to the frequent misdiagnosis of this entity. They explained that when these lesions are accompanied by smaller periventricular lesions, these may be mistaken for tumefactive demyelination.…”

Section: Discussionmentioning

confidence: 99%

“…Case 1 was treated with rituximab and CPM and was apparently stable during the 24-month follow-up period after the clinical event. There is no documented data related to these treatment options; only one report suggests the use of natalizumab for RVCL 11 . It would be interesting to evaluate these therapeutic options for a longer period in these patients.…”

Section: Discussionmentioning

confidence: 99%

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Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6

Monroy-Jaramillo

Cerón

León

et al. 2018

RIC

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6

Monroy-Jaramillo

Cerón

León

et al. 2018

RIC

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“…Proof of calcifications in the basal ganglia and cerebellar hemispheres would be a new finding in RVCL-S. 9 In the past, neuroimaging findings of RVCL-S have been mistaken for multiple sclerosis, vasculitis, or neoplasms, and unnecessary brain biopsies have been performed in some cases. 7,11 Diffusion restriction may be falsely interpreted as a sign of ischemia or infarction, and the features of disrupted blood-brain barrier somewhat resemble late radiotherapeutic effects and necrosis. However, the long-lasting contrast enhancement and diffusion restriction of RVCL-S lesions have not been reported in any other brain disease.…”

Section: Discussionmentioning

confidence: 99%

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations

Hoogeveen¹,

Pelzer

Boer

et al. 2021

AJNR Am J Neuroradiol

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Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is caused by TREX1 mutations. Highquality systematic follow-up neuroimaging findings have not been described in presymptomatic and symptomatic mutation carriers. We present MR imaging findings of 29 TREX1 mutation carriers (20-65 years of age) and follow-up of 17 mutation carriers (30-65 years of age). Mutation carriers younger than 40 years of age showed a notable number of punctate white matter lesions, but scan findings were generally unremarkable. From 40 years of age onward, supratentorial lesions developed with long-term contrast enhancement (median, 24 months) and diffusion restriction (median, 8 months). In these lesions, central susceptibility artifacts developed, at least partly corresponding to calcifications on available CT scans. Some lesions (n ¼ 2) additionally showed surrounding edema and mass effect (pseudotumors). Cerebellar punctate enhancing lesions developed mainly in individuals older than 50 years of age. These typical neuroimaging findings should aid neuroradiologic recognition of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, which may enable early treatment of manifestations of the disease. ABBREVIATIONS: Gd ¼ gadolinium; MC ¼ mutation carrier; RVCL-S ¼ retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations; WML ¼ white matter lesion R etinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a dominantly inherited disease caused by mutations in the TREX1 gene. 1 RVCL-S is histologically characterized by a systemic vasculopathy of mediumand small-caliber arteries as well as veins. 2,3 Clinically, the disease manifests from 35 to 40 years of age onward and is characterized by vascular retinopathy, Raynaud phenomenon, migraine, and dysfunction of multiple internal organs (including kidney disease, liver disease, anemia, and subclinical hypothyroidism). 4 So far, few studies have described neuroimaging findings, mostly in symptomatic RVCL-S patients with advanced disease. 2,5-17 A previous study described 3 types of lesions: 1) focal-to-confluent nonenhancing white matter lesions (WMLs), 2) WMLs with punctate enhancement, and 3) rim-enhancing lesions with surrounding T2-hyperintensity (edema/gliosis) and/or diffusion restriction. 9 These lesions with surrounding edema may become large with mass effect and are referred to as pseudotumors.RVCL-S remains a frequently missed diagnosis, partly due to lack of recognition by radiologists. We systematically studied the neuroimaging characteristics of RVCL-S and describe the frequency and evolution of these findings in a large set of presymptomatic and symptomatic carriers.

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“…Other immunotherapies, such as natalizumab, tofacitinib, and hydroxychloroquine, are hypothesized to have beneficial effects. However, successful practical experience is lacking due to complications [ 2 , 21 ]. As aforementioned, in our pedigree, the inflammatory markers' level is significantly higher in the symptomatic mutation carriers compared to the asymptomatic ones.…”

Section: Discussionmentioning

confidence: 99%

High clinical heterogeneity in a Chinese pedigree of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)

Xie

Sun

Yang

et al. 2021

Orphanet J Rare Dis

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Background Being a newly defined disease, RVCL-S is underrecognized by clinicians globally. It is an autosomal dominantly inherited small vessel disease caused by the heterozygous C-terminal frameshift mutation in TREX1 gene. RVCL-S is featured by cerebral dysfunction, retinopathy, and vasculopathy in multiple internal organs. Misdiagnosis may cause devastating consequences in patients, such as iatrogenic PML caused by misuse of immunosuppressants. Thus, increasing awareness of this disease is in urgent need. Results We uncovered a large Chinese origin RVCL-S pedigree bearing the TREX1 mutation. A comprehensive characterization combining clinical, genetic, and neuropathological analysis was performed. The Intrafamilial comparison showed highly heterogeneous clinical phenotypes. Mutation carriers in our pedigree presented with retinopathy (8/13), seizures (2/13), increased intracranial pressure (1/13), mild cognitive impairment (3/13), stroke-like episode (3/13), mesenteric ischemia (1/13), nephropathy (9/13), ascites (3/13), hypertension (9/13), hyperlipidemia (3/8), hypoalbuminemia (3/8), normocytic anemia (3/8), subclinical hypothyroidism (1/8), hyperfibrinogenemia (1/8), hyperparathyroidism (2/8), and abnormal inflammatory markers (4/8). The constellation of symptoms is highly varied, making RVCL-S a challenging diagnosis. Comparison with reported RVCL-S pedigrees further revealed that the mesenteric ischemia is a novel clinical finding and the MRS pattern of brain lesions is emulating neoplasm and tumefactive demyelination. Conclusion Our reports characterize a highly heterogeneous RVCL-S pedigree, highlight the probability of misdiagnosis in clinical practice, and broaden the clinical spectrum of RVCL-S.

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Tumefactive lesions in retinal vasculopathy with cerebral leucoencephalopathy and systemic manifestations (RVCL-S): a role for neuroinflammation?

Cited by 13 publications

References 12 publications

Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6

Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations

High clinical heterogeneity in a Chinese pedigree of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)

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