Lesion evolution and neurodegeneration in RVCL-S

Ford, Andria L.; Chin, Victoria W.; Fellah, Slim; Binkley, Michael M.; Bodin, A.; Balasetti, Vamshi; Taiwo, Yewande; Kang, Peter M.; Lin, Doris; Jen, Joanna C.; Grand, M. Gilbert; Bogacki, Madonna; Liszewski, M. Kathryn; Hourcade, Dennis E.; Chen, Yasheng; Hassenstab, Jason; J, Lee; An, Hongyu; Miner, Jonathan J.; Atkinson, John P.

doi:10.1212/wnl.0000000000010659

Cited by 14 publications

(14 citation statements)

References 52 publications

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“…One recent study also reported WMLs in 5 patients with RVCL-S younger than 40 years of age with comparable WML volumes. 17 Nonspecific WMLs become more apparent in individuals older than 40 years of age. While some MCs still have only discrete punctate WMLs, some develop more extensive confluent WMLs.…”

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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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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“…This syndrome is also referred to as cerebroretinal vasculopathy (CRV), hereditary systemic angiopathy (HSA), hereditary endotheliopathy, retinopathy, nephropathy and stroke (HERNS), hereditary vascular retinopathy (HVR), TREX1 vasculopathy, retinal vasculopathy with cerebral leukodystrophy (RVCL). This is a rare genetic disease with an autosomal-dominant inheritance pattern that causes progressive loss of tiny blood vessels, ultimately resulting in visual deterioration and a series of mini-strokes in the brain [ 17 , 18 ].…”

Section: Resultsmentioning

confidence: 99%

Monogenic Causes of Strokes

Chojdak-Łukasiewicz¹,

Dziadkowiak²,

Budrewićz³

2021

Genes

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Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

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“…One study based on serial MRI scans of six RVCL-S patients indicated the long duration of diffusion restriction and rim-enhancement of lesions [ 6 ]. Another recent study compared the MRI images between RVCL-S patients and healthy controls and concluded that white matter atrophy was a prominent feature in RVCL-S [ 2 ]. However, few studies built up the relation between different lesion categories.…”

Section: Discussionmentioning

confidence: 99%

“…Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an exceedingly rare hereditary cerebral small vessel disease caused by mutations in the gene encoding the three-prime repair exonuclease 1 (TREX1) [ 1 ]. No more than 200 individuals have been identified worldwide so far [ 2 ]. RVCL-S patients exhibit a core constellation of neurological and visual symptoms.…”

Section: Introductionmentioning

confidence: 99%

Serial magnetic resonance imaging changes of pseudotumor lesions in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a case report

et al. 2021

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Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an adult-onset rare monogenic microvasculopathy. Its typical neuroimaging features are punctate white matter lesions or pseudotumor alterations. RVCL-S is often under-recognized and misdiagnosed because of its rarity and similar imaging manifestations to multiple sclerosis or brain malignant mass. Case presentation Here we report a case of a 36-year-old Chinese man who developed multiple tumefactive brain lesions spanning over two years leading to motor aphasia, cognitive decline, and limb weakness. He also presented with slight vision loss, and fundus fluorescein angiography indicated retinal vasculopathy. He underwent brain biopsies twice and showed no evidence of malignancy. Given the family history that his father died of a brain mass of unclear etiology, RVCL-S was suspected, and genetic analysis confirmed the diagnosis with a heterozygous insertion mutation in the three-prime repair exonuclease 1 gene. He was given courses of corticosteroids and cyclophosphamide but received little response. Conclusions The present case is one of the few published reports of RVCL-S with two-year detailed imaging data. Serial magnetic resonance images showed the progression pattern of the lesions. Our experience emphasizes that a better understanding of RVCL-S and considering it as a differential diagnosis in patients with tumefactive brain lesions may help avoid unnecessary invasive examinations and make an earlier diagnosis.

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Lesion evolution and neurodegeneration in RVCL-S

Cited by 14 publications

References 52 publications

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations

Monogenic Causes of Strokes

Serial magnetic resonance imaging changes of pseudotumor lesions in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a case report

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