RESUMEN
PURPOSE: To assess the onset, treatment frequency, and visual outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment due to secondary choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE). DESIGN: Retrospective cohort study METHODS: One-hundred six eyes of 53 patients with PXE were analyzed. The assessment of CNV activity relied on hemorrhage visible on funduscopy and intra- / subretinal fluid on optical coherence tomography (OCT), individually defining a shortening or extension of treatment interval. Best-corrected visual acuity (BCVA) at baseline, age at anti-VEGF therapy initiation, and BCVA-drop events at exudation onset (worsening of BCVA of 2 or more lines) were documented. Further, we assessed the number of injections during the first year and the total number of injections, the time to treatment initiation of the fellow eye, and BCVA over time. RESULTS: During a median observation period of 77 months (IQR 49; 126) patients received a median number of 28.0 anti-VEGF-injections (IQR 9.8; 43.5). Eight patients received no injection (median age at baseline 38.1 years), 11 patients underwent anti-VEGF treatment in one eye (median age 47.2 years) and 34 patients in both eyes (median age 51.8 years). The median age at the first anti-VEGF treatment was 52.80 years (IQR 47.2-57.6). Applying Cox regression models, the median "survival" time of fellow eye until treatment initiation was 16.8 months. In the group of bilateral treated patients, the median time difference was 9.6 months (IQR 2.1- 32.4, range 0-122) The median number of injections was 5.5 per eye in the first year of treatment (IQR 3-7) and was associated with the total number of injections in the observation period (2.33, CI 1.22-3.44, P < .001). A better BCVA at the last follow-up visit was associated with a better baseline BCVA (P < .001, R2 = 0.318) and with the absence of a BCVA drop at the onset of exudation (P = 0.035, R2 = 0.339). CONCLUSIONS: The results of this study indicate that anti-VEGF treatment is required for most PXE patients at a relatively young age. Once treatment in one eye is initiated, the time to fellow eye treatment is relatively short. A BCVA drop before treatment initiation is a risk factor for worse visual outcomes, suggesting that treatment is prudent before exudation affects the central retina. Given the young age of onset and intensive treatment needs, patients with PXE might particularly benefit from longer-acting anti-VEGF therapeutics.
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Inhibidores de la Angiogénesis , Bevacizumab , Neovascularización Coroidal , Angiografía con Fluoresceína , Inyecciones Intravítreas , Seudoxantoma Elástico , Ranibizumab , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Humanos , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/tratamiento farmacológico , Seudoxantoma Elástico/fisiopatología , Seudoxantoma Elástico/diagnóstico , Estudios Retrospectivos , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Agudeza Visual/fisiología , Masculino , Femenino , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Persona de Mediana Edad , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/fisiopatología , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/etiología , Adulto , Ranibizumab/uso terapéutico , Ranibizumab/administración & dosificación , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Edad de Inicio , Resultado del Tratamiento , Estudios de Seguimiento , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , AncianoAsunto(s)
Seudoxantoma Elástico , Humanos , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico , Accidente Cerebrovascular Isquémico/etiología , Femenino , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico , Persona de Mediana Edad , Diagnóstico DiferencialRESUMEN
BACKGROUND AND PURPOSE: Carotid siphon calcification might contribute to the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum through increased arterial flow pulsatility. This study aimed to compare intracranial artery flow pulsatility, brain volumes, and small-vessel disease markers between patients with pseudoxanthoma elasticum and controls and the association between arterial calcification and pulsatility in pseudoxanthoma elasticum. MATERIALS AND METHODS: Fifty patients with pseudoxanthoma elasticum and 40 age- and sex-matched controls underwent 3T MR imaging, including 2D phase-contrast acquisitions for flow pulsatility in the assessment of ICA and MCA and FLAIR acquisitions for brain volumes, white matter lesions, and infarctions. All patients with pseudoxanthoma elasticum underwent CT scanning to measure siphon calcification. Flow pulsatility (2D phase-contrast), brain volumes, white matter lesions, and infarctions (3D T1 and 3D T2 FLAIR) were compared between patients and controls. The association between siphon calcification and pulsatility in pseudoxanthoma elasticum was tested with linear regression models. RESULTS: Patients with pseudoxanthoma elasticum (mean age, 57 [SD, 12] years; 24 men) had significantly higher pulsatility indexes (1.05; range, 0.94-1.21 versus 0.94; range, 0.82-1.04; P = .02), lower mean GM volumes (597 [SD, 53] mL versus 632 [SD, 53] mL; P < .01), more white matter lesions (2.6; range, 0.5-7.5 versus 1.1; range, 0.5-2.4) mL; P = .05), and more lacunar infarctions (64 versus 8, P = .04) than controls (mean age, 58 [SD, 11] years; 20 men). Carotid siphon calcification was associated with higher pulsatility indexes in patients with pseudoxanthoma elasticum (ß = 0.10; 95% CI, 0.01-0.18). CONCLUSIONS: Patients with pseudoxanthoma elasticum have increased intracranial artery flow pulsatility and measures of small-vessel disease. Carotid siphon calcification might underlie the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum.
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Lesiones Encefálicas , Calcinosis , Trastornos Cerebrovasculares , Seudoxantoma Elástico , Masculino , Humanos , Persona de Mediana Edad , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico por imagen , Seudoxantoma Elástico/patología , Arteria Carótida Interna/patología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/complicaciones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , InfartoRESUMEN
Physiological calcification of soft tissues is a common occurrence in aging and various acquired and inherited disorders. ABCC6 sequence variations cause the calcification phenotype of pseudoxanthoma elasticum (PXE) as well as some cases of generalized arterial calcification of infancy, which is otherwise caused by defective ENPP1. ABCC6 is primarily expressed in the liver, which has given the impression that the liver is central to the pathophysiology of PXE/generalized arterial calcification of infancy. The emergence of inflammation as a contributor to the calcification in PXE suggested that peripheral tissues play a larger role than expected. In this study, we investigated whether bone marrow-derived ABCC6 contributes to the calcification in PXE. In Abcc6â/â mice, we observed prevalent mineralization in several lymph nodes and surrounding connective tissues and an extensive network of lymphatic vessels within vibrissae, a calcified tissue in Abcc6â/â mice. Furthermore, we found evidence of lymphangiogenesis in patients with PXE and mouse skin, suggesting an inflammatory process. Finally, restoring wild-type bone marrow in Abcc6â/â mice produced a significant reduction of calcification, suggesting that the liver alone is not sufficient to fully inhibit mineralization. With evidence that ABCC6 is expressed in lymphocytes, we suggest that the adaptative immune system and inflammation largely contribute to the calcification in PXE/generalized arterial calcification of infancy.
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Modelos Animales de Enfermedad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Seudoxantoma Elástico , Seudoxantoma Elástico/genética , Seudoxantoma Elástico/patología , Seudoxantoma Elástico/metabolismo , Seudoxantoma Elástico/complicaciones , Animales , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Ratones , Humanos , Ratones Noqueados , Linfangiogénesis/genética , Femenino , Masculino , Médula Ósea/patología , Vibrisas , Calcinosis/patología , Calcinosis/genética , Calcinosis/etiología , Calcificación Vascular/patología , Calcificación Vascular/genética , Calcificación Vascular/etiología , Calcificación Vascular/metabolismo , Vasos Linfáticos/patología , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition caused by mutations in the ABCC6 gene. Ocular features include angioid streaks, peau d'orange fundus, and drusen. We report a novel ABCC6 mutation causing PXE in a patient with a mixed phenotype of PXE and retinitis pigmentosa (RP). CASE: A 37-year-old female presented with decreased peripheral vision and nyctalopia. Ocular imaging revealed angioid streaks emanating from the optic nerve as well as peripheral pigmentary changes and bone spicules. Genetic testing revealed two mutations in ABCC6 in trans. No other mutation was identified. CONCLUSION: We present a rare case with ocular findings of PXE and RP in a patient with a novel ABCC6 mutation. The patient presented both with peripheral pigmentary changes and angioid streaks. Further investigation into this novel mutation would be beneficial to determine if the mutation is involved in the RP phenotype.
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Estrías Angioides , Seudoxantoma Elástico , Retinitis Pigmentosa , Femenino , Humanos , Adulto , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico , Seudoxantoma Elástico/genética , Estrías Angioides/diagnóstico , Estrías Angioides/genética , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genética , Mutación , Fondo de Ojo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genéticaRESUMEN
Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder caused by an autosomal recessive mutation in the ABCC6 gene. It manifests with distinctive clinical symptoms impacting the skin, eyes, and cardiovascular system, along with an elevated risk of cardiovascular diseases. We present a case of a 34-year-old male patient who was initially referred to the rheumatology clinic for evaluation due to suspected large vessel vasculitis. The patient's primary complaint was severe hemifacial pain radiating to the neck and upper limb. Radiological imaging studies unveiled substantial vascular narrowing and collateral vessel formation, prompting further investigation to exclude systemic vasculitis. Intriguingly, the patient also exhibited cutaneous manifestations, which were later confirmed via skin biopsy as consistent with PXE. An ophthalmological examination further revealed the presence of the classic PXE findings of angioid streaks. Given the rarity of PXE and its multifaceted clinical presentation, it can be particularly challenging to diagnose and manage. As such, cases like the one presented here may necessitate a referral to a rheumatologist for evaluation of potential systemic involvement. To provide a comprehensive perspective on PXE, we conducted a systematic review of case reports published in the past decade in English, collected from PubMed, Scopus, and the Directory of Open Access databases. The analysis of these cases will be discussed to shed light on the diversity of PXE's clinical features and the diagnostic and management dilemmas it poses and to facilitate ongoing exploration and research into this intricate condition, ultimately leading to improved care for individuals affected by PXE.
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Sistema Cardiovascular , Seudoxantoma Elástico , Vasculitis , Masculino , Humanos , Adulto , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico , Seudoxantoma Elástico/genética , Piel/patología , Mutación , Sistema Cardiovascular/patología , Vasculitis/patología , Enfermedades Raras/patologíaRESUMEN
Ectopic calcification in the cardiovascular system adversely affects life prognosis. DBA/2 mice experience calcification owing to low expression of Abcc6 as observed in pseudoxanthoma elasticum (PXE) patients; however, little is known about its characteristics as a calcification model. In this study, we explore the suitability of a DBA/2 sub-strain as a PXE-like tissue calcification model, and the effect of a bisphosphonate which prevents calcification of soft tissues in hypercalcemic models was evaluated. The incidence of calcification of the heart was compared among several sub-strains and between both sexes of DBA/2 mice. mRNA expression of calcification-related genes was compared with DBA/2 sub-strains and other mouse strains. In addition, progression of calcification and calciprotein particle formation in serum were examined. Among several sub-strains of DBA/2 mice, male DBA/2CrSlc mice showed the most remarkable cardiac calcification. In DBA/2CrSlc mice, expression of the anti-calcifying genes Abcc6, Enpp1 and Spp1 was lower than that in C57BL/6J, and expression of Enpp1 and Spp1 was lower compared with other sub-strains. Calcification was accompanied by accelerated formation of calciprotein particle, which was prevented by daily treatment with bisphosphonate. A model suitable for ectopic calcification was identified by choosing a sub-strain of DBA/2 mice, in which genetic characteristics would contribute to extended calcification.
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Calcinosis , Seudoxantoma Elástico , Humanos , Femenino , Masculino , Ratones , Animales , Seudoxantoma Elástico/genética , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Calcinosis/complicaciones , Calcinosis/genética , Calcinosis/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , DifosfonatosRESUMEN
PURPOSE: To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era. METHODS: Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT"). RESULTS: Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively. CONCLUSION: Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.
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Estrías Angioides , Neovascularización Coroidal , Retinopatía Diabética , Seudoxantoma Elástico , Humanos , Estrías Angioides/complicaciones , Estrías Angioides/diagnóstico , Factores de Crecimiento Endotelial , Retinopatía Diabética/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de Seguimiento , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/etiología , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico , Pronóstico , Inyecciones Intravítreas , Tomografía de Coherencia Óptica/métodos , Atrofia , Pigmentos RetinianosRESUMEN
Purpose: To quantify choriocapillaris flow alterations in patients with pseudoxanthoma elasticum (PXE) in pre-atrophic stages and its association with structural changes of the choroid and outer retina. Methods: Thirty-two eyes of 21 patients with PXE and 35 healthy eyes of 35 controls were included. The density of choriocapillaris flow signal deficits (FDs) was quantified on 6 × 6-mm optical coherence tomography angiography (OCTA) images. Spectral-domain optical coherence tomography (SD-OCT) images were analyzed for thicknesses of the choroid and outer retinal microstructure and correlated with choriocapillaris FDs in the respective Early Treatment Diabetic Retinopathy Study subfield. Results: The multivariable mixed model analysis for choriocapillaris FDs revealed significantly higher FDs associated with the group (PXE patients vs. controls +13.6; 95% confidence interval [CI] 9.87-17.3; P < 0.001), with increasing age (+0.22% per year; 95% CI 0.12-0.33; P < 0.001), and with retinal location (significantly higher FDs in nasal compared to temporal subfields). Choroidal thickness (CT) did not differ significantly between both groups (P = 0.078). The CT and choriocapillaris FDs were inversely correlated (-1.92 µm per %FDs; interquartile range -2.81 to -1.03; P < 0.001). Larger values of the choriocapillaris FDs were associated with significant thinning of the overlying photoreceptor layers (outer segments: -0.21 µm per %FDs, P < 0.001; inner segments: -0.12 µm per %FDs, P = 0.001; outer nuclear layer: -0.72 µm per %FDs; P < 0.001). Conclusions: Patients with PXE display significant alterations of the choriocapillaris on OCTA even in pre-atrophic stages and in the absence of significant choroidal thinning. The analysis favors choriocapillaris FDs over choroidal thickness as a potential early outcome measure for future interventional trials in PXE. Further, increased FDs in nasal compared to temporal locations mirror the centrifugal spread of Bruch's membrane calcification in PXE.
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Seudoxantoma Elástico , Humanos , Seudoxantoma Elástico/complicaciones , Coroides , Retina , Lámina Basal de la Coroides , Angiografía , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodosRESUMEN
BACKGROUND/OBJECTIVES: To assess systemic associations of angioid streaks (AS) using a large US healthcare database. SUBJECTS/METHODS: A retrospective cross-sectional study was conducted of patients diagnosed with AS in a large, national US insurer from 2000-2019. Cases were matched 1:5 to controls. The prevalence rates of established associated disease states and other systemic diseases were calculated and compared using logistic regression. Additionally, the rate of anti-VEGF treatment was assessed as a proxy for the incidence of choroidal neovascularization (CNV). RESULTS: One thousand eight hundred fifty-two cases of AS and 9028 matched controls were included. The rates of association between AS and the well-characterized conditions included: Pseudoxanthoma elasticum (PXE)-228 patients (12.3%), Ehlers-Danlos syndrome-18 patients (1.0%), Paget's disease-6 patients (0.3%), hemoglobinopathies-30 patients (1.6%), and idiopathic-1573 patients (84.9%). There was a statistically higher prevalence of the following less classically associated diseases among patients with AS compared to controls: hereditary spherocytosis (1.7% vs. 0.6%, p < 0.001), connective tissue disease (1.0% vs 0.3%, p < 0.001) and non-exudative age-related macular degeneration (33.9% vs 10.6%, p < 0.001). Among 1442 eligible cases analyzed, 427 (29.6%) received at least 1 anti-VEGF injection with 338 (23.4%) patients having the injection after their AS diagnosis. CONCLUSIONS: In the largest collection of AS patients to date, the classical teaching of systemic disease associations occur at rates far, far lower than previously reported. The association of AS with other less reported diseases highlights new potential associations and may contribute to the understanding of AS formation.
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Estrías Angioides , Neovascularización Coroidal , Seudoxantoma Elástico , Humanos , Estrías Angioides/epidemiología , Estrías Angioides/diagnóstico , Estudios Retrospectivos , Estudios Transversales , Seudoxantoma Elástico/complicaciones , Neovascularización Coroidal/complicaciones , Atención a la Salud , Angiografía con FluoresceínaRESUMEN
BACKGROUND/AIMS: To determine the association of age, presence of optic nerve head drusen (ONHD) and number of previous intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections with inner retinal layer thicknesses in patients with pseudoxanthoma elasticum (PXE). METHODS: In this retrospective case-control study, longitudinal spectral-domain optical coherence tomography imaging data from patients with PXE were compared with controls. A custom deep-learning-based segmentation algorithm was trained and validated to quantify the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL). The association of age, number of anti-VEGF injections and ONHD with the RNFL and GCL thickness in the outer ETDRS subfields as dependent variables was investigated using mixed model regression. RESULTS: Fourty-eight eyes of 30 patients with PXE were compared with 100 healthy eyes. The mean age was 52.5±12.9 years (range 21.3-68.2) for patients and 54.2±18.7 years (range 18.0-84.5) for controls. In patients, ONHD were visible in 15 eyes from 13 patients and 31 eyes had received anti-VEGF injections. In the multivariable analysis, age (-0.10 µm/year, p<0.001), the diagnosis of PXE (-2.03 µm, p=0.005) and an interaction term between age and the presence of ONHD (-0.20 µm/year, p=0.001) were significantly associated with the GCL thickness. Including the number of intravitreal injections did not improve the model fit. The RNFL thickness was not significantly associated with any of these parameters. CONCLUSIONS: This study demonstrates a significant association of ageing and ONHD with GCL thinning in patients with PXE, but not with the number of anti-VEGF injections. Given the severity of inner retinal degeneration in PXE, a clinical trial investigating neuroprotective therapy warrants consideration.
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Drusas del Disco Óptico , Disco Óptico , Seudoxantoma Elástico , Degeneración Retiniana , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Células Ganglionares de la Retina , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico , Degeneración Retiniana/complicaciones , Estudios Retrospectivos , Estudios de Casos y Controles , Fibras Nerviosas , Drusas del Disco Óptico/complicaciones , Drusas del Disco Óptico/diagnóstico , Tomografía de Coherencia ÓpticaRESUMEN
Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder showing phenotypic heterogeneity giving rise to complex comorbidities. The most 'visible' signs are dermatological; however, these may be subtle and hidden from the view of an affected individual. Ophthalmic signs can be easily missed, and here we highlight the importance of a multisystem assessment. We report a patient who developed advanced sight loss due to maculopathy whose underlying PXE aetiology went unnoticed until subtle skin signs were noticed on the lateral aspect of his neck. He was aware of the skin changes. Careful review of his previous retinal imaging showed the presence of 'angioid streaks' and anatomic alteration at the outer retina-Bruch membrane associated with his prior history of choroidal neovascularisation. The diagnosis was subsequently confirmed by skin biopsy and genetic testing. This case highlights the subtlety of both dermatological and ophthalmic signs in PXE.
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Estrías Angioides , Seudoxantoma Elástico , Estrías Angioides/complicaciones , Estrías Angioides/diagnóstico , Biopsia , Humanos , Masculino , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/genética , Seudoxantoma Elástico/patología , Piel/patologíaAsunto(s)
Dermopatía Fibrosante Nefrogénica , Seudoxantoma Elástico , Insuficiencia Renal Crónica , Insuficiencia Renal , Enfermedades de la Piel , Fibrosis , Gadolinio/efectos adversos , Humanos , Dermopatía Fibrosante Nefrogénica/inducido químicamente , Dermopatía Fibrosante Nefrogénica/diagnóstico , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnósticoRESUMEN
BACKGROUND AND AIMS: Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by systemic calcification of elastin fibers. Additionally, PXE is associated with an increased risk of stroke. It has been hypothesized that this may be caused by accelerated (intracranial) atherogenesis, as a consequence of specific genetic mutations underlying PXE. Hence, we compared the distribution and burden of intracranial atherosclerosis between PXE patients and healthy controls. METHODS: Fifty PXE patients and 40 age-and-sex-matched healthy controls (without previous ischemic cerebrovascular disease) underwent 3T MRI to visualize atherosclerotic intracranial vessel wall lesions (VWLs). We compared the presence and burden of VWLs (total and for the anterior cerebral, middle cerebral, intracranial internal carotid, posterior cerebral, and basilar arteries separately) between PXE patients and healthy controls using logistic (presence versus absence) and negative binomial regression models (VWL count) adjusted for relevant confounders. All regressions included group (PXE patients vs. healthy controls) as independent variable. RESULTS: We found that 34 (68.0%) PXE patients and 28 (70.0%) healthy controls had a VWL (odds ratio for presence 1.06 [95%CI 0.38-2.91]). In addition, the total burden of VWLs was similar between PXE patients (68 VWLs) and healthy controls (73 VWLs, incidence rate ratio for count 0.81 [95%CI 0.55-1.20]). Findings were similar when analyses were stratified for artery. CONCLUSIONS: The distribution and burden of intracranial atherosclerosis were similar between PXE patients and healthy controls. This implies PXE and its underlying mutations do not involve increased (intracranial) atherogenesis and that vascular calcification or other mechanisms explains the increased stroke risk in PXE.