Intracranial Calcification Research Articles

Symptomatic Intracranial Hemorrhage after Ischemic Stroke Treated with Bridging Revascularization Therapy.

(1) Background: bridging revascularization therapy is now the standard of care in patients with ischemic stroke due to large vessel occlusion. This study aimed to determine the frequency of symptomatic intracranial hemorrhage (sICH) related to this treatment, and to assess contributing factors and patients' outcomes. (2) Methods: consecutive ischemic stroke patients treated with bridging therapy were prospectively enrolled. sICH (intracranial hemorrhage with an increase in NIHSS score of ≥4 points) was assessed on imaging at 24 h. The functional status of patients was measured at 6 months using the mRS score; (3) Results: 176 patients were included (mean age 68.7 ± 1.2 years, 52.3% women), among whom 15 (8.5%) had sICH. Patients with sICH had more frequent alcohol abuse (30.1% versus 9.7%, p = 0.023), prestroke use of dual antiplatelet therapy (14.3% versus 1.3%, p = 0.002), higher NIHSS scores at admission (median score 20.5 versus 15, p = 0.01), greater systolic blood pressure upon admission, more frequent vascular intracranial calcifications (p = 0.004), leukoaraiosis (p = 0.001), and intracranial atheroma (p = 0.02), and higher neutrophil-to-lymphocyte ratios (p = 0.02) and neutrophil-to-platelet ratios (p = 0.04). At 6-month follow-up, 9 (60%) patients with sICH died, versus 18% of patients without sICH (p < 0.001). Only 1 (7%) patient with sICH had a good functional outcome, defined as an mRS score of 0 to 2, versus 51% of patients without sICH. (4) Conclusions: one in twelve ischemic stroke patients treated with bridging therapy suffered sICH. Given the observed poor outcomes after sICH, further studies are required to better identify patients at risk to help clinicians in guiding therapeutic strategies.

Association between intracranial vessel calcifications, structural brain damage, and cognitive impairment after minor strokes: a prospective study.

Vascular calcifications are a hallmark of atherosclerosis, and in the coronary arteries are routinely used as a prognostic marker. Calcifications of intracranial vessels (ICC) are frequently observed on non-contrast CT (NCCT) and their effect on post-stroke cognitive impairment (PSCI) remains unclear. Our aim was to explore the association of ICC with prospective long-term cognitive function and advanced MRI-measures in a large prospective cohort of cognitively intact mild stroke survivors. Data from the Tel-Aviv brain acute stroke cohort (TABASCO) study [ClinicalTrials.gov #NCT01926691] were analyzed. This prospective cohort study (n = 575) aimed to identify predictors of PSCI, in cognitively intact mild stroke survivors. A quantitative assessment of the intracranial calcium content - The ICC score (ICCS) was calculated semi-automatically on NCCT using a validated calcium quantification application. Participants underwent a 3 T-MRI and prospective comprehensive cognitive clinical and laboratory assessments at enrollment, 6, 12, and 24-months. Data were available for 531 participants (67.4 years, 59.5% males). The incidence of PSCI at two-years doubled in the high ICCS group (26% vs. 13.7%, p < 0.001). The high ICCS group had significantly greater small-vessel-disease (SVD) tissue changes and reduced microstructural-integrity assessed by Diffusion-Tensor-Imaging (DTI) maps (p < 0.05 for all). In multivariate analysis, a higher ICCS was independently associated with brain atrophy manifested by lower normalized white and gray matter, hippocampal and thalamic volumes (β = -0.178, β = -0.2, β = -0.137, β = -0.157; p < 0.05) and independently predicted PSCI (OR 1.83, 95%CI 1.01-3.35). Our findings suggest that the ICCS, which is a simple and readily available imaging marker on NCCT, is associated with brain atrophy, microstructural damage, the extent of SVD, and may predict PSCI. This finding has implications for identifying individuals at risk for PSCI and implementing targeted interventions to mitigate this risk.

Hypocalcemia in thalassemia major patients requires an extra-careful approach

Thalassemia is a hematological disorder caused by a gene mutation that leads to defective synthesis of hemoglobin complex. One of the complications of thalassemia is hypocalcemia which is presented with paresthesia, muscle spasm, low-serum calcium, and intracranial calcification. Hypocalcemia can affect thalassemic patients via various mechanisms. Blood transfusion-related and transfusion-independent iron overload, drug side effects, vitamin D3 deficiency, and genetic disorders and polymorphisms are among the etiologies of hypocalcemia in major thalassemia. A careful approach to the differential etiology of this phenomenon is crucial for a resultful treatment.

Hemorrhagic transformation of ischemic stroke in a patient with Fahr’s disease

BackgroundFahr’s disease is a very rare inherited neurodegenerative disorder characterized by diffuse and symetric intracranial calcification of the bilateral basal ganglia and cerebellum. Although the disease is slowly progressive, several acute forms have been described. We would like to present a very rare case of Fahr’s disease with an ischemic stroke and its hemorrhagic transformation.Case presentationA 70-year-old woman presented to our emergency department with rapid cognitive decline, dysarthria and right limb weakness. Cranial computed tomography showed diffuse and symmetric hyperdense areas at the level of the bilateral dentate nuclei of cerebellar hemispheres and basal ganglia, suggestive of calcification consistent with Fahr's disease on a background of thyroidectomy history, and effacement in the left caudate region. The patient was admitted to the intensive care unit with suspected left cerebral ischemic stroke. Because of clinical deterioration with increasing drowsiness and right hemiplegia, a control computed tomography scan was performed. Upon detection of a 6 * 8 cm lesion corresponding to an intracerebral hematoma in the left temporoparietal area with intraventricular component, she underwent surgery. The patient did not become hemodynamically stable and died on post-operative day 3.ConclusionsThe calcium deposits in the walls of the cerebral vessels in Fahr’s disease may exacerbate inflammatory processes leading to disruption of the blood-brain barrier. In addition, peripheral blood extravasation into the disrupted blood brain barrier due to ischemic stroke may lead to hemorrhagic transformation.

Fahr disease presenting with multiple cerebral calcifications

Fahr disease, also known as idiopathic basal ganglion calcification, is a rare and genetically heterogeneous neurological disorder. Herein, we report a rare case of Fahr disease presenting with multiple cerebral calcifications. A 63-year-old woman presented with dizziness to a local clinic. Brain computed tomography performed on admission revealed multiple high-intensity lesions in both basal ganglia, both cerebellar hemispheres, and the left frontal lobe. In contrast, brain magnetic resonance imaging (MRI) showed no prominent lesions on T2- and T1-weighted images, and there was no contrast enhancement after gadolinium injection. However, multiple dark signals were detected on gradient echo MRI. The location and radiological appearance of the lesion resembled those of a physiological intracranial calcification, except for asymmetric calcification in both cerebellar hemispheres and the left frontal subcortical white matter. The patient was diagnosed with basal ganglion calcification with multiple cerebral cavernous malformations or, less likely, brain tumors. Through a careful radiological and clinical review, the calcifications were diagnosed as Fahr disease. Follow-up was planned. It is important to consider the presence of multiple intracranial calcifications in the basal ganglia, cerebellum, or deep subcortical white matter as a warning sign for Fahr disease.

Intracranial physiological calcifications: A computed tomography study

AbstractBackground and aimIntracranial calcifications (ICs) occur when metals such as calcium or iron accumulate in blood vessels, glands or other structures related to the brain. They can be physiological or pathological. Currently, the most sensitive method for imaging IC is cranial computed tomography (CT). The aim of this retrospective study was to evaluate physiological ICs and the co-existence of them by CT.Patients and methods1,000 cranial CT scans of patients were retrospectively evaluated. Pineal calcification, choroid plexus calcification, habenular calcification, petroclinoid ligament calcification, basal ganglia calcification, falx cerebri and tentorium cerebelli calcification were evaluated and recorded.ResultsOf 1,000 patients, 65.7% had IC. The incidence of ICs in different sites were as follows: pineal calcification (37.7%), choroid plexus calcification (52.1%), habenular calcification (33.5%), petroclinoid calcification (21.8%), basal ganglia calcification (0.6%), falx cerebri calcification (6.2%) and tentorium cerebelli calcification (0.2%). The incidence and co-existence of calcifications were significantly higher in females than in males (P &lt; 0.05). Pineal, choroid plexus, petroclinoid ligament calcifications were significantly higher in females than in males (P &lt; 0.05). The incidence and co-existence of calcifications increased with age. Tentorium Cerebelli calcification did not differ significantly between age groups (P &gt; 0.05).ConclusionsICs may be a common finding and encountered incidentally on CT scans which is gold standard to evaluate them. It is important to distinguish physiological calcifications from pathological ones, in the differentiation of pathological lesions with calcifications.

Comparative study of calcification in human choroid plexus, pineal gland, and habenula.

Choroid plexus, pineal gland, and habenula tend to accumulate physiologic calcifications (concrements) over a lifetime. However, until now the composition and causes of the intracranial calcifications remain unclear. The detailed analysis of concrements has been done by us using X-ray diffraction analysis (XRD), X-ray diffraction topography (XRDT), micro-CT, X-ray phase-contrast tomography (XPCT), as well as histology and immunohistochemistry (IHC). By combining physical (XRD) and biochemical (IHC) methods, we identified inorganic (hydroxyapatite) and organic (vimentin) components of the concrements. Via XPCT, XRDT, histological, and IHC methods, we assessed the structure of concrements within their appropriate tissue environment in both two and three dimensions. The study found that hydroxyapatite was a major component of all calcified depositions. It should be noted, however, that the concrements displayed distinctive characteristics corresponding to each specific structure of the brain. As a result, our study provides a basis for assessing the pathological and physiological changes that occur in brain structure containing calcifications.

DIAGNOSIS OF GORLIN-GOLTZ SYNDROME: CLINCIAL CASE REPORT

The diagnosis of Gorlin-Goltz syndrome involves clinical, radiographic, and histopathological aspects. Computed tomography contributes to the evaluation of the characteristics, to the extension of cystic lesions, and to the diagnosis of signs, such as calcifications in the falx cerebri. A 22-year-old male presented a complaint of halitosis. Upon extraoral examination, a slight increase in volume in the lower third of the right face, suggestive of a cystic lesion in the soft tissue, and a scar on the skin of the nasolabial region, were noted. Tomographic imaging revealed hypodense lesions involving impacted teeth, two in the maxilla (with extension to the maxillary sinuses) and two in the mandible. The intraosseous lesions underwent biopsy, and the histopathological findings were consistent with keratocysts. Intracranial calcifications were also detected. Additionally, an anatomical alteration of the incisive foramen and nasal cavity was identified. Basal cell carcinomas were not observed. The patient is undergoing follow-up. The diagnosis of Gorlin-Goltz syndrome involves clinical, radiographic, and histopathological aspects. Computed tomography contributes to the evaluation of the characteristics, to the extension of cystic lesions, and to the diagnosis of signs, such as calcifications in the falx cerebri. A 22-year-old male presented a complaint of halitosis. Upon extraoral examination, a slight increase in volume in the lower third of the right face, suggestive of a cystic lesion in the soft tissue, and a scar on the skin of the nasolabial region, were noted. Tomographic imaging revealed hypodense lesions involving impacted teeth, two in the maxilla (with extension to the maxillary sinuses) and two in the mandible. The intraosseous lesions underwent biopsy, and the histopathological findings were consistent with keratocysts. Intracranial calcifications were also detected. Additionally, an anatomical alteration of the incisive foramen and nasal cavity was identified. Basal cell carcinomas were not observed. The patient is undergoing follow-up.

Correlation Between Intracranial Calcification and Extracranial Stenosis of the Internal Carotid Artery.

Intracranial artery calcification is a marker of vascular atherosclerosis and has a high prevalence worldwide. Both atherosclerosis of the internal carotid artery at the carotid sinus in the neck and intracranial calcification have been associated with ischemic stroke. The relationship between the two has not been well studied. The present study investigated how carotid sinus narrowing could relate to calcification located in the distal intracranial artery at the cavernous carotid. We examined a population not selected for cerebral disease. This retrospective study contained 179 subjects aged 18 years and older from the Hawaii Diagnostic Radiology database. Extracranial internal carotid artery stenosis was determined using the absolute diameter, North American Symptomatic Carotid Endarterectomy Trial, and common carotid artery methods. Calcification was scored using the modified Woodcock method. A positive correlation between intracranial calcification and extracranial carotid stenosis was found using all three methods. Individuals with intracranial calcification were more likely to be older, have a smaller internal carotid artery diameter, and have a greater percent stenosis at the internal carotid artery than those without intracranial artery calcification (p<0.001 for all). These results may help refocus interest in calcification in studies of cerebral vasculature and its correlation with extracranial carotid stenosis.

AORTIC STIFFNESS IS INDEPENDENTLY ASSOCIATED WITH INTRACRANIAL CAROTID ARTERY CALCIFICATION IN PATIENTS WITH ISCHEMIC STROKE

Objective: Intracranial carotid artery calcification (ICAC), as a strong contributor to the occurrence of ischemic stroke, might be present in the medial or intimal arterial layer. Traditional vascular risk factors are associated with ICAC; however, its association with new markers of vascular function are less understood. The paper aims to evaluate the relationship between carotid-femoral pulse wave velocity (CF-PWV) and ICAC subtypes. Design and method: We enrolled 65 patients with acute ischemic stroke. CF-PWV, systolic, diastolic and mean blood pressure, and pulse pressure (SBP, DBP, MBP, PP) were measured within 6±2 days of stroke onset. CT was performed within 24 hours of stroke onset and ICAC on the stroke site was classified by two methods: volume- and score-based. Tertiles of ICAC volume were determined, and low-grade ICAC (T1) was regarded as a reference. According to the score-based method, medial and intimal ICAC subtypes were determined. Data were analyzed with multivariate logistic regression. Results: Medial and intimal ICAC subtypes were found in 34 (52%) and 24 (37%) patients, respectively. In 11% of patients no ICAC calcifications were found. CF-PWV was higher in patients with high-grade ICAC (OR = 1.56, 95%CI = 1.03-2.35, p = 0.035). CF-PWV was higher in patients with the medial ICAC subtype than in patients with the intimal ICAC subtype (OR = 1.60, 95%CI = 1.00-2.55, p = 0.049) after adjustment for age, MBP, diabetes mellitus, arterial hypertension, hyperlipidemia, and smoking status. Conclusions: Our study demonstrates that among patients with ischemic stroke, aortic stiffness is independently associated with ICAC, and that medial ICAC, compared with intimal ICAC, is accompanied by more advanced aortic stiffness.

Changes in intra- and extracranial carotid plaque calcification: a 2-year follow-up study

Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58–0.90 respectively OR = 2.24, 95% CI 1.60–3.13).We found significant correlation for change in ECAC volume with diabetes (β = 0.46, 95% CI 0.03–0.89) and baseline ECAC volume (β = 0.81, 95% CI 0.73–0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48–3.16), age (OR = 2.00, 95% CI 1.19–3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20–11.96]).The overall change of ICAC volume was also significantly correlated with diabetes (β = 0.92, 95% CI 1.59–7.02), use of oral hypoglycemic drugs (β = 0.86, 95% CI 0.12–1.59) and baseline ICAC volume (β = 0.71, 95% CI 0.55–0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.

The role of intracranial artery calcification (IAC) in stroke subtype and risk of vascular events

ObjectiveTo test the hypothesis that intracranial arterial calcification (IAC) is associated with intracranial large artery stenosis (ILAS) and a higher risk of vascular events and mortality. MethodWe leveraged data from two cohorts, the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry Study (NYP/CUIMC-SRS) and the Northern Manhattan Study (NOMAS) to test our hypotheses. We measured IAC using CT scans of participants in both cohorts and expressed IAC as present (vs not) and in tertiles. For the CUIMC-SRS, demographic, clinical and ILAS status was collected retrospectively. In NOMAS, we used research brain MRI and MRA to define asymptomatic ILAS and covert brain infarcts(CBI). We built models adjusted for demographics and vascular risk factors for cross-sectional and longitudinal analyses. ResultsCross-sectionally, IAC was associated with ILAS in both cohorts (OR 1.78, 95% CI: 1.16-2.73 for ILAS-related stroke in the NYP/CUIMC-SRS and OR 3.07, 95%CI 1.13-8.35 for ILAS-related covert brain infarcts in NOMAS). In a meta-analysis of both cohorts, IAC in the upper (HR 1.25, 95%CI 1.01-1.55) and middle tertile (HR 1.27, 95%CI 1.01-1.59) was associated with higher mortality compared with participants with no IAC. There were no longitudinal associations between IAC and risk of stroke or other vascular events. ConclusionIn these multiethnic populations, IAC is associated with symptomatic and asymptomatic ILAS as well as higher mortality. IAC may be a useful marker of higher mortality, the role of IAC as an imaging marker of risk of stroke is less certain.

Amount and Distribution of Intracranial Calcification in Symptomatic and Asymptomatic Primary Familial Brain Calcification.

In clinical practice, it can be difficult to differentiate between intracranial calcifications related to primary familial brain calcification (PFBC) or aging. Also, little is known about the consequences of the amount of intracranial calcifications in patients with PFBC. Therefore, we aimed to compare the amount and distribution of intracranial calcifications in persons with PFBC with controls and between asymptomatic and symptomatic PFBC cases. This was a case-control study including patients with PFBC and controls. Controls received a CT of the brain because of a trauma and had at least some basal ganglia calcification. The Nicolas score and volume of calcification were used to quantify intracranial calcifications on the CT scans. Receiver operating characteristic curves were obtained to calculate optimal cutoff points to discriminate between cases and controls. Mann-Whitney U tests and logistic regression, adjusted for age and sex, were used to compare the amount of calcification. Twenty-eight cases (median age 65 years, 50.0% male) and 90 controls (median age 74 years, 46.1% male) were included. Calcification scores were higher in cases (median volume: 4.91 cm3 against 0.03 cm3, p < 0.001, median Nicolas score: 26.5 against 2.0, p < 0.001) than controls. Calcifications were also more diffusely distributed in cases. To differentiate between cases and controls, optimal cutoff points were ≥0.2 cm3 for the calcification volume and ≥6.0 for the Nicolas score. Calcification was higher for symptomatic than asymptomatic cases (calcification volume: 13.62 cm3 against 1.61 cm3, p = 0.01, Nicolas score: 39.0 against 15.5, p = 0.02). After adjustment for age and sex, the Nicolas score remained significantly higher in symptomatic patients, and the calcification volume did not. Patients with PFBC had more severe intracranial calcifications, and these calcifications were more diffusely distributed through the brain compared with controls. Symptomatic patients with PFBC might have more intracranial calcifications than asymptomatic persons.

USP18 Partial Deficiency Leads to Early-Onset Childhood Inflammation

Type I interferonopathies are characterized by an overabundance of IFN-I, which cause a broad spectrum of clinical presentation. Ubiquitin Specific Peptidase 18 (USP18) plays an important role in regulating the interferon (IFN) response by dampening the IFN-I signaling pathway. Additionally, USP18 removes ISG15 from proteins, in a process termed de-ISGylation. Synergistically, ISG15 prevents proteasomal degradation of USP18. Autosomal-recessive USP18 deficiency results in severe systemic inflammation and neurological anomalies, which is fatal in the perinatal period, unless treated with a JAK-STAT inhibitor. In our study, we identified three patients with genetic variations in USP18, who exhibited a spectrum of clinical features, including intracranial calcifications, lung opacities, hepatosplenomegaly, developmental delay, and high levels of circulating IFN-I. We sought to understand the pathophysiology of these USP18 mutations and the mechanistic process by which they cause disease. Expression of USP18 mRNA and protein was retained in all four of the patient’s mutations. Additionally, in all four patient mutations, USP18 maintained catalytic competencyand was capable of de-ISGylation. USP18 mutations also retained stabilization by ISG15. However, all four USP18 variants demonstrated higher levels of phosphorylation of STAT1 and STAT2 as compared to WT USP18, indicating an inability to negatively regulate interferon signaling, an important function of USP18. Additionally, both patient-derived fibroblasts and fibroblasts transduced and stimulated with IFNα2b had persistence of interferon-stimulated genes as compared to WT fibroblasts after a 36-hour recovery period. In conclusion, partial USP18 deficiency leads to early-onset childhood inflammation through an inability to control IFN-I signaling.

The correlation between intracranial arterial calcification and the outcome of reperfusion therapy.

Intracranial arterial calcification (IAC) is a risk factor of ischemic stroke. However, the relationship between IAC patterns and clinical outcome of ischemic stroke remains controversial. We aimed to investigate the correlation between IAC patterns and the effects of reperfusion therapy among acute stroke patients. Consecutive acute ischemic stroke patients who underwent reperfusion therapy were included. IAC was categorized as intimal or medial. Based on its involvement, IAC was further classified as diffuse or focal. Neurologic dysfunction was assessed by the National Institute of Health stroke scale (NIHSS). Clinical outcome including favorable neurologic outcome (FNO) and early neurologic deterioration (END) were assessed. Of 130 patients, 117 had IAC. Intimal IAC was identified in 74.6% of patients and medial IAC was present in 64.6% of patients. Diffuse IAC was present in 31.5% of patients. All diffuse IACs were medial pattern. Diffuse IAC was associated with higher baseline NIHSS (p = 0.011) and less FNO (p = 0.047). Compared with patients with focal or single diffuse IAC, patients with multiple diffuse IAC had higher baseline NIHSS (p = 0.002) and less FNO (p = 0.024). Multivariable linear regression (p < 0.001) and logistic regression (p = 0.027) suggested that multiple diffuse IAC was associated with higher baseline NIHSS and less FNO. No significant association was found between END and different IAC patterns. Multiple diffuse medial IAC may predict severer neurologic dysfunction and less favorable neurologic outcome after reperfusion therapy in acute stroke patients.

Lipoprotein(a) is associated with a larger systemic burden of arterial calcification.

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for cardiovascular disease. However, population-based evidence on the link between Lp(a) and subclinical arteriosclerosis is lacking. We assessed associations of Lp(a) concentrations with arteriosclerosis in multiple arteries. From the population-based Rotterdam study, 2354 participants (mean age: 69.5 years, 52.3% women) underwent non-contrast computed tomography to assess arterial calcification as a hallmark of arteriosclerosis. We quantified the volume of coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC), and intracranial carotid artery calcification (ICAC). All participants underwent blood sampling, from which plasma Lp(a) concentrations were derived. The association of plasma Lp(a) levels was assessed with calcification volumes and with severe calcification (upper quartile of calcification volume) using sex-stratified multivariable linear and logistic regression models. Higher Lp(a) levels were associated with larger ln-transformed volumes of CAC [fully adjusted beta 95% confidence interval (CI) per 1 standard deviation (SD) in women: 0.09, 95% CI 0.04-0.14, men: 0.09, 95% CI 0.03-0.14], AAC (women: 0.06, 95% CI 0.01-0.11, men: 0.09, 95% CI 0.03-0.14), ECAC (women: 0.07, 95% CI 0.02-0.13, men: 0.08, 95% CI 0.03-0.14), and ICAC (women: 0.09, 95% CI 0.03-0.14, men: 0.05, 95% CI -0.02 to 0.11]. In the highest Lp(a) percentile, severe ICAC was most prevalent in women [fully adjusted odds ratio (OR) 2.41, 95% CI 1.25-4.63] and severe AAC in men (fully adjusted OR 3.29, 95% CI 1.67-6.49). Higher Lp(a) was consistently associated with a larger calcification burden in all major arteries. The findings of this study indicate that Lp(a) is a systemic risk factor for arteriosclerosis and thus potentially an effective target for treatment. Lp(a)-reducing therapies may reduce the burden from arteriosclerotic events throughout the arterial system. In 2354 participants from the Rotterdam study, we assessed the link between Lp(a) concentrations and arterial calcifications, as proxy for arteriosclerosis, in major arteries. We found that higher Lp(a) levels were consistently associated with larger volumes of calcification in the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries. The findings of our study indicate that Lp(a) is a systemic risk factor for arteriosclerosis, suggesting that the systemic burden of arteriosclerosis throughout the arterial system could be reduced by targeting Lp(a).

Evaluation of prophylactic efficacy of sodium thiosulfate in combating I/R injury in rat brain: exploring its efficiency further in vascular calcified brain slice model.

Cerebral ischemia reperfusion injury (CIR) is one of the clinical manifestations encountered during the management of stroke. High prevalence of intracranial arterial calcification is reported in stroke patients. However, the impact of vascular calcification (VC) in the outcome of CIR and the efficacy of mechanical preconditioning (IPC) and pharmacological conditioning with sodium thiosulphate (STS) in ameliorating IR remains unclear. Two experimental models namely carotid artery occlusion (n=36) and brain slice models (n=18) were used to evaluate the efficacy of STS in male Wistar rats. IR was inflicted in rat by occluding carotid artery for 30min followed by 24-h reperfusion after STS (100mg/kg) administration. Brain slice model was used to reconfirm the results to account blood brain barrier permeability. Further, brain slice tissue was utilised to evaluate the efficacy of STS in VC rat brain by measuring the histological alterations and biochemical parameters. Pre-treatment of STS prior to CIR in intact animal significantly reduced the IR-associated histopathological alterations in brain, declined oxidative stress and improved the mitochondrial function found to be similar to IPC. Brain slice model data also confirmed the neuroprotective effect of STS similar to IPC in IR challenged tissue slice. Higher tissue injury was noted in VC brain IR tissue than normal IR tissue. Therapeutic efficacy of STS was evident in VC rat brain tissues and normal tissues subjected to IR. On the other hand, IPC-mediated protection was noted only in IR normal and adenine-induced VC brain tissues not in high-fat diet (HFD) induced VC brain tissues. Based on the results, we concluded that similar to IPC, STS was effective in attenuating IR injury in CIR rat brain. Vascular calcification adversely affected the recovery protocol of brain tissues from ischemic insult. STS was found to be an effective agent in ameliorating the IR injury in both adenine and HFD induced vascular calcified rat brain, but IPC-mediated neuroprotection was absent in HFD-induced VC brain tissues.

Noninvasive real‐time imaging of palmar pits in basal cell nevus syndrome with line‐field confocal optical coherence tomography

Palmar and plantar pits are, besides childhood onset of multiple basal cell carcinomas (BCCs), odontogenic jaw cysts, intracranial calcification, and affected first-degree relatives, one of the major criteria for diagnosis of basal cell nevus syndrome (BCNS). These defective areas of keratinization are present in up to 90% of affected individuals. Lesions may be subtle and easily missed clinically. Dermoscopy or histopathological examination may be useful to diagnose them.1 Palmar pits in a 49-year-old woman with BCNS (deletion exon 2 and 3 PTCH1 gene) are shown using a new diagnostic imaging device: line-field confocal optical coherence tomography (LC-OCT). The device provides real-time and bedside visualization of the features that are typically observed in histopathology (hypokeratosis with inconstant hypogranulosis and palisading proliferation of basal keratinocytes). LC-OCT provides effective, noninvasive, and quick diagnosis of palmar pits and BCCs,2 two of the major diagnostic criteria of BCNS (Figure 1). Sergio del Río-Sancho: Visualization; writing—original draft; writing—review and editing. Caroline Gallay: Investigation; writing—review and editing. Sarah Ventéjou: Investigation; writing—review and editing. Stephanie Christen-Zaech: Conceptualization; resources; supervision; writing—review and editing. All authors read and approved the final manuscript. This study was funded by the Accentus foundation via the CHUV foundation. The authors declare have no conflict of interest. The study was approved by the Local Ethics Committee (Protocol Number: 2021_00683_2104). All patients in this manuscript have given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. The data that support the findings of this study are available on request from the corresponding author.

Intracranial calcification in Fam20c-deficient mice recapitulates human Raine syndrome

FAM20C (family with sequence similarity 20-member C) is a protein kinase that phosphorylates secretory proteins, including the proteins that are essential to the formation and mineralization of calcified tissues. FAM20C loss-of-function mutations cause Raine syndrome in humans, characterized by generalized osteosclerosis, distinctive craniofacial dysmorphism, along with extensive intracranial calcification. Our previous studies revealed that inactivation of Fam20c in mice led to hypophosphatemic rickets. In this study, we examined the expression of Fam20c in the mouse brain and investigated brain calcification in Fam20c-deficient mice. Reverse transcription polymerase chain reaction (RT-PCR), Western-blotting and in situ hybridization analyses demonstrated the broad expression of Fam20c in the mouse brain tissue. X-ray and histological analyses showed that the global deletion of Fam20c (mediated by Sox2-cre) resulted in brain calcification in mice after postnatal 3 months and that the calcifications were bilaterally distributed within the brain. There was mild perifocal microgliosis as well as astrogliosis around calcospherites. The calcifications were first observed in the thalamus, and later in the forebrain and hindbrain. Furthermore, brain-specific deletion (mediated by Nestin-cre) of Fam20c in mice also led to cerebral calcification at an older age (postnatal 6 months), but no obvious skeletal or dental defects. Our results suggest that the local loss of FAM20C function in the brain may directly account for intracranial calcification. We propose that FAM20C plays an essential role in maintaining normal brain homeostasis and preventing ectopic brain calcification.

Feasibility and intra-and interobserver reproducibility of quantitative susceptibility mapping with radiomic features for intracranial dissecting intramural hematomas and atherosclerotic calcifications

Quantitative susceptibility mapping (QSM) for 61 patients with dissecting intramural hematomas (n = 36) or atherosclerotic calcifications (n = 25) in intracranial vertebral arteries were collected to assess intra- and interobserver reproducibility in a 3.0-T MR system between January 2015 and December 2017. Two independent observers each segmented regions of interest for lesions twice. The reproducibility was evaluated using intra-class correlation coefficients (ICC) and within-subject coefficients of variation (wCV) for means and concordance correlation coefficients (CCC) and ICC for radiomic features (CCC and ICC > 0.85) were used. Mean QSM values were 0.277 ± 0.092 ppm for dissecting intramural hematomas and − 0.208 ± 0.078 ppm for atherosclerotic calcifications. ICCs and wCVs were 0.885–0.969 and 6.5–13.7% in atherosclerotic calcifications and 0.712–0.865 and 12.4–18.7% in dissecting intramural hematomas, respectively. A total of 9 and 19 reproducible radiomic features were observed in dissecting intramural hematomas and atherosclerotic calcifications, respectively. QSM measurements in dissecting intramural hematomas and atherosclerotic calcifications were feasible and reproducible between intra- and interobserver comparisons, and some reproducible radiomic features were demonstrated.