Total Calcification Score Research Articles

Inter-and intrarater agreement of Computed Tomographic brain calcification scoring in Primary Familial Brain Calcification.

The Total Calcification Score (TCS) is a visual rating scale to measure Primary Familial Brain Calcification (PFBC) related calcification severity on Computed Tomography (CT). We investigated the inter-and intrarater agreement of a modified TCS. Patients aged ≥18 years with PFBC or Fahr's syndrome who visited the outpatient clinic of a Dutch academic hospital were included. The TCS was modified, for example by adding hippocampal calcification, and ranged from 0 to 95 points. Fifteen raters evaluated all CTs, of whom three evaluated the CTs twice. Their Entrustable Professional Activity (EPA) level ranged from II (medical student) to V (neuroradiologist). Agreement was assessed using the intraclass correlation coefficient (ICC) for the total score. Kendall's W and weighted Cohen's Kappa were used to determine the inter- and intrarater agreement for individual locations, respectively. Forty patients were included (mean age 60 years, 53% female). The median modified TCS was 34 (range 4-76). For all EPA levels, the interrater agreement of the modified TCS was excellent (ICC=0.97 (95% CI 0.95-0.98)). Kendall's W's were good to excellent for commonly affected locations, but poor to moderate for less commonly affected locations for raters with lower levels of expertise. The intrarater agreement of the modified TCS was excellent. Kappa's of most locations were substantial to almost perfect. The modified TCS can be used with excellent reproducibility of the overall amount of brain calcifications and with limited training, although for some individual calcification locations more expertise is needed. CI, Confidence Interval; CT, Computed Tomography; EPA, Entrustable Professional Activity; IBGC, Idiopathic Basal Ganglia Calcification; ICC, Intraclass Correlation Coefficient; IQR, Interquartile Range; PFBC, Primary Familial Brain Calcification; SD, Standard Deviation, TCS, Total Calcification Score; UMCU, University Medical Center Utrecht.

Novel findings in a Swedish primary familial brain calcification cohort

IntroductionBrain calcifications are frequent findings on imaging. In a small proportion of cases, these calcifications are associated with pathogenic gene variants, hence termed primary familial brain calcification (PFBC). The clinical penetrance is incomplete and phenotypic variability is substantial. This paper aims to characterize a Swedish PFBC cohort including 25 patients: 20 from seven families and five sporadic cases. MethodsLongitudinal clinical assessment and CT imaging were conducted, abnormalities were assessed using the total calcification score (TCS). Genetic analyses, including a panel of six known PFBC genes, were performed in all index and sporadic cases. Additionally, three patients carrying a novel pathogenic copy number variant in SLC20A2 had their cerebrospinal fluid phosphate (CSF-Pi) levels measured. ResultsAmong the 25 patients, the majority (76%) displayed varying symptoms during the initial assessment including motor (60%), psychiatric (40%), and/or cognitive abnormalities (24%). Clinical progression was observed in most patients (78.6%), but there was no significant difference in calcification between the first and second scans, with mean scores of 27.3 and 32.8, respectively. In three families and two sporadic cases, pathogenic genetic variants were identified, including a novel finding, in the SLC20A2 gene. In the three tested patients, the CSF-Pi levels were normal. ConclusionsThis report demonstrates the variable expressivity seen in PFBC and includes a novel pathogenic variant in the SLC20A2 gene. In four families and three sporadic cases, no pathogenic variants were found, suggesting that new PFBC genes remain to be discovered.

Vascular calcification in Takayasu arteritis: relationship with metabolic syndrome, left ventricular mass index, and intima-media thickness

ObjectiveThe present study aims to determine the frequency of vascular calcification in Takayasu arteritis (TA) and the risk factors for it and to evaluate its relation with atherosclerotic predictors such as metabolic syndrome (MS), left ventricular mass index (LVMI) and carotid intima-media thickness (CIMT). MethodsA cross-sectional study was conducted in patients with TA; MS was defined according to the US National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) criteria. The study included 49 TA patients (22 with MS, 27 without MS) and 31 healthy controls (HCs). Non-contrast computed tomography measured calcification in coronary arteries, aorta, and branches. ResultsForty-seven patients (95.9%) were female and mean age was 33.45 ± 8.53 years. Total calcification score (mean ± SD; 5223.9 ± 18041.1 AU vs. 35.87 ± 72.70 AU (p = 0.05)), CIMT, and LVMI were found to be significantly higher in TA patients than HCs (p < 0.05). While there was no significant difference between the total calcification score of MS (+) TA patients and MS (−) TA patients, in both patient groups, the total calcification score was found to be significantly higher than HCs. MS (+) and MS (−) groups were found to have significantly higher CIMT and LVMI values than the control group, in addition, MS (+) patients were found to have significantly higher LVMI and CIMT values than MS (−) group (p < 0.05). ConclusionVascular calcification, CIMT, and LVMI are elevated in all TA patients, with greater impact in the presence of MS.

The Association between Intracranial Calcifications and Symptoms in Patients with Primary Familial Brain Calcification

(1) Background: Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcifications of the basal ganglia and other intracranial areas. Many patients experience symptoms of motor dysfunction and cognitive disorders. The aim of this study was to investigate the association between the amount and location of intracranial calcifications with these symptoms. (2) Methods: Patients with suspected PFBC referred to our outpatient clinic underwent a clinical work-up. Intracranial calcifications were visualized on Computed Tomography (CT), and a Total Calcification Score (TCS) was constructed. Logistic and linear regression models were performed. (3) Results: Fifty patients with PFBC were included in this study (median age 64.0 years, 50% women). Of the forty-one symptomatic patients (82.0%), 78.8% showed motor dysfunction, and 70.7% showed cognitive disorders. In multivariate analysis, the TCS was associated with bradykinesia/hypokinesia (OR 1.07, 95%-CI 1.02–1.12, p &lt; 0.01), gait ataxia (OR 1.06, 95%-CI 1.00–1.12, p = 0.04), increased fall risk (OR 1.04, 95%-CI 1.00–1.08, p = 0.03), and attention/processing speed disorders (OR 1.06, 95%-CI 1.01–1.12, p = 0.02). Calcifications of the lentiform nucleus and subcortical white matter were associated with motor and cognitive disorders. (4) Conclusions: cognitive and motor symptoms are common among patients with PFBC, and there is an association between intracranial calcifications and these symptoms.

Association of the Calcification Score of the Abdominal Aorta, Common Iliac, and Renal Arteries with Outcomes in Living Kidney Donors.

Vascular calcification is an ever-more-common finding in protocoled pre-transplant imaging in living kidney donors. We intended to explore whether a connection could be found between the Agatston calcification score, prior to kidney donation, and post-donation renal function. This is a retrospective analysis of 156 living kidney donors who underwent living donor nephrectomy between January 2010 and December 2016. We quantified the total calcification score (TCaScore) by calculating the Agatston score for each vessel, abdominal aorta, common iliac, and renal arteries. Donors were placed into two different groups based on their TCaScore: <100 TCaScore group and ≥100 TCaScore group. The relationship between TCaScore, 1-year eGFR, proteinuria, and risk of 1 measurement of decreased renal function (eGFR < 60 mL/min/1.73 m2) over 5 years of follow-up was investigated. The ≥100 TCaScore group consisted of 29 (19%) donors, with a median (interquartile range) calcification score of 164 (117-358). This group was significantly older, 56.7 ± 6.9 vs. 45.5 ± 10.6 (p < 0.001), had a higher average BMI (p < 0.019), and had a lower preoperative eGFR (p < 0.014). The 1-year eGFR was similarly diminished, 69.9 ± 15.7 vs. 76.3 ± 15.5 (p < 0.048), while also having an increased risk of decreased renal function during the follow-up, 22% vs. 48% (p < 0.007). Our study, through univariate analyses, found a relationship between a TCaScore > 100, lower 1-year eGFR, and decreased renal function in 5 years. However, a higher-than-expected vascular calcification should not be an excluding factor in donors, although they may require closer monitoring during follow-up.

Relationship between aortic calcifications and DXA and Radiofrequency Echographic Multi-Spectrometry (REMS) acquisitions

Data on the relationship between peritoneal dialysis (PD), BMD and aortic calcifications (AOC) are lacking. to study the relationship between the degree of AOC and DXA and Radiofrequency Echographic Multi-Spectrometry (REMS) acquisitions. Consecutive patients referring to the PD our clinic were enrolled. Lumbar spine (LS) and proximal femur REMS scans were performed, and LS (anteroposterior and laterolateral) and proximal femur DXA scans were performed as well. The degree of AOC was assessed through the semiquantitative score described by Kauppila et al and applied to the laterolateral LS DXA scans. To test for correlations between different variables, we used the Pearson's correlation for continuous variables and Spearman's rho for discrete variables. Multiple regression analysis was performed to adjust for age and body mass index (BMI) the correlation between BMD and the CKD duration. Written informed consent was obtained from all participants (protocol 1483CESC). 41 total patients were enrolled (table 1). We found a statistically significant positive correlation of moderate strength between the total calcification score and the difference between the DXA AP T-score and the DXA LL T-score at the LS (p< 0.01, Spearman's rho = 0.402), figure 1. After adjustment for confounders, we found a significant negative between the LS and femoral neck BMD measured through REMS and CKD duration (table 2). The same correlation was not significant then BMD was assessed with DXA. Our study confirmed that the overestimation of DXA BMD assessed with the anteroposterior scan is indeed influenced by AOC. Furthermore, our data suggest that REMS might be an interesting tool for the investigation of bone changes in CKD. Figure 1: scatter plot reporting the relationship between the difference between the AP and LL T-scores and the aortic calcifications score.

Clinical characteristics of severe aortic stenosis patients combined with diabetes mellitus after transcatheter aortic valve replacement and short-term outcome.

Type 2 diabetes (T2DM) is a common comorbidity in patients with degenerative aortic stenosis (AS).As a key item of the American Society of Thoracic Surgeons (STS) score, it has a vital impact on the clinical prognosis of traditional thoracic surgery. T2DM has an adverse effect on the morbidity and mortality of cardiovascular diseases. At the same time, studies have shown that T2DM are associated with myocardial hypertrophy and remodeling, decreased left ventricular function, and worsening heart failure symptoms in the AS patients. Transcatheter aortic valve replacement (TAVR) as an interventional method to replace the aortic valve has better safety for middle and high risk patients in surgery, but the impact of T2DM on the clinical outcome of TAVR in AS patients is not clear.By analyzing the clinical and image characteristics of patients with AS and T2DM who received TAVR treatment, so as to explore the effect of T2DM on the perioperative complications and prognosis of TAVR. A total of 100 consecutive patients with severe AS, who underwent TAVR treatment and were followed up for more than 1 month, were selectedin the Second Xiangya Hospital of Central South University from January 2016 to December 2020.Among them, 5 patients who were treated with TAVR due to simple severe aortic regurgitation were not included, therefore a total of 95 patients with severe aortic stenosis were enrolled in this study.The age of the patients was (72.7±4.8) years old, and there were 58 males (61.1%), and the patients with moderate or above aortic regurgitation had 30 cases (31.6%). The patients were divided into a diabetic group and a non-diabetic group according to whether they were combined with T2DM.There was no statistical difference in age, gender, body mass index (BMI), STS score, and New York Heart Association (NYHA) cardiac function classification between the 2 groups (all P>0.05). The primary end point was defined as a composite event consisting of all-cause death and stroke one month after surgery, and the secondary end point was defined as TAVR-related complications immediately after surgery and one month after surgery.The preoperative clinical data, cardiac ultrasound data, CT data, postoperative medication and the incidence of each endpoint event were compared between the 2 groups.The predictive model of adverse events was constructed by single factor and multivariate logistic regression. Compared with the non-diabetic group, the diabetic group had high blood pressure and chronic renal insufficiency.There was no significant difference in preoperative ultrasound echocardiography between the 2 groups. Preoperative CT evaluation found that the anatomical structure of the aortic root in the diabetic group was smaller than that in the non-diabetic group, and there was no significant difference in the incidence of bicuspid aortic valve between the 2 groups (all P<0.05). In terms of postoperative medication, the use of statins in the diabetes group was significantly higher than that in the non-diabetic group. In the diabetes group, 6 patients (37.5%) received insulin therapy, and 9 patients (56.3%) received oral medication alone.Univariate logistic regression analysis showed that the all-cause death and stroke compound events was increased in the diabetes group in 30 days after TAVR (OR=6.86; 95% CI: 2.14 to 21.79; P<0.01). Heart disease (OR=2.80; 95% CI: 0.99 to 7.88; P<0.05) and chronic renal insufficiency (OR=3.75; 95% CI: 1.24 to 11.34; P<0.05) were also risk factors for all-cause death and stroke compound events.In a multivariate analysis, after adjusting for age, gender, BMI, comorbidities, N-terminal pro-B type natriuretic peptide (NT-proBNP), total calcification score, ejection fraction, and degree of aortic regurgitation, T2DM was still a risk factor for all-cause death and stroke compound events in 30 days after TAVR (OR=12.68; 95% CI: 1.76 to 91.41; P<0.05). T2DM is a risk factor for short-term poor prognosis in patients with symptomatic severe AS after TAVR treatment. T2DM should play an important role in the future construction of the TAVR surgical risk assessment system, but the conclusions still need to be further verified by long-term follow-up of large-scale clinical studies.

Evaluation of headaches in primary brain calcification in Japan

AbstractBackgroundPrimary brain calcification (PBC) is a rare neurodegenerative disorder characterized by bilateral calcification in the brain. No nationwide survey on headache has been performed in Japan.AimA questionnaire survey was performed to clarify the situation of headache in PBC patients.MethodsThe first questionnaire survey was conducted on 173 patients diagnosed as having PBC in Japan. Subsequently, the second survey was performed using two types of questionnaire: Headache Impact Test (HIT‐6) and Migraine Disability Assessment (MIDAS).ResultsIn the first survey, 27 of 82 patients had headaches. Only one patient was able to be classified in accordance with the criteria as having migraine without aura. In the second survey, 10 of 17 patients showed a significant score of 50 and higher in HIT‐6, and five of 17 patients showed a significant score of 6 and higher in MIDAS. No significant correlation was found between total calcification score and HIT‐6 score or MIDAS score in the second survey. All patients carrying the PDGFB variant and two of three patients carrying the SLC20A2 variant showed some effects of headache on their daily life as judged from their MIDAS scores or HIT‐6 score.ConclusionsThe headaches in PBC patients could not be classified as the primary headache. Those headaches in PBC patients may be of the secondary headache caused by the dysfunction of the blood‐brain barrier. This first report on headaches of Japanese patients with PBC will contribute to the understanding of PBC patients' difficulties in their daily lives.

Biallelic loss-of-function mutations in JAM2 cause primary familial brain calcification.

Primary familial brain calcification is a monogenic disease characterized by bilateral calcifications in the basal ganglia and other brain regions, and commonly presents motor, psychiatric, and cognitive symptoms. Currently, four autosomal dominant (SLC20A2, PDGFRB, PDGFB, XPR1) and one autosomal recessive (MYORG) causative genes have been identified. Compared with patients with autosomal dominant primary familial brain calcification, patients with the recessive form of the disease present with more severe clinical and imaging phenotypes, and deserve more clinical and research attention. Biallelic mutations in MYORG cannot explain all autosomal recessive primary familial brain calcification cases, indicating the existence of novel autosomal recessive genes. Using homozygosity mapping and whole genome sequencing, we detected a homozygous frameshift mutation (c.140delT, p.L48*) in the JAM2 gene in a consanguineous family with two affected siblings diagnosed with primary familial brain calcification. Further genetic screening in a cohort of 398 probands detected a homozygous start codon mutation (c.1A>G, p.M1?) and compound heterozygous mutations [c.504G>C, p.W168C and c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL], respectively, in two unrelated families. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages. All patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas (lenticular nuclei, caudate nuclei, thalamus, cerebellar hemispheres, ± brainstem; total calcification scores: 43-77). JAM2 encodes junctional adhesion molecule 2, which is highly expressed in neurovascular unit-related cell types (endothelial cells and astrocytes) and is predominantly localized on the plasma membrane. It may be important in cell-cell adhesion and maintaining homeostasis in the CNS. In Chinese hamster ovary cells, truncated His-tagged JAM2 proteins were detected by western blot following transfection of p.Y23_V131delinsL mutant plasmid, while no protein was detected following transfection of p.L48* or p.1M? mutant plasmids. In immunofluorescence experiments, the p.W168C mutant JAM2 protein failed to translocate to the plasma membrane. We speculated that mutant JAM2 protein resulted in impaired cell-cell adhesion functions and reduced integrity of the neurovascular unit. This is similar to the mechanisms of other causative genes for primary familial brain calcification or brain calcification syndromes (e.g. PDGFRB, PDGFB, MYORG, JAM3, and OCLN), all of which are highly expressed and functionally important in the neurovascular unit. Our study identifies a novel causative gene for primary familial brain calcification, whose vital function and high expression in the neurovascular unit further supports impairment of the neurovascular unit as the root of primary familial brain calcification pathogenesis.

Obesity and calcification of the ligaments of the spine: a comprehensive CT analysis of the entire spine in a random trauma population

Background ContextObesity, which is currently surging to epidemic levels within the United States, has been linked to hyperostotic conditions like diffuse idiopathic skeletal hyperostosis (DISH) and ossification of the posterior longitudinal ligament (OPLL). Excess adipose tissue and insulin-resistance may cause a systemic increase in serum levels of proinflammatory cytokines and these signals can affect bone metabolism. Spinal ligaments and discs may have receptors for these signaling molecules. Anecdotal observations at this institution suggested that there is a clinically important subset of younger patients with obesity and multilevel stenosis in the presence of unusual calcification of the spinal ligaments that is distinct from DISH. PurposeTo determine if there is an association between truncal obesity and calcifications of the spine in nonelderly adults. Study Design/SettingThis is a retrospective analysis of 214 sequential trauma patients between the ages of 29 and 50. Patients’ age, sex, truncal obesity, history of hypertension, and diabetes were assessed for association with ligamentous calcification of the spine. Patient SampleSequential trauma patients were chosen from our institution's trauma database between 2006 and 2007. MethodsFull spine computed tomography (CT) imaging was examined for bone formation in the region of the anterior longitudinal ligament (ALL) and annulus, posterior longitudinal ligament (PLL) and annulus, and the ligamentum flavum (LF). Visceral and subcutaneous abdominal fat were also evaluated. The authors report no study funding sources or conflicts of interest. Outcome MeasuresCalcification of the ALL, PLL, and LF were assigned a score at each level and then combined for a total calcification score (TCS) for the entire spine. Obesity was estimated using a truncal body mass index (TBMI) by using a previously validated CT derived truncal total adiposity volume (TAV). ResultsALL calcification was associated with age, male gender, hypertension, and increased adiposity. PLL calcification was significantly associated with age and hypertension. LF calcification was only associated with increased obesity. ConclusionsIn our analysis of nonelderly patients, LF calcification was independently associated with truncal obesity. This implies obesity plays a greater role in calcification than could be accounted for by simply age-related degeneration or gender.

Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Could BMP-2 and BMP-7 be biomarkers of coronary artery disease? A pilot clinical study

BackgroundCoronary artery calcification (CAC) is utilized as an important tool for the global risk assessment of cardiovascular events in individuals with intermediate risk. BMP-2 is a powerful inducer of bone formation and exposure to BMP-2 in the arteries leads to the loss of vascular smooth muscle cells (VSMC) markers and increase gene expression in favor of osteoblasts. BMP-7 is key factor in the bone and kidney and is suggested as inhibitor of vascular calcification. The main purpose of this clinical study was to find out the correlation between BMP-2 and BMP-7serum concentration and CAC in human for the first time. MethodsIn this study 84 patients with coronary artery disease who fulfilled inclusion and exclusion criteria, entered the study. For all patients a questionnaire consisting demographic data and traditional cardiovascular risk factors were completed. CT-Angiography was carried out to determine coronary artery calcium score and ELISA method was used for measuring BMP-2 and BMP-7serum concentrations. ResultsThere was a significant positive correlation between BMP-2 serum concentration and total CAC score and also CAC of right coronary artery (RCA), left anterior descending (LAD), circumflex (CX), left main coronary artery (LMCA) (P < 0.05). Similar result was found for BMP-7 serum concentration except in LMCA (P > 0.05). ConclusionBased on our results, we can suggest BMP-2 and BMP-7 serum concentration as a probable biomarker for coronary artery disease. However, more studies with higher sample size are necessary for its confirmation.

Clinical and quantitative analysis of patients with crowned dens syndrome

BackgroundCrowned dens syndrome (CDS) is a radioclinical entity defined by calcium deposition on the transverse ligament of atlas (TLA). In this study, the novel semi-quantitative diagnostic criteria for CDS to evaluate the degree of calcification on TLA by cervical CT are proposed. MethodFrom January 2010 to September 2014, 35 patients who were diagnosed with CDS by cervical CT were adopted as subjects in this study. Based on novel criteria, calcium deposition on TLA was classified into “Stage” and “Grade”, to make a score, which was evaluated semi-quantitatively. The correlation between calcification score and CRP level or pain score, and the effects of treatments, such as NSAIDs and corticosteroids, were statistically analyzed. ResultsThe total calcification score from added “Stage” and “Grade” scores demonstrated a significantly strong and linear correlation with CRP level (R2=0.823, **p<0.01). In the multiple comparison test for the treatment effects, significant improvement of the CRP level and pain score were demonstrated after corticosteroid therapy (**p<0.01) compared with NSAIDs. In the conditional logistic regression analysis, the rapid end of corticosteroid therapy was an independent risk factor for relapse of cervico-occipital pain [OR=50.761, *p=0.0419]. ConclusionThe degree of calcification on TLA evaluated by the novel semi-quantitative criteria significantly correlated with CRP level. In the treatment of CDS, it is recommended that a low dosage (15–30mg) of corticosteroids be used as first-line drugs rather than conventional NSAID therapy. Additionally, it is also recommended to gradually decrease the dosage of corticosteroids.

The role of CT in predicting the need for surgery in patients diagnosed with mesenteric phlebosclerosis.

To determine if imaging findings on computed tomography (CT) can predict the need of surgery in patients with idiopathic mesenteric phlebosclerosis (IMP).This retrospective study included 28 patients with IMP. Abdominal CT images were reviewed to determine the extent and severity of mesenteric calcifications and the presence of findings related to colitides. We compared the number of colonic segments with mesenteric venous calcification, a total calcification score, and the rate of colonic wall thickening, pericolic fat stranding, and bowel loop dilatation between patients undergoing surgery (surgery group) and patients without surgery (nonsurgery group). Comparisons were made using the Mann–Whitney U test and Fisher exact test. Receiver operating characteristic analysis was also performed. Inter-reader agreement for the calcification scores was analyzed using kappa statistics.The number of colonic segments with mesenteric venous calcification and the total calcification scores were both significantly higher in the surgery group than the nonsurgery group (4.33 vs 2.96, P = 0.003; and 15.00 vs 8.96, P <0.001). The areas under the receiver operating characteristics to identify patients who need surgery were 0.96 and 0.92, respectively. The prevalence of bowel loop dilatation in the surgery group was also significantly higher than that in the nonsurgery group (16% vs 100%, P = 0.011).Evaluation of the severity and extent of IMP based on the total mesenteric venous calcification score, number of involved colonic segments, and the presence bowel loop dilatation on CT may be useful to indicate the outcomes of conservative treatment and need for surgery.

Brain calcification process and phenotypes according to age and sex: Lessons from SLC20A2, PDGFB, and PDGFRB mutation carriers

Primary Familial Brain Calcification (PFBC) is a dominantly inherited cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Three causative genes have been identified: SLC20A2, PDGFRB and, recently, PDGFB, whose associated phenotype has not yet been extensively studied. We included in the largest published case series of genetically confirmed PFBC, 19 PDGFB (including three new mutations), 24 SLC20A2 (including 4 new mutations), and 14 PDGFRB mutation carriers, from two countries (France and Brazil). We studied clinical features and applied our visual rating scale on all 49 available CT scans. Among the symptomatic mutation carriers (33/57, 58%), the three most frequently observed categories of clinical features were psychiatric signs (72.7%, 76.5%, and 80% for PDGFB, SLC20A2, and PDGFRB, respectively), movement disorders (45.5%, 76.5%, and 40%), and cognitive impairment (54.6%, 64.7%, and 40%). The median age of clinical onset was 31 years, 25% had an early onset (before 18) and 25% a later onset (after 53). Patients with an early clinical onset exhibited mostly isolated psychiatric or cognitive signs, while patients with a later onset exhibited mostly movement disorders, especially in association with other clinical features. CT scans rating allowed identifying four patterns of calcification. The total calcification score was best predicted by the combined effects of gene (SLC20A2 > PDGFB > PDGFRB mutations), sex (male), and (increasing) age, defining three risk classes, which correlated with the four patterns of calcification. These calcification patterns could reflect the natural history of the calcifying process, with distinct risk classes characterized by different age at onset or rate of progression.

The association between mortality and abdominal aortic calcification and relation between its progression and serum calcium concentration in chronic hemodialysis patients

BackgroundThe composite summary score (range, 0–24) of abdominal aortic calcification (AAC) devised by Kauppila et al is a simple method of assessing AAC severity. However, few studies have been conducted to determine an optimal AAC cutoff score for the prediction of mortality or to investigate the relation between mineral metabolism and AAC progression using the scoring system. MethodsThe medical records of 112 patients on hemodialysis who had undergone simple lateral lumbar radiography every 6 months from August 2009 were reviewed. Patients were followed until November 2012, and the relationship between the degree of AAC at baseline and mortality was evaluated. In addition, the relationship between the progression of AAC and serum concentrations of calcium and phosphate was evaluated in the 75 patients who were successfully followed until November 2012. ResultsThe mean AAC score at baseline was 5.5±4.8, and the cutoff calcification score for the prediction of mortality was 7.75 (sensitivity=61%, specificity=81%). Patients were allocated to Group A (baseline total calcification score ≤8.0, n=85) or Group B (baseline total calcification score>8.0, n=27), and multivariate analysis showed that Group B was an independent risk factor of all-cause mortality and cardiovascular events. Of the 75 patients successfully followed, 51 showed AAC progression (Group 1) and 24 showed no change or improvement (Group 2). Group 1 was found to have significantly higher mean serum corrected calcium levels during the 2nd year and 3rd year of follow-up than Group 2. Furthermore, repeated-measures analysis of variance showed higher monthly corrected calcium concentrations (P=0.099) and mean corrected calcium levels during the 1st year, 2nd year, and 3rd year of follow-up (P=0.062) in Group 1, but without statistical significance. The cutoff values of mean corrected calcium of the 2nd year and 3rd year for the prediction of AAC progression during follow-up years were 8.96mg/dL and 9.45mg/dL, respectively. Serum phosphate levels and corrected calcium×phosphate values were similar in Groups 1 and 2. ConclusionPatients with an AAC score of>8 at baseline seem to be at higher risk of mortality during follow-up. Of the serum variables examined, such as corrected calcium, phosphate, and corrected calcium×phosphate, corrected calcium was found to be marginally associated with AAC progression. However, a larger-scale prospective study is required to confirm our findings.

Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification

Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: <40, 40-60, and >60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis revealed that the total calcification scores correlated positively with age in controls and patients, but increased more rapidly with age in patients. The expected total calcification score was greater in SLC20A2 than PDGFRB mutation carriers, beyond the effect of the age alone. No patient with a PDGFRB mutation exhibited a cortical or a vermis calcification. The total calcification score was more severe in symptomatic versus asymptomatic individuals. We provide the first phenotypical description of a case series of patients with idiopathic basal ganglia calcification since the identification of the first causative genes. Clinical and radiological diversity is confirmed, whatever the genetic status. Quantification of calcification is correlated with the symptomatic status, but the location and the severity of the calcifications don't reflect the whole clinical diversity. Other biomarkers may be helpful in better predicting clinical expression.

Structural and functional changes of the coronary arteries in elderly senile patients with essential hypertension

The aim of this study was to evaluate the effect of aging on the changes to the structure and function of coronary arteries in senile elderly patients with essential hypertension. Patients (aged 60-80 years) were divided into three groups. The 195 hypertensive patients were divided into four sub-groups according to the duration of hypertension. The changes to the coronary arteries (left and right) of all those patients were tested using the following index by 64 coronary computed tomography (CT) scans. The 24 h systolic blood pressure (SBP) and other blood biochemical parameters were assayed for all patients. We found that the value of the body mass index (BMI), total cholesterol (TC) and low density lipoproteins (LDL) were lower, but age and high density lipoproteins (HDL) were higher in the group of very elderly patients with hypertension (Group I; P<0.05) compared with those of a group of elderly patients with hypertension (Group III). The left anterior descending branch calcification score (CSLAD), total calcification score (CST), pulse pressure (PP), the left main branch calcification score (CSLM), the left circumflex branch calcification score (CSLCX) were significantly increased in Group I compared with Group III (P<0.01 and P<0.05, respectively). In addition, the 24 h SBP value for Group I was higher than in the 'very elderly without hypertension' group (Group II). Hence, in elderly patients, a decrease in the levels of BMI, HDL, TC and LDL accompanies aging. Furthermore, the decline of arterial compliance and increase in arterial stiffness develops with age. Aging is more likely to lead to atherosclerosis in the coronary arteries, particularly in the left main coronary artery and its main branches. Aging is an uncontrollable risk factor, which plays a crucial role in coronary artery atherosclerosis.

CT Emphysema Predicts Thoracic Aortic Calcification in Smokers with and Without COPD

ABSTRACTCOPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects’ demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD.

The correlation between carotid siphon calcification and lacunar infarction

The aim of this study was to evaluate the correlation between carotid siphon (CS) calcification and lacunar infarction caused by small-vessel disease. This retrospective study included 445 patients (M/F = 256:189) older than 40years (mean age 60.0 ± 12.3years, range 41-98years) without large intracranial lesions who had undergone both brain CT and MRI within an interval of 6months. The patients were classified into three groups according to the number of lacunar infarctions: group I-zero infarctions (n = 328), group II-one to three infarctions (n = 94), and group III-four or more infarctions (n = 23). The severity of CS calcification was evaluated on CT and scored on a five-point scale (0-none, 1-stippled, 2-thin continuous or thick discontinuous, 3-thick continuous, 4-double tracts), and the calcification scores on both sides were summed. An ANOVA test was used to compare calcification scores among the three groups, and a logistic regression test was used to evaluate the influence of CS calcification and known cerebrovascular risk factors on the occurrence of lacunar infarction. On the ANOVA test, total calcification scores were significantly different among the three groups (group I = 1.28 ± 1.99, group II = 3.31 ± 2.39, group III = 4.36 ± 2.08; P < 0.05). Higher rates of lacunar infarction were associated with higher CS calcification scores. On the logistic regression test, CS calcification, age, and hypertension were significant risk factors for lacunar infarction (P < 0.05). CS calcification was correlated with the occurrence of lacunar infarction. The degree of CS calcification may be used to predict the possibility of a future lacunar infarction.