Seizure Incidence Rates in Children and Adults With Familial Cerebral Cavernous Malformations

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012569
Author(s):  
Christine K. Fox ◽  
Jeffrey Nelson ◽  
Charles E. McCulloch ◽  
Shantel Weinsheimer ◽  
Ludmila Pawlikowska ◽  
...  

Background and Objectives:Seizure incidence rates related to Familial Cerebral Cavernous Malformation (FCCM) are not well described, especially for children. To measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity, we studied a cohort of children and adults with FCCM enrolled in the Brain Vascular Malformation Consortium (BVMC).Methods:Seizure data were collected from participants with FCCM in the BVMC at enrollment and during follow-up. We estimated seizure probability by age, and tested whether cerebral cavernous malformation (CCM) counts or genotype were associated with earlier seizure onset.Results:The study cohort included 479 FCCM cases. Median age at enrollment was 42.5 years (Interquartile Range [IQR] 22.5-55.0) and 19% were children (<18 years old). Median large CCM count was 3 (IQR: 1-5). Among 393 with genotyping, mutations were: CCM1-Common Hispanic Mutations (88%), another CCM1 mutation (5%), CCM2 mutations (5%), and CCM3 mutations (2%). Prior to or during the study, 202 (42%) had a seizure. The cumulative incidence of a childhood seizure was 20.3% (95% CI 17.0 – 23.4) and by age 80 years was 60.4% (95% CI 54.2-65.7). More total CCMs (Hazard Ratio [HR] 1.24 per SD unit increase, 95% CI 1.1 – 1.4) or more large CCMs (HR=1.5 per SD unit increase, 95% CI 1.2-1.9) than expected for age and sex increased seizure risk. A CCM3 mutation also increased risk compared to other mutations (HR 3.11, 95% CI 1.15-8.45). Individuals with a seizure prior to enrollment had increased hospitalization rates during follow-up (Incidence Rate Ratio 10.9, 95% CI 2.41 – 49.32) compared to patients without a seizure history.Discussion:Individuals with FCCM have a high seizure incidence, and those with more CCMs or CCM3 genotype are at greater risk. Seizures increase health care utilization in FCCM.

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 2997-3006
Author(s):  
Li Ma ◽  
Shuo Zhang ◽  
Zongze Li ◽  
Chun-Xue Wu ◽  
Zhaozhao Wang ◽  
...  

Background and Purpose: Symptomatic hemorrhage contributes to an increased risk of repeated bleeding and morbidity in cerebral cavernous malformation (CCM). A better understanding of morbidity after CCM hemorrhage would be helpful to identify patients of higher risk for unfavorable outcome and tailor individualized management. Methods: We identified 282 consecutive patients who referred to our institute from 2014 to 2018 for CCM with symptomatic hemorrhage and had an untreated follow-up period over 6 months after the first hemorrhage. The morbidity after hemorrhage was described in CCM of different features. Nomogram to predict morbidity was formulated based on the multivariable model of risk factors. The predictive accuracy and discriminative ability of nomogram were determined with concordance index (C-index) and calibration curve, and further validated in an independent CCM cohort of a prospective multicenter study from 2019 to 2020. Results: The overall morbidity of CCM was 26.2% after a mean follow-up of 1.9 years (range 0.5–3.5 years) since the first hemorrhage. The morbidity during untreated follow-up was associated with hemorrhage ictus (adjusted odds ratio per ictus increase, 4.17 [95% CI, 1.86–9.33]), modified Rankin Scale score at initial hemorrhage (adjusted odds ratio per point increase, 2.57 [95% CI, 1.82–3.63]), brainstem location (adjusted odds ratio, 2.93 [95% CI, 1.28–6.68]), and associated developmental venous anomaly (adjusted odds ratio, 2.21 [95% CI, 1.01–4.83]). Subgroup analysis revealed similar findings in brainstem and non-brainstem CCM. Nomogram was contracted based on these features. The calibration curve showed good agreement between nomogram prediction and actual observation. The C-index of nomogram predicting morbidity was 0.83 (95% CI, 0.77–0.88). In validation cohort, the nomogram maintained the discriminative ability (C-index, 0.87 [95% CI, 0.78–0.96]). Conclusions: Multiple symptomatic hemorrhages, initial neurological function after hemorrhage, brainstem location, and associated developmental venous anomaly were associated with morbidity of CCM hemorrhage. The nomogram represented a practical approach to provide individualized risk assessment for CCM patients. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04076449.


2021 ◽  
Vol 65 (3) ◽  
pp. 245-250
Author(s):  
Anna V. Rumyantseva ◽  
Tamara V. Azizova ◽  
Mariya V. Bannikova ◽  
Ol’ga V. Zubkova

Introduction. Breast cancer (BC) is one of the most common malignancies within female incidence and mortality patterns in the RF. Study objective. To analyze BC incidence in females exposed to occupational ionizing radiation over prolonged periods. Materials and methods. The study cohort included 5689 females who had been occupationally exposed to ionizing radiation throughout 1948-1982 and followed up until 31.12.2018. Results. BC was on the top of the list among females of the study cohort (11.9%). BC prevalence rate in the female cohort understudy was 28.3% as of 31.12.2018. The standardized BrCa incidence rate was 0.88 ± 0.07 per 1000 person-years of the follow-up. The absolute BrCa case increase in the females was 1.29, with the rise of 232.48% by the end of the follow-up due to the rise in age categories of females and the elevating risk of the disease occurrence. Discussion. The study cohort of females demonstrated standardized BrCa incidence rates consistent with the corresponding estimates for the general female population of the RF. Meanwhile, the observed rates were lower than those estimated for the female population of the Chelyabinsk region. The increasing trend of the standardized BC incidence rate by the end of the follow-up period (31.12.2018) was consistent with WHO statistics. The extended follow-up for an updated assessment of ionizing radiation effect on BC incidence is required to develop new cancer prevention strategies. Conclusion. The study demonstrated that BC incidence rates in the study cohort varied by age and calendar period of the follow-up. The increasing trend of the standardized rates of BC incidence was observed by the end of the follow-up.


2019 ◽  
Vol 65 (3) ◽  
pp. 441-446
Author(s):  
Valentina Rybkina ◽  
Tamara Azizova ◽  
Yevgeniya Grigoreva

Purpose of the study. The study is aimed to investigate skin melanoma incidence in workers occupationally exposed to radiation over a prolonged period. Materials and methods. Skin melanoma incidence was studied in a cohort of workers first employed at nuclear facility Mayak Production Association (PA) between 1948 and 1982 who had been followed up till 31.12.2013 (22,377 individuals). Mean cumulative doses from external gamma-rays over the whole follow-up period were 0.54±0.001 Sv in males and 0.44±0.002 Sv in females. Incident rates for skin melanoma were analyzed by sex, attained age, calendar period of diagnostics and radiation dose using worldwide standard and the direct standardization technique. Results. 60 skin melanoma cases (37 in males and 23 in females) were registered in the study cohort over the whole follow-up period. The standardized skin melanoma incident rate was 8.51±1.46 in males and 8.78±2.27 in females per 100000 workers revealing statistically higher rates compared to corresponding rates for general populations of the Russian Federation, Urals Federal District and Chelyabinsk region. Skin melanoma incidence was significantly increased in the period of 1994 - 2013 as compared to the period of 1974 - 1993. Skin melanoma incidence excess in females was greater than that for males. Skin melanoma incidence increment in females was mostly driven by modifications of disease occurrence risk while in males it was driven by a combined effect of age pattern modifications in the study cohort and increase of disease risk. Conclusions. Skin melanoma incidence rates in the cohort of workers occupationally exposed to ionizing radiation over a prolonged period were associated with sex and attained age workers and the calendar period of diagnostics. No significant association of skin melanoma incidence with dose from external gamma-rays was observed. A significantly increasing trend was observed for skin melanoma incidence by the end of the follow-up in both males and females.


Diabetologia ◽  
2021 ◽  
Author(s):  
Peter Ueda ◽  
Viktor Wintzell ◽  
Mads Melbye ◽  
Björn Eliasson ◽  
Ann-Marie Svensson ◽  
...  

Abstract Aims/hypothesis Concerns have been raised regarding a potential association of use of the incretin-based drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists with risk of cholangiocarcinoma. We examined this association in nationwide data from three countries. Methods We used data from nationwide registers in Sweden, Denmark and Norway, 2007–2018, to conduct two cohort studies, one for DPP4 inhibitors and one for GLP-1-receptor agonists, to investigate the risk of incident cholangiocarcinoma compared with an active-comparator drug class (sulfonylureas). The cohorts included patients initiating treatment episodes with DPP4 inhibitors vs sulfonylureas, and GLP-1-receptor agonists vs sulfonylureas. We used Cox regression models, adjusted for potential confounders, to estimate hazard ratios from day 366 after treatment initiation to account for cancer latency. Results The main analyses of DPP4 inhibitors included 1,414,144 person-years of follow-up from 222,577 patients receiving DPP4 inhibitors (median [IQR] follow-up time, 4.5 [2.6–7.0] years) and 123,908 patients receiving sulfonylureas (median [IQR] follow-up time, 5.1 [2.9–7.8] years) during which 350 cholangiocarcinoma events occurred. Use of DPP4 inhibitors, compared with sulfonylureas, was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.15 [95% CI 0.90, 1.46]; absolute rate difference 3 [95% CI -3, 10] events per 100,000 person-years). The main analyses of GLP-1-receptor agonists included 1,036,587 person-years of follow-up from 96,813 patients receiving GLP-1-receptor agonists (median [IQR] follow-up time, 4.4 [2.4–6.9] years) and 142,578 patients receiving sulfonylureas (median [IQR] follow-up time, 5.5 [3.2–8.1] years) during which 249 cholangiocarcinoma events occurred. Use of GLP-1-receptor agonists was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.25 [95% CI 0.89, 1.76]; absolute rate difference 3 [95% CI -5, 13] events per 100,000 patient-years). Conclusions/interpretation In this analysis using nationwide data from three countries, use of DPP4 inhibitors and GLP-1-receptor agonists, compared with sulfonylureas, was not associated with a significantly increased risk of cholangiocarcinoma. Graphical abstract


2015 ◽  
Vol 113 (01) ◽  
pp. 185-192 ◽  
Author(s):  
Chun-Cheng Wang ◽  
Cheng-Li Lin ◽  
Guei-Jane Wang ◽  
Chiz-Tzung Chang ◽  
Fung-Chang Sung ◽  
...  

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.


2012 ◽  
Vol 107 (03) ◽  
pp. 485-493 ◽  
Author(s):  
Sigrid K. Brækkan ◽  
Ida J. Hansen-Krone ◽  
John-Bjarne Hansen ◽  
Kristin F. Enga

SummaryEmotional states of depression and loneliness are reported to be associated with higher risk and optimism with lower risk of arterial cardiovascular disease (CVD) and death. The relation between emotional states and risk of venous thromboembolism (VTE) has not been explored previously. We aimed to investigate the associations between self-reported emotional states and risk of incident VTE in a population-based, prospective study. The frequency of feeling depressed, lonely and happy/optimistic were registered by self-administered questionnaires, along with major co-morbidities and lifestyle habits, in 25,964 subjects aged 25–96 years, enrolled in the Tromsø Study in 1994–1995. Incident VTE-events were registered from the date of inclusion until September 1, 2007. There were 440 incident VTE-events during a median of 12.4 years of follow-up. Subjects who often felt depressed had 1.6-fold (95% CI:1.02–2.50) higher risk of VTE compared to those not depressed in analyses adjusted for other risk factors (age, sex , body mass index, oes-trogens), lifestyle (smoking, alcohol consumption, educational level) and co-morbidities (diabetes, CVD, and cancer). Often feeling lonely was not associated with VTE. However, the incidence rate of VTE in subjects who concurrently felt often lonely and depressed was higher than for depression alone (age-and sex-adjusted incidence rate: 3.27 vs. 2.21). Oppositely, subjects who often felt happy/optimistic had 40% reduced risk of VTE (HR 0.60, 95% CI: 0.41–0.87). Our findings suggest that self-reported emotional states are associated with risk of VTE. Depressive feelings were associated with increased risk, while happiness/ optimism was associated with reduced risk of VTE.


2001 ◽  
Vol 85 (03) ◽  
pp. 430-434 ◽  
Author(s):  
James Blanchard ◽  
Donald Houston ◽  
Andre Wajda ◽  
Charles Bernstein

Summary Background: There is an impression mostly from specialty clinics that patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolic disorders. Our aim was to determine the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) from a population-based database of IBD patients and, to compare the incidence rates to that of an age, gender and geographically matched population control group. Methods: IBD patients identified from the administrative claims data of the universal provincial insurance plan of Manitoba were matched 1:10 to randomly selected members of the general population without IBD by year, age, gender, and postal area of residence using Manitoba Health’s population registry. The incidence of hospitalization for DVT and PE was calculated from hospital discharge abstracts using ICD-9-CM codes 451.1, 453.x for DVT and 415.1x for PE. Rates were calculated based on person-years of follow-up for 1984-1997. Comparisons to the population cohort yielded age-adjusted incidence rate ratios (IRR). Rates were calculated based on person-years of follow-up (Crohn’s disease = 21,340, ulcerative colitis = 19,665) for 1984-1997. Results: In Crohn’s disease the incidence rate of DVT was 31.4/10,000 person-years and of PE was 10.3/10,000 person-years. In ulcerative colitis the incidence rates were 30.0/10,000 person-years for DVT and 19.8/10,000 person-years for PE. The IRR was 4.7 (95% CI, 3.5-6.3) for DVT and 2.9 (1.8-4.7) for PE in Crohn’s disease and 2.8 (2.1-3.7) for DVT and 3.6 (2.5-5.2) for PE, in ulcerative colitis. There were no gender differences for IRR. The highest rates of DVT and PE were seen among patients over 60 years old; however the highest IRR for these events were among patients less than 40 years. Conclusion: IBD patients have a threefold increased risk of developing DVT or PE.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Cesare Russo ◽  
Zhezhen Jin ◽  
Ralph L Sacco ◽  
Shunichi Homma ◽  
Tatjana Rundek ◽  
...  

BACKGROUND: Aortic arch plaques (AAP) are a risk factor for cardiovascular embolic events. However, the risk of vascular events associated with AAP in the general population is unclear. AIM: To assess whether AAP detected by transesophageal echocardiography (TEE) are associated with an increased risk of vascular events in a stroke-free cohort. METHODS: The study cohort consisted of stroke-free subjects over age 50 from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. AAP were assessed by multiplane TEE, and considered large if ≥ 4 mm in thickness. Vascular events including myocardial infarction, ischemic stroke and vascular death were recorded during the follow-up. The association between AAP and outcomes was assessed by univariate and multivariate Cox proportional hazards models. RESULTS: A group of 209 subjects was studied (mean age 67±9 years; 45% women; 14% whites, 30% blacks, 56% Hispanics). AAP of any size were present in 130 subjects (62%); large AAP in 50 (24%). Subjects with AAP were older (69±8 vs. 63±7 years), had higher systolic BP (146±21 vs.139±20 mmHg), were more often white (19% vs. 8%), smokers (20% vs. 9%) and more frequently had a history of coronary artery disease (26% vs. 14%) than those without AAP (all p<0.05). Lipid parameters, prevalence of atrial fibrillation and diabetes mellitus were not significantly different between the two groups. During the follow up (94±29 months) 30 events occurred (13 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for other risk factors, AAP of any size were not associated with an increased risk of combined vascular events (HR 1.07, 95% CI 0.44 to 2.56). The same result was observed for large AAP (HR 0.94, CI 0.34 to 2.64). Age (HR 1.05, CI 1.01 to 1.10), body mass index (HR 1.08, CI 1.01 to 1.15) and atrial fibrillation (HR 3.52, CI 1.07 to 11.61) showed independent association with vascular events. In a sub-analysis with ischemic stroke as outcome, neither AAP of any size nor large AAP were associated with an increased risk. CONCLUSIONS: In this cohort without prior stroke, the incidental detection of AAP was not associated with an increased risk of future vascular events. Associated co-factors may affect the AAP-related risk of vascular events reported in previous studies.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Silvia Koton ◽  
Andrea L Schneider ◽  
B. Gwen Windham ◽  
Thomas H Mosley ◽  
Rebecca F Gottesman ◽  
...  

Background and Purpose: Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts measures progression for the incidence of clinical stroke are scarce. We aimed to study associations between the progression in measures of microvascular brain disease over time and risk of stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: We analyzed data on 907 ARIC participants who underwent a brain MRI in 1993-95, a second brain MRI in 2004-6, and were subsequently followed for incident stroke through December 31 st , 2017 (median [IQR] follow-up of 12.6 [8.9-13.4] years from the second brain MRI in 2004-6). At each MRI, WMH was categorized according to the Cardiovascular Health Study 0-9 rating scale and scans were centrally reviewed for lacunar infarcts. A combined measure of microvascular brain disease was defined, and progression from the first to the second brain MRI, manifesting as new WMHs and lacunes at the second brain MRI, was categorized as: no progression; increase of ≥1 unit in WMH grade or incident lacune; increase of ≥1 unit in WMH grade and incident lacune. All fatal and non-fatal strokes occurring in the participants during the study period, and adjudicated as definite/probable ischemic or hemorrhagic incident stroke, were included in this analysis. Associations between progression of microvascular brain disease and incidence of stroke were studied with Cox proportional hazard models, adjusting for age, gender, race, education level, BMI, smoking, hypertension, diabetes and coronary heart disease. Results: At the second brain MRI (mean age 72y), no progression in the combined measure of microvascular disease was found in 38% of participants, while 57% showed ≥1 unit increase in WMH grade or new lacune, and 5% showed increased WMH grade and new lacune. Sixty-four incident strokes occurred during follow-up. Compared to no change in the combined measure, progression of microvascular brain disease expressed as ≥1 unit increase in WMH grade and incident lacune was significantly associated with higher risk of stroke (adjusted HR 3.01, 95% CI 1.30-6.95). Conclusion: Progression of combined measures of microvascular brain disease over a decade is associated with a significant increased risk of stroke.


2020 ◽  
Vol 31 (9) ◽  
pp. 2133-2144
Author(s):  
Young Su Joo ◽  
Changhyun Lee ◽  
Hyung Woo Kim ◽  
Jonghyun Jhee ◽  
Hae-Ryong Yun ◽  
...  

BackgroundAlthough hypertension is a well known risk factor for CKD, few studies have evaluated the association between temporal trends of systolic BP and kidney function decline in persons without hypertension.MethodsWe studied whether changes in systolic BP over time could influence incident CKD development in 4643 individuals without CKD and hypertension participating in the Korean Genome and Epidemiology Study, a prospective community-based cohort study. Using group-based trajectory modeling, we categorized three distinct systolic BP trajectories: decreasing, stable, and increasing. The primary outcome was incident CKD development, defined as two consecutive eGFR measurements <60 ml/min per 1.73 m2.ResultsAmong participants with an increasing systolic BP trajectory, systolic BP increased from 105 to 124 mm Hg. During 31,936 person-years of follow-up (median 7.7 years), 339 participants developed incident CKD. CKD incidence rates were 8.9, 9.6, and 17.8 cases per 1000 person-years in participants with decreasing, stable, and increasing systolic BP trajectories, respectively. In multivariable cause-specific Cox analysis, after adjustment of baseline eGFR, systolic BP, and other confounders, increasing systolic BP trajectory associated with a 1.57-fold higher risk of incident CKD (95% confidence interval, 1.20 to 2.06) compared with a stable trajectory. There was a significant effect modification of baseline systolic BP on the association between systolic BP trajectories and CKD risk (P value for interaction =0.02), and this association was particularly evident in participants with baseline systolic BP <120 mm Hg. In addition, increasing systolic BP trajectory versus a stable trajectory was associated with higher risk of new development of albuminuria.ConclusionsIncreasing systolic BP over time without reaching the hypertension threshold is associated with a significantly increased risk of incident CKD in healthy adults.


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