Early detection of skin and cardiac amyloid deposits among asymptomatic carriers of hereditary pathogenic transthyretin mutation with normal electroneuromyography

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Slama ◽  
L Eliahou ◽  
E Piekarski ◽  
F Rouzet ◽  
D Beauvais ◽  
...  
Keyword(s):  
Skin Biopsy ◽  
Index Case ◽  
Age Of Onset ◽  
Interventricular Septum ◽  
Disease Onset ◽  
Age Difference ◽  
Asymptomatic Carriers ◽  
Cardiac Amyloid ◽  
Amyloid Deposits

Abstract Introduction During the last decade, disease modifying therapies have been proposed for hereditary amyloidogenic transthyretin (ATTRv) amyloidosis. It is essential to screen for disease onset among asymptomatic mutation carriers in order to trigger effective therapy as early as possible. We describe clinical and paraclinical data from ATTRv asymptomatic carriers, as a baseline assessment to detect disease onset and progression. Methods We retrospectively collected data of asymptomatic ATTRv carriers with normal electroneuromyography (ENMG), between March 1st 2015 and January 31st 2019, including: demographics, symptoms, physical exam, ENMG (initial and follow-up obtained in 73 patients, 56.2%), neurovegetative tests, skin biopsy (amyloid deposition, denervation), and cardiac evaluation (multimodal imaging, cardiac denervation and arrhythmias). Results We included 130 patients, aged 43.6 years (± 13.5), selected in family of a proband with an age of onset of 52.7 years (±15.7), 40.8% male, carrying 20 different variants of the TTR gene, including 63.8% Val30Met. Amyloid deposits on skin biopsy and/or cardiac fixation on bone scintigraphy, characteristic of amyloid infiltration, were found in 22/130 patients (16%). Skin biopsy was positive in 11 patients, and cardiac fixation on bone scintigraphy was positive in 15 patients. Amyloid infiltration was statistically associated with age (p=0.024), age difference from index case (p<0.001), electrophysiological carpal tunnel syndrome (p=0.022), interventricular septum thickness >12 mm (p<0.001), contrast enhancement in cardiac MRI (p=0.002), cardiac denervation using MIBG scintigraphy C/M ratio <1.85 (p=0.044). Multivariate analysis showed that age difference with index case and interventricular septum thickness were predictors for amyloid infiltration (OR=1.11, IC [1,04–1,19] and OR=1,76, IC [1,19–2,60]). Subgroup analysis showed electroneuromyography alteration during follow up in 11 patients (delay 26.9 months, range 10–49) with statistic association with amyloid deposits (55.6 versus 7.1% when ENMG was unchanged, p<0.001) and interventricular septum thickness (p<0.010). Conclusion Clinical and paraclinical assessment of asymptomatic carriers of ATTRv mutations shows that skin or cardiac amyloid infiltration may precede ENMG abnormalities in 16% of patients. This may trigger specific therapies in borderline cases. Age close to age of onset among index case and septum interventricular thickness appear as risk factors for developing electroneuromyogram alteration. Funding Acknowledgement Type of funding source: None

Clinical Course and Features of Seizures Associated With LGI1-Antibody Encephalitis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012465
Author(s):  
Kelsey M. Smith ◽  
Divyanshu Dubey ◽  
Greta B. Liebo ◽  
Eoin P. Flanagan ◽  
Jeffrey W. Britton
Keyword(s):  
Risk Factors ◽  
Proportional Hazards ◽  
Age Of Onset ◽  
Disease Onset ◽  
Cox Proportional Hazards ◽  
Binary Logistic Regression Analysis ◽  
Chronic Epilepsy ◽  
Female Sex ◽  
Steroid Sparing

Objective:To determine risk factors associated with clinical relapses and development of chronic epilepsy in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) IgG encephalitis.Methods:Patients with seizures related to LGI1-antibody encephalitis with ≥ 24 months of follow-up from disease onset were identified in the Mayo Clinic electronic medical record and Neuroimmunology lab records. Charts were reviewed to determine clinical factors, seizure types, imaging, treatment, occurrence of relapse, and outcome. Binary logistic regression analysis was performed to identify predictors of the development of chronic epilepsy. Univariate Cox proportional hazards regression was used to examine the influence of baseline characteristics on relapse risk.Results:Forty-nine patients with LGI1-antibody encephalitis and acute symptomatic seizures were identified. Almost all patients (n=48, 98%) were treated with immunotherapy. Eight had definite, and two had possible chronic epilepsy at last follow-up (10/49, 20.4%). Female sex (P=0.048) and younger age at disease onset (P=0.02) were associated with development of chronic epilepsy. Relapses occurred in 20 (40.8%), with a median time to first relapse of 7.5 months (range 3-94 months). Initial treatment with chronic steroid sparing immunotherapy was associated with reduced risk of relapse (hazards ratio=0.28, 95% CI 0.11-0.73, P=0.009).Conclusions:Chronic epilepsy occurred in 20.4% of our patients with LGI1-antibody encephalitis despite aggressive immunotherapy. Risk factors for chronic epilepsy were female sex and earlier age of onset. Relapses occurred in 40.8% of patients with prolonged follow-up, and chronic steroid sparing immunotherapy was associated with a lower relapse rate.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

Regression of cardiac amyloid deposits with novel therapeutics: reaching new frontiers in cardiac ATTR amyloidosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cardiac Amyloidosis ◽  
T1 Mapping ◽  
Group Versus ◽  
Control Group ◽  
Cardiac Amyloid ◽  
Attr Amyloidosis ◽  
Amyloid Load ◽  
The Impact

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p&lt;0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p&lt;0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None

scholarly journals Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Henriette Schermacher Marstein ◽  
Kristin Godang ◽  
Berit Flatø ◽  
Ivar Sjaastad ◽  
Jens Bollerslev ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Inflammatory Markers ◽  
Juvenile Dermatomyositis ◽  
Inflammatory Myopathy ◽  
Disease Onset ◽  
Whole Body ◽  
Mineral Density ◽  
Z Scores

Abstract Background Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children and adolescents. Both the disease and its treatment with glucocorticoids may negatively impact bone formation. In this study we compare BMD in patients (children/adolescence and adults) with long-standing JDM with matched controls; and in patients, explore how general/disease characteristics and bone turnover markers are associated with BMD. Methods JDM patients (n = 59) were examined median 16.8y (range 6.6–27.0y) after disease onset and compared with 59 age/sex-matched controls. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD of the whole body and lumbar spine (spine) in all participants, and of ultra-distal radius, forearm and total hip in participants ≥20y only. Markers of bone turnover were analysed, and associations with outcomes explored. Results Reduced BMD Z-scores (<−1SD) were found in 19 and 29% of patients and 7 and 9% of controls in whole body and spine, respectively (p-values < 0.05). BMD and BMD Z-scores for whole body and spine were lower in all patients and for < 20y compared with their respective controls. In participants ≥20y, only BMD and BMD Z-score of forearm were lower in the patients versus controls. In patients, BMD Z-scores for whole body and/or spine were found to correlate negatively with prednisolone use at follow-up (yes/no) (age < 20y), inflammatory markers (age ≥ 20y) and levels of interferon gamma-induced protein 10 (IP-10) (both age groups). In all patients, prednisolone use at follow-up (yes/no) and age ≥ 20y were independent correlates of lower BMD Z-scores for whole body and spine, respectively. Conclusion In long-term JDM, children have more impairment of BMD than adults in spine and whole-body. Associations with BMD were found for both prednisolone and inflammatory markers, and a novel association was discovered with the biomarker of JDM activity, IP-10.

scholarly journals Association between Neonatal Intakes and Hyperglycemia, and Left Heart and Aortic Dimensions at 6.5 Years of Age in Children Born Extremely Preterm

2021 ◽  
Vol 10 (12) ◽  
pp. 2554
Author(s):  
Jawwad Hamayun ◽  
Lilly-Ann Mohlkert ◽  
Elisabeth Stoltz Sjöström ◽  
Magnus Domellöf ◽  
Mikael Norman ◽  
...  
Keyword(s):  
Interventricular Septum ◽  
Posterior Wall ◽  
Root Diameter ◽  
Left Ventricular ◽  
Left Heart ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Nutritional Data ◽  
Aortic Dimensions

Survivors of extremely preterm birth (gestational age < 27 weeks) have been reported to exhibit an altered cardiovascular phenotype in childhood. The mechanisms are unknown. We investigated associations between postnatal nutritional intakes and hyperglycemia, and left heart and aortic dimensions in children born extremely preterm. Postnatal nutritional data and echocardiographic dimensions at 6.5 years of age were extracted from a sub-cohort of the Extremely Preterm Infants in Sweden Study (EXPRESS; children born extremely preterm between 2004–2007, n = 171, mean (SD) birth weight = 784 (165) grams). Associations between macronutrient intakes or number of days with hyperglycemia (blood glucose > 8 mmol/L) in the neonatal period (exposure) and left heart and aortic dimensions at follow-up (outcome) were investigated. Neonatal protein intake was not associated with the outcomes, whereas higher lipid intake was significantly associated with larger aortic root diameter (B = 0.040, p = 0.009). Higher neonatal carbohydrate intake was associated with smaller aorta annulus diameter (B = −0.016, p = 0.008). Longer exposure to neonatal hyperglycemia was associated with increased thickness of the left ventricular posterior wall (B = 0.004, p = 0.008) and interventricular septum (B = 0.004, p = 0.010). The findings in this study indicate that postnatal nutrition and hyperglycemia may play a role in some but not all long-lasting developmental adaptations of the cardiovascular system in children born extremely preterm.

scholarly journals AB0702 PITFALLS IN THE DIAGNOSIS OF COVID-19 – EXPERIENCES FROM A RHEUMATOLOGY OUTPATIENT CLINIC

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1383.2-1383
Author(s):  
S. G. Werner ◽  
H. E. Langer ◽  
P. Höhenrieder ◽  
R. Chatelain
Keyword(s):  
Outpatient Clinic ◽  
Virus Disease ◽  
Disease Onset ◽  
Signs And Symptoms ◽  
Contact Tracing ◽  
Igg Antibodies ◽  
Antibody Testing ◽  
Antibody Titers ◽  
Rheumatology Outpatient

Background:PCR (Polymerase Chain Reaction) is generally considered the gold standard for confirming the diagnosis in the early stages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. However, in our rheumatology outpatient clinic we observed a significant discrepancy between clinical evidence of COVID-19 and PCR results.Objectives:Aim of this retrospective study was to analyze the significance of PCR and serologic tests in the diagnosis of COVID-19 (Corona Virus Disease 2019) in a cohort of patients with rheumatic diseases.Methods:Between March 2020 and January 2021, 35 patients with a history of established COVID-19 or typical signs and symptoms were identified on the occasion of a routine rheumatology follow-up examination in our institution. Previous diagnostic work-up in external facilities (results of PCR or antibody testing, imaging) was documented. Antibody ELISA-tests (IgG, IgA, IgM, Euroimmun) were performed in patients reporting typical signs and symptoms of COVID-19 in the past.Results:PCR diagnostics had been performed in 15/35 patients (43%), in 13/35 (39%) at the onset of the first symptoms, in 2 subjects only 2 months later. PCR was positive in 7/13 (54%) of those tested early, but negative in the two patients tested later. In 29/35 patients (83%) SARS-CoV-2-ELISA tests were performed on the occasion of the routine rheumatologic examination (interval between first symptoms and testing on average 98 days, median86, range 4-283 days). In two of the initially negative individuals the second PCR was positive. ELISA tests were positive in all patients. SARS-CoV-2 IgM antibodies were positive in only two patients (however 55 and 71 days after disease onset), n=8/29 (28%) IgG only, n=9/29 (31%) IgG and IgA, n=12/29 (41%) IgA only. In these subjects, IgG antibodies did not develop even in the further course. Antibody titers were in part very high, but in part also very low (only just above the normal value), so even low titers were diagnostic obviously. In all patients with negative PCR, ELISA was positive and retrospectively led to confirmation of the diagnosis. Only in 13/35 patients (37%) diagnosis had been made with the onset of the first symptoms or in the course of clinically manifest disease and had led to appropriate quarantine measures and contact tracing by the health authorities. In contrast, in the majority of patients (63%), the diagnosis of COVID-19 infection was only made retrospectively on the occasion of a routine rheumatologic follow-up. However, 5 of these 22 patients (23%) had quarantined themselves during the symptomatic phase. Titer histories were available from 12 patients. The titer became negative in 7 patients, after a mean of 188 days (median 202, min 51, max 296 days), and remained positive in 5 individuals (mean 190 days, median 191, min 122, max 260 days). The change of the titer was independent of disease severity or antirheumatic therapy.Conclusion:The results suggest that the importance of PCR in the diagnosis of COVID-19 may be overestimated. Therefore, antibody testing for SARS-CoV-2 should be performed in cases of clinical suspicion and negative PCR. In antibody diagnostics, special features were observed compared to other viruses, in particular, in some patients only low antibody titers or the absence of seroconversion with lack of development of IgG antibodies. Normalization of antibody titers in some patients supports the recommendation to vaccinate even after expired COVID-19 disease.Disclosure of Interests:None declared

scholarly journals Fibromuscular dysplasia with recurrence after “long-term” following percutaneous transcatheter renal angioplasty: two case reports with a review of 26 patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shuntaro Oribe ◽  
Takafumi Toyohara ◽  
Eikan Mishima ◽  
Takehiro Suzuki ◽  
Koichi Kikuchi ◽  
...  
Keyword(s):  
Fibromuscular Dysplasia ◽  
Age Of Onset ◽  
Case Reports ◽  
Case Presentation ◽  
Renal Angioplasty ◽  
Long Term Follow Up ◽  
Percutaneous Transluminal Renal Angioplasty ◽  
The Difference

Abstract Background Fibromuscular dysplasia (FMD) often causes renal artery stenosis with renovascular hypertension. Recent clinical outcomes encourage percutaneous transluminal renal angioplasty (PTRA) to treat FMD; however, the necessary follow-up period remains unclear. Moreover, previous studies have not revealed the difference in the period until recurrence between two major types of FMD—multifocal and focal. Case presentation We describe two patients with multifocal FMD who developed hypertension during their teenage years and had recurrence of FMD > 10 years after PTRA. We further examined the types of FMD and age of onset in 26 patients who underwent PTRA. The period until recurrence of multifocal FMD was longer than that of focal FMD. Moreover, patients with early-onset multifocal FMD are likely to have a delayed recurrence after PTRA compared to other types. Conclusions Our report suggests that patients with multifocal FMD, especially those with onset at an early age, may need long-term follow-up for at least ≥ 10 years.

scholarly journals Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 512
Author(s):  
Aleksandra Gilis-Januszewska ◽  
Anna Bogusławska ◽  
Kornelia Hasse-Lazar ◽  
Beata Jurecka-Lubieniecka ◽  
Barbara Jarząb ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Clinical Presentation ◽  
Age Of Onset ◽  
Malignant Tumors ◽  
Genetic Disorder ◽  
Family Members ◽  
Pancreatic Neuroendocrine Tumor ◽  
Index Patient ◽  
Generation Family

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.

“Re-Emergence” of Silicosis and Coal Workers Pneumoconiosis in Australia

2020 ◽  
Vol 119 (1) ◽  
pp. 65-92
Author(s):  
Beris Penrose
Keyword(s):  
Data Collection ◽  
Coal Mining ◽  
Disease Onset ◽  
Latency Period ◽  
Dust Exposure ◽  
Long Latency ◽  
History Of ◽  
Coal Workers Pneumoconiosis ◽  
Coal Workers

Some reporters, politicians, and doctors have described current cases as a “re-emergence” of these diseases, based on the notion that they had been eliminated. However, silicosis persisted in centuries-old industries like sandblasting and stonemasonry and coal workers pneumoconiosis (CWP) continued in coal mining. Until recently, their presence was obscured by a combination of factors such as misdiagnosis, especially if there was a history of smoking; the failure to follow up workers thought to have silicosis or CWP; the long latency period between dust exposure and disease onset that can conceal the link between the two; and the lack of data collection that may have revealed their presence. As the recent Queensland government inquiry into CWP noted, current cases are more accurately a reidentification.

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