Citations

OBJECTIVES: We assessed the adherence to neuroimaging guidelines and the diagnostically relevant yield of neuroimaging in newly presenting early life epilepsy (ELE). METHODS: There were 775 children with a new diagnosis of epilepsy (<3 years old at onset) who were recruited through the ELE study at 17 US pediatric epilepsy centers (2012–2015) and managed prospectively for 1 year. The data were analyzed to assess the proportion of children who underwent neuroimaging, the type of neuroimaging, and abnormalities. RESULTS: Of 725 children (93.5%) with neuroimaging, 714 had an MRI (87% with seizure protocols) and 11 had computed tomography or ultrasound only. Etiologically relevant abnormalities were present in 290 individuals (40%) and included: an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%). Neuroimaging was abnormal in 160 of 262 (61%) children with abnormal development at diagnosis versus 113 of 463 (24%) children with typical development. Neuroimaging abnormalities were most common in association with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%). In children without spasms or focal semiology with typical development, 29 of 185 (16%) had imaging abnormalities. Pathogenic genetic variants were identified in 53 of 121 (44%) children with abnormal neuroimaging in whom genetic testing was performed. CONCLUSIONS: Structural abnormalities occur commonly in ELE, and adherence to neuroimaging guidelines is high at US pediatric epilepsy centers. These data support the universal adoption of imaging guidelines because the yield is substantially high, even in the lowest risk group.

Purpose: The aim of this study was to evaluate the ability of computer-aided detection (CAD) and human readers to detect pulmonary nodules ≥5 mm using 100 kV ultra–low-dose computed tomography (ULDCT) utilizing a tin filter. Materials and Methods: After informed consent, 55 patients prospectively underwent standard-dose chest CT (SDCT) using 120 kV followed by ULDCT using 100 kV/tin. Reference nodules ≥5 mm were identified by a thoracic radiologist using SDCT. Four thoracic radiologists marked detected nodules on SDCT and ULDCT examinations using a dedicated computer workstation. After a 6-month memory extinction, readers were shown the same ULDCT cases with all CAD markings as well as their original detections, and characterized CAD detections as true positive or false positive. Results: Volume CT Dose index (CTDIvol) for SDCT and ULDCT were 5.3±2 and 0.4±0.2 mGy (P<0.0001), respectively. Forty-five reference nodules were detected in 30 patients. Reader sensitivity varied widely but similarly for SDCT (ranging from 45% to 87%) and ULDCT (45% to 83%). CAD sensitivity was 76% (34/45) for SDCT and 71% (32/45) for ULDCT. After CAD, reader sensitivity substantially improved by 19% and 18% for 2 readers, and remained nearly unchanged for the other 2 readers (0% and 2%), despite reader perception that many more nodules were identified with CAD. There was a mean of 2 false-positive CAD detections/case. Conclusions: ULDCT with 100 kV/tin reduced patient dose by over 90% without compromising pulmonary nodule detection sensitivity. CAD can substantially improve nodule detection sensitivity at ULDCT for some readers, maintaining interobserver performance.

Abstract Background Antinuclear antibody (ANA)5 testing is routinely performed during evaluation of patients with a suspected connective tissue disease (CTD), yet the question of which method is most appropriate remains controversial. The purpose of this study was to evaluate the clinical utility of ANA testing by an enzyme immunoassay (EIA), an immunofluorescence assay (IFA), and a multiplex immunoassay (MIA) in a routine laboratory population. Methods Samples (n = 1000) were collected from specimens submitted for ANA testing by EIA (Bio-Rad). All samples were subsequently analyzed by IFA (Zeus) and MIA (Bio-Rad). The sample cohort was weighted to represent the routine testing population. Diagnostic information was obtained by chart review. Results For the diagnosis of a CTD, ROC curve analysis demonstrated no significant differences between IFA (area under the curve 0.81) and EIA (0.84) (P = 0.25), with overlay of a single point for the MIA. When normalized to a specificity of approximately 90%, the sensitivities of the MIA, EIA, and IFA were 67%, 67%, and 56%, respectively. By varying the clinical cutoff, the IFA could achieve the highest sensitivity of 94%; however, the corresponding specificity was only 43%. In contrast, a strongly positive EIA had a specificity of 97%, although, at this cutoff, the sensitivity was only 40%. Conclusions Although the overall diagnostic performance of the IFA, EIA, and MIA were not statistically different, the clinical sensitivity and specificity varied dramatically based on the positive/negative cutoff. Knowledge about the performance characteristics of each method will significantly aid in the interpretation of ANA testing.

Objectives: Catecholamine-secreting jugular paragangliomas (JPs) represent a rare subset of head and neck paragangliomas that may present with hypertension, arrhythmia, or syncopal episodes. Subtotal resection to protect critical neurovascular structures may result in persistent catecholamine excess from residual tumor. Herein, we report our experience with stereotactic radiosurgery (SRS) for salvage treatment of catecholamine-secreting JP following subtotal microsurgical resection. Patients: Adult patients treated with SRS after subtotal microsurgical resection of catecholamine-secreting JP. Interventions: SRS. Main Outcome Measures: Post-treatment catecholamine and metanephrine levels, clinical outcomes, and tumor control. Results: Of 85 patients with JPs treated with primary or salvage radiosurgery between 1990 and 2017, 2 (2%) harbored nonmalignant secreting tumors. Patient 1 developed catecholamine excess with elevated norepinephrine (NE) at 475 mcg/24 hours (normal < 80 mcg/24 h). Following subtotal resection, she developed catecholamine excess with radiographic evidence of tumor growth and therefore underwent SRS. Three years post-SRS and beyond, catecholamine levels remained normalized (NE 62 mcg/24 h at 10 yr) and tumor volume remained stable on serial MRI studies over the 17-year follow-up period. Patient 2 developed symptomatic arrhythmia and was found to have a JP. Urine norepinephrine (NE) was elevated at 213 mcg/24 hours. She underwent nerve-sparing subtotal resection and upfront SRS was used to treat residual tumor. Twenty months following SRS, the area of residual JP had not enlarged in size and catecholamine levels remained normal (NE 46 mcg/24 h). Conclusions: Radiosurgery can be used in salvage treatment of catecholamine-secreting JP, providing durable tumor control and resolution of catecholamine excess. For patients with large catecholamine-secreting JP and normal lower cranial nerve function, aggressive nerve-sparing subtotal resection with adjuvant radiosurgery may offer a low-morbidity alternative to gross total resection. Further study of this subset of patients is warranted to substantiate these promising, yet preliminary findings.

Abstract Background True population-based clinical and outcomes data are lacking for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Therefore we aimed to estimate the incidence, prevalence and mortality of AAGN, as well as the relationship between the grade of chronic renal damage at presentation and renal and non-renal outcomes. Methods Patients with AAGN were identified among a population-based incident cohort of 57 Olmsted County residents diagnosed with ANCA-associated vasculitis (AAV) in 1996–2015. Incidence rates were age and sex adjusted to the 2010 US white population. Age- and sex-adjusted prevalence was calculated for 1 January 2015. Survival rates were compared with expected rates in the Minnesota population. Chronic renal damage was assessed by chronicity score (CS) on biopsies performed at diagnosis. Results Thirty-four (60%) patients had AAGN. Of these, 65% had microscopic polyangiitis (MPA) and 74% were myeloperoxidase (MPO)-ANCA positive. The annual incidence of AAGN was 2.0/100 000 population [95% confidence interval (CI) 1.3–2.7] and the overall prevalence was 35/100 000 (95% CI 24–47). Mortality for AAGN was increased (P &lt; 0.001), whereas mortality for AAV without glomerulonephritis did not differ from the general population. Minimal to mild CS predicted recovery of renal function at 1 year; clinical diagnosis (granulomatosis with polyangiitis versus MPA) and ANCA specificity (proteinase 3 versus MPO) did not. This observation was replicated in an independent cohort of 38 newly diagnosed AAGN patients seen at our centre over the 1999–2014 period. Conclusions The annual incidence and prevalence of AAGN in Minnesota are 2.0/100 000 and 35/100 000, respectively. Mortality is worse compared with AAV patients without glomerulonephritis. More advanced renal damage at diagnosis predicts less renal recovery.

AbstractNursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but the VTE burden within the NH population is uncertain. This study estimates VTE incidence and VTE-associated mortality among NH residents. We identified all NH residents in any NH in Olmsted County, Minnesota, United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE among county residents to estimate VTE incidence while resident of local NHs (NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and Rochester Epidemiology Project resources. We tested associations between NHVTE and age, sex and time since each NH admission using Poisson modelling. Additionally, we tested incident NHVTE as a potential predictor of survival using Cox proportional hazards, adjusting for age, sex and NH residency. Between 1 October 1998 and 31 December 2005, 3,465 Olmsted County residents with ≥1 admission to a local NH, contributed 4,762 NH stays. Of the 3,465 NH residents, 111 experienced incident NHVTE (2.3% of all eligible stays), for an overall rate of 3,653/100,000 NH person-years (NH-PY). VTE incidence was inversely associated with time since each NH admission, and was highest in the first 7 days after each NH admission (18,764/100,000 NH-PY). The adjusted hazard of death for incident NHVTE was 1.90 (95% confidence interval [CI]: 1.38–2.62). In conclusion, VTE incidence among NH residents was nearly 30-fold higher than published incidence rates for the general Olmsted County population. VTE incidence was highest within 7 days after NH admission, and NHVTE was associated with significantly reduced survival. These data can inform future research and construction of clinical trials regarding short-term prophylaxis.