LGI1 and CASPR2 neurological autoimmunity in children.

The clinical phenotype of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated proteinlike 2 (CASPR2) autoimmunity is well defined in adults. Data for children are limited (<10 cases). Among 13,319 pediatric patients serologically tested for autoimmune neurological disorders (2010-2017), 264 were seropositive for voltage-gated potassium channel-complex-IgG (radioimmunoprecipitation). Only 13 (4.9%) were positive by transfected cell-binding assay for LGI1-IgG (n = 7), CASPR2-IgG (n = 3), or both (n = 3). This is significantly less than in adults. Encephalopathy, seizures, and peripheral nerve hyperexcitability were common, as was coexisting autoimmunity. No faciobrachial dystonic seizures or cancers were identified. Functional neurologic disorders were frequently the initial diagnosis, and immunotherapy appeared beneficial. Ann Neurol 2018;84:473-480.

An inflection point in high-throughput proteomics with Orbitrap Astral: analysis of biofluids, cells, and tissues.

This technical note presents a comprehensive proteomics workflow for the new combination of Orbitrap and Astral mass analyzers across biofluids, cells, and tissues. Central to our workflow is the integration of Adaptive Focused Acoustics (AFA) technology for cells and tissue lysis, to ensure robust and reproducible sample preparation in a high-throughput manner. Furthermore, we automated the detergent-compatible single-pot, solid-phase-enhanced sample Preparation (SP3) method for protein digestion, a technique that streamlines the process by combining purification and digestion steps, thereby reducing sample loss and improving efficiency. The synergy of these advanced methodologies facilitates a robust and high-throughput approach for cells and tissue analysis, an important consideration in translational research. This work disseminates our platform workflow, analyzes the effectiveness, demonstrates reproducibility of the results, and highlights the potential of these technologies in biomarker discovery and disease pathology. For cells and tissues (heart, liver, lung, and intestine) proteomics analysis by data-independent acquisition mode, identifications exceeding 10,000 proteins can be achieved with a 24-minute active gradient. In 200ng injections of HeLa digest across multiple gradients, an average of more than 80% of proteins have a CV less than 20%, and a 45-minute run covers ~90% of the expressed proteome. In plasma samples including naive, depleted, perchloric acid precipitated, and Seer nanoparticle captured, all with a 24-minute gradient length, we identified 87, 108, 96 and 137 out of 216 FDA approved circulating protein biomarkers, respectively. This complete workflow allows for large swaths of the proteome to be identified and is compatible across diverse sample types.

Triacetyluridine treats epileptic encephalopathy from CAD mutations: a case report and review.

Refractory epilepsy and encephalopathy are frequently encountered in patients with inborn errors of metabolism. We report a case of an 8-year-old girl with history of developmental delay, autism and intractable epilepsy that was found to have a pathogenic variant in CAD. We briefly review the biochemical pathway of CAD and the preclinical and clinical studies that suggest uridine supplementation can rescue the CAD deficiency phenotypes. Our case demonstrates a relatively late-onset case of refractory epilepsy with a rapid response to treatment using the uridine pro-drug triacetyluridine (TAU), the FDA-approved treatment for hereditary orotic aciduria.

Early-Onset Alzheimer's Disease Masquerading as Catatonia.

A 35-year-old woman with a history of sexual trauma was brought in by her family for further evaluation of depressive symptoms and progressive decline in activities of daily living. She was admitted to the inpatient psychiatric unit for the treatment of suspected catatonia. After failure to respond to standard medical treatment, she received an extensive workup, which ultimately revealed a PSEN1 mutation consistent with early-onset Alzheimer's disease. Diagnosis was challenging because of her young age, lack of reliable family history, and reports of recent sexual abuse by her biological father. This case is a cautionary reminder for clinicians that end stages of dementia can present similar to catatonia with mutism, lack of spontaneous movement, and refusal to eat. The clues to the diagnosis were profound cortical atrophy and lack of improvement with optimal medical management.

Characterization and Analysis of the Skin Microbiota in Rosacea: A Case-Control Study.

BACKGROUND: The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea. OBJECTIVE: We performed a case-control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race. METHODS: Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software. RESULTS: Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%). CONCLUSIONS: The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.

Magnetic resonance microscopy of mammalian neurons.

Magnetic resonance imaging (MRI) is now a leading diagnostic technique. As technology has improved, so has the spatial resolution achievable. In 1986 MR microscopy (MRM) was demonstrated with resolutions in the tens of micrometers, and is now an established subset of MRI with broad utility in biological and non-biological applications. To date, only large cells from plants or aquatic animals have been imaged with MRM limiting its applicability. Using newly developed microsurface coils and an improved slice preparation technique for correlative histology, we report here for the first time direct visualization of single neurons in the mammalian central nervous system (CNS) using native MR signal at a resolution of 4-8 microm. Thus MRM has matured into a viable complementary cellular imaging technique in mammalian tissues.

Cyclic hypersomnolence with symptoms of narcolepsy with cataplexy: An unusual presentation of probable immune-mediated encephalitis.

We report a case of probable encephalitis presenting as narcolepsy with cataplexy, but with cyclical exacerbation and cognitive difficulties. Our patient continued to worsen despite treatment for narcolepsy and later was thought to have an immune-mediated encephalopathy. Treatment with intravenous gamma immunoglobulin (IVIG) led to complete recovery. Cyclic symptoms of narcolepsy with cataplexy are thus one presentation of probable immune-mediated encephalitis.

Utility of Physician Selection of Cardiac Tests in a Chest Pain Unit to Exclude Acute Coronary Syndrome Among Patients Without a History of Coronary Artery Disease.

There are few data on the utility of physician selection of cardiac tests, including no-test, in a chest pain unit (CPU) to rule out acute coronary syndrome in low-risk patients without a history of coronary artery disease. We analyzed consecutive low-risk patients admitted to our CPU between 2012 and 2014 and determined the proportion of patients selected for testing, the type of initial cardiac test selected, and the incidence of major adverse cardiac events (MACEs) at 30 days and 6 months. The study group comprised 619 patients: mean age 57 years (27 to 92), 332 women (54%), and 360 (58%) with multiple cardiac risk factors. Cardiac testing included 283 no-test (46%); 179 exercise treadmill (29%); 113 myocardial perfusion stress scintigraphy (18%); <10% each for exercise stress echocardiography and coronary angiography. Testing was negative in 296 (88%), nondiagnostic in 30 (9%), and positive in 10 patients (3%). There were no MACEs at 30 days in any patients, and at 6 months, MACEs were 5 (1.1%). Length of stay was less in no-test than in tested patients (5.4 hours vs 9.8 hours, p <0.0001), and there was no difference in incidence of MACE at 6 months in no-test vs tested patients (2 MACEs vs 3 MACEs). Physician selection of cardiac tests, including no-test, promptly identified patients at low risk of acute coronary syndrome who could be safely and rapidly discharged from the CPU. Exclusion of cardiac testing shortened length of stay and was not associated with increase in MACE at 6 months.

Non-invasive evaluation of alginate/poly-l-lysine/alginate microcapsules by magnetic resonance microscopy.

In this report, we present data to demonstrate the utility of (1)H MR microscopy to non-invasively examine alginate/poly-l-lysine/alginate (APA) microcapsules. Specifically, high-resolution images were used to visualize and quantify the poly-l-lysine (PLL) layer, and monitor temporal changes in the alginate gel microstructure during a month long in vitro culture. The thickness of the alginate/PLL layer was quantified to be 40.6+/-6.2 microm regardless of the alginate composition used to generate the beads or the time of alginate/PLL interaction (2, 6, or 20 min). However, there was a notable difference in the contrast of the PLL layer that depended upon the guluronic content of the alginate and the alginate/PLL interaction time. The T(2) relaxation time and the apparent diffusion coefficient (ADC) of the alginate matrix were measured periodically throughout the month long culture period. Alginate beads generated with a high guluronic content alginate demonstrated a temporal decrease in T(2) over the duration of the experiment, while ADC was unaffected. This decrease in T(2) is attributed to a reorganization of the alginate microstructure due to periodic media exchanges that mimicked a regular feeding regiment for cultured cells. In beads coated with a PLL layer, this temporal decrease in T(2) was less pronounced suggesting that the PLL layer helped maintain the integrity of the initial alginate microstructure. Conversely, alginate beads generated with a high mannuronic content alginate (with or without a PLL layer) did not display temporal changes in either T(2) or ADC. This observation suggests that the microstructure of high mannuronic content alginate beads is less susceptible to culture conditions.

Central neurogenic hyperventilation: a case report and discussion of pathophysiology.

BACKGROUND: Central neurogenic hyperventilation is a rare condition with poorly understood pathophysiology. OBJECTIVE: To describe a patient with central neurogenic hyperventilation caused by an infiltrative brainstem lymphoma. CONCLUSION: Based on analysis of this patient and other case reports, we propose that central neurogenic hyperventilation is uniquely the result of infiltrative tumors that stimulate pontine respiratory centers and central chemoreceptors.