Cell type mapping of inflammatory muscle diseases highlights selective myofiber vulnerability in inclusion body myositis.

Inclusion body myositis (IBM) is the most prevalent inflammatory muscle disease in older adults with no effective therapy available. In contrast to other inflammatory myopathies such as subacute, immune-mediated necrotizing myopathy (IMNM), IBM follows a chronic disease course with both inflammatory and degenerative features of pathology. Moreover, causal factors and molecular drivers of IBM progression are largely unknown. Therefore, we paired single-nucleus RNA sequencing with spatial transcriptomics from patient muscle biopsies to map cell-type-specific drivers underlying IBM pathogenesis compared with IMNM muscles and noninflammatory skeletal muscle samples. In IBM muscles, we observed a selective loss of type 2 myonuclei paralleled by increased levels of cytotoxic T and conventional type 1 dendritic cells. IBM myofibers were characterized by either upregulation of cell stress markers featuring GADD45A and NORAD or protein degradation markers including RNF7 associated with p62 aggregates. GADD45A upregulation was preferentially seen in type 2A myofibers associated with severe tissue inflammation. We also noted IBM-specific upregulation of ACHE encoding acetylcholinesterase, which can be regulated by NORAD activity and result in functional denervation of myofibers. Our results provide promising insights into possible mechanisms of myofiber degeneration in IBM and suggest a selective type 2 fiber vulnerability linked to genomic stress and denervation pathways.

Comparing Expert and Non-Expert Assessment of Patients Presenting with Neurological Symptoms to the Emergency Department: A Retrospective Observational Study.

OBJECTIVE: Referrals to neurology in emergency departments (ED) are continuously increasing, currently representing 15% of all admissions. Existing triage systems were developed for general medical populations and have not been validated for patients with neurological symptoms. METHODS: To characterize neurological emergencies, we first retrospectively analyzed symptoms, service times and resources of the cohort of neurological referrals to a German interdisciplinary ED (IED) during 2017 according to urgency determined by final IED diagnosis. In a second step, we performed a retrospective assignment of consecutive patients presenting in April 2017 according to internal guidelines as either acute (requiring diagnostic/therapeutic procedures within 24 hrs) or non-acute neurological conditions as well as a retrospective classification according to the Emergency Severity Index (ESI). Both assessments were compared with the urgency according to the final ER diagnosis. RESULTS: In a 12-month period, 36.4% of 5340 patients were rated as having an urgent neurological condition; this correlated with age, door-to-doctor time, imaging resource use and admission (p < 0.001, respectively). In a subset of 275 patients, 59% were retrospectively triaged as acute according to neurological expertise and 48% according to ESI categories 1 and 2. Neurological triage identified urgency with a significantly higher sensitivity (94.8, p < 0.01) but showed a significantly lower specificity (55.1, p < 0.05) when compared to ESI (80.5 and 65.2, respectively). CONCLUSION: The ESI may not take specific aspects of neurological emergency (eg, time-sensitivity) sufficiently into account. Refinements of existing systems or supplementation with dedicated neurological triage tools based on neurological expertise and experience may improve the triage of patients with neurological symptoms.

The use of a dedicated neurological triage system improves process times and resource utilization: a prospective observational study from an interdisciplinary emergency department.

BACKGROUND: Patients with neurological symptoms have been contributing to the increasing rates of emergency department (ED) utilization in recent years. Existing triage systems represent neurological symptoms rather crudely, neglecting subtler but relevant aspects like temporal evolution or associated symptoms. A designated neurological triage system could positively impact patient safety by identifying patients with urgent need for medical attention and prevent inadequate utilization of ED and hospital resources. METHODS: We compared basic demographic information, chief complaint/presenting symptom, door-to-doctor time and length of stay (LOS) as well as utilization of ED resources of patients presenting with neurological symptoms or complaints during a one-month period before as well as after the introduction of the Heidelberg Neurological Triage System (HEINTS) in our interdisciplinary ED. In a second step, we compared diagnostic and treatment processes for both time periods according to assigned acuity. RESULTS: During the two assessment periods, 299 and 300 patients were evaluated by a neurologist, respectively. While demographic features were similar for both groups, overall LOS (p < 0.001) was significantly shorter, while CT (p = 0.023), laboratory examinations (p = 0.006), ECG (p = 0.011) and consultations (p = 0.004) were performed significantly less often when assessing with HEINTS. When considering acuity, an epileptic seizure was less frequently evaluated as acute with HEINTS than in the pre-HEINTS phase (p = 0.002), while vertigo patients were significantly more often rated as acute with HEINTS (p < 0.001). In all cases rated as acute, door-to-doctor-time (DDT) decreased from 41.0 min to 17.7 min (p < 0.001), and treatment duration decreased from 304.3 min to 149.4 min (p < 0.001) after introduction of HEINTS triage. CONCLUSION: A dedicated triage system for patients with neurological complaints reduces DDT, LOS and ED resource utilization, thereby improving ED diagnostic and treatment processes.

Acute Corticonuclear Tract Ischemic Stroke with Isolated Central Facial Palsy.

OBJECTIVE: The clinical distinction between habitual facial asymmetry, early stage peripheral facial palsy, and isolated central facial palsy is sometimes difficult. The diagnosis of acute central facial palsy is of importance to identify patients for stroke work-up and appropriate treatment. We aimed to evaluate the prevalence and localization of acute ischemic lesions associated with isolated central facial palsy. METHODS: We screened our stroke database for patients presenting with isolated central facial palsy related to ischemic stroke between 2012 and 2017. All identified patients were comprehensively characterized including magnetic resonance (MR) diffusion-weighted imaging (DWI). RESULTS: We identified four out of 5169 patients (one male; 62-83 years) with isolated facial palsy as a result of acute ischemic stroke (NIHSS 1-2). All four had circumscribed DWI lesions in different regions of the corticonuclear tract in different areas with different etiologies. CONCLUSION: Isolated central facial palsy is a rare manifestation of acute ischemic stroke and may be missed if clinical suspicion is not raised. MR-DWI identifies small ischemic lesions in the corticonuclear tract, which results in appropriate diagnostic work-up and secondary prophylaxis.