A Combined Clinical and Serum Biomarker-Based Approach May Allow Early Differentiation Between Patients With Minor Stroke and Transient Ischemic Attack as Well as Mid-term Prognostication

Background: Early differentiation between transient ischemic attack (TIA) and minor ischemic stroke (MIS) impacts on the patient’s individual diagnostic work-up and treatment. Furthermore, estimations regarding persisting impairments after MIS are essential to guide rehabilitation programs. This study evaluated a combined clinical- and serum biomarker-based approach for the differentiation between TIA and MIS as well as the mid-term prognostication of the functional outcome, which is applicable within the first 24 h after symptom onset. Methods: Prospectively collected data were used for a retrospective analysis including the neurological deficit at admission (National Institutes of Health Stroke Scale, NIHSS) and the following serum biomarkers covering different pathophysiological aspects of stroke: Coagulation (fibrinogen, antithrombin), inflammation (C reactive protein), neuronal damage in the cellular [neuron specific enolase], and the extracellular compartment [matrix metalloproteinase-9, hyaluronic acid]. Further, cerebral magnetic resonance imaging was performed at baseline and day 7, while functional outcome was evaluated with the modified Rankin Scale (mRS) after 3, 6, and 12 months. Results: Based on data from 96 patients (age 64 ± 14 years), 23 TIA patients (NIHSS 0.6 ± 1.1) were compared with 73 MIS patients (NIHSS 2.4 ± 2.0). In a binary logistic regression analysis, the combination of NIHSS and serum biomarkers differentiated MIS from TIA with a sensitivity of 91.8% and a specificity of 60.9% [area under the curve (AUC) 0.84]. In patients with NIHSS 0 at admission, this panel resulted in a still acceptable sensitivity of 81.3% (specificity 71.4%, AUC 0.69) for the differentiation between MIS (n = 16) and TIA (n = 14). By adding age, remarkable sensitivities of 98.4, 100, and 98.2% for the prediction of an excellent outcome (mRS 0 or 1) were achieved with respect to time points investigated within the 1-year follow-up. However, the specificity was moderate and decreased over time (83.3, 70, 58.3%; AUC 0.96, 0.92, 0.91). Conclusion: This pilot study provides evidence that the NIHSS combined with selected serum biomarkers covering pathophysiological aspects of stroke may represent a useful tool to differentiate between MIS and TIA within 24 h after symptom onset. Further, this approach may accurately predict the mid-term outcome in minor stroke patients, which might help to allocate rehabilitative resources

Axonal Degeneration of the Vagus Nerve in Parkinson's Disease—A High-Resolution Ultrasound Study

Background: Recent histopathological studies revealed degeneration of the dorsal motor nucleus early in the course of Parkinson's disease (PD). Degeneration of the vagus nerve (VN) axons following neurodegeneration of brainstem vagal nuclei should be detectable by high-resolution ultrasound (HRUS) as a thinning of the VNs.Methods: We measured both VNs cross-sectional area (VN-CSA) of 35 patients with PD and 35 age- and sex-matched healthy controls at the level of the thyroid gland using HRUS.Results: On both sides, the VN-CSA was significantly smaller in PD patients than in controls (right: 2.1 ± 0.4 vs. 2.3 ± 0.5 mm2, left 1.5 ± 0.4 vs. 1.8 ± 0.4 mm2; both p < 0.05). There was no correlation between the right or left VN-CSA and age, the Hoehn & Yahr stage, disease duration, the motor part of the Unified Parkinson's Disease Rating Scale score, the Montreal Cognitive Assessment score, or the Non-motor Symptoms Questionnaire, and Scale for Parkinson's disease score including its gastrointestinal domain.Conclusions: These findings provide evidencethat atrophy of the VNs in PD patients can be detected in-vivo by HRUS

Enlarged cross-sectional area of the left vagus nerve in patients with major depressive disorder

PurposeAutonomic dysfunction and a chronic low-grade inflammation are supposed to play a role in the etiology of major depressive disorder (MDD). The vagus nerves (VN) form a major part of the parasympathetic nervous system and of the gut-brain axis. They are supposed to exert anti-inflammatory and epithelial barrier protective effects in the gut. A reduced vagal activity was described in patients with MDD. We aimed to examine the VN in patients with MDD with high-resolution ultrasound (HRUS) and hypothesized that the cross-sectional area (CSA) and the echogenicity of the VNs were altered in comparison to healthy controls.Materials and methodsThe echogenicity (gray scale mean) and the CSA of the cervical VNs at the level of the thyroid gland and both median nerves were examined with HRUS in 50 patients with MDD and 50 matched healthy controls.ResultsThe left VN-CSA was significantly larger in the MDD group compared to the control group (1.7 ± 0.4 mm2 versus 1.5 ± 0.4 mm2; p = 0.045). The CSA of the right VN and both median nerves (MN) were similar between groups. In MDD subgroup analyses, recurrent depressive disorders were the main contributing factor for the left VN-CSA enlargement. Echogenicity was not altered in the VN and MN between groups.ConclusionThe enlargement of the left VN-CSA in patients with MDD, and especially in these patients with recurrent depressive disorders, might turn out as a promising imaging biomarker. Longitudinal studies are warranted to examine whether the VNs-CSA change in the course of MDD

Elevated serum levels of anti-collagen type I antibodies in patients with spontaneous cervical artery dissection and ischemic stroke: a prospective multicenter study

IntroductionSpontaneous cervical artery dissection (sCAD) is a rare vasculopathy whose trigger is still unknown. We hypothesized that autoimmunity against components of the vascular wall might play a critical role in sCAD and examined anti-collagen type I antibodies in patients with sCAD, acute ischemic stroke, patients with thromboendarterectomy, and controls.MethodsFifty-seven patients with sCAD (age 45.7 ± 10.2 years, female 18 (31.6%)) were prospectively enrolled in four German stroke centers. Blood samples were collected at baseline, at day 10 ± 3, and after 6 ± 1 months. Patients with ischemic stroke not related to CAD (n=54, age 56.7 ± 13.7 years, female 15 (27.8%)), healthy probands (n=80, age 57.4 ± 12.9 years, female 56 (70%)), and patients undergoing thromboendarterectomy of the carotid artery (n=9, age 70.7 ± 9.3 years, female 2 (22.2%)) served as controls. Anti-collagen type I antibodies were determined by enzyme-linked immunosorbent assays (ELISAs).ResultsPatients with acute sCAD had higher serum levels of anti-collagen type I antibodies (33.9 ± 24.6 µg/ml) than probands (18.5 ± 11.0 µg/ml; p <0.001) but lower levels than patients with ischemic stroke not related to sCAD (47.8 ± 28.4 µg/ml; p=0.003). In patients with sCAD, serum levels of anti-collagen type I antibodies were similar in the acute, subacute, and chronic phase. Levels of anti-collagen type I antibodies significantly correlated with circulating collagen type I (rho=0.207, p=0.003).ConclusionAnti-collagen type I antibodies seem not to represent a trigger for acute sCAD or ischemic stroke but may rather be linked to the metabolism and turnover of collagen type I

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11034-w

Evaluation of Freehand B-Mode and Power-Mode 3D Ultrasound for Visualisation and Grading of Internal Carotid Artery Stenosis.

BACKGROUNDCurrently, colour-coded duplex sonography (2D-CDS) is clinical standard for detection and grading of internal carotid artery stenosis (ICAS). However, unlike angiographic imaging modalities, 2D-CDS assesses ICAS by its hemodynamic effects rather than luminal changes. Aim of this study was to evaluate freehand 3D ultrasound (3DUS) for direct visualisation and quantification of ICAS.METHODSThirty-seven patients with 43 ICAS were examined with 2D-CDS as reference standard and with freehand B-mode respectively power-mode 3DUS. Stenotic value of 3D reconstructed ICAS was calculated as distal diameter respectively distal cross-sectional area (CSA) reduction percentage and compared with 2D-CDS.RESULTSThere was a trend but no significant difference in successful 3D reconstruction of ICAS between B-mode and power mode (examiner 1 {Ex1} 81% versus 93%, examiner 2 {Ex2} 84% versus 88%). Inter-rater agreement was best for power-mode 3DUS and assessment of stenotic value as distal CSA reduction percentage (intraclass correlation coefficient {ICC} 0.90) followed by power-mode 3DUS and distal diameter reduction percentage (ICC 0.81). Inter-rater agreement was poor for B-mode 3DUS (ICC, distal CSA reduction 0.36, distal diameter reduction 0.51). Intra-rater agreement for power-mode 3DUS was good for both measuring methods (ICC, distal CSA reduction 0.88 {Ex1} and 0.78 {Ex2}; ICC, distal diameter reduction 0.83 {Ex1} and 0.76 {Ex2}). In comparison to 2D-CDS inter-method agreement was good and clearly better for power-mode 3DUS (ICC, distal diameter reduction percentage: Ex1 0.85, Ex2 0.78; distal CSA reduction percentage: Ex1 0.63, Ex2 0.57) than for B-mode 3DUS (ICC, distal diameter reduction percentage: Ex1 0.40, Ex2 0.52; distal CSA reduction percentage: Ex1 0.15, Ex2 0.51).CONCLUSIONSNon-invasive power-mode 3DUS is superior to B-mode 3DUS for imaging and quantification of ICAS. Thereby, further studies are warranted which should now compare power-mode 3DUS with the angiographic gold standard imaging modalities for quantification of ICAS, i.e. with CTA or CE-MRA

Comparing the accuracy of ultrasound-based measurements of the cervical vagus nerve

Abstract Vagus nerve stimulation (VNS) has become a promising therapy especially for drug resistant epilepsy and other pathologies. Side effects or missing therapeutic success are observed due to cuff electrodes that are too narrow or too wide. Preoperative high-resolution ultrasound is used to evaluate the size of the cervical vagus nerve (CVN) to estimate the size of cuff electrodes for VNS. It remains unclear how precise ultrasound reflects the CVN dimensions, which has been the objective of this study. CVN cross-sections and diameters were investigated in 23 sides from 12 bodies, using ultrasound, histology, and CVN casting in situ as a reference. Morphometric data were obtained including fascicle count and nerve composition in histology. CVN yielded significant side-, age-, and BMI-related differences. CVN cross-sections were smaller in ultrasound when compared to casting and histology (1.5 ± 0.4 vs. 3.1 ± 0.9 vs. 2.3 ± 0.7 mm2). With the given setting in ultrasound, CVN cross-sections were consistently underestimated when compared to casting. Ultrasound-based cross-section measurements are related to a biased estimation of CVN size. A factor to correct for method related differences may help to adjust for accurate cuff electrode sizes for patient needs and to reduce undesired effects and potentially material consumption

Inter-method agreement between power-mode 3DUS and 2D-CDS.

<p><b>(A</b> and <b>B</b>) Inter-method agreements between power-mode 3DUS and 2D-CDS for grading ICAS are visualised by Bland and Altman analyses with the differences in stenotic values—assessed as distal <i>diameter</i> (<b>A</b> = examiner 1 and <b>A’</b> = examiner 2) respectively <i>CSA</i> (<b>B</b> = examiner 1 and <b>B’</b> examiner 2) reduction percentage—plotted against the mean stenotic value of both modalities. For the comparison of stenotic values assessed as distal <i>diameter</i> reduction percentage with 2D-CDS the Bland and Altman analyses (<b>A</b> and <b>A’</b>) showed no evidence of bias between methods but moderate limits of agreement (<b>A</b> bias 0.4%, limits of agreement 20.0 and -19.2; <b>A’</b> bias 0.4, limits of agreement 25.0 and -24.2). Assessment of stenotic value with power-mode 3DUS as distal <i>CSA</i> reduction percentage accounted for a permanent overestimation of ICAS in comparison to 2D-CDS and wide limits of agreement (<b>B</b> bias -9.3, limits of agreement 17.1 and -35.7; <b>B’</b> bias -11.4, limits of agreement 15.2 and -37.6). Note that ICAS number 33 (marked in red) was assumed to be an outlier when assessing stenotic value via CSA reduction percentage by both examiners as shown in the box-and-whisker plots (<b>C</b> and <b>C’</b>). Hence, Bland and Altman analyses with stenotic value assessed as distal CSA reduction percentage (<b>B</b> and <b>B’</b>) were performed without ICAS number 33. 3DUS three-dimensional ultrasound, 2D-CDS 2D colour-coded duplexsonography, ICAS internal carotid artery stenosis, SD standard deviation.</p

Intra-rater, inter-rater and inter-method agreement of 3D ultrasound (3DUS) for quantification of internal carotid artery stenosis (ICAS).

<p>Intra-rater, inter-rater and inter-method agreement of 3D ultrasound (3DUS) for quantification of internal carotid artery stenosis (ICAS).</p