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

Introduction: Spontaneous 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. Methods: Fifty-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). Results: Patients 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). Conclusion: Anti-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.

Impaired Modulation of the Autonomic Nervous System in Adult Patients with Major Depressive Disorder.

Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate variability (HRV) was only examined while resting. So far, it remains unclear whether the dysbalance of the ANS in patients with MDD is restricted to resting or whether it is also evident during sympathetic and parasympathetic activation. The aim of this study was to compare the responses of the ANS to challenges that stimulated the sympathetic and, respectively, the parasympathetic nervous systems in patients with MDD. Forty-six patients with MDD (female 27 (58.7%), mean age 44 ± 17 years) and 46 healthy controls (female 26 (56.5%), mean age 44 ± 20 years) underwent measurement of time- and frequency-dependent domains of HRV at rest, while standing (sympathetic challenge), and during slow-paced breathing (SPB, vagal, i.e., parasympathetic challenge). Patients with MDD showed a higher heart rate, a reduced HRV, and a diminished vagal tone during resting, standing, and SPB compared to controls. Patients with MDD and controls responded similarly to sympathetic and vagal activation. However, the extent of modulation of the ANS was impaired in patients with MDD, who showed a reduced decrease in the vagal tone but also a reduced increase in sympathetic activity when switching from resting to standing. Assessing changes in the ANS during sympathetic and vagal activation via respective challenges might serve as a future biomarker and help to allocate patients with MDD to therapies like HRV biofeedback and psychotherapy that were recently found to modulate the vagal tone.

Imbalance of the von Willebrand Factor - ADAMTS-13 axis in patients with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an ultra-rare, autosomal-dominant small vessel disease caused by loss-of-function variants in the gene TREX1. Recently, elevated serum levels of von Willebrand Factor Antigen (vWF-Ag) pointed to an underlying endotheliopathy, and microvascular ischemia was suggested to contribute to the neurodegeneration in RVCL-S. Aim of this study was to further elucidate the endotheliopathy in RVCL-S. METHODS: vWF-Ag and ADAMTS-13 activity were repeatedly measured in two patients with genetically confirmed RVCL-S. Renal biopsy of both RVCL-S patients and autoptic brain, renal, hepatic, and pulmonary specimen of one patient with RVCL-S were examined immunohistochemically in comparison to matched controls. In addition, cerebral methylome analysis was performed in the autoptic brain specimen calculating differentially methylated positions compared to controls. RESULTS: While vWF-Ag and activity was strongly elevated, ADAMTS-13 activity was low in RVCL-S and further decreased over the course of the disease. Autoptic brain specimen showed signs of thromboinflammation in cerebral small vessels, and vWF-Ag staining was strongly positive in cerebral and renal small vessels in RVCL-S, while only a light to moderate vWF-Ag staining was found in controls. Cerebral methylome analysis yielded 115 differentially methylated CpGs (p < 0.05) in the deceased RVCL-S patient compared to the eight controls without brain pathology. One of the hypomethylated genes coded for ADAMTS-13 (p = 0.00056). CONCLUSIONS: These findings point to an imbalance of the vWF - ADAMTS-13 axis in patients with RVCL-S, that may finally lead to an accumulation of vWF-Ag in renal and cerebral small vessels. Elevated vWF-Ag levels may serve as an early serum marker reflecting disease activity. If confirmed, therapeutic approaches might aim at an inhibition of vWF-Ag or increase of ADAMTS-13 activity in the future.

A Specific Pattern of Routine Cerebrospinal Fluid Parameters Might Help to Identify Cases of West Nile Virus Neuroinvasive Disease.

BACKGROUND: Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease. The prompt identification of the respective virus is important to guide not only treatment but also potential public health countermeasures. However, in about 40% of cases, no virus is identified despite an extensive diagnostic workup. The aim of the present study was to analyze demographic, seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their utility for the prediction of the causative virus. METHODS: Demographic data, season, and routine CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio, and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME. RESULTS: In total, 156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally, 64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older, predominantly male, showed a severe disruption of the blood-CSF-barrier, a high proportion of neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a multinominal logistic regression analysis, the accuracy of these CSF parameters together with age and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology (66.7%), VZV (61.8%), and enteroviruses (51.9%). CONCLUSIONS: Cases with WNV ME showed a specific pattern of routine CSF parameters and demographic data that allowed for their identification with good accuracy. These findings might help to guide the diagnostic workup in cases with viral ME, in particular allowing the timely identification of cases with ME due to WNV.

No Harmful Effect of Endovascular Treatment before Decompressive Surgery-Implications for Handling Patients with Space-Occupying Brain Infarction.

This study explored short- and mid-term functional outcomes in patients undergoing decompressive hemicraniectomy (DHC) due to space-occupying cerebral infarction and asked whether there is a potentially harmful effect of a priorly performed endovascular treatment (EVT). Medical records were screened for patients requiring DHC due to space-occupying cerebral infarction between January 2016 and July 2021. Functional outcomes at hospital discharge and at 3 months were assessed by the modified Rankin Scale (mRS). Out of 65 patients with DHC, 39 underwent EVT before DHC. Both groups, i.e., EVT + DHC and DHC alone, had similar volumes (280 ± 90 mL vs. 269 ± 73 mL, t-test, p = 0.633) and proportions of edema and infarction (22.1 ± 6.5% vs. 22.1 ± 6.1%, t-test, p = 0.989) before the surgical intervention. Patients undergoing EVT + DHC tended to have a better functional outcome at hospital discharge compared to DHC alone (mRS 4.8 ± 0.8 vs. 5.2 ± 0.7, Mann-Whitney-U, p = 0.061), while the functional outcome after 3 months was similar (mRS 4.6 ± 1.1 vs. 4.8 ± 0.9, Mann-Whitney-U, p = 0.352). In patients initially presenting with a relevant infarct demarcation (Alberta Stroke Program Early CT Score ≤ 5), the outcome was similar at hospital discharge and after 3 months between patients with EVT + DHC and DHC alone. This study provided no evidence for a harmful effect of EVT before DHC in patients with space-occupying brain infarction.

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study.

BACKGROUND: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. METHODS: This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. RESULTS: Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043). CONCLUSIONS: Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

Long-Term Course of Circulating Elastin, Collagen Type I, and Collagen Type III in Patients with Spontaneous Cervical Artery Dissection: a Prospective Multicenter Study.

An impaired integrity of vascular elements and the extracellular matrix (ECM) has been discussed to play a critical role in the pathophysiology of spontaneous cervical artery dissection (sCAD). This study aimed to explore the temporal course of circulating elastin, collagen type I, and collagen type III in patients with sCAD and evaluated their eligibility as diagnostic biomarkers. Patients with sCAD were prospectively enrolled in four German stroke centers. Blood samples were collected at baseline (acute phase), at day 10 ± 3 (subacute phase), and after 6 ± 1 months (chronic phase). Patients with acute ischemic stroke not related to sCAD, healthy probands, and patients undergoing thromboendarterectomy of the carotid artery served as control groups. Serum levels of elastin and collagen types I and III were determined by ELISAs. Fifty-seven patients with sCAD were enrolled. Compared to all three control groups, patients with sCAD had significantly lower levels of elastin and collagen type III at baseline and after 6 months. Compared to healthy probands, patients with sCAD showed similar collagen type I levels at baseline and in the subacute phase, but significantly increased levels after 6 months. As serum levels of elastin, collagen types I and III were not elevated in the acute phase, they do not appear eligible as biomarkers for the diagnosis of sCAD. Persisting low serum levels of elastin and collagen type III towards the chronic phase of sCAD strengthens the hypothesis of a subtle, in most cases clinically inapparent affection of the ECM in patients with sCAD.

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

Purpose: Autonomic 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 methods: The 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. Results: The 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. Conclusion: The 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.

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

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.

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.

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.

Evaluation of the interrater and intermethod agreement of the German multiparametric ultrasound criteria for the grading of internal carotid artery stenosis.

PURPOSE: The interdisciplinary German guidelines for the diagnosis and treatment of internal carotid artery stenosis (ICAS) recommend a multiparametric approach for the sonographic grading of extracranial ICAS. The aim of this study is to evaluate the interrater and intermethod agreement of this elaborated sonographic approach with different angiographic modalities. METHODS: Patients with extracranial ICAS were examined twice with colour-coded duplex sonography (CDS) by two experienced vascular neurologists. Each of the ten criteria and the resulting stenotic value were assessed. Grading of ICAS based on the multiparametric ultrasound criteria was compared with different angiography modalities (magnetic resonance angiography (MRA), computed tomography angiography (CTA), digital subtraction angiography (DSA)). RESULTS: Seventy-four consecutive patients with 91 extracranial ICAS were recruited from our stroke unit and neurovascular outpatient clinic. Interrater agreement for each single ultrasound criterion ranged from moderate to excellent (for the peak systolic velocity). Concerning the absolute stenotic value of ICAS, an excellent agreement between both ultrasound examiners with an ICC of 0.91 (range 0.87-0.94; p < 0.001) was found. In 96% of ICAS, the difference between the stenotic values was ≤ 10%. Intermethod agreements between CDS and DSA, CTA, and MRA were also good for both sonographers. CONCLUSION: Strictly adhering to the multiparametric "DEGUM ultrasound criteria", we found an excellent interrater agreement and a good intermethod agreement compared with angiography for the sonographic grading of extracranial ICAS. Thus, multiparametric CDS is in particular suitable for the follow up of extracranial ICAS even when examinations are done by different sonographers.

Multiparametric 3D Contrast-Enhanced Ultrasound to Assess Internal Carotid Artery Stenosis: A Pilot Study.

BACKGROUND AND PURPOSE: Extracranial internal carotid artery stenoses (ICASs) may greatly differ with respect to morphological and hemodynamical aspects. The aim of this pilot study was to evaluate the use of multiparametric 3-dimensional (3D) contrast-enhanced ultrasound (3D-CEUS) to comprehensively examine ICAS. METHODS: Fifteen patients with moderate to severe ICAS were examined with multiparametric 3D-CEUS, power-mode 3D ultrasound (3DUS), color-coded duplex sonography (CDS), and digital subtraction angiography (DSA) (n = 9). Multiparametric 3D-CEUS comprised the assessment of the morphology and the stenotic degree of ICAS and the measurement of the ipsistenotic cerebral circulation time (CCT). RESULTS: Multiparametric 3D-CEUS reliably visualized even complex aspects of ICAS such as ulcerated or heavily calcified plaques with high spatial resolution. When comparing the different methods to quantify ICAS, the intermethod agreement was good (ranging from poor to excellent) between 3D-CEUS and CDS, moderate (ranging from poor to good) between 3D-CEUS and DSA, and poor (ranging from poor to good) between CDS and DSA. The CCT was significantly longer in patients with ICAS than in healthy subjects (8.2 ± 1.5 seconds vs. 6.5 ± 1.3 seconds, P = .026). CONCLUSION: In this pilot study, bedside multiparametric 3D-CEUS provided reliable estimations of different morphological and hemodynamical aspects of ICAS, thus ideally complementing CDS.

Fluid Balance Variations During the Early Phase of Large Hemispheric Stroke Are Associated With Patients' Functional Outcome.

Background: From the variety of factors underlying the ischemia-associated edema formation in large hemispheric stroke (LHS), an increased brain water content during the early phase seems to have a pivotal role for long-lasting tissue damage. However, the importance of the fluid management during the acute phase of LHS has so far not been adequately studied. Therefore, this study explored the association between the fluid balance and functional outcome in patients suffering from LHS. Methods: We analyzed hospital-based medical records of 39 consecutive patients with LHS and decompressive hemicraniectomy. Over the first 10 days after admission, the volumes of all administered fluids were assessed daily and corrected for daily urinary output and insensible loss. Functional outcome at 3 months was assessed with the modified Rankin Scale (mRS) and dichotomized into an acceptable (mRS ≤ 4) vs. a poor outcome (mRS ≥ 5). Results: Compared to patients with a poor functional outcome (n = 19), those with an acceptable outcome (n = 20) were characterized by a significantly lower cumulative net fluid balance at day 5 (1.6 ± 2.5 vs. 3.4 ± 4.4 l), day 7 (2.0 ± 2.9 vs. 4.6 ± 5.2 l), and day 10 (0 ± 2.5 vs. 5.6 ± 6.2 l). In addition to age, only the cumulative net fluid balance at day 10 served as an independent factor for poor functional outcome in multiple regression analyses. Conclusion: These data provide evidence for a critical role of the early phase net fluid balance with respect to the functional outcome after LHS. This observation leads to the hypothesis that patients with LHS might benefit from a more restrictive volume therapy. However, prospective studies are warranted to establish a causal relationship and recommendations for treatment strategies.

Correlation between sonographic morphology and function of the cervical vagus nerves.

The heart receives parasympathetic and to a lesser degree sympathetic input via the vagus nerve. Here, we investigated whether morphological changes of the cervical vagus nerves (VN) as assessed by high-resolution ultrasound (HRUS) correlated with the autonomic cardiac innervation. Measurement of heart rate variability (HRV) and HRUS of the VNs were performed in 88 healthy subjects (50 female; mean age 56 ±â€¯18 years). HRV parameters and the cross-sectional area (CSA) of the VNs correlated both inversely with age. We also found an inverse correlation between the left VN-CSA and HRV as well as parasympathetic parameters. The results imply an asymmetric parasympathetic (vagal) innervation of the heart.

Assessing blink reflex circuits by three different afferent routes in Parkinson's disease.

OBJECTIVE: Degeneration of nuclei of the brainstem, especially parts of the vagal nuclei complex and the reticular formation, in Parkinson's disease (PD) may in part be responsible for nonmotor signs like obstipation, cardiac dysfunction and rapid eye movement sleep behavior disorder (RBD). The aim of the study was to establish a new blink reflex (BR) variant involving the vagal nuclei complex and the reticular formation and to investigate BR comprehensively using 3 different afferent routes in PD. METHODS: In this cross-sectional observational study in 30 PD patients and 30 age and sex matched healthy controls, BR was elicited by stimulation of the auricular branch of the vagus nerve (ABVN) and compared to conventional BR variants evoked by the trigeminal and median nerve. RESULTS: BRs could be elicited reliably by stimulation of ABVN in both groups. In none of the three BR variants, latencies or amplitudes differed between PD patients and controls. In PD, BR parameters were not related to cognition or presence of RBD. CONCLUSION: The present study did not provide evidence for malfunctioning of neural circuits subserving BRs elicited by three different afferents in PD. SIGNIFICANCE: Brainstem circuits mediating these BR variants may be spared from neurodegeneration in PD.

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.

Blood flow reversal from the external into the internal carotid artery-New insights into the hemodynamics at the carotid bifurcation.

BACKGROUND: Complex blood flow patterns are a well-known phenomenon at the carotid bifurcation. However, unlike for the descending aorta, a blood flow reversal has not been detected at the carotid bifurcation, so far. METHODS: In 17 subjects, flow patterns with focus on blood flow reversal were examined at the carotid bifurcation with vector flow imaging. RESULTS: We found a blood flow reversal from the external carotid artery (ECA) into the internal carotid artery (ICA) in 13 of 25 (52%) carotid bifurcations. The blood flow reversal ranged 5.3 ± 1.7 mm (range 2.6-8.3 mm) distally to the beginning of the ECA and lasted 105 ± 59 ms (range 32-225 ms). The mean peak systolic velocity within the blood flow reversal was 12.5 ± 4.6 cm/s (range 5-18 cm/s). CONCLUSION: A blood flow reversal from the ECA into the ICA during the systole is a frequent finding at the carotid bifurcation. Considering ischemic stroke, retrograde embolism from plaques in the proximal ECA into the ICA might play a role.

Sonographic evaluation of the vagus nerves: Protocol, reference values, and side-to-side differences.

INTRODUCTION: Reported sonographic reference values for the vagus nerves (VNs) vary greatly. We aimed to generate reference values in a large cohort and examine intrarater, interrater, and across-ultrasound systems agreement. METHODS: The VNs of 60 healthy subjects were examined by 2 sonographers and with 2 ultrasound systems. Cross-sectional areas (CSAs) of each VN were assessed at the level of the carotid sinus [proximal measurement level (ML)] and thyroid gland (distal ML). RESULTS: Mean VN CSA was significantly larger on the right side (proximal ML: 2.7 ± 0.6 mm2 vs. 2.1 ± 0.5 mm2 ; distal ML: 2.6 ± 0.6 mm2 vs. 1.9 ± 0.4 mm2 ). VN CSA decreased with increasing age. There were good intrarater, interrater, and across-ultrasound systems agreements. DISCUSSION: The right VN CSA is significantly larger than the left. These side- and age-specific reference values for the VN may be useful for future studies. Muscle Nerve 57: 766-771, 2018.