Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome.

BACKGROUND: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. METHODS: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). RESULTS: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. CONCLUSIONS: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.

Detection of a pituitary macroadenoma with transcranial ultrasonography: Principles and potential clinical applications.

Transcranial color-coded duplex sonography (TCCS) allows to study intracranial vessels through the intact skull, but the visualization of normal and pathologic brain structures in adults is often suboptimal due to inadequate acoustic window. The full potential of TCCS for clinical practice remains unfulfilled. Here, we describe the ability of TCCS to detect a non-functioning pituitary macroadenoma in a 58-year-old man affected by headache. The macroadenoma was visualized as a roundish, well-defined mass, mildly hyperechogenic compared to the hypoechogenic mesencephalic brainstem but mainly hypoechogenic compared to the surrounding intracranial structures. Intracranial vessels represented useful landmarks. Using tissue harmonic imaging mode, the borders of the macroadenoma were visualized more clearly. Macroadenoma characteristics were confirmed by magnetic resonance imaging. Neurosonologists should be aware of the possibility to incidentally find, during routinary TCCS, pituitary macroadenomas or other brain tumors (as incidentalomas), worthy to be recognized and referred for further investigations.

Transcranial color-coded duplex sonography assessment of cerebrovascular reactivity to carbon dioxide: an interventional study.

BACKGROUND: The investigation of CO2 reactivity (CO2-CVR) is used in the setting of, e.g., traumatic brain injury (TBI). Transcranial color-coded duplex sonography (TCCD) is a promising bedside tool for monitoring cerebral hemodynamics. This study used TCCD to investigate CO2-CVR in volunteers, in sedated and mechanically ventilated patients without TBI and in sedated and mechanically ventilated patients in the acute phase after TBI. METHODS: This interventional investigation was performed between March 2013 and February 2016 at the surgical ICU of the University Hospital of Zurich. Ten volunteers (group 1), ten sedated and mechanically ventilated patients (group 2), and ten patients in the acute phase (12-36 h) after severe TBI (group 3) were included. CO2-CVR to moderate hyperventilation (∆ CO2 -5.5 mmHg) was assessed by TCCD. RESULTS: CO2-CVR was 2.14 (1.20-2.70) %/mmHg in group 1, 2.03 (0.15-3.98) %/mmHg in group 2, and 3.32 (1.18-4.48)%/mmHg in group 3, without significant differences among groups. CONCLUSION: Our data did not yield evidence for altered CO2-CVR in the early phase after TBI examined by TCCD. TRIAL REGISTRATION: Part of this trial was performed as preparation for the interventional trial in TBI patients (clinicaltrials.gov NCT03822026 , 30.01.2019, retrospectively registered).

Cerebral metabolism is not affected by moderate hyperventilation in patients with traumatic brain injury.

BACKGROUND: Hyperventilation-induced hypocapnia (HV) reduces elevated intracranial pressure (ICP), a dangerous and potentially fatal complication of traumatic brain injury (TBI). HV decreases the arteriolar diameter of intracranial vessels, raising the risk of cerebral ischemia. The aim of this study was to characterize the effects of moderate short-term HV in patients with severe TBI by using concomitant monitoring of cerebral metabolism, brain tissue oxygen tension (PbrO2), and cerebral hemodynamics with transcranial color-coded duplex sonography (TCCD). METHODS: This prospective trial was conducted between May 2014 and May 2017 in the surgical intensive care unit (ICU) at the University Hospital of Zurich. Patients with nonpenetrating TBI older than 18 years of age with a Glasgow Coma Scale (GCS) score < 9 at presentation and with ICP monitoring, PbrO2, and/or microdialysis (MD) probes during ICU admission within 36 h after injury were included in our study. Data collection and TCCD measurements were performed at baseline (A), at the beginning of moderate HV (C), after 50 min of moderate HV (D), and after return to baseline (E). Moderate HV was defined as arterial partial pressure of carbon dioxide 4-4.7 kPa. Repeated measures analysis of variance was used to compare variables at the different time points, followed by post hoc analysis with Bonferroni adjustment as appropriate. RESULTS: Eleven patients (64% males, mean age 36 ± 14 years) with an initial median GCS score of 7 (IQR 3-8) were enrolled. During HV, ICP and mean flow velocity (CBFV) in the middle cerebral artery decreased significantly. Glucose, lactate, and pyruvate in the brain extracellular fluid did not change significantly, whereas PbrO2 showed a statistically significant reduction but remained within the normal range. CONCLUSION: Moderate short-term hyperventilation has a potent effect on the cerebral blood flow, as shown by TCCD, with a concomitant ICP reduction. Under the specific conditions of this study, this degree of hyperventilation did not induce pathological alterations of brain metabolites and oxygenation. TRIAL REGISTRATION: NCT03822026 . Registered on 30 January 2019.

Symptomatic intracranial atherosclerotic disease: an ultrasound 2-year follow-up pilot study.

INTRODUCTION: The objective of this single-center pilot study was to assess if symptomatic intracranial atherosclerotic disease (ICAD) ultrasound features change through the 2 years after acute ischemic stroke or TIA, being ICAD a relevant cause of acute ischemic stroke or TIA, linked to high rates of recurrent stroke. METHODS: We consecutively enrolled 48 patients with acute ischemic stroke or TIA with symptomatic ICAD detected by transcranial color-coded duplex sonography (TCCS) and confirmed by MR-angiography and/or CT-angiography. We set a neurosonological and clinical follow-up at 3, 6, 12, and 24 months (T0, T1, T2, T3, and T4). RESULTS: We observed that the hemodynamic effect of the stenosis changed during the 2-year follow-up, as revealed by the modifications of Peak Systolic Velocity (PSV) (Friedman-ANOVA test, p < 0.001). The pairwise post-hoc analysis showed a statistically significant difference between PSV at T0 and PSV at T3 (p = 0.005) and between PSV at T0 and PSV at T4 (p < 0.001) being PSV at T3 and T4 lower than PSV at T0. Seven patients had a new event in the first 12 months. CONCLUSIONS: The high rate of recurrent stroke or death among ICAD patients seems to be independent of progressive arterial narrowing. A wide multicenter follow-up study is needed in order to identify the factors that, alongside the hemodynamic features, contribute to the high risk of recurrent stroke among patient with symptomatic ICAD.

The characteristics of transcranial color-coded duplex sonography in children with cerebral arteriovenous malformation presenting with headache.

PURPOSE: Cerebral arteriovenous malformations (AVM) are uncommon lesions. They are most often presented in childhood as intracranial hemorrhage. The aim of this report is to present the use of transcranial color-coded duplex sonography (TCCS) in detection of AVMs in children suffering headache. METHODS: This report describes five pediatric patients with headache and cerebral AVM which were initially discovered by TCCS. Diagnosis was confirmed by magnetic resonance imaging and digital subtraction angiography. RESULTS: In all patients, TCCS showed saccular enlargement of the vessels with a multicolored pattern corresponding to the different directions of blood flow. Spectral analysis showed significantly high flow systolic and diastolic velocities and low resistance index. CONCLUSIONS: In this report, we describe TCCS as a valuable non-invasive, harmless, low-cost, widely available method for the detection and follow-up of hemodynamic changes of AVMs in children with headache, before and after treatment.

Evaluation of cerebral blood flow in acute ischemic stroke patients with atrial fibrillation: A sonographic study.

BACKGROUND/PURPOSE: Although cerebral emboli are a frequent cause of cardiogenic stroke, the possibility of a reduction in cerebral perfusion consequent to arrhythmia or impaired cardiac function should be considered in patients with atrial fibrillation (AF). METHODS: We reviewed sonographic studies and clinical features of patients with acute ischemic stroke. A total of 144 patients with AF and 144 age- and sex-matched patients with small vessel occlusion but without AF were included. RESULTS: Patients with AF had significantly lower peak systolic velocity (PSV), mean velocity, flow volume (p < 0.001), and end-diastolic velocity (p = 0.035) of the internal carotid artery (ICA); significantly lower cerebral blood flow (p < 0.001); and lower flow velocities of the middle cerebral artery (p < 0.01) than patients with small vessel occlusion but without AF. In patients with AF, there was an inverse linear correlation between ICA end-diastolic velocity, mean velocity (p < 0.001), flow volume (p = 0.025), middle cerebral artery flow velocities (p < 0.05), and age. Cardiac ejection fraction had a positive linear correlation with ICA PSV (p = 0.016) but an inverse correlation with the heart rate (p = 0.009). There was a significant decline in PSV (p = 0.002), resistance index (p < 0.001), and flow volume (p = 0.0121) of the ICA as well as cerebral blood flow (p = 0.009) as the heart rate increased. CONCLUSION: Cerebral blood flow is markedly reduced in ischemic stroke patients with AF as compared with that in patients with small vessel disease but without AF.

Transcranial Color Coded Duplex Sonography Findings in Stroke Patients Undergoing Rehabilitation: An Observational Study.

Background Transcranial color-coded duplex sonography (TCCD) provides information on intracranial blood flow status in stroke patients and can predict rehabilitation outcomes. Objective This study aimed to assess middle cerebral artery (MCA) parameters using TCCD in MCA territory stroke patients admitted for rehabilitation and correlate with clinical outcome measures. Materials and Methods Patients aged 18 to 65 years with a first MCA territory stroke, within 6 months of onset were recruited. The clinical outcome scales and TCCD parameters were assessed at both admission and discharge. The scales used were the Scandinavian stroke scale (SSS), Barthel Index (BI), modified Rankin Scale (mRS), Fugl-Meyer upper extremity scale (FMA-UE), modified motor assessment scale (mMAS) scores. TCCD parameters measured were MCA peak systolic, end diastolic, mean flow velocities (MFV), and index of symmetry (SI) and were correlated with clinical scores. Results Fourteen patients were recruited with median age of 56.5 years, median duration of stroke was 42.5 days. Mean flow velocities of affected and unaffected MCA were 46.2 and 50.7 cm/s, respectively. Flow velocities and SI did not change between the two assessments. There was significant improvement in clinical outcome scores at discharge. Significant correlation was observed for patient group with SI > 0.9 at admission with FMA-UE, SSS, and BI scores at discharge ( p < 0.05). Conclusion Flow velocity parameters did not change during in-patient rehabilitation. Patients with symmetric flow at admission had improved clinical outcomes measure scores at discharge. Thus SI can predict rehabilitation outcomes in stroke survivors.

Validation of an Oscillation Test for the Sonographic Assessment of Fetal-Type Posterior Cerebral Artery Variants in Migraine Patients with Visual Aura.

Anatomic variants of the posterior circle of Willis, including the fetal-type posterior cerebral artery (FPCA), may contribute to the formation of visual aura in migraine. We sought to validate an oscillation test to investigate FPCA frequency in migraine using transcranial color-coded duplex ultrasonography (TCCS). First, the diagnostic accuracy of the oscillation test used to identify FPCA variants by TCCS was assessed in stroke patients with available computed tomography angiography (CTA) as the set gold standard. Second, in a cross-sectional study, patients with migraine with visual aura (MWVA) and migraine without aura (MWOA), as well as healthy controls, were prospectively recruited for sonographic assessment of FPCA variants. We compared FPCA frequency between migraine patients and controls using χ2-testing and performed logistic regression analysis to investigate a potential association between MWVA and the presence of FPCA variants. Specificity, sensitivity and positive and negative predictive values for sonographic identification of FPCA with CTA as the set gold standard were 93%, 77%, 63% and 96% (partial FPCA) and 99%, 78%, 88% and 98% (complete FPCA), respectively. One hundred forty-two migraine patients (39 ± 12 y, 90 MWVA and 52 MWOA) and 49 healthy controls (31 ± 12 y) were recruited. The χ2 testing did not reveal significant differences in FPCA frequency as assessed by TCCS (unilateral or bilateral, partial and/or complete) between migraine patients and controls (MWVA: 40/90 or 44.4%, MWOA: 22/52 or 42.3%, controls: 24/49 or 49%, p = 0.79). Similarly, the frequencies of partial FPCA (p = 0.61) and complete FPCA (p = 0.27) did not vary significantly among groups. Logistic regression analysis revealed no interaction effect between migraine diagnosis and FPCA prevalence (any FPCA), when adjusted for age and sex. The sonographic oscillation test can be used as a non-invasive method to identify partial and complete FPCA variants with high specificity and reasonable sensitivity. Our findings suggest that FPCA variants do not contribute to the formation of visual migraine aura.

Clinical Value of TCCD for Evaluating the Prognosis of Patients with Severe Traumatic Brain Injury After Large Decompressive Craniectomy: A Retrospective Study.

INTRODUCTION: It is challenging to assess the prognosis of patients with severe traumatic brain injury (sTBI) after large decompressive craniectomy (DC). The aim of this study was to evaluate the clinical value of transcranial color-coded duplex sonography (TCCD) for assessing the prognosis of sTBI patients 6 months after large DC. METHODS: This was a retrospective observational study that consecutively enrolled 84 patients with sTBI who were followed up for prognosis until 6 months after large DC. The primary endpoint was the Glasgow Outcome Score (GOS). According to the GOS, patients were divided into an unfavorable prognosis group (GOS 1-3, n = 47) and a favorable prognosis group (GOS 4-5, n = 37). RESULTS: Significant between-group differences were found in age and hemodynamic parameters (systolic peak blood flow velocity, end-diastolic blood flow velocity, mean blood flow velocity, pulsatility index and resistance index) of the middle cerebral artery detected by TCCD (P < 0.05 for all). Subsequently, ridge regression was used to build a prognostic model for patients with large DC. Based on the cerebral hemodynamic parameters measured by TCCD and age, the mean (± standard deviation) area under the curve of the prognostic model in patients with sTBI after large DC was 0.76 ± 0.22. The sensitivity and specificity were 82.08% and 74.17%, respectively. CONCLUSIONS: The cerebral hemodynamic parameters detected by TCCD, combined with age, may be used to predict the outcomes of patients with sTBI at 6 months after large DC. As a noninvasive method, TCCD has the potential to assess the prognosis of these patients. TRIAL REGISTRATION: ChiCTR: ChiCTR1800019758. Registered 27 November 2018-retrospectively registered ( http://www.chictr.org.cn/index.aspx ).

Classification of Intracranial Stenoses: Discrepancies between Transcranial Duplex Sonography and Computed Tomography Angiography.

Transcranial color-coded duplex sonography (TCCS) and computed tomography angiography (CTA) are widely used to identify intracranial stenoses (ISs). We assessed concordance of IS grading between TCCS and CTA and proposed new TCCS criteria for severe IS ≥70%. One hundred two stroke patients (70 ± 13 y) with TCCS-identified IS were included. TCCS and CTA were performed within 24 h after admission. TCCS peak systolic velocity cutoffs for <50%/50%-69% stenoses were ≥155/≥220 cm/s (middle cerebral artery [MCA]-M1), ≥100/≥140 cm/s (MCA-M2), ≥120/≥155 cm/s (anterior cerebral artery [ACA]-A1), ≥100/≥145 cm/s (posterior cerebral artery [PCA]-P1 and PCA-P2), ≥90/≥120 cm/s (vertebral artery [VA]-V4) and ≥100/≥140 cm/s (basilar artery [BA]). Criteria for ≥70% stenoses were, despite variable flow velocities, post-stenotic flow alterations and/or leptomeningeal collateral flow. One hundred seventy-seven ISs were detected by TCCS. The number and grade (<50%/50%-69%/≥70%) of ISs were MCA 70 (39/19/12), BA 24 (9/11/4), ACA 21 (14/7/0), PCA 49 (29/15/5) and VA 13 (2/6/5). IS localization was confirmed by CTA in 84 of 177 cases (48%): MCA, 41/70 (59%); BA, 16/24 (67%); ACA 2/21, (10%); PCA, 17/49 (35%); VA, 8/13 (62%). Concordance between TCCS and CTA grading was (<50%/50%-69%/≥70%) 17%/19%/77%. TCCS and CTA exhibited substantial differences in the detection and grading of IS. Higher concordance rates for severe stenosis support our proposed TCCS criteria.

Assessment of intracranial venous blood flow after subarachnoid hemorrhage: a new approach to diagnose vasospasm with transcranial color-coded duplex sonography.

OBJECTIVETranscranial color-coded duplex sonography (TCCS) is a reliable tool that is used to assess vasospasm in the M1 segment of the middle cerebral artery (MCA) after subarachnoid hemorrhage (SAH). A distinct increase in blood flow velocity (BFV) is the principal criterion for vasospasm. The MCA/internal carotid artery (ICA) index (Lindegaard Index) is also widely used to distinguish between vasospasm and cerebral hyperperfusion. However, extracranial ultrasonography assessment of the neck vessels might be difficult in an intensive care unit. Therefore, the authors evaluated whether the relationship of intracranial arterial to venous BFV might indicate vasospasm with similar or even better accuracy.METHODSPatients who presented between 2008 and 2015 with aneurysmal SAH were prospectively enrolled in the study. Digital subtraction angiography (DSA) and TCCS were performed within 24 hours of each other to assess vasospasm 8-10 days after SAH. The following different TCCS parameters were analyzed to assess vasospasm in the MCA and were compared with the gold-standard DSA parameters: 1) mean time-averaged maximum BFV (Vmean) of the MCA, 2) peak systolic velocity (PSV) of the MCA, 3) the Lindegaard Index using Vmean as well as PSV, and 4) a new arteriovenous index (AVI) between the MCA and the basal vein of Rosenthal using Vmean and PSV. The best cutoff values for these parameters to distinguish vasospasm from normal perfusion or hyperperfusion were calculated using receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, and negative predictive value as well as the overall accuracy for each cutoff value were analyzed.RESULTSA total of 102 patients (mean age 52 ± 12 years) were evaluated. Bilateral MCA assessment by TCCS was successful in all patients. In 6 cases (3%), the BFV of the basal vein of Rosenthal could not be analyzed. The AVI could not be calculated in 50 of 204 cases (25%) because the insonation quality was very low in one of the ICAs. An AVI > 10 for Vmean and an AVI > 12 for systolic velocity provided the highest accuracies of 87% and 86%, respectively. Regarding the Lindegaard Index, the accuracy was highest using a threshold of > 3 for the mean BFV (84%) as well as systolic BFV (80%). BFVs in the MCA of ≥ 120 cm/sec (Vmean) and ≥ 200 cm/sec (PSV) predicted vasospasm with accuracies of 84% and 83%, respectively. A combined analysis of the MCA BFV and the AVI led to a slight increase in specificity (Vmean, 94%; PSV, 93%) and positive predictive value (Vmean, 88%; PSV 86%) without further improvement in accuracy (Vmean, 88%; PSV, 84%).CONCLUSIONSThe intracranial AVI is a reliable parameter that can be used to assess vasospasm after SAH. Its reliability for differentiating vasospasm and hyperperfusion is slightly higher than that for the established Lindegaard Index, and this method has the additional advantage of a remarkably lower failure rate.

Transcranial color-coded duplex sonography for evaluation of midline-shift after chronic-subdural hematoma evacuation (TEMASE): A prospective study.

OBJECTIVE: The incidence of chronic Subdural hematoma (cSDH) is increasing and its rate of recurrence varies from 5 to 33%. A postoperative brain midline-shift (MLS) on computed tomography (CT) equal or larger than 5mm is a risk factor for recurrence. Transcranial color-coded duplex sonography (TCCDS) is a noninvasive bedside reproducible technique useful to detect MLS. The aim of our study was to compare in patients affected by cSDH, the values of MLS obtained pre- and post-operatively by TCCDS and brain CT. PATIENTS AND METHODS: 32 patients affected by cSDH entered the study between July 2016 and January 2017. MLS values obtained by TCCDS and brain CT were compared using Bland-Altman plot and linear regression analysis. Using the same techniques we also explored if the agreement between the two imaging modes was comparable in pre- and post-operative data pairs. RESULTS: 64 data pairs of MLS values obtained by TCCDS and CT were analysed. Bland-Altman diagrams did not show any systematic bias of the data and linear regression indicated a significant correlation between the two measures both before and after hematoma evacuation. CONCLUSION: In patients affected by cSDH, MLS values obtained before and after surgery by TCCDS are comparable to those obtained by CT; TCCDS might be considered an alternative to CT scan in the management of patients after cSDH evacuation. We suggest that close clinical bedside examination and TCCDS might be appropriate for the post-operative management of cSDH, reserving CT scan only to patients with overt clinical deterioration and/or increasing MLS.

Adding blood to agitated saline significantly improves detection of right-to-left shunt by contrast-transcranial color-coded duplex sonography.

Contrast-transcranial Doppler and contrast-transcranial color-coded duplex sonography (c-TCCD) have been reported to have high sensitivity in detecting patent foramen ovale as compared with transesophageal echocardiography. An international consensus meeting (Jauss and Zanette 2000) recommended that the contrast agent for right-to left-shunt (RLS) detection using contrast-transcranial Doppler be prepared by mixing 9 mL of isotonic saline solution and 1 mL of air. The aim of our study was to determine whether adding blood to the contrast agent results in improved detection of RLS. We enrolled all consecutive patients admitted to our neurosonology laboratory for RLS diagnosis. For each patient, we performed c-TCCD both at rest and during the Valsalva maneuver using two different contrast agents: ANSs (1 mL of air mixed with 9 mL of normal saline) and ANSHBs (1 mL of air mixed with 8 mL of normal saline and 1 mL of the patient's blood). To classify RLS, we used a four-level visual categorization: (i) no occurrence of micro-embolic signals; (ii) grade I, 1-10 signals; (iii) grade II, >10 signals but no curtain; grade III, curtain pattern. We included 80 patients, 33 men and 47 women. RLS was detected in 18.8% at rest and in 35% during the Valsalva maneuver using ANSs, and in 31.3% and in 46.3% using ANSHBs, respectively (p < 0.0001). There was a statistically significant increase in the number of micro-embolic signals with the use of ANSHBs. The use of blood mixed with saline solution and air as a c-TCCD contrast agent produced an increase in positive tests and a higher grade of RLS compared with normal saline and air alone, either with or without the Valsalva maneuver.