Non-Invasive Tools in Perioperative Stroke Risk Assessment for Asymptomatic Carotid Artery Stenosis with a Focus on the Circle of Willis.

This review aims to explore advancements in perioperative ischemic stroke risk estimation for asymptomatic patients with significant carotid artery stenosis, focusing on Circle of Willis (CoW) morphology based on the CTA or MR diagnostic imaging in the current preoperative diagnostic algorithm. Functional transcranial Doppler (fTCD), near-infrared spectroscopy (NIRS), and optical coherence tomography angiography (OCTA) are discussed in the context of evaluating cerebrovascular reserve capacity and collateral vascular systems, particularly the CoW. These non-invasive diagnostic tools provide additional valuable insights into the cerebral perfusion status. They support biomedical modeling as the gold standard for the prediction of the potential impact of carotid artery stenosis on the hemodynamic changes of cerebral perfusion. Intraoperative risk assessment strategies, including selective shunting, are explored with a focus on CoW variations and their implications for perioperative ischemic stroke and cognitive function decline. By synthesizing these insights, this review underscores the potential of non-invasive diagnostic methods to support clinical decision making and improve asymptomatic patient outcomes by reducing the risk of perioperative ischemic neurological events and preventing further cognitive decline.

Impaired cerebrovascular reactivity correlates with reduced retinal vessel density in patients with carotid artery stenosis: Cross-sectional, single center study.

BACKGROUND: The cerebral and retinal circulation systems are developmentally, anatomically, and physiologically interconnected. Thus, we hypothesized that hypoperfusion due to atherosclerotic stenosis of the internal carotid artery (ICA) can result in disturbances of both cerebral and retinal microcirculations. We aimed to characterize parameters indicating cerebrovascular reactivity (CVR) and retinal microvascular density in patients with ICA stenosis, and assess if there is correlation between them. METHODS: In this cross-sectional study the middle cerebral artery (MCA) blood flow velocity was measured by transcranial Doppler (TCD) and, simultaneously, continuous non-invasive arterial blood pressure measurement was performed on the radial artery by applanation tonometry. CVR was assessed based on the response to the common carotid artery compression (CCC) test. The transient hyperemic response ratio (THRR) and cerebral arterial resistance transient hyperemic response ratio (CAR-THRR) were calculated. Optical coherence tomography angiography (OCTA) was used to determine vessel density (VD) on the papilla whole image for all (VDP-WIall) and for small vessels (VDP-WIsmall). The same was done in the peripapillary region: all (VDPPall), and small (VDPPsmall) vessels. The VD of superficial (VDMspf) and deep (VDMdeep) macula was also determined. Significance was accepted when p<0.05. RESULTS: Twenty-four ICA stenotic patients were evaluated. Both CVR and retinal VD were characterized. There was a significant, negative correlation between CAR-THRR (median = -0.40) and VDPPsmall vessels (median = 52%), as well as between VDPPall vessels (median = 58%), and similar correlation between CAR-THRR and VDP-WIsmall (median = 49.5%) and between VDP-WIall (median = 55%). CONCLUSION: The significant correlation between impaired cerebrovascular reactivity and retinal vessel density in patients with ICA stenosis suggests a common mechanism of action. We propose that the combined use of these diagnostic tools (TCD and OCTA) helps to better identify patients with increased ischemic or other cerebrovascular risks.

The Effect of Circle of Willis Morphology on Retinal Blood Flow in Patients with Carotid Stenosis Measured by Optical Coherence Tomography Angiography.

The Circle of Willis (CoW) is the main collateral system, and its morphological variants are more common in patients who have severe carotid artery stenosis. Earlier data suggest that optical coherence tomography angiography (OCTA) may help to assess the changes in cerebral vascular perfusion by imaging the retinal blood flow. In this single-center prospective clinical study, patients scheduled for carotid endarterectomy (CEA) underwent preoperative computed tomography angiography (CTA) of the extra- and intracranial cerebral circulation. OCTA imaging was performed one week before surgery and postoperatively one month later. The patients were divided into two subgroups based on CTA evaluation of CoW: compromised CoW or non-compromised CoW (containing hypoplastic and normal segments). The effect of the patient's age, OCTA scan quality (SQ), CoW morphology, laterality, and surgery on superficial capillary vessel density (VD) in the macula were assessed in multivariable regression models using linear mixed models. We found that VD significantly decreased with aging (-0.12%; 95%CI: -0.07--0.15; p < 0.001) and was significantly higher in patients with non-compromised CoW morphology (by 0.87% 95%CI (0.26-1.50); p = 0.005). After CEA, retinal blood flow significantly improved by 0.71% (95%CI: 0.18-1.25; p = 0.01). These results suggest that in the case of carotid artery occlusion, patients with non-compromised CoW have more preserved ocular blood flow than subjects with compromised CoW due to remodeling of the intra-orbital blood flow. Measuring the retinal blood flow might be used as a relevant and sensitive indicator of collateral cerebrovascular circulation.

Assessment of cerebral autoregulatory function and inter-hemispheric blood flow in older adults with internal carotid artery stenosis using transcranial Doppler sonography-based measurement of transient hyperemic response after carotid artery compression.

Unhealthy vascular aging promotes atherogenesis, which may lead to significant internal carotid artery stenosis (CAS) in 5 to 7.5% of older adults. The pathogenic factors that promote accelerated vascular aging and CAS also affect the downstream portion of the cerebral microcirculation in these patients. Primary treatments of significant CAS are eversion endarterectomy or endarterectomy with patch plasty. Factors that determine adequate hemodynamic compensation and thereby the clinical consequences of CAS as well as medical and surgical complications of carotid reconstruction surgery likely involve the anatomy of the circle of Willis (CoW), the magnitude of compensatory inter-hemispheric blood flow, and the effectiveness of cerebral microcirculatory blood flow autoregulation. This study aimed to test two hypotheses based on this theory. First, we hypothesized that patients with symptomatic and asymptomatic CAS would exhibit differences in autoregulatory function and inter-hemispheric blood flow. Second, we predicted that anatomically compromised CoW would associate with impaired inter-hemispheric blood flow compensation. We enrolled older adults with symptomatic or asymptomatic internal CAS (>70% NASCET criteria; n = 46) and assessed CoW integrity by CT angiography. We evaluated transient hyperemic responses in the middle cerebral arteries (MCA) after common carotid artery compression (CCC; 10 s) by transcranial Doppler sonography (TCD). We compared parameters reflecting autoregulatory function (e.g., transient hyperemic response ratio [THRR], return to baseline time [RTB], changes of vascular resistance) and inter-hemispheric blood flow (residual blood flow velocity). Our findings revealed that CAS was associated with impaired cerebral vascular reactivity. However, we did not observe significant differences in autoregulatory function or inter-hemispheric blood flow between patients with symptomatic and asymptomatic CAS. Moreover, anatomically compromised CoW did not significantly affect these parameters. Notably, we observed an inverse correlation between RTB and THRR, and 49% of CAS patients exhibited a delayed THRR, which associated with decreased inter-hemispheric blood flow. Future studies should investigate how TCD-based evaluation of autoregulatory function and inter-hemispheric blood flow can be used to optimize surgical techniques and patient selection for internal carotid artery revascularization.

Corrigendum: Two-Tiered Response of Cardiorespiratory-Cerebrovascular Network to Orthostatic Challenge.

[This corrects the article DOI: 10.3389/fphys.2021.622569.].

Two-Tiered Response of Cardiorespiratory-Cerebrovascular Network to Orthostatic Challenge.

Dynamic interdependencies within and between physiological systems and subsystems are key for homeostatic mechanisms to establish an optimal state of the organism. These interactions mediate regulatory responses elicited by various perturbations, such as the high-pressure baroreflex and cerebral autoregulation, alleviating the impact of orthostatic stress on cerebral hemodynamics and oxygenation. The aim of this study was to evaluate the responsiveness of the cardiorespiratory-cerebrovascular networks by capturing linear and nonlinear interdependencies to postural changes. Ten young healthy adults participated in our study. Non-invasive measurements of arterial blood pressure (from that cardiac cycle durations were derived), breath-to-breath interval, cerebral blood flow velocity (BFV, recorded by transcranial Doppler sonography), and cerebral hemodynamics (HbT, total hemoglobin content monitored by near-infrared spectroscopy) were performed for 30-min in resting state, followed by a 1-min stand-up and a 1-min sit-down period. During preprocessing, noise was filtered and the contribution of arterial blood pressure was regressed from BFV and HbT signals. Cardiorespiratory-cerebrovascular networks were reconstructed by computing pair-wise Pearson-correlation or mutual information between the resampled signals to capture their linear and/or nonlinear interdependencies, respectively. The interdependencies between cardiac, respiratory, and cerebrovascular dynamics showed a marked weakening after standing up persisting throughout the sit-down period, which could mainly be attributed to strikingly attenuated nonlinear coupling. To summarize, we found that postural changes induced topological changes in the cardiorespiratory-cerebrovascular network. The dissolution of nonlinear networks suggests that the complexity of key homeostatic mechanisms maintaining cerebral hemodynamics and oxygenation is indeed sensitive to physiological perturbations such as orthostatic stress.

[Serum biomarkers in acute low back pain and sciatica]. / Szérumbiomarkerek akut lumbalis-lumbosacralis fájdalomban.

Inflammation contributes to the pathogenesis of low back pain and sciatica. Growing evidence suggests that elevated levels of some inflammatory biomarkers are associated with these conditions. Much of the research evaluating the association between pro- and anti-inflammatory cytokines, chemokines, other regulatory molecules, and low back pain and sciatica, focused on patients with chronic low back pain, while fewer studies addressed the issue of detectable biomarkers in the acute phase. Previous studies suggest that pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 and anti-inflammatory IL-4 and IL-10 play an important role in the inflammatory response following intervertebral disc herniation. According to the approach of personalized medicine it is important to identify subsets of patients within the acute patient group regarding etiology, prognosis and treatment. In addition, if we can identify subgroups based on levels of pro-inflammatory biomarkers, where inflammation may be the leading cause of pain, we assume that this subgroup would likely be effectively treated with anti-inflammatory medication. The efficacy of TNF-α inhibitors and IL-6 inhibitors in treating low back pain and sciatica has already been tested in clinical trials, but further studies are required. Overall, identification of circulating biomarkers of acute low back pain and sciatica may assist in refining personalized diagnosis and treatment. Further research is needed to evaluate the role of inflammation in acute low back pain and sciatica, to identify what methods are appropriate for evaluation in clinical practice, and whether there are biomarkers of prognostic value in these patients. Orv Hetil. 2020; 161(13): 483-490.

[The significance of high-resolution ultrasonography in the diagnosis of peripheral nerve disorders]. / A nagy felbontású ideg-ultrahangvizsgálatok jelentosége a periférias idegek betegségeinek diagnosztikájában.

High resolution ultrasonography is an emerging technique for the investigation of peripheral nerves and is increasingly used worldwide in the diagnosis of peripheral nerve disorders, however, until now it is not widespread in Hungary. According to the literature this method is especially useful in entrapment neuropathies, traumatic peripheral nerve injuries, tumors of the peripheral nerves and sonographically guided interventions. Ultrasonography allows precise morphological analysis and quantitative measurements of the nerves providing useful complementary information to electrodiagnostic data. In entrapment neuropathies ultrasound shows nerve swelling mainly proximal to the sites of compression and a focal change of echotexture. On longitudinal scan, an abrupt caliber change and spindle-like swelling of the compressed nerve segment can be seen. Evaluation of the anatomical background and visualisation of the postoperative and posttraumatic changes provide useful information for planning of the therapy. Ultrasound may be of significant help in localizing the pathological nerve segment when it is at an electrophysiologically inaccessible site or when substantial secondary axonal loss precludes precise electrophysiological localization and it might even show pathological changes when nerve conduction studies are normal. Contrary to electrophysiological investigation ultrasonography might discover neurotmesis in the akute phase of traumatic nerve injuries indicating the necessity of surgical intervention. We provide a summary of the main indications and further application areas of this method.

Hypocapnia induced by involuntary hyperventilation during mental arithmetic reduces cerebral blood flow velocity.

Functional neuroimaging studies have shown that cognitive processes increase regional cerebral blood flow in relation with enhanced neuronal activity. However, cognition induces elevation of blood pressure, heart rate and respiratory rate, each of which also affects cerebral circulation. For proper interpretation of functional neuroimaging data, it is necessary to dissociate the effects of systemic and local metabolic reactions on regional cerebral circulation. To elucidate this interaction, we examined the changes in cerebral blood flow velocity, which were caused by voluntary hyperventilation-induced hypocapnia without cognitive effort and hypocapnia evolving during mental arithmetic task. The cerebral blood flow velocity was recorded in the middle cerebral arteries, using transcranial Doppler sonography. Respiratory rate, end-tidal partial pressure of CO(2), heart rate and arterial blood pressure were simultaneously monitored. Data were statistically evaluated. Hypocapnia induced by voluntary hyperventilation without cognition decreased the cerebral blood flow velocity. During mental arithmetic, the cerebral blood flow velocity first increased, but the hypocapnia, which was induced by involuntary hyperventilation related to cognitive effort, reduced it. This implies temporary vasoconstriction of cerebral microvessels, and the increase in cerebral vascular resistance index supports this finding. These results suggest that hypocapnia, which develops during cognition, may decrease blood flow velocity in the middle cerebral arteries, which interferes with the neuronal activity-driven regulation of cerebral circulation. In conclusion, when interpreting the results of functional neuroimaging studies on cognitive mechanisms, the tight coupling of the effects of mental processes and autonomic/metabolic reactions should be considered.

[Intracerebral steal after acetazolamide administration]. / Intracerebralis steal jelenség acetazolamidterhelés alatt.

Occlusion or high grade stenosis of the internal carotid artery may be asymptomatic depending on the collateral patterns in the circle of Willis and the reserve capacity of the microvascular (arteriolar) system. The distensibility of the cerebral arterioles may be described quantitatively by the vasomotor reactivity. We present three patients with severe stenosis of an internal carotid artery associated with more severe stenosis or occlusion of the contralateral internal carotid artery. We continuously measured blood flow velocity in both middle cerebral arteries by transcranial Doppler ultrasound in rest and for 20 minutes after IV administration of 1 g acetazolamide. Arterial blood pressure was determined with tonometry, end-tidal CO2 was determined by a capnometer. In resting condition the anterior communicating artery, the posterior communicating artery and the ophthalmic artery supplied collateral blood flow towards the side of the more severe internal carotid artery disease. Blood flow velocity decreased after acetazolamide administration in all patients in the middle cerebral arteries on the side of the more severe occlusive carotid disease, while increased on the contralateral side. We assume that the exhausted arteriolar system on the more severely affected side was not able to further dilate and the open collateral system could have driven blood towards the other side with preserved reserve capacity. The reduced blood flow velocity in the middle cerebral arteries after acetazolamide may reflect this intracerebral steal phenomenon.

[Aids-related toxoplasma-encephalitis presenting with acute psychotic episode]. / Akut psychosis mint az AIDS-hez társuló toxoplasma-encephalitis elso tünete.

The most frequent neurological manifestations of the Acquired Immunodeficiency Syndrome-(AIDS) are Cerebral Toxoplasmosis, Primary Central Nervous System Lymphoma (PCNSL), Progressive Multifocal Leukoencephalopathy (PML) and AIDS-encephalitis (AIDS-dementia complex, multinucleated giant cell encephalitis, HIV-encephalopathy). Neurological complications usually occur in the advanced stages of the disease, and they are uncommon in the beginning as presenting illness, but may result in life-threatening condition or in death. Rarely the disease presents as a neuropsychiatric illness in an undiagnosed AIDS patient, delaying a proper diagnosis. We present the case of a 34 years old patient treated for AIDS-related Toxoplasma-encephalitis in our department. His illness started as an acute psychosis followed by rapid mental and somatic decline, leading to death in three months. His HIV-seropositivity was not known at his admission, and the extraneural manifestations were slight. The diagnosis was established by serology, imaging methods and histopathological investigation. After presenting the medical history and results of autopsy studies of the patient we discuss the problems of the differential diagnosis, especially regarding the findings of the imaging methods.

[Investigation of cerebral autoregulation in Parkinson's disease--a transcranial Doppler study]. / Az agyi autoreguláció vizsgálata Parkinson-betegségben.

BACKGROUND AND PURPOSE: The frequent orthostatic intolerance in Parkinson's disease could be the consequence of cardiovascular autonomic failure and/or a damaged cerebral autoregulation (AR). To clarify this question the regulation of cerebral circulation was investigated by polygraphic method. METHODS: On a tilt table simultaneous and continuous registrations were made of MCA velocity (V(MCA)) by transcranial Doppler, arterial blood pressure by non-invasive method, and end-tidal CO2, in supine and in tilted positions of 10 degrees, 30 degrees, 70 degrees grades. The cerebral autoregulation was characterized by the slope of the curve of the arterial blood pressure at the level of the Willis-circle (BP(W) as MCA perfusion pressure) plotted against the MCA velocity, achieved by linear regression (y = ax + b function, a=AR, or index of autoregulation). PATIENTS: The data of 17 parkinsonian patients (PP) and eight age-matched controls (C) were analyzed. RESULTS: The decrease of blood pressure in parkinsonian patients was significantly lower than in the controls when supine position was restored from 70 degrees (deltaABP 70 degrees - 0 degree pp = -3.1 +/- 7.5 Hgmm; deltaABP 70 degrees - 0(C) degrees = -11.1 +/- 7.3 Hgmm; p < 0.05), which suggests a damage to the sympathetic cardiovascular system. A disturbance of the cerebral autoregulation in patients was suggested by a 'progressively decreasing MCA average velocity (V(MCA)) during graded tilt, which was significant at 70 degrees (deltaV(ACM) = 9.8 +/- 8.82% cms(-1); p(C-PP) P 0.5), and by a higher slope of pressure-velocity curve (AR(C) = 0.143 +/- .125% cms(-1)/Hgmm; AR(PP) = 0.38 +/- 0.25% cms(-1)/Hgmm; p(C-PP) < 0.05). CONCLUSIONS: The results show that the cerebral blood flow of patients is more dependent on perfusion pressure compared to healthy controls. The disturbance of the sympathetic cardiovascular system and of cerebral autoregulation could be the consequence of a damage to the postganglionic structures in Parkinson's disease. These results could explain the frequent orthostatic intolerance of patients even with normal blood pressure.

Correlation between blood flow velocity in the middle cerebral artery and EEG during cognitive effort.

Cognitive effort modifies blood flow velocity (BFV) in the middle cerebral artery (MCA) which can be recorded by transcranial Doppler sonography (TCD). EEG parameters can be used as indicators of cortical activation. To find temporal and spatial relation between circulatory and bioelectric phenomena, we used combined EEG and TCD measurements during cognitive experiments. Bilateral BFV in the MCAs and 16-channel scalp EEG were recorded during mental arithmetic (MA) and verbal fluency (VF) tests in 12 healthy volunteers. Temporal profile of BFV, heart rate (HR), EEG central frequency (CF), relative alpha power (ralphap), and laterality index (Li) for BFV and CF were statistically analysed. During mental effort, BFV changes showed a reproducible pattern, which was different in MA and VF tests. The Li(BFV) correlated with handedness in 9/12 subjects (75%) in the VF, and in 6/12 subjects (50%) in the MA test. Significant correlation was found between Li(BFV) and Li(CF) during VF (r(2) = 0.69). Li was more indicative for the hemispheric dominance in the VF than in the MA test. During VF test, correlation between HR and BFV was significant in 7/12 subjects. CF and ralphap provide real time assessment of the functional state of the brain tissue during cognition. The correlation between CF and BFV during mental activity suggests a short latency neurogenic and a long latency, supposedly chemical regulation of regional blood flow. Parallel analysis of EEG and flow parameters increases the confidence of determining hemispheric dominance and provides an alternative to study physiological consequences of cognitive processes.

[Effect of mental arithmetic and verbal fluency on blood flow velocity in the middle cerebral arteries]. / A fejszámolás és a szóalkotás hatása az arteria cerebri mediákban mért véráramlás-sebességre.

INTRODUCTION: Using transcranial Doppler sonography (TCD), changes in blood flow velocity (BFV) can be measured in the Medial Cerebral Artery (MCA) during cognitive effort. Our goal was to define the time-course and laterality of BFV in healthy volunteers during arithmetic and verbal fluency tasks according to handedness. METHODS: Twelve subjects (8 right-handed, 4 left-handed) were assessed. The TCD registered BFV in both MCA simultaneously. Heart rate was also recorded using TCD. Finally we included a 16-channel EEG. BFV laterality index (LI) was calculated. Participants were asked to count silently and generate words beginning with a specified letter. To estimate hemispheric differences in BFV, two-tailed Wilcoxon tests were utilized along with correlational analyses. RESULTS: During cognitive effort the BFV changed in a tri-phasic manner in all participants. A 6-8% elevation of BFV was observed in MCAs without latency at the time of the evoking signal. Laterality of BFV developed after 5-13 seconds during cognitive effort in right-, and several seconds later in left-handed subjects. During tasks the BFV increased in the dominant hemisphere up to 2.6-4.7% compared to the subdominant one. We also calculated the LI. During the verbal task the LI agreed with the handedness in 9 out of 12 subjects. During the mental arithmetic task, agreement was found in 6 out of 12 subjects. According to LI results we found a discrepancy between verbal and arithmetic tests in 3 out of 12 subjects. CONCLUSION: Cognitive effort elicites significant bilateral BFV increases in the MCAs, which suggests fast neurogenic regulation. The course of BFV during mental arithmetic proved to be different from course BFV assessed during the word fluency task. Based on the laterality of the BFV, the word-generation task was more sensitive in determining the dominant hemisphere when compared to the mental arithmetic task. The use of LI may help to estimate hemispheric functions even in pathologic circumstances.

[Cerebral sinus thrombosis and ulcerative colitis: two cases]. / Agyi sinusthrombosis és colitis ulcerosa--két eset ismertetése.

Inflammatory bowel diseases (IBD)--ulcerative colitis and Crohn's disease--are associated with increased risk for thrombotic complications both in the arterial and venous system. Cerebral sinus thrombosis is a rare but potentially fatal consequence of these diseases. Modern imaging methods made this uncommon complication of IBD more frequently recognized. The link between IBDs and thrombosis has been extensively studied. Inherited coagulation disorders (APC resistance, antithrombin III and protein-S deficiency), acquired diseases (antiphospholipid syndrome), and the frequent use of corticosteroids were suspected. Two cases of ulcerative colitis associated with cerebral sinus thrombosis successfully treated are reported. The connection between IBD and thrombotic complications and the therapeutic risks are discussed as well.