The Association of Cerebral Autoregulation Dysfunction and Postoperative Memory Impairment in Cardiac Surgery Patients.

Background and Objectives: Cardiac surgery is associated with various durations of cerebral autoregulation (CA) impairment and can significantly impact cognitive function. Cognitive functions such as memory, psychomotor speed, and attention are significantly impacted after cardiac surgery, necessitating prioritization of these areas in cognitive function tests. There is a lack of research connecting cerebral autoregulation impairment to specific cognitive function domains after cardiac surgery. This study aimed to determine if impaired cerebral autoregulation is associated with postoperative memory impairment and to test the hypothesis that the duration of this impairment affects the development of postoperative memory issues. Materials and Methods: A prospective study was conducted in 2021-2023. After approval of the Ethics Committee and with patient's written consent, 83 adult patients undergoing elective on-pump coronary artery bypass graft (CABG) surgery were enrolled. All patients were assessed for cognitive function 1 day before surgery using the Mini-Mental state examination (MMSE-2) test as a screening tool and the Hopkins Verbal Learning Test-Revised (HVLT-R) to assess memory specifically. To diagnose possible memory impairment (IM), all patients underwent a repeat assessment of cognitive function on the 7th-10th postoperative day. Cerebral autoregulation monitoring using transcranial Doppler was performed. Cerebral autoregulation status index (Mx) was recorded using Intensive Care Brain Monitoring System software, 9.1.5.23 (Cambridge, UK). Results: According to our research, the incidence of postoperative memory impairment is 30.1%. Temporary cerebral autoregulation impairment occurs in all patients undergoing elective in-pump CABG surgery. The duration of the single longest CA impairment event in seconds (LCAI) and the LCAI dose were higher in patients with postoperative memory impairment, p = 0.006 and p < 0.007, respectively. Conclusions: Cerebral autoregulation impairment is important in developing memory loss after cardiac surgery. The duration and dose of the LCAI event are predictive of postoperative memory impairment.

Intraorbital pressure-volume characteristics in a piglet model: In vivo pilot study.

Intracranial pressure measurement is frequently used for diagnosis in neurocritical care but cannot always accurately predict neurological deterioration. Intracranial compliance plays a significant role in maintaining cerebral blood flow, cerebral perfusion pressure, and intracranial pressure. This study's objective was to investigate the feasibility of transferring external pressure into the eye orbit in a large-animal model while maintaining a clinically acceptable pressure gradient between intraorbital and external pressures. The experimental system comprised a specifically designed pressure applicator that can be placed and tightly fastened onto the eye. A pressure chamber made from thin, elastic, non-allergenic film was attached to the lower part of the applicator and placed in contact with the eyelid and surrounding tissues of piglets' eyeballs. External pressure was increased from 0 to 20 mmHg with steps of 1 mmHg, from 20 to 30 mmHg with steps of 2 mmHg, and from 30 to 50 mmHg with steps of 5 mmHg. An invasive pressure sensor was used to measure intraorbital pressure directly. An equation was derived from measured intraorbital and external pressures (intraorbital pressure = 0.82 × external pressure + 3.12) and demonstrated that external pressure can be linearly transferred to orbit tissues with a bias (systematic error) of 3.12 mmHg. This is close to the initial intraorbital pressure within the range of pressures tested. We determined the relationship between intraorbital compliance and externally applied pressure. Our findings indicate that intraorbital compliance can be controlled across a wide range of 1.55 to 0.15 ml/mmHg. We observed that external pressure transfer into the orbit can be achieved while maintaining a clinically acceptable pressure gradient between intraorbital and external pressures.

Prospective Pilot Clinical Study of Noninvasive Cerebrovascular Autoregulation Monitoring in Open-Angle Glaucoma Patients and Healthy Subjects.

PURPOSE: To analyze the cerebrovascular autoregulation (CA) dynamics in patients with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) as well as healthy subjects using noninvasive ultrasound technologies for the first time. METHODS: The CA status of 10 patients with NTG, 8 patients with HTG, and 10 healthy subjects was assessed, using an innovative noninvasive ultrasonic technique, based on intracranial blood volume slow-wave measurements. Identified in each participant were intraocular pressure, ocular perfusion pressure, and CA-related parameter volumetric reactivity index (VRx), as well as the duration and doses of the longest cerebral autoregulation impairment (LCAI). In addition, we calculated the associations of these parameters with patients' diagnoses. RESULTS: The VRx value, the LCAI dose, and duration in healthy subjects were significantly lower than in patients with NTG (P < 0.05). However, no significant differences were noted in these parameters between healthy subjects and HTG and between NTG and HTG groups. CONCLUSIONS: NTG is associated with the disturbed cerebral blood flow and could be diagnosed by performing noninvasive CA assessments. TRANSLATIONAL RELEVANCE: The VRx monitoring method can be applied to a wider range of patient groups, especially patients with normal-tension glaucoma.

Can the Treatment of Normal-Pressure Hydrocephalus Induce Normal-Tension Glaucoma? A Narrative Review of a Current Knowledge.

Ventriculoperitoneal shunt placement is the most commonly used treatment of normal-pressure hydrocephalus (NPH). It has been hypothesized that normal-tension glaucoma (NTG) is caused by the treatment of NPH by using the shunt to reduce intracranial pressure (ICP). The aim of this study is to review the literature published regarding this hypothesis and to emphasize the need for neuro-ophthalmic follow-up for the concerned patients. The source literature was selected from the results of an online PubMed search, using the keywords "hydrocephalus glaucoma" and "normal-tension glaucoma shunt". One prospective study on adults, one prospective study on children, two retrospective studies on adults and children, two case reports, three review papers including medical hypotheses, and one prospective study on monkeys were identified. Hypothesis about the association between the treatment of NPH using the shunt to reduce ICP and the development of NTG were supported in all reviewed papers. This suggests that a safe lower limit of ICP for neurological patients, especially shunt-treated NPH patients, should be kept. Thus, we proposed to modify the paradigm of safe upper ICP threshold recommended in neurosurgery and neurology into the paradigm of safe ICP corridor applicable in neurology and ophthalmology, especially for shunt-treated hydrocephalic and glaucoma patients.

Human ophthalmic artery as a sensor for non-invasive intracranial pressure monitoring: numerical modeling and in vivo pilot study.

Intracranial pressure (ICP) monitoring is important in managing neurosurgical, neurological, and ophthalmological patients with open-angle glaucoma. Non-invasive two-depth transcranial Doppler (TCD) technique is used in a novel method for ICP snapshot measurement that has been previously investigated prospectively, and the results showed clinically acceptable accuracy and precision. The aim of this study was to investigate possibility of using the ophthalmic artery (OA) as a pressure sensor for continuous ICP monitoring. First, numerical modeling was done to investigate the possibility, and then a pilot clinical study was conducted to compare two-depth TCD-based non-invasive ICP monitoring data with readings from an invasive Codman ICP microsensor from patients with severe traumatic brain injury. The numerical modeling showed that the systematic error of non-invasive ICP monitoring was < 1.0 mmHg after eliminating the intraorbital and blood pressure gradient. In a clinical study, a total of 1928 paired data points were collected, and the extreme data points of measured differences between invasive and non-invasive ICP were - 3.94 and 4.68 mmHg (95% CI - 2.55 to 2.72). The total mean and SD were 0.086 ± 1.34 mmHg, and the correlation coefficient was 0.94. The results show that the OA can be used as a linear natural pressure sensor and that it could potentially be possible to monitor the ICP for up to 1 h without recalibration.

Prospective Clinical Study of Non-Invasive Intracranial Pressure Measurements in Open-Angle Glaucoma Patients and Healthy Subjects.

Background and Objective: Glaucoma is a progressive optic neuropathy in which the optic nerve is damaged. The optic nerve is exposed not only to intraocular pressure (IOP) in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Here, we analyse ICP differences between patients with glaucoma and healthy subjects (HSs). Materials and Methods: Ninety-five patients with normal-tension glaucoma (NTG), 60 patients with high-tension glaucoma (HTG), and 62 HSs were included in the prospective clinical study, and ICP was measured non-invasively by two-depth transcranial Doppler (TCD). Results: The mean ICP of NTG patients (9.42 ± 2.83 mmHg) was significantly lower than that of HSs (10.73 ± 2.16 mmHg) (p = 0.007). The mean ICP of HTG patients (8.11 ± 2.68 mmHg) was significantly lower than that of NTG patients (9.42 ± 2.83 mmHg) (p = 0.008) and significantly lower than that of HSs (10.73 ± 2.16 mmHg) (p < 0.001). Conclusions: An abnormal ICP value could be one of the many influential factors in the optic nerve degeneration of NTG patients and should be considered as such instead of just being regarded as a "low ICP".

Drosophila carboxypeptidase D (SILVER) is a key enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate.

Neuropeptides are processed from larger preproproteins by a dedicated set of enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing enzymes are well-characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a key enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a key enzyme for neuropeptide processing and peptide-regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.

Non-invasive Cerebrovascular Autoregulation Assessment Using the Volumetric Reactivity Index: Prospective Study.

BACKGROUND: This prospective study of an innovative non-invasive ultrasonic cerebrovascular autoregulation (CA) monitoring method is based on real-time measurements of intracranial blood volume (IBV) reactions following changes in arterial blood pressure. In this study, we aimed to determine the clinical applicability of a non-invasive CA monitoring method by performing a prospective comparative clinical study of simultaneous invasive and non-invasive CA monitoring on intensive care patients. METHODS: CA was monitored in 61 patients with severe traumatic brain injuries invasively by calculating the pressure reactivity index (PRx) and non-invasively by calculating the volumetric reactivity index (VRx) simultaneously. The PRx was calculated as a moving correlation coefficient between intracranial pressure and arterial blood pressure slow waves. The VRx was calculated as a moving correlation coefficient between arterial blood pressure and non-invasively-measured IBV slow waves. RESULTS: A linear regression between VRx and PRx averaged per patients' monitoring session showed a significant correlation (r = 0.843, p < 0.001; 95% confidence interval 0.751 - 0.903). The standard deviation of the difference between VRx and PRx was 0.192; bias was - 0.065. CONCLUSIONS: This prospective clinical study of the non-invasive ultrasonic volumetric reactivity index VRx monitoring, based on ultrasonic time-of-flight measurements of IBV dynamics, showed significant coincidence of non-invasive VRx index with invasive PRx index. The ultrasonic time-of-flight method reflects blood volume changes inside the acoustic path, which crosses both hemispheres of the brain. This method does not reflect locally and invasively-recorded intracranial pressure slow waves, but the autoregulatory reactions of both hemispheres of the brain. Therefore, VRx can be used as a non-invasive cerebrovascular autoregulation index in the same way as PRx and can also provide information about the CA status encompassing all intracranial hemodynamics.

Graphical and statistical analyses of the oculocardiac reflex during a non-invasive intracranial pressure measurement.

PURPOSE: This study aimed to examine the incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement when gradual external pressure was applied to the orbital tissues and eye. METHODS: Patients (n = 101) and healthy volunteers (n = 56) aged 20-75 years who underwent a non-invasive intracranial pressure measurement were included in this retrospective oculocardiac reflex analysis. Prespecified thresholds greater than a 10% or 20% decrease in the heart rate from baseline were used to determine the incidence of the oculocardiac reflex. RESULTS: None of the subjects had a greater than 20% decrease in heart rate from baseline. Four subjects had a greater than 10% decrease in heart rate from baseline, representing 0.9% of the total pressure steps. Three of these subjects were healthy volunteers, and one was a glaucoma patient. CONCLUSION: The incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement procedure was very low and not associated with any clinically relevant effects.

Location of the internal carotid artery and ophthalmic artery segments for non-invasive intracranial pressure measurement by multi-depth TCD.

The aim of the present study was to locate the ophthalmic artery by using the edge of the internal carotid artery (ICA) as the reference depth to perform a reliable non-invasive intracranial pressure measurement via a multi-depth transcranial Doppler device and to then determine the positions and angles of an ultrasonic transducer (UT) on the closed eyelid in the case of located segments. High tension glaucoma (HTG) patients and healthy volunteers (HVs) undergoing non-invasive intracranial pressure measurement were selected for this prospective study. The depth of the edge of the ICA was identified, followed by a selection of the depths of the IOA and EOA segments. The positions and angles of the UT on the closed eyelid were measured. The mean depth of the identified ICA edge for HTG patients was 64.3 mm and was 63.0 mm for HVs (p = 0.21). The mean depth of the selected IOA segment for HTG patients was 59.2 mm and 59.3 mm for HVs (p = 0.91). The mean depth of the selected EOA segment for HTG patients was 48.5 mm and 49.8 mm for HVs (p = 0.14). The difference in the located depths of the segments between groups was not statistically significant. The results showed a significant difference in the measured UT angles in the case of the identified edge of the ICA and selected ophthalmic artery segments (p = 0.0002). We demonstrated that locating the IOA and EOA segments can be achieved using the edge of the ICA as a reference point. ABBREVIATIONS: OA: ophthalmic artery; IOA: intracranial segments of the ophthalmic artery; EOA: extracranial segments of the ophthalmic artery; ICA: internal carotid artery; UT: ultrasonic transducer; HTG: high tension glaucoma; SD: standard deviation; ICP: intracranial pressure; TCD: transcranial Doppler.