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.

Changing the paradigm of intracranial hypertension in brain tumor patients: a study based on non-invasive ICP measurements.

BACKGROUND: The ultrasound based non-invasive ICP measurement method has been recently validated. Correlation of symptoms and signs of intracranial hypertension with actual ICP measurements in patients with large intracranial tumors is controversial. The purpose of this study was to assess ICP in patients with brain tumors, presenting with neurological signs and symptoms of elevated ICP and to further evaluate the value and utility of non-invasive ICP monitoring. METHODS: Twenty patients underwent non-invasive ICP measurement using a two-depth transcranial Doppler ultrasound designed to simultaneously compare pulse dynamics in the proximal (intracranial), and the distal (extracranial) intraorbital segments of the ophthalmic artery through the closed eyelid. RESULTS: Forty-eight measurements were analyzed. Radiological characteristics included tumor volume (range = 5.45-220.27cm3, mean = 48.81 cm3), perilesional edema (range = 0-238.27cm3, mean = 74.40 cm3), and midline shift (mean = 3.99 mm). All ICP measurements were in the normal range of 7-16 mmHg (ICPmean: 9.19 mmHg). The correlation of demographics, clinical and radiological variables in a bivariate association, showed a statistically significant correlation with neurological deficits and ICPmax (p = 0.02) as well as ICPmean (p = 0.01). The correlation between ICP and neurological deficits, showed a negative value of the estimate. The ICP was not increased in all cases, whether ipsilateral nor contralateral to the tumor. The multivariate model analysis demonstrated that neurological deficits were associated with lower ICPmax values, whereas maximum tumor diameter was associated with larger ICPmax values. CONCLUSIONS: This study demonstrated that ICP in patients with intracranial tumors and mass effect is not necessarily increased. Therefore, clinical signs of intracranial hypertension do not necessarily reflect increased ICP.

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".

Can intracranial pressure be measured non-invasively bedside using a two-depth Doppler-technique?

Measurement of intracranial pressure (ICP) is necessary in many neurological and neurosurgical diseases. To avoid lumbar puncture or intracranial ICP probes, non-invasive ICP techniques are becoming popular. A recently developed technology uses two-depth Doppler to compare arterial pulsations in the intra- and extra-cranial segments of the ophthalmic artery for non-invasive estimation of ICP. The aim of this study was to investigate how well non-invasively-measured ICP and invasively-measured cerebrospinal fluid (CSF) pressure correlate. We performed multiple measurements over a wide ICP span in eighteen elderly patients with communicating hydrocephalus. As a reference, an automatic CSF infusion apparatus was connected to the lumbar space. Ringer's solution was used to create elevation to pre-defined ICP levels. Bench tests of the infusion apparatus showed a random error (95 % CI) of less than ±0.9 mmHg and a systematic error of less than ±0.5 mmHg. Reliable Doppler signals were obtained in 13 (72 %) patients. An infusion test could not be performed in one patient. Thus, twelve patients and a total of 61 paired data points were studied. The correlation between invasive and non-invasive ICP measurements was good (R = 0.74), and the 95 % limits of agreements were -1.4 ± 8.8 mmHg. The within-patient correlation varied between 0.47 and 1.00. This non-invasive technique is promising, and these results encourage further development and evaluation before the method can be recommended for use in clinical practice.

Accuracy, Precision, Sensitivity, and Specificity of Noninvasive ICP Absolute Value Measurements.

An innovative absolute intracranial pressure (ICP) value measurement method has been validated by multicenter comparative clinical studies. The method is based on two-depth transcranial Doppler (TCD) technology and uses intracranial and extracranial segments of the ophthalmic artery as pressure sensors. The ophthalmic artery is used as a natural pair of "scales" that compares ICP with controlled pressure Pe, which is externally applied to the orbit. To balance the scales, ICP = Pe a special two-depth TCD device was used as a pressure balance indicator. The proposed method is the only noninvasive ICP measurement method that does not need patient-specific calibration.

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.

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.

Comparative Study of Novel Noninvasive Cerebral Autoregulation Volumetric Reactivity Indices Reflected by Ultrasonic Speed and Attenuation as Dynamic Measurements in the Human Brain.

This is a comparative study of two novel noninvasive cerebrovascular autoregulation (CA) monitoring methods based on intracranial blood volume (IBV) changes in the human brain. We investigated the clinical applicability of the new volumetric reactivity index (VRx2), reflected by intracranial ultrasonic attenuation dynamics for noninvasive CA monitoring. The CA was determined noninvasively on 43 healthy participants by calculating the volumetric reactivity index (VRx1 from time-of-flight of ultrasound, VRx2 from attenuation of ultrasound). The VRx was calculated as a moving correlation coefficient between the arterial blood pressure and noninvasively measured IBV slow waves. Linear regression between VRx1 and VRx2 (averaged per participants) showed a significant correlation (r = 0.731, p < 0.0001, 95% confidence interval [0.501-0.895]) in data filtered by bandpass filtering. On the other hand, FIR filtering demonstrated a slightly better correlation (r = 0.769, p < 0.0001, 95% confidence interval [0.611-0.909]). The standard deviation of the difference by bandpass filtering was 0.1647 and bias -0.3444; and by FIR filtering 0.1382 and bias -0.3669. This comparative study showed a significant coincidence of the VRx2 index compared to that of VRx1. Hence, VRx2 could be used as an alternative, cost-effective noninvasive cerebrovascular autoregulation index in the same way as VRx1 values are used.

Validation of Noninvasive Absolute Intracranial Pressure Measurements in Traumatic Brain Injury and Intracranial Hemorrhage.

BACKGROUND: Increased intracranial pressure (ICP) causes secondary damage in traumatic brain injury (TBI), and intracranial hemorrhage (ICH). Current methods of ICP monitoring require surgery and carry risks of complications. OBJECTIVE: To validate a new instrument for noninvasive ICP measurement by comparing values obtained from noninvasive measurements to those from commercial implantable devices through this pilot study. METHODS: The ophthalmic artery (OA) served as a natural ICP sensor. ICP measurements obtained using noninvasive, self-calibrating device utilizing Doppler ultrasound to evaluate OA flow were compared to standard implantable ICP measurement probes. RESULTS: A total of 78 simultaneous, paired, invasive, and noninvasive ICP measurements were obtained in 11 ICU patients over a 17-mo period with the diagnosis of TBI, SAH, or ICH. A total of 24 paired data points were initially excluded because of questions about data independence. Analysis of variance was performed first on the 54 remaining data points and then on the entire set of 78 data points. There was no difference between the 2 groups nor was there any correlation between type of sensor and the patient (F[10, 43] = 1.516, P = .167), or the accuracy and precision of noninvasive ICP measurements (F[1, 43] = 0.511, P = .479). Accuracy was [-1.130; 0.539] mm Hg (CL = 95%). Patient-specific calibration was not needed. Standard deviation (precision) was [1.632; 2.396] mm Hg (CL = 95%). No adverse events were encountered. CONCLUSION: This pilot study revealed no significant differences between invasive and noninvasive ICP measurements (P < .05), suggesting that noninvasive ICP measurements obtained by this method are comparable and reliable.

Cerebrovascular autoregulation impairments during cardiac surgery with cardiopulmonary bypass are related to postoperative cognitive deterioration: prospective observational study.

BACKGROUND: Postoperative cognitive dysfunction (POCD) occurs in approximately 33-83% of patients after cardiac surgery with cardiopulmonary bypass (CPB). Recent clinical data suggest that real-time, intraoperative monitoring of patient-specific cerebrovascular autoregulation (CA) may help to prevent POCD by detecting individual critical limits for mean arterial pressure (MAP) outside which CA is impaired. Objectives of the study were to detect the episodes of impaired CA during cardiac surgery with CPB, and to investigate the association between CA impairment and POCD. METHODS: The observational study of non-invasive ultrasonic volumetric CA monitoring included 59 patients undergoing elective coronary artery bypass graft surgery with CPB. All patients underwent series of neuropsychological tests the day before and ten days after the surgery in order to evaluate cognitive function. RESULTS: Twenty-two patients (37%) experienced POCD, 37 patients (63%) showed no cognitive deterioration. The duration of the single longest CA impairment event was found reliably associated with occurrence of POCD (P<0.05). The critical duration of the single longest CA impairment event was 5.03 minutes (odds ratio 14.5; CI 3.9-51.8) for studied population. CONCLUSIONS: Prospective clinical study showed that single longest CA impairment may result in post-operative deterioration of mental abilities. The duration of the single longest CA impairment event is the risk factor that is associated with POCD.

Correlation among decreased regional cerebral oxygen saturation, blood levels of brain injury biomarkers, and cognitive disorder.

Objective This study was performed to investigate the correlation among decreased regional cerebral oxygen saturation (rSO2), blood levels of brain injury biomarkers, and postoperative cognitive disorder (POCD) after cardiac surgery with cardiopulmonary bypass (CPB). Methods This prospective observational study included 59 patients undergoing coronary artery bypass graft surgery with CPB. All patients underwent neuropsychological tests (Mini Mental State Evaluation, Rey Auditory Verbal Learning Test, digit span test, digit symbol substitution test, and Schulte table) the day before and 10 days after the surgery. The blood levels of two brain injury biomarkers, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were measured before and 1 day after the surgery. Results The rSO2 decreased during surgery in 21 (35%) patients. POCD was detected in 22 (37%) patients. After the surgery, no significant changes in the GFAP blood level occurred in any patients. No significant correlations were found among the decreased rSO2, increased NSE blood level, and rate of POCD. Conclusion These results suggest that a decrease in rSO2 during cardiac surgery is not necessarily related to the development of POCD or an increased blood level of the brain injury biomarker NSE.

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.

Improved diagnostic value of a TCD-based non-invasive ICP measurement method compared with the sonographic ONSD method for detecting elevated intracranial pressure.

OBJECTIVES: To compare the diagnostic reliability of optic nerve sheath diameter (ONSD) ultrasonography with a transcranial Doppler (TCD)-based absolute intracranial pressure (ICP) value measurement method for detection of elevated ICP in neurological patients. The ONSD method has been only tested previously on neurosurgical patients. METHODS: A prospective clinical study of a non-invasive ICP estimation method based on ONSD correlation with ICP and an absolute ICP value measurement method based on a two-depth TCD technology has recruited 108 neurological patients. Ninety-two of these patients have been enrolled in the final analysis of the diagnostic reliability of ONSD ultrasonography and 85 patients using the absolute ICP value measurement method. All non-invasive ICP measurements were compared with 'Gold Standard' invasive cerebrospinal fluid (CSF) pressure measurements obtained by lumbar puncture. Receiver-operating characteristic (ROC) analysis has been used to investigate the diagnostic value of these two methods. RESULTS: The diagnostic sensitivity, specificity, and the area under the ROC curve (AUC) of the ONSD method for detecting elevated intracranial pressure (ICP >14·7 mmHg) were calculated using a cutoff point of ONSD at 5·0 mm and found to be 37·0%, 58·5%, and 0·57, respectively. The diagnostic sensitivity, specificity, and AUC for the non-invasive absolute ICP measurement method were calculated at the same ICP cutoff point of 14·7 mmHg and were determined to be 68·0%, 84·3%, and 0·87, respectively. CONCLUSIONS: The non-invasive ICP measurement method based on two-depth TCD technology has a better diagnostic reliability on neurological patients than the ONSD method when expressed by the sensitivity and specificity for detecting elevated ICP >14·7 mmHg.