ARTICLE | doi:10.20944/preprints202110.0115.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: intracranial compliance; intracranial pressure; intracranial hypertension; acute brain injury
Online: 7 October 2021 (10:54:26 CEST)
We validated a new noninvasive tool (B4C) to assess intracranial pressure waveform (ICPW) morphology in a set of neurocritical patients, correlating the data with ICPW obtained from invasive catheter monitoring. Materials and Methods: Patients undergoing invasive intracranial pressure (ICP) monitoring were consecutively evaluated using the B4C sensor. Ultrasound-guided manual internal jugular vein (IJV) compression was performed to elevate ICP from the baseline. ICP values, amplitudes, and time intervals (P2/P1 ratio and time-to-peak [TTP]) between the ICP and B4C waveform peaks were analyzed. Results: Among 41 patients, the main causes for ICP monitoring included traumatic brain injury, subarachnoid hemorrhage, and stroke. Bland-Altman’s plot indicated agreement between the ICPW parameters obtained using both techniques. The strongest Pearson’s correlation for P2/P1 and TTP was observed among patients with no cranial damage (r = 0.72 and 0.85, respectively) in detriment of those who have undergone craniotomies or craniectomies. P2/P1 values of 1 were equivalent between the two techniques (area under the receiver operator curve [AUROC], 0.9) whereas B4C cut-off 1.2 was predictive of intracranial hypertension (AUROC 0.9, p < 000.1 for ICP > 20 mmHg). Conclusion: B4C provided biometric amplitude ratios correlated with ICPW variation morphology and is useful for noninvasive critical care monitoring.
ARTICLE | doi:10.20944/preprints202302.0044.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Brain death diagnosis; Intracranial Pressure; Intracranial compliance
Online: 2 February 2023 (11:30:01 CET)
Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.
ARTICLE | doi:10.20944/preprints202106.0716.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: intracranial compliance; intracranial pressure; decompressive craniectomy; acute brain damage
Online: 29 June 2021 (23:58:09 CEST)
Background: Morphological alterations in intracranial pressure pulse waveform (ICPPW) secondary to intracranial hypertension (ICP >20 mmHg) and reduction in intracranial compliance (ICC) are well known indicators of neurological severity. To date, no studies have documented the ICPPW modifications after intracranial hypertension resolution with decompressive craniectomy (DC). The present study aimed to assess the morphological alterations in ICPPW among neurocritical care patients with and without DC, by comparing the variations of ICPPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of severe traumatic or spontaneous conditions were included. Mean ICP values were compared with ICPPW features (P2/P1 ratio, TTP and pulse amplitude). Elevation in ICP was produced by means of ultrasound-guided manual internal jugular veins compression. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. 21 (36%) presented no skull defects, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±13.59 for intact and ±17.66 mmHg for DC, with ICP induced elevation also similar between groups (p= 0.56). Significant elevation was observed for P2/P1 ratio for groups 1 and 2, whereas reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, whereas reduction of 0.03 for group 3, p=0.01). Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPPW indicated DC to be protective for further influences of ICP elevations over the brain. Analysis of ICPPW seems to be an alternative to real time ICC assessment.
CASE REPORT | doi:10.20944/preprints202011.0397.v1
Online: 16 November 2020 (08:30:08 CET)
A 31-year-old male noticed blurred vision in his right eye for five days with no obvious predisposing causes, accompanied by mild dizziness. No obvious nodular lesions were found in the body. The patient’s binocular visual acuity was 20/20. Fundus photography showed the optic nerve swelling and radial superficial retinal hemorrhage of both eyes. Blood panel, urine routine, liver, and kidney function were all normal. Total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein were all in the normal limits. Head MRI showed a mass in the right temporal lobe, clear boundary, and multiple separations, which thinned and disappeared closer to the skull. The right temporal lobe and lateral ventricle were all compressed, with the midline structure shifted to the left. The patient was then transferred to Neurosurgery. During the operation, we observed the tumor had invaded the skull. The actual size of the tumor was 5.6 cm × 7.5 cm × 10.1 cm. Histology revealed foam cell accumulation in the mucous connective tissue of the right temporal lobe. The immunohistochemistry showed: CD34 (+), CD99 (+), EMA (−), GFAP (−), IDH-1 (−), Ki-67 (+) index about 10%, Oliga-2 (−), PR (−), S-100 (−), Vim (+), β-Catenin (+), CD1a (−), CD68 (+). Three months after the removal of the tumor, the visual acuity of both eyes was 20/20; The visual fields were normal, the optic disc edema and retinal hemorrhages had disappeared. MRI indicated the midline structure was back to normal.
ARTICLE | doi:10.20944/preprints202306.1815.v2
Subject: Social Sciences, Cognitive Science Keywords: neurofeedback; memory enhancement; medial temporal lobe; intracranial electrode; bidirectional control; memory encoding; intracranial electroencephalogram; intractable epilepsy
Online: 28 June 2023 (12:56:15 CEST)
Neurofeedback (NF) shows promise in enhancing memory, but its application to the medial temporal lobe (MTL) still needs to be studied. Therefore, we aimed to develop an NF system for the memory function of the MTL and examine neural activity changes, and memory task score changes through NF training. We created a memory NF system using intracranial electrodes to acquire and visualise the neural activity of the MTL during memory encoding. Twenty trials of a tug-of-war game per session were employed for NF and designed to control neural activity bidirectionally (Up/Down condition). NF training was conducted with three patients with intractable epilepsy, and we observed an increasing difference in NF signal between conditions (Up−Down) as NF training progressed. Similarities and negative correlation tendencies between the transition of neural activity and the transition of memory function were also observed. Our findings demonstrate NF's potential to modulate MTL activity and memory encoding. Future research needs further improvements to the NF system to validate its effects on memory functions. Nonetheless, this study represents a crucial step in understanding NF's application to memory and provides valuable insights for developing more efficient memory enhancement strategies.
ARTICLE | doi:10.20944/preprints202112.0150.v3
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Image Detection; Intracranial Hemorrhage; Deep Learning; Decision Support System.
Online: 20 December 2022 (10:31:23 CET)
Intracranial hemorrhage is a serious medical problem that requires rapid and often intensive medical care. Identifying the location and type of any hemorrhage present is a critical step in the treatment of the patient. Diagnosis requires an urgent procedure, and the detection of hemorrhage is a difficult and time-consuming process for human experts. In this paper, we propose methods based on EfficientDet’s deep-learning technology that can be applied to the diagnosis of hemorrhages and thus become a decision-support system. Our proposal is two-fold. On the one hand, the proposed technique classifies slices of computed tomography scans for the presence hemorrhage or its lack, achieving 92.7% accuracy and 0.978 ROC-AUC. On the other hand, our methodology provides visual explanations of the classification chosen using the Grad-CAM methodology.
REVIEW | doi:10.20944/preprints202107.0551.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: epidermal growth factor receptor; ErbB; biomarker; meningioma; intracranial tumor
Online: 23 July 2021 (22:06:24 CEST)
Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets. The role of receptor tyrosine kinase (RTKs), including those of the ErbB family of receptors, as oncogenes has been well established in several cancer types. Here, we review histological, molecular, and clinical evidence suggesting that RTKs, including the epidermal growth factor receptor (EGFR, ErbB 1), as well as other members of the ErbB family, may be useful as biomarkers in MGM.
ARTICLE | doi:10.20944/preprints202311.1529.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: microgravity; space flight; human neural stem cells; autophagy; intracranial hypertension
Online: 24 November 2023 (02:36:02 CET)
Mammalian cells have evolved to function under Earth’s gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for the maintenance of central nervous system (CNS) functions during development and the regeneration of all CNS cell populations. Here, we examined the behavior of space (SPC)-flown NSCs as they readapted to Earth’s gravity. We found that most of these cells survived the space flight and self-renewed. Yet, some showed autophagy-like behaviors (ALB). To ascertain if the secretome from SPC-flown NSCs contained molecules inducing this behavior, we incubated naïve, non-starved NSCs in a medium containing SPC-NSCs secretome. We found a four-fold increase in the ALB rate. Proteomic analysis of the secretome revealed that the protein of highest content produced by SPC-NSCs was secreted protein acidic and rich in cysteine (SPARC), which triggers endoplasmic reticulum (ER) stress leading to lethal ALB. These results offer novel knowledge on the response of neural cells, particularly NSCs, subjected to space microgravity. Moreover, some secreted proteins have been identified as microgravity sensing, paving a new venue for future research aiming at targeting SPARC metabolism. Although we did not establish a direct relationship between ALB and SPARC as a potential marker, these results represent the first step in the identification of gravity sensing molecules as targets to be modulated and to design effective countermeasures to mitigate intracranial hypertension in astronauts using structure-based-protein design.
ARTICLE | doi:10.20944/preprints202304.0754.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: intracranial pressure (ICP) monitoring; probe placement; air-pouch balloon-assisted probe
Online: 23 April 2023 (03:57:28 CEST)
Background: Air-pouch balloon-assisted probes have proven to be both simple and reliable tools for intracranial pressure (ICP) monitoring. However, we experienced reproducible falsely high ICP measurement when the ICP probe was inserted in the intracerebral hematoma cavity. Thus, the aim of the experimental and translational study was to analyze the influence of ICP probe placement with regard to measured ICP values. Methods: Two Spiegelberg 3PN-sensors were simultaneously inserted into a closed drain system and were connected to two separate ICP monitors thereby allowing for simultaneous ICP measurements. This closed system was also engineered to allow for pressure to be gradually increased in a controlled fashion. Once the pressure was verified using two identical ICP probes, one of the probes was coated with blood in an effort to replicate placement within an intraparenchymal hematoma. Pressures recorded using the coated probe and control probe were then recorded and compared across a range of 0-60 mmHg. In an effort to further the translational relevance of our results two ICP probes were inserted in a patient that presented with a large basal ganglia hemorrhage that met criteria for ICP monitoring. One probe was inserted into the hematoma and the other into brain parenchyma; ICP values were recorded from both probes and the results compared. Results: The experimental set-up demonstrated a reliable correlation between both control ICP probes. Interestingly, the ICP probe covered with clot displayed a significantly higher average ICP value when compared to the control probe between 0mmHg and 50mmHg (p<0.001); at 60mmHg there was no significant difference noted. Critically, this trend in discordance was even more pronounced in the clinical setting with the ICP probe placed within the hematoma cavity having reported significantly higher ICP values as compared to the probe within brain parenchyma. Conclusion: Our experimental study and clinical pilot highlight a potential pitfall in ICP measurement that may result secondary to probe placement within hematoma. Such aberrant results may lead to inappropriate interventions in an effort to falsely addresses falsely elevated ICPs.
ARTICLE | doi:10.20944/preprints202310.1558.v1
Subject: Physical Sciences, Biophysics Keywords: Computational haemodynamics; Intracranial aneurysms; Circle of Willis; Wall shear stress; Boundary conditions
Online: 24 October 2023 (17:32:53 CEST)
Haemodynamic simulations are increasingly used to study vascular diseases like Intracranial Aneurysms (IA) and to further develope treatment options. However, due to limited data, some aspects must rely on heuristics, especially at the simulation’s distal ends. In literature, Murray’s Law is often used to model the outflow split based on vessel cross-section area, but this poses challenges for the communicating arteries in the Circle of Willis (CoW). In this study, we contribute by assessing the impact of Murray’s Law in patient-specific geometries featuring IA at the posterior communication. We simulate different domain extensions, representing common modelling choices. We establish Full CoW simulations as a baseline to evaluate the effect of these modelling assumptions on haemodynamic indicators, focusing on IA growth and rupture-related factors like Wall Shear Stress (WSS) and Oscillatory Shear Index (OSI). Our findings reveal qualitative alterations in haemodynamics when not modeling posterior communication. Comparisons between computing the anterior circulation and computing the whole Circle of Willis reveal quantitative changes in WSS may reach up to 80%, highlighting the significance of modelling choices in assessing IA risks and treatment strategies.
ARTICLE | doi:10.20944/preprints202306.0454.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: intracranial pressure; cerebral compliance; deep neural networks; recurrent neural networks; convolutional neural networks
Online: 6 June 2023 (11:50:05 CEST)
The intracranial pressure (ICP) signal, as monitored on patients in intensive care units, contains pulses of cardiac origin where P1 and P2 subpeaks can often be observed. When calculable, the ratio of their relative amplitudes is an indicator of the patient’s cerebral compliance. This characterization is particularly informative on the overall state of the cerebrospinal system. We developed a recurrent neural network-based framework for P2/P1 ratio computation that only takes a raw ICP signal as an input. Two tasks are performed, namely pulse classification and subpeak designation. Pulse classification was achieved with an area under the curve of 0.90 on a 4,344-pulse testing dataset, while the peak designation algorithm identified pulses with a P2/P1 ratio > 1 with a 97.3% accuracy. Although it still needs to be evaluated on a larger number of labeled recordings, our automated P2/P1 ratio calculation framework appears to be a promising tool for improving bedside monitoring devices.
ARTICLE | doi:10.20944/preprints202305.0125.v1
Subject: Biology And Life Sciences, Biophysics Keywords: trade-off; dialectic; TRIZ; Inventive Principle; wood wasp ovipositor; intracranial endoscope; Pareto curve
Online: 3 May 2023 (09:44:40 CEST)
Our knowledge of physics and chemistry is relatively well defined. Results from that knowledge are predictable as, largely, are those of their technical offspring such as electrical, chemical, me-chanical and civil engineering. By contrast biology is relatively unconstrained and unpredictable. A factor common to all areas is the trade-off, which provides a means of defining and quantifying a problem and, ideally, its solution. In order to understand the anatomy of the trade-off and how to handle it, its development (as the dialectic) is tracked from Hegel and Marx to its implementa-tion as dialectical materialism in Russian philosophy and TRIZ, the Theory of Invention. With the ready availability of mathematical techniques, such as multi-objective analysis and the Pareto set, the trade-off is well-adapted to bridging the gaps between the quantified and the unquantifiable, allowing modelling and the transfer of concepts by analogy. It is thus an ideal tool for biomimet-ics. An intracranial endoscope can be derived with little change from the egg-laying tube of a wood wasp. More complex transfers become available as the technique is developed. Most im-portant, as more trade-offs are analyzed, their results are stored to be used again in the solution of problems. There is no other system in biomimetics which can do this.
REVIEW | doi:10.20944/preprints202306.1457.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Coronavirus disease 2019; COVID-19; Stroke; Cerebral vein thrombosis; Intracranial hemorrhage; Anticoagulation; Mechanical thrombectomy; Intravenous thrombolysis
Online: 20 June 2023 (15:13:35 CEST)
Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus, SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in health care. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.
REVIEW | doi:10.20944/preprints202012.0322.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Cerebrospinal fluid; real-time MRI; hydrocephalus; space flight disease; aquaporin; spontaneous intracranial hypotension; neural tube defect
Online: 14 December 2020 (10:21:21 CET)
New experimental and clinical findings question the historic view of hydrocephalus and its 100-year-old classification. In particular, real-time MRI evaluation of CSF flow and detailed insights into brain water regulation on the molecular scale indicate the existence of at least three main mechanisms that determine the dynamics of neurofluids. (i) Inspiration is a major driving force (ii) Adequate filling of brain ventricles by balanced cerebrospinal fluid upsurge is sensed by cilia (iii) The perivascular glial network connects the ependymal surface to the pericapillary Virchow-Robin spaces. Hitherto, these aspects have not been considered a common physiologic framework improving knowledge and therapy for severe disorders of normal-pressure and post-haemorrhagic hydrocephalus, spontaneous intracranial hypotension and spaceflight disease.
REVIEW | doi:10.20944/preprints202310.1786.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Intracranial compliance; Viscous component; Time-dependent disorders; Brain disorder; Strain rate; Cerebrospinal fluid; Brain biomechanics; Clinical application.
Online: 27 October 2023 (10:33:52 CEST)
Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.
REVIEW | doi:10.20944/preprints202305.0122.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Non-small cell lung cancer (NSCLC); EGFR; Tyrosine kinase inhibitors (TKIs); Uncommon mutation; Compound mutation; Intracranial activity; Immunotherapy
Online: 3 May 2023 (09:29:08 CEST)
The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.
CASE REPORT | doi:10.20944/preprints202301.0379.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Combined Peripheral Nerve Stimulation; occipital nerve stimulation; secondary headache disor-ders; chronic post-intracranial disorder headache and case report
Online: 23 January 2023 (00:57:59 CET)
The introduction of ventricular shunts dramatically changed the outcome and quality of life of hydrocephalic patients. However, shunt surgery continues to be associated with numerous adverse events. Headache is one of the most common complications after shunt operation. It is often over a prolonged duration, the symptoms resemble migraine, and pain does not respond to medication. We propose invasive peripheral nerve stimulation as a possible solution in the treatment of patients suffering from chronic headache associated with shunted hydrocephalus. A young woman with daily holocephalic headache with diffuse pain exacerbated by lying down. Imaging revealed panventricular enlargement and possible stenosis of the aqueduct. When a ventriculoperitoneal shunt was placed, clinical symptoms resolved. Nevertheless, she gradually exacerbated after a second valve replacement due to wound infection. Imaging revealed decompressed ventricles and appropriate shunt placement. The diagnosis of chronic post-intracranial disorder headache was set. Therefore, occipital nerve stimulation was applied and considering that the patient had not a total response, bilateral parietal stimulation was added. Three months after the combined PNS she experienced total remission of headache. Combined PNS eases refractory headaches much more than occipital nerve stimulation alone and could be considered as a solution for shunted hydrocephalus associated headache.