Noninvasive Assessment of Intracranial Pressure: Deformability Index as an Adjunct to Optic Nerve Sheath Diameter to Increase Diagnostic Ability.

BACKGROUND: Today, invasive intracranial pressure (ICP) measurement remains the standard, but its invasiveness limits availability. Here, we evaluate a novel ultrasound-based optic nerve sheath parameter called the deformability index (DI) and its ability to assess ICP noninvasively. Furthermore, we ask whether combining DI with optic nerve sheath diameter (ONSD), a more established parameter, results in increased diagnostic ability, as compared to using ONSD alone. METHODS: We prospectively included adult patients with traumatic brain injury with invasive ICP monitoring, which served as the reference measurement. Ultrasound images and videos of the optic nerve sheath were acquired. ONSD was measured at the bedside, whereas DI was calculated by semiautomated postprocessing of ultrasound videos. Correlations of ONSD and DI to ICP were explored, and a linear regression model combining ONSD and DI was compared to a linear regression model using ONSD alone. Ability of the noninvasive parameters to distinguish dichotomized ICP was evaluated using receiver operating characteristic curves, and a logistic regression model combining ONSD and DI was compared to a logistic regression model using ONSD alone. RESULTS: Forty-four ultrasound examinations were performed in 26 patients. Both DI (R = - 0.28; 95% confidence interval [CI] R < - 0.03; p = 0.03) and ONSD (R = 0.45; 95% CI R > 0.23; p < 0.01) correlated with ICP. When including both parameters in a combined model, the estimated correlation coefficient increased (R = 0.51; 95% CI R > 0.30; p < 0.01), compared to using ONSD alone, but the model improvement did not reach statistical significance (p = 0.09). Both DI (area under the curve [AUC] 0.69, 95% CI 0.53-0.83) and ONSD (AUC 0.72, 95% CI 0.56-0.86) displayed ability to distinguish ICP dichotomized at ICP ≥ 15 mm Hg. When using both parameters in a combined model, AUC increased (0.80, 95% CI 0.63-0.90), and the model improvement was statistically significant (p = 0.02). CONCLUSIONS: Combining ONSD with DI holds the potential of increasing the ability of optic nerve sheath parameters in the noninvasive assessment of ICP, compared to using ONSD alone, and further study of DI is warranted.

Transorbital neuroendoscopy-assisted resection of a giant optic pathway glioma in a neonate.

Congenital giant orbital tumors in infancy are relatively rare, especially when the tumors are associated with significant intracranial extension. We describe the use of a transorbital neuroendoscopy-assisted resection of such a lesion. While this approach is increasingly gaining popularity for certain anterior and middle skullbase lesions in adults, this report represents the youngest patient reported on where this minimally invasive approach has been successfully used to resect the intracranial tumor. This surgical approach obviated the need for a separate craniotomy, with the additional benefit of minimizing blood loss.

Noninvasive intracranial pressure assessment by optic nerve sheath diameter: Automated measurements as an alternative to clinician-performed measurements.

Introduction: Optic nerve sheath diameter (ONSD) has shown promise as a noninvasive parameter for estimating intracranial pressure (ICP). In this study, we evaluated a novel automated method of measuring the ONSD in transorbital ultrasound imaging. Methods: From adult traumatic brain injury (TBI) patients with invasive ICP monitoring, bedside manual ONSD measurements and ultrasound videos of the optic nerve sheath complex were simultaneously acquired. Automatic ONSD measurements were obtained by the processing of the ultrasound videos by a novel software based on a machine learning approach for segmentation of the optic nerve sheath. Agreement between manual and automated measurements, as well as their correlation to invasive ICP, was evaluated. Furthermore, the ability to distinguish dichotomized ICP for manual and automatic measurements of ONSD was compared, both for ICP dichotomized at ≥20 mmHg and at the 50th percentile (≥14 mmHg). Finally, we performed an exploratory subgroup analysis based on the software's judgment of optic nerve axis alignment to elucidate the reasons for variation in the agreement between automatic and manual measurements. Results: A total of 43 ultrasound examinations were performed on 25 adult patients with TBI, resulting in 86 image sequences covering the right and left eyes. The median pairwise difference between automatically and manually measured ONSD was 0.06 mm (IQR -0.44 to 0.38 mm; p = 0.80). The manually measured ONSD showed a positive correlation with ICP, while automatically measured ONSD showed a trend toward, but not a statistically significant correlation with ICP. When examining the ability to distinguish dichotomized ICP, manual and automatic measurements performed with similar accuracy both for an ICP cutoff at 20 mmHg (manual: AUC 0.74, 95% CI 0.58-0.88; automatic: AUC 0.83, 95% CI 0.66-0.93) and for an ICP cutoff at 14 mmHg (manual: AUC 0.70, 95% CI 0.52-0.85; automatic: AUC 0.68, 95% CI 0.48-0.83). In the exploratory subgroup analysis, we found that the agreement between measurements was higher in the subgroup where the automatic software evaluated the optic nerve axis alignment as good as compared to intermediate/poor. Conclusion: The novel automated method of measuring the ONSD on the ultrasound videos using segmentation of the optic nerve sheath showed a reasonable agreement with manual measurements and performed equally well in distinguishing high and low ICP.

Microbiomics in Collusion with the Nervous System in Carcinogenesis: Diagnosis, Pathogenesis and Treatment.

The influence of the naturally occurring population of microbes on various human diseases has been a topic of much recent interest. Not surprisingly, continuously growing attention is devoted to the existence of a gut brain axis, where the microbiota present in the gut can affect the nervous system through the release of metabolites, stimulation of the immune system, changing the permeability of the blood-brain barrier or activating the vagus nerves. Many of the methods that stimulate the nervous system can also lead to the development of cancer by manipulating pathways associated with the hallmarks of cancer. Moreover, neurogenesis or the creation of new nervous tissue, is associated with the development and progression of cancer in a similar manner as the blood and lymphatic systems. Finally, microbes can secrete neurotransmitters, which can stimulate cancer growth and development. In this review we discuss the latest evidence that support the importance of microbiota and peripheral nerves in cancer development and dissemination.

Many Voices in a Choir: Tumor-Induced Neurogenesis and Neuronal Driven Alternative Splicing Sound Like Suspects in Tumor Growth and Dissemination.

During development, as tissues expand and grow, they require circulatory, lymphatic, and nervous system expansion for proper function and support. Similarly, as tumors arise and develop, they also require the expansion of these systems to support them. While the contribution of blood and lymphatic systems to the development and progression of cancer is well known and is targeted with anticancer drugs, the contribution of the nervous system is less well studied and understood. Recent studies have shown that the interaction between neurons and a tumor are bilateral and promote metastasis on one hand, and the formation of new nerve structures (neoneurogenesis) on the other. Substances such as neurotransmitters and neurotrophins being the main actors in such interplay, it seems reasonable to expect that alternative splicing and the different populations of protein isoforms can affect tumor-derived neurogenesis. Here, we report the different, documented ways in which neurons contribute to the development and progression of cancer and investigate what is currently known regarding cancer-neuronal interaction in several specific cancer types. Furthermore, we discuss the incidence of alternative splicing that have been identified as playing a role in tumor-induced neoneurogenesis, cancer development and progression. Several examples of changes in alternative splicing that give rise to different isoforms in nerve tissue that support cancer progression, growth and development have also been investigated. Finally, we discuss the potential of our knowledge in alternative splicing to improve tumor diagnosis and treatment.

ICP-based decision-making in pediatric neurosurgery.

Decision-making in pediatric neurosurgery routinely involves assessing intracranial pressure (ICP). The level of injury and severity of disease play an important role in determining which method of ICP measurement is preferred. Invasive and non-invasive techniques have described indications, advantages and shortcomings. This collection of papers from some of the world's leading thinkers in this field is a refreshing perspective on some mundane techniques and a few innovative and promising advances.

Non-invasive assessment of ICP in children: advances in ultrasound-based techniques.

The assessment of intracranial pressure (ICP) in children with neurological disease remains a cornerstone in their routine management. The quest for a reliable, reproducible and radiation-free non-invasive technique for assessing ICP in children remains somewhat of a holy grail for neurosurgery. This work assesses some of the recent advances in ultrasound-based techniques, addressing both novel processes and modifications aimed at improving the accuracy of existing techniques.

Brain ultrasonography: methodology, basic and advanced principles and clinical applications. A narrative review.

Brain ultrasonography can be used to evaluate cerebral anatomy and pathology, as well as cerebral circulation through analysis of blood flow velocities. Transcranial colour-coded duplex sonography is a generally safe, repeatable, non-invasive, bedside technique that has a strong potential in neurocritical care patients in many clinical scenarios, including traumatic brain injury, aneurysmal subarachnoid haemorrhage, hydrocephalus, and the diagnosis of cerebral circulatory arrest. Furthermore, the clinical applications of this technique may extend to different settings, including the general intensive care unit and the emergency department. Its increasing use reflects a growing interest in non-invasive cerebral and systemic assessment. The aim of this manuscript is to provide an overview of the basic and advanced principles underlying brain ultrasonography, and to review the different techniques and different clinical applications of this approach in the monitoring and treatment of critically ill patients.

Noninvasive Transorbital Assessment of the Optic Nerve Sheath in Children: Relationship Between Optic Nerve Sheath Diameter, Deformability Index, and Intracranial Pressure.

BACKGROUND: Measurement of optic nerve sheath diameter (ONSD) is a promising technique for noninvasive assessment of intracranial pressure (ICP), but has certain limitations. A recent study showed that the deformability index (DI), a dynamic parameter quantifying the pulsatile nature of the optic nerve sheath, could differentiate between patients with high vs normal ICP. OBJECTIVE: To further evaluate the diagnostic accuracy of the DI, when interpreted together with ONSD. METHODS: This prospective study included children undergoing invasive ICP measurement as part of their clinical management. Ultrasound images of the optic nerve sheath were acquired prior to measuring ICP, the images were further processed to obtain the DI. Patients were dichotomized into high (≥20 mm Hg) or normal ICP groups and compared using the Mann-Whitney U-test. Diagnostic accuracy was described using area under the receiver operating characteristic curve (AUC), sensitivity and specificity, correlation between DI, ONSD, and ICP was investigated using linear regression. RESULTS: A total of 28 patients were included (19 high ICP). The DI was lower in the high ICP group (0.105 vs 0.28, P = .001). AUC was 0.87, and a cut-off value of DI ≤ 0.185 demonstrated sensitivity of 89.5% and specificity of 88.9%. Diagnostic accuracy improved when combining DI with ONSD (AUC 0.98, sensitivity 94.7%, specificity 88.9%) and correlation with ICP improved when combined analysis of DI and ONSD was performed (Pearson correlation coefficient: 0.82 vs 0.42, respectively, P = .012). CONCLUSION: The DI was significantly lower for patients with high vs normal ICP. This relationship improved further when the DI and ONSD were interpreted together.

Functional outcome and survival following spontaneous intracerebral hemorrhage: A retrospective population-based study.

BACKGROUND: Accurate and reliable clinical and radiological predictors of intracerebral hemorrhage (ICH) outcomes are needed to optimize treatment of ICH. The aim of this study was to investigate functional outcome and identify predictors of severe disability or death following ICH. MATERIALS AND METHODS: Retrospective population-based study of spontaneous ICH. Clinical and radiological data were obtained from electronic medical records, and functional outcome estimated using the modified Rankin Scale (mRS) before ICH and at 3 and 12 months after ICH. RESULTS: Four hundred and fifty-two patients were included (mean age 74.8 years, 45.6% females). Proportion of fatal outcome at 1 week was 22.1%, at 3 months 39.2%, and at 12 months 44.9%. Median mRS score before the ICH was 1 (interquartile range [IQR] 2); for survivors at 3 months, it was 5 (IQR 3); and at 12 months, it was 3 (IQR 2). Independent predictors of severe disability (mRS of 5) or death (mRS of 6) were use of oral antithrombotic drugs (OR 2.2, 95% CI 1.3-3.8, p = 0.04), mRS score before the ICH (OR 1.8, 95% CI 1.4-2.2, p < 0.001), Glasgow Coma Scale (GCS) on admission (OR 8.3, 95% CI 3.5-19.7, p < 0.001), hematoma volume >60 ml (OR 4.5, 05% CI 2.0-10.2, p < 0.001), and intraventricular hematoma extension (OR 1.8, 95% CI 0.8-4.2, p < 0.001). CONCLUSION: Intracerebral hemorrhage is associated with high mortality, and more than one third of survivors end up with severe disability or death 3 months later. Predictors of severe disability or death were use of oral antithrombotic drugs, functional disability prior to ICH, low GCS on admission, larger hematoma volume, and intraventricular hematoma extension.

Hydatid disease (Echinococcus) of the central nervous system.

Hydatid disease of the central nervous system is rare and comprises about 2-3% of all the hydatid cyst cases reported in the world. Spinal hydatid is still rare. It is endemic in sheep and cattle-raising regions, seen mainly in Mediterranean countries including Turkey and Syria. Pediatric neurosurgeons in nonendemic countries face a challenge when they are encountered with hydatid cyst of the central nervous system due to lack of awareness and diagnostic dilemmas. It is also a mammoth economic problem in developing countries due to improper hygiene and lack of dedicated veterinary practice. The clinical features are largely nonspecific. However, with the advent of MR imaging, the diagnostic accuracy has increased. Intact removal of the cyst without causing any spillage is the goal and key to cure. In this manuscript, the current literature on hydatid cyst of the brain and spine is reviewed to understand the epidemiological, diagnostic accuracy and advances in therapeutics. A heightened clinical suspicion about hydatid disease, role of MR imaging and improving surgical strategies is discussed. A nationwide prevention of the disease is the ultimate goal.

Optic nerve sheath diameter measured sonographically as non-invasive estimator of intracranial pressure: a systematic review and meta-analysis.

PURPOSE: Although invasive intracranial devices (IIDs) are the gold standard for intracranial pressure (ICP) measurement, ultrasonography of the optic nerve sheath diameter (ONSD) has been suggested as a potential non-invasive ICP estimator. We performed a meta-analysis to evaluate the diagnostic accuracy of sonographic ONSD measurement for assessment of intracranial hypertension (IH) in adult patients. METHODS: We searched on electronic databases (MEDLINE/PubMed®, Scopus®, Web of Science®, ScienceDirect®, Cochrane Library®) until 31 May 2018 for comparative studies that evaluated the efficacy of sonographic ONSD vs. ICP measurement with IID. Data were extracted independently by two authors. We used the QUADAS-2 tool for assessing the risk of bias (RB) of each study. A diagnostic meta-analysis following the bivariate approach and random-effects model was performed. RESULTS: Seven prospective studies (320 patients) were evaluated for IH detection (assumed with ICP > 20 mmHg or > 25 cmH2O). The accuracy of included studies ranged from 0.811 (95% CI 0.678‒0.847) to 0.954 (95% CI 0.853‒0.983). Three studies were at high RB. No significant heterogeneity was found for the diagnostic odds ratio (DOR), positive likelihood ratio (PLR) and negative likelihood ratio (NLR), with I2 < 50% for each parameter. The pooled DOR, PLR and NLR were 67.5 (95% CI 29‒135), 5.35 (95% CI 3.76‒7.53) and 0.088 (95% CI 0.046‒0.152), respectively. The area under the hierarchical summary receiver-operating characteristic curve (AUHSROC) was 0.938. In the subset of five studies (275 patients) with IH defined for ICP > 20 mmHg, the pooled DOR, PLR and NLR were 68.10 (95% CI 26.8‒144), 5.18 (95% CI 3.59‒7.37) and 0.087 (95% CI 0.041‒0.158), respectively, while the AUHSROC was 0.932. CONCLUSIONS: Although the wide 95% CI in our pooled DOR suggests caution, ultrasonographic ONSD may be a potentially useful approach for assessing IH when IIDs are not indicated or available (CRD42018089137, PROSPERO).

Infections in the immunocompromised child.

Prevention and management of opportunistic infections in children is particularly relevant in an era demonstrating an increased prevalence of immunocompromising conditions. The presence of an unusual organism which results in serious infection in a child should therefore always raise the consideration of immune compromise. The more common opportunistic infections have become easier to recognize in recent times due to improved awareness and more refined diagnostic testing. Targeted treatment is usually followed by long-term prophylactic medication. The impact of these conditions on patient outcome is of clear significance and certainly warrants further discussion.

The relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children. : Part II: age-related ONSD cut-off values and patency of the anterior fontanelle.

PURPOSE: To analyse the diagnostic accuracy of age-related optic nerve sheath diameter (ONSD) cut-off values in children for detecting raised intracranial pressure (ICP) and to assess the benefit of using patency of the anterior fontanelle in describing a different set of cut-off values. METHODS: The ONSD measurement was performed prior to invasive ICP measurement in children under general anesthesia. The diagnostic accuracy of the ONSD measurement was compared to ICP at thresholds of 20, 15, 10, and 5 mmHg. This was further analysed in children above and below the age of 1 year, with a subgroup analysis of age at 4 years, and assessment of the anterior fontanelle (AF) as a reliable physiological marker in part II of this study. RESULTS: Data from 174 children were analysed. In children ≤1 year old, the ONSD measurement with the best diagnostic accuracy for detecting ICP ≥ 20 mmHg was 5.16 mm, compared to 5.75 mm in children >1 year old (p < 0.001). In addition, patency of the anterior fontanelle (AF) was found to be a useful clinical marker for defining different ONSD cut-off values at ICP thresholds of 20, 15, 10 and 5 mmHg. CONCLUSION: Transorbital ultrasound measurement of the ONSD is a reliable non-invasive marker of ICP particularly at higher thresholds of 20 and 15 mmHg. Patency of the AF is a useful clinical marker for defining different ONSD cut-off values in children.

The relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children : Part I: repeatability, observer variability and general analysis.

PURPOSE: The aim of this study was to investigate the relationship between optic nerve sheath diameter (ONSD) measurement and invasively measured intracranial pressure (ICP) in children. METHODS: ONSD measurement was performed prior to invasive measurement of ICP. The mean binocular ONSD measurement was compared to the ICP reading. Physiological variables including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse rate, temperature, respiratory rate and end tidal carbon dioxide (ETCO2) level were recorded at the time of ONSD measurement. Diagnostic accuracy analysis was performed at various ICP thresholds and  repeatability, intra- and inter-observer variability, correlation between measurements in different imaging planes as well the relationship over the entire patient cohort were examined in part I of this study. RESULTS: Data from 174 patients were analysed. Repeatability and intra-observer variability were excellent (α = 0.97-0.99). Testing for inter-observer variability revealed good correlation (r = 0.89, p < 0.001). Imaging in the sagittal plane demonstrated a slightly better correlation with ICP (r = 0.66, p < 0.001). The ONSD measurement with the best diagnostic accuracy for detecting an ICP ≥ 20 mmHg over the entire patient cohort was 5.5 mm, sensitivity 93.2 %, specificity 74 % and odds ratio (OR) of 39.3. CONCLUSION: Transorbital ultrasound measurement of the OSND is a reliable and reproducible technique, demonstrating a good relationship with ICP and high diagnostic accuracy for detecting raised ICP.

Non-invasive intracranial pressure assessment.

Assessing intracranial pressure (ICP) remains a cornerstone in neurosurgical care. Invasive techniques for monitoring ICP remain the gold standard. The need for a reliable, safe and reproducible technique to non-invasively assess ICP in the context of early screening and in the neurocritical care environment is obvious. Numerous techniques have been described with several novel advances. While none of the currently available techniques appear independently accurate enough to quantify raised ICP, there is some promising work being undertaken.