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.

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.

Correction: Rehabilitation Needs, Service Provision, and Costs in the First Year Following Traumatic Injuries: Protocol for a Prospective Cohort Study.

[This corrects the article DOI: 10.2196/25980.].

Rehabilitation Needs, Service Provision, and Costs in the First Year Following Traumatic Injuries: Protocol for a Prospective Cohort Study.

BACKGROUND: Traumatic injuries, defined as physical injuries with sudden onset, are a major public health problem worldwide. There is a paucity of knowledge regarding rehabilitation needs and service provision for patients with moderate and major trauma, even if rehabilitation research on a spectrum of specific injuries is available. OBJECTIVE: This study aims to describe the prevalence of rehabilitation needs, the provided services, and functional outcomes across all age groups, levels of injury severity, and geographical regions in the first year after trauma. Direct and indirect costs of rehabilitation provision will also be assessed. The overarching aim is to better understand where to target future efforts. METHODS: This is a population-based prospective follow-up study. It encompasses patients of all ages with moderate and severe acute traumatic injury (New Injury Severity Score >9) admitted to the regional trauma centers in southeastern and northern Norway over a 1-year period (2020). Sociodemographic and injury data will be collected. Upon hospital discharge, rehabilitation physicians estimate rehabilitation needs. Rehabilitation needs are assessed by the Rehabilitation Complexity Scale Extended-Trauma (RCS E-Trauma; specialized inpatient rehabilitation), Needs and Provision Complexity Scale (NPCS; community-based rehabilitation and health care service delivery), and Family Needs Questionnaire-Pediatric Version (FNQ-P). Patients, family caregivers, or both will complete questionnaires at 6- and 12-month follow-ups, which are supplemented by telephone interviews. Data on functioning and disability, mental health, health-related quality of life measured by the EuroQol Questionnaire (EQ-5D), and needs and provision of rehabilitation and health care services are collected by validated outcome measures. Unmet needs are represented by the discrepancies between the estimates of the RCS E-Trauma and NPCS at the time of a patient's discharge and the rehabilitation services the patient has actually received. Formal service provision (including admission to inpatient- or outpatient-based rehabilitation), informal care, and associated costs will be collected. RESULTS: The project was funded in December 2018 and approved by the Regional Committee for Medical and Health Research Ethics in October 2019. Inclusion of patients began at Oslo University Hospital on January 1, 2020, and at the University Hospital of North Norway on February 1, 2020. As of February 2021, we have enrolled 612 patients, and for 286 patients the 6-month follow-up has been completed. Papers will be drafted for publication throughout 2021 and 2022. CONCLUSIONS: This study will improve our understanding of existing service provision, the gaps between needs and services, and the associated costs for treating patients with moderate and major trauma. This may guide the improvement of rehabilitation and health care resource planning and allocation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25980.

MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR.

BACKGROUND: Methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method. METHOD: We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. RESULTS: When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods. CONCLUSION: In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method.

Assessment of continuous intracranial pressure recordings in childhood craniosynostosis.

In this study, we explored two strategies of assessing continuous intracranial pressure (ICP) recordings in children with craniosynostosis, namely either by computation of the mean ICP or by computation of the accurate numbers of ICP elevations of different durations. The ICP recordings of 121 consecutive patients with a tentative diagnosis of craniosynostosis who underwent continuous ICP monitoring were examined. The relationship between mean ICP and numbers of ICP elevations was defined. The distribution of numbers of ICP elevations between patients either undergoing surgery or conservative treatment was also compared, since the choice of treatment was heavily dependent on the results of ICP monitoring. At the time of ICP monitoring, calculation of mean ICP was the main parameter for assessment of ICP curves. After a median observation period of 16 months, the ICP curves were reexamined by means of the software Sensometrics Pressure Analyser, which presents the ICP curve as a matrix of numbers of ICP elevations of different levels (20-40 mm Hg) and durations (0.5- 20 min). Since the recording period differed between the cases, the numbers were standardized to a given recording time of 10 h, to allow for comparisons between patients. Cases with a borderline mean ICP during sleep (mean ICP 10-15 mm Hg) constituted 40.5% of the 121 patients. In this group, a rather weak relationship between mean ICP and the number of ICP elevations above 20 mm Hg was found, as well as a relatively high number of ICP elevations above 20 mm Hg of various durations. As compared to the patients undergoing surgery, a rather high number of ICP elevations above 20 mm Hg of various durations was found in patients undergoing conservative treatment. The study confirmed our hypothesis that in children with craniosynostosis, calculation of mean ICP does not describe the ICP curve in a reliable way. Decision-making should also include the computation of the distribution of numbers of ICP elevations, since this procedure represents a more sensitive strategy of detecting intracranial hypertension.