Significance of navigated transcranial magnetic stimulation and tractography to preserve motor function in patients undergoing surgery for motor eloquent gliomas.

Resection of gliomas in or close to motor areas is at high risk for morbidity and development of surgery-related deficits. Navigated transcranial magnetic stimulation (nTMS) including nTMS-based tractography is suitable for presurgical planning and risk assessment. The aim of this study was to investigate the association of postoperative motor status and the spatial relation to motor eloquent brain tissue in order to increase the understanding of postoperative motor deficits. Patient data, nTMS examinations and imaging studies were retrospectively reviewed, corticospinal tracts (CST) were reconstructed with two different approaches of nTMS-based seeding. Postoperative imaging and nTMS-augmented preoperative imaging were merged to identify the relation between motor positive cortical and subcortical areas and the resection cavity. 38 tumor surgeries were performed in 36 glioma patients (28.9% female) aged 55.1 ± 13.8 years. Mean distance between the CST and the lesion was 6.9 ± 5.1 mm at 75% of the patient-individual fractional anisotropy threshold and median tumor volume reduction was 97.7 ± 11.6%. The positive predictive value for permanent deficits after resection of nTMS positive areas was 66.7% and the corresponding negative predictive value was 90.6%. Distances between the resection cavity and the CST were higher in patients with postoperative stable motor function. Extent of resection and distance between resection cavity and CST correlated well. The present study strongly supports preoperative nTMS as an important surgical tool for preserving motor function in glioma patients at risk.

Risk factors for prolonged length of stay after first single-level lumbar microdiscectomy.

OBJECTIVE: The objective is to identify risk factors that potentially prolong the hospital stay in patients after undergoing first single-level open lumbar microdiscectomy. METHODS: A retrospective single-centre study was conducted. Demographic data, medical records, intraoperative course, and imaging studies were analysed. The outcome measure was defined by the number of days stayed after the operation. A prolonged length of stay (LOS) stay was defined as a minimum of one additional day beyond the median hospital stay in our patient collective. Bivariate analysis and multiple stepwise regression were used to identify independent factors related to the prolonged hospital stay. RESULTS: Two hundred consecutive patients who underwent first lumbar microdiscectomy between 2018 and 2022 at our clinic were included in this study. Statistical analysis of factors potentially prolonging postoperative hospital stay was done for a total of 24 factors, seven of them were significantly related to prolonged LOS in bivariate analysis. Sex (p = 0.002, median 5 vs. 4 days for females vs. males) and age (rs = 0.35, p ≤ 0.001, N = 200) were identified among the examined demographic factors. Regarding preoperative physical status, preoperative immobility reached statistical significance (p ≤ 0.001, median 5 vs. 4 days). Diabetes mellitus (p = 0.043, median 5 vs. 4 days), anticoagulation and/or antiplatelet agents (p = 0.045, median 5 vs. 4 days), and postoperative narcotic consumption (p ≤ 0.001, median 5 vs. 4 days) as comorbidities were associated with a prolonged hospital stay. Performance of nucleotomy (p = 0.023, median 5 vs. 4 days) was a significant intraoperative factor. After linear stepwise multivariable regression, only preoperative immobility (p ≤ 0.001) was identified as independent risk factors for prolonged length of postoperative hospital stay. CONCLUSION: Our study identified preoperative immobility as a significant predictor of prolonged hospital stay, highlighting its value in preoperative assessments and as a tool to pinpoint at-risk patients. Prospective clinical trials with detailed assessment of mobility, including grading, need to be done to verify our results.

Influence of clinical and tumor-specific factors on the resting motor threshold in navigated transcranial magnetic stimulation.

OBJECTIVE: Preoperative non-invasive mapping of motor function with navigated transcranial magnetic stimulation (nTMS) has become a widely used diagnostic procedure. Determination of the patient-individual resting motor threshold (rMT) is of great importance to achieve reliable results when conducting nTMS motor mapping. Factors which contribute to differences in rMT of brain tumor patients have not been fully investigated. METHODS: We included adult patients with all types of de novo and recurrent intracranial lesions, suspicious for intra-axial brain tumors. The outcome measure was the rMT of the upper extremity, defined as the stimulation intensity eliciting motor evoked potentials with amplitudes greater than 50µV in 50 % of applied stimulations. RESULTS: Eighty nTMS examinations in 75 patients (37.5 % female) aged 57.9 ± 14.9 years were evaluated. In non-parametric testing, rMT values were higher in patients with upper extremity paresis (p = 0.024) and lower in patients with high grade gliomas (HGG) (p = 0.001). rMT inversely correlated with patient age (rs=-0.28, p = 0.013) and edema volume (rs=-0.28, p = 0.012) In regression analysis, infiltration of the precentral gyrus (p<0.001) increased rMT values. Values of rMT were reduced in high grade gliomas (p<0.001), in patients taking Levetiracetam (p = 0.019) and if perilesional edema infiltrated motor eloquent brain (p<0.001). Subgroup analyses of glioma patients revealed similar results. Values of rMT did not differ between hand and forearm muscles. CONCLUSION: Most factors confounding rMT in our study were specific to the lesion. These factors contributed to the variability in cortical excitability and must be considered in clinical work with nTMS to achieve reliable results with nTMS motor mapping.

Embolization of the middle meningeal artery vs. second surgery-treatment response and volume course of recurrent chronic subdural hematomas.

BACKGROUND: Despite multiple studies on the embolization of the middle meningeal artery, there is limited data on the treatment response of recurrent chronic subdural hematomas (CSDH) to embolization and on the volume change. METHODS: We retrospectively compared the treatment response and volume change of recurrent CSDHs in a conventional group (second surgery) with an embolization group (embolization as stand-alone treatment) during the time-period from August 2019 until June 2022. Different clinical and radiological factors were assessed. Treatment failure was defined as necessity of treatment for second recurrence. Hematoma volumes were determined in the initial CT scan before first surgery, after the first surgery, before retreatment as well as in an early (1 day-2 weeks) and in a late follow-up CT scan (2-8 weeks). RESULTS: Fifty recurrent hematomas after initial surgery were treated either by second surgery (n = 27) or by embolization (n = 23). 8/27 (26,6%) surgically treated and 3/23 (13%) of the hematomas treated by embolization needed to be treated again. This leads to an efficacy in recurrent hematomas of 73,4% in surgically treated and of 87% in embolized hematomas (p = 0.189). In the conventional group, mean volume decreased significantly already in the first follow-up CT scan from 101.7 ml (SD 53.7) to 60.7 ml (SD 40.3) (p = 0.001) and dropped further in the later follow-up scan to 46.6 ml (SD 37.1) (p = 0.001). In the embolization group, the mean volume did decrease insignificantly from 75.1 ml (SD 27.3) to 68 ml (SD 31.4) in the first scan (p = 0.062). However, in the late scan significant volume reduction to 30.8 ml (SD 17.1) could be observed (p = 0.002). CONCLUSIONS: Embolization of the middle meningeal artery is an effective treatment option for recurrent CSDH. Patients with mild symptoms who can tolerate slow volume reduction are suitable for embolization, whereas patients with severe symptoms should be reserved for surgery.

Case report: Scattered intraventricular lesions on MRI following epidermoid cyst resection.

Local recurrence after epidermoid cyst surgery is a frequently reported complication, but intraventricular spread after surgery has not yet been described in literature. We present the case of a 61-year-old male patient with steadily progressive headaches after surgical excision of an epidermoid cyst in the right cerebellopontine angle about two months ago. The MRI showed multiple intraventricular FLAIR-hyperintensities with diffusion restriction, suggestive of scattered remnants of the epidermoid cyst. We recommend early postoperative MRI-scans after cranial epidermoid surgery, which should be carefully inspected not only for local remnants but also rare complications like intraventricular spread.

Evaluating uncertainty to strengthen epidemiologic data for use in human health risk assessments.

BACKGROUND: There is a recognized need to improve the application of epidemiologic data in human health risk assessment especially for understanding and characterizing risks from environmental and occupational exposures. Although there is uncertainty associated with the results of most epidemiologic studies, techniques exist to characterize uncertainty that can be applied to improve weight-of-evidence evaluations and risk characterization efforts. METHODS: This report derives from a Health and Environmental Sciences Institute (HESI) workshop held in Research Triangle Park, North Carolina, to discuss the utility of using epidemiologic data in risk assessments, including the use of advanced analytic methods to address sources of uncertainty. Epidemiologists, toxicologists, and risk assessors from academia, government, and industry convened to discuss uncertainty, exposure assessment, and application of analytic methods to address these challenges. SYNTHESIS: Several recommendations emerged to help improve the utility of epidemiologic data in risk assessment. For example, improved characterization of uncertainty is needed to allow risk assessors to quantitatively assess potential sources of bias. Data are needed to facilitate this quantitative analysis, and interdisciplinary approaches will help ensure that sufficient information is collected for a thorough uncertainty evaluation. Advanced analytic methods and tools such as directed acyclic graphs (DAGs) and Bayesian statistical techniques can provide important insights and support interpretation of epidemiologic data. CONCLUSIONS: The discussions and recommendations from this workshop demonstrate that there are practical steps that the scientific community can adopt to strengthen epidemiologic data for decision making.

Deriving uncertainty factors for threshold chemical contaminants in drinking water.

Uncertainty factors are used in the development of drinking-water guidelines to account for uncertainties in the database, including extrapolations of toxicity from animal studies and variability within humans, which result in some uncertainty about risk. The application of uncertainty factors is entrenched in toxicological risk assessment worldwide, but is not applied consistently. This report, prepared in collaboration with Health Canada, provides an assessment of the derivation of the uncertainty factor assumptions used in developing drinking-water quality guidelines for chemical contaminants. Assumptions used by Health Canada in the development of guidelines were compared to several other major regulatory jurisdictions. This assessment has revealed that uncertainty factor assumptions have been substantially influenced by historical practice. While the application of specific uncertainty factors appears to be well entrenched in regulatory practice, a well-documented and disciplined basis for the selection of these factors was not apparent in any of the literature supporting the default assumptions of Canada, the United States, Australia, or the World Health Organization. While there is a basic scheme used in most cases in developing drinking-water quality guidelines for nonthreshold contaminants by the jurisdictions included in this report, additional factors are sometimes included to account for other areas of uncertainty. These factors may include extrapolating subchronic data to anticipated chronic exposure, or use of a LOAEL instead of a NOAEL. The default value attributed to each uncertainty factor is generally a factor of 3 or 10; however, again, no comprehensive guidance to develop and apply these additional uncertainty factors was evident from the literature reviewed. A decision tree has been developed to provide guidance for selection of appropriate uncertainty factors, to account for the range of uncertainty encountered in the risk assessment process. Recent development of a series of "decision trees" by WHO to derive chemical specific adjustment factors for inter- and intraspecies variability may present an opportunity for a more systematic approach for the identification of evidence-based uncertainty factors.

Can exposure characterization explain concurrence or discordance between toxicology and epidemiology?

The importance of reliable exposure assessment, as a key component of the overall risk assessment process, has been well described for some considerable time. Yet, despite this widely accepted tenet, many studies conclude significant adverse health effects, with associated public policy implications, in the absence of adequate or, in some cases, even rudimentary, exposure quantification. Moreover, it appears that epidemiological studies in humans and toxicological studies in experimental animals may both suffer from inadequate exposure assessment. In this review, we discuss the nature and quality of the exposure assessment in both epidemiologic and toxicologic studies using examples from the pesticides and phthalate literature. Each type of study has its strengths and weaknesses in how exposure is assessed and often the strength of one is also a weakness. It would appear that insufficient or incomplete information about differences in exposure assessment could explain, at least in some cases, the differences in outcome between toxicological and epidemiological studies. Research efforts should focus on improving the feasibility of including biomonitoring in both animal and human studies to facilitate comparisons between animal and human models and improve exposure assessment in epidemiologic studies. Animal and human studies should measure the same biomarkers, where possible, to facilitate human health risk assessment.