Prospective review of 30-day morbidity and mortality in a paediatric neurosurgical unit

Purpose: The purpose of this study is to record the 30-day and inpatient morbidity and mortality in paediatric patients in a tertiary neuroscience centre over a 2-year period. The intentions were to establish the frequency of significant adverse events, review the current published rates of morbidity in paediatric neurosurgical patients and propose three clinical indicators for future comparison. Methods: All deaths and adverse events were prospectively recorded from 1 January 2014 to 31 December 2015. Each adverse event was categorised, allocated a clinical impact severity score and linked to a neurosurgical procedure wherever possible. Where a patient suffered several adverse events in the same admission, each event was recorded separately. If a patient had been discharged home, an adverse event was recorded if it occurred within 30 days of admission. Results: Five hundred forty-nine procedures were performed in 287 patients (aged <16 years). One hundred thirty significant adverse events were identified. The following are the three clinical indicators: significant adverse event rate: 111 (20.2%) operations were linked to at least one significant adverse event; unscheduled return to theatre rate: 81 (14.8%) operations were associated with an adverse event that resulted in an unscheduled return to theatre; and surgical site infection rate: 29 (5.3%) operations were associated with an infection. Conclusion: Complications and adverse events are common in paediatric neurosurgery. Prospective, continuous surveillance will promote both quality assurance and quality improvement in the neurosurgical care delivered to patients

Pharmacological targeting of secondary brain damage following ischemic or hemorrhagic stroke, traumatic brain injury, and bacterial meningitis - a systematic review and meta-analysis

Background: The effectiveness of pharmacological strategies exclusively targeting secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI) and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD targeted treatment on clinical outcome across the pathological entities. Methods: Randomized, controlled, double-blinded trials on aforementioned entities with ‘death’ as endpoint were identified. Effect sizes were analyzed and expressed as pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies fulfilled the criteria, with data on 66,561 patients. Results: In the pooled analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85–1.02)], ICH [RR 0.92 (95% CI:0.82–1.03)] and bacterial meningitis [RR 0.86 (95% CI:0.68–1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05 (95% CI:1.00–1.11)] and TBI [RR 1.03 (95% CI:0.93–1.15)]. Additional analysis of “poor outcome” as endpoint gave similar results. Subgroup analysis with respect to effector mechanisms showed a tendency towards a reduced mortality for the effector mechanism category “oxidative metabolism/stress” for aSAH with a risk ratio of 0.86 [95% CI: 0.73–1.00]. Regarding specific medications, a statistically significant reduction of mortality and poor outcome was confirmed only for nimodipine for aSAH and dexamethasone for bacterial meningitis. Conclusions: Our results show that only a few selected SBD directed medications are likely to reduce the rate of death and poor outcome following aSAH, and bacterial meningitis, while no convincing evidence could be found for the usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However, a subtle effect on good or excellent outcome might remain undetected. These results should lead to a new perspective of secondary reactions following cerebral injury. These processes should not be seen as suicide mechanisms that need to be fought. They should be rather seen as well orchestrated clean-up mechanisms, which may today be somewhat too active in a few very specific constellations, such as meningitis under antibiotic treatment and aSAH after surgical or endovascular exclusion of the aneurysm

Clinical prediction models

Objective!#!The aim of this study was to evaluate the validity of a semiautomated volumetric approach (5DCNS+) for the detailed assessment of the fetal brain in a clinical setting.!##!Methods!#!Stored 3D volumes of > 1100 consecutive 2nd and 3rd trimester pregnancies (range 15-36 gestational weeks) were analyzed using a workflow-based volumetric approach 5DCNS+, enabling semiautomated reconstruction of diagnostic planes of the fetal central nervous system (CNS). All 3D data sets were examined for plane accuracy, the need for manual adjustment, and fetal-maternal characteristics affecting successful plane reconstruction. We also examined the potential of these standardized views to give additional information on proper gyration and sulci formation with advancing gestation.!##!Results!#!Based on our data, we were able to show that gestational age with an OR of 1.085 (95% CI 1.041-1.132) and maternal BMI with an OR of 1.022 (95% CI 1.041-1.054) only had a slight impact on the number of manual adjustments needed to reconstruct the complete volume, while maternal age and fetal position during acquisition (p = 0.260) did not have a significant effect. For the vast majority (958/1019; 94%) of volumes, using 5DCNS+ resulted in proper reconstruction of all nine diagnostic planes. In less than 1% (89/9171 planes) of volumes, the program failed to give sufficient information. 5DCNS+ was able to show the onset and changing appearance of CNS folding in a detailed and timely manner (lateral/parietooccipital sulcus formation seen in < 65% at 16-17 gestational weeks vs. 94.6% at 19 weeks).!##!Conclusions!#!The 5DCNS+ method provides a reliable algorithm to produce detailed, 3D volume-based assessments of fetal CNS integrity through a standardized reconstruction of the orthogonal diagnostic planes. The method further gives valid and reproducible information regarding ongoing cortical development retrieved from these volume sets that might aid in earlier in utero recognition of subtle structural CNS anomalies

Application of clinical prediction modeling in pediatric neurosurgery: a case study

There has been an increasing interest in articles reporting on clinical prediction models in pediatric neurosurgery. Clinical prediction models are mathematical equations that combine patient-related risk factors for the estimation of an individual’s risk of an outcome. If used sensibly, these evidence-based tools may help pediatric neurosurgeons in medical decision-making processes. Furthermore, they may help to communicate anticipated future events of diseases to children and their parents and facilitate shared decision-making accordingly. A basic understanding of this methodology is incumbent when developing or applying a prediction model. This paper addresses this methodology tailored to pediatric neurosurgery. For illustration, we use original pediatric data from our institution to illustrate this methodology with a case study. The developed model is however not externally validated, and clinical impact has not been assessed; therefore, the model cannot be recommended for clinical use in its current form

Functional tracts of the cerebellum—essentials for the neurosurgeon

The cerebellum is historically implicated in motor coordination, but accumulating modern evidence indicates involvement in non-motor domains, including cognition, emotion, and language. This correlates with the symptoms observed in postoperative cerebellar mutism syndrome (CMS). Profound knowledge of cerebellar functional topography and tractography is important when approaching cerebellar tumors, as surgical trauma to relevant structures of cerebellar pathways plays a role in the pathogenesis of CMS. The aim of this systematic review is to provide a concise overview of relevant modern neuroimaging data and cerebellar functional tracts with regard to neurosurgical procedures

Neuroprotective Strategies in Aneurysmal Subarachnoid Hemorrhage (aSAH)

Aneurysmal subarachnoid hemorrhage (aSAH) remains a disease with high mortality and morbidity. Since treating vasospasm has not inevitably led to an improvement in outcome, the actual emphasis is on finding neuroprotective therapies in the early phase following aSAH to prevent secondary brain injury in the later phase of disease. Within the early phase, neuroinflammation, thromboinflammation, disturbances in brain metabolism and early neuroprotective therapies directed against delayed cerebral ischemia (DCI) came into focus. Herein, the role of neuroinflammation, thromboinflammation and metabolism in aSAH is depicted. Potential neuroprotective strategies regarding neuroinflammation target microglia activation, metalloproteases, autophagy and the pathway via Toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1), NF-κB and finally the release of cytokines like TNFα or IL-1. Following the link to thromboinflammation, potential neuroprotective therapies try to target microthrombus formation, platelets and platelet receptors as well as clot clearance and immune cell infiltration. Potential neuroprotective strategies regarding metabolism try to re-balance the mismatch of energy need and supply following aSAH, for example, in restoring fuel to the TCA cycle or bypassing distinct energy pathways. Overall, this review addresses current neuroprotective strategies in aSAH, hopefully leading to future translational therapy options to prevent secondary brain injury

Evaluation of Volumetric Change of Intracerebral Hemorrhage in Patients Treated with Thrombolysis for Intraventricular Hemorrhage

Background!#!Intraventricular hemorrhage (IVH) is often caused by irruption of intracerebral hemorrhage (ICH) of basal ganglia or thalamus into the ventricular system. Instillation of recombinant tissue plasminogen activator (rtPA) via an external ventricular drainage (EVD) has been shown to effectively decrease IVH volumes while the impact of rtPA instillation on ICH volumes remains unclear. In this series, we analyzed volumetric changes of ICH in patients with and without intrathecal lysis therapy.!##!Methods!#!Between 01/2013 and 01/2019, 36 patients with IVH caused by hemorrhage of basal ganglia, thalamus or brain stem were treated with rtPA via an EVD (Group A). Initial volumes were determined in the first available computed tomography (CT) scan, final volumes in the last CT scan before discharge. During the same period, 41 patients with ICH without relevant IVH were treated without intrathecal lysis therapy at our neurocritical care unit (Group B). Serial CT scans were evaluated separately for changes in ICH volumes for both cohorts using OsiriX DICOM viewer. The Wilcoxon signed-rank test was performed for statistical analysis in not normally distributed variables.!##!Results!#!Median initial volume of ICH for treatment Group A was 6.5 ml and was reduced to 5.0 ml after first instillation of rtPA (p < 0.01). Twenty-six patients received a second treatment with rtPA (ICH volume reduction 4.5 to 3.3 ml, p < 0.01) and of this cohort further 16 patients underwent a third treatment (ICH volume reduction 3.0 ml to 1.5 ml, p < 0.01). Comparison of first and last CT scan in Group A confirmed an overall median percentage reduction of 91.7% (n = 36, p < 0.01) of ICH volumes and hematoma resolution in Group A was significantly more effective compared to non-rtPA group, Group B (percentage reduction = 68%) independent of initial hematoma volume in the regression analysis (p = 0.07, mean 11.1, 95%CI 7.7-14.5). There were no adverse events in Group A related to rtPA instillation.!##!Conclusion!#!Intrathecal lysis therapy leads to a significant reduction in the intraparenchymal hematoma volume with faster clot resolution compared to the spontaneous hematoma resorption. Furthermore, intrathecal rtPA application had no adverse effect on ICH volume