Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Under pressure - A historical vignette on surgical timing in traumatic spinal cord injury.

Introduction: It was not even a century ago when a spinal cord injury (SCI) would inevitably result in a fatal outcome, particularly for those with complete SCI. Throughout history, there have been extensive endeavours to change the prospects for SCI patients by performing surgery, even though many believed that there was no way to alter the catastrophic course of SCI. To this day, the debate regarding the efficacy of surgery in improving the neurological outcome for SCI patients persists, along with discussions about the timing of surgical intervention. Research question: How have the historical surgical results shaped our perspective on the surgical treatment of SCI? Material and methods: Narrative literature review. Results: Throughout history there have been multiple surgical attempts to alter the course of SCI, with conflicting results. While studies suggest a potential link between timing of surgery and neurological recovery, the exact impact of immediate surgery on individual cases remains ambiguous. It is becoming more evident that, alongside surgical intervention, factors specific to both the patient and their surgical treatment will significantly influence neurological recovery. Conclusion: Although a growing number of studies indicates a potential correlation of surgical timing and neurological outcome, the precise influence of urgent surgery on an individual basis remains uncertain. It is increasingly apparent that, despite surgery, patient- and treatment-specific factors will also play a role in determining the neurological outcome. Notably, these very factors have influenced the results in previous studies and our views concerning surgical timing.

Torticollis with Atlantoaxial Rotatory Subluxation in Children: A Clinical Review.

A small proportion of children with a sudden onset torticollis ("wry neck") presents with an atlantoaxial rotatory subluxation, usually after mild trauma or recent head or neck infection. Torticollis is a clinical diagnosis and imaging is usually not indicated, though often performed in clinical practice. Atlantoaxial rotatory subluxation on imaging is often a physiological phenomenon in torticollis, and concomitant neurological symptoms are therefore rare. Treatment is primarily conservative, with analgesics, a rigid neck collar, and if needed benzodiazepines to counteract muscle spasms and anxiety. In case of treatment failure or chronic subluxation, cervical repositioning and fixation under general anesthesia may be considered. Surgical treatment is only indicated in a small percentage of patients with chronic refractory subluxation, concomitant cervical fractures, or congenital anomalies. Early diagnosis and treatment are important, since this is associated with a more successful conservative outcome than a prolonged approach.

Impact of time to start of tranexamic acid treatment on rebleed risk and outcome in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: The ULTRA-trial investigated effectiveness of ultra-early administration of tranexamic acid (TXA) in subarachnoid hemorrhage (SAH) and showed that TXA reduces the risk of rebleeding without concurrent improvement in clinical outcome. Previous trials in bleeding conditions, distinct from SAH, have shown that time to start of antifibrinolytic treatment influences outcome. This post-hoc analysis of the ULTRA-trial investigates whether the interval between hemorrhage and start of TXA impacts the effect of TXA on rebleeding and functional outcome following aneurysmal SAH. PATIENTS AND METHODS: A post-hoc comparative analysis was conducted between aneurysmal SAH patients of the ULTRA-trial, receiving TXA and usual care to those receiving usual care only. We assessed confounders, hazard ratio (HR) of rebleeding and odds ratio (OR) of good outcome (modified Rankin Scale 0-3) at 6 months, and investigated the impact of time between hemorrhage and start of TXA on the treatment effect, stratified into time categories (0-3, 3-6 and >6 h). RESULTS: Sixty-four of 394 patients (16.2%) in the TXA group experienced a rebleeding, compared to 83 of 413 patients (19.9%) with usual care only (HR 0.86, 95% confidence interval (CI): 0.62-1.19). Time to start of TXA modifies the effect of TXA on rebleeding rate (p < 0.001), with a clinically non-relevant reduction observed only when TXA was initiated after 6 h (absolute rate reduction 1.4%). Tranexamic acid treatment showed no effect on good outcome (OR 0.96, 95% CI: 0.72-1.27) with no evidence of effect modification on the time to start of TXA (p = 0.53). DISCUSSION AND CONCLUSIONS: This study suggests that the effect of TXA on rebleeding is modified by time to treatment, providing a protective, albeit clinically non-relevant, effect only when started after 6 h. No difference in functional outcome was seen. Routine TXA treatment in the aneurysmal SAH population, even within a specified time frame, is not recommended to improve functional outcome.

Sodium and Its Impact on Outcome After Aneurysmal Subarachnoid Hemorrhage in Patients With and Without Delayed Cerebral Ischemia.

OBJECTIVES: To perform a detailed examination of sodium levels, hyponatremia and sodium fluctuations, and their association with delayed cerebral ischemia (DCI) and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). DESIGN: An observational cohort study from a prospective SAH Registry. SETTING: Tertiary referral center focused on SAH treatment in the Amsterdam metropolitan area. PATIENTS: A total of 964 adult patients with confirmed aSAH were included between 2011 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 277 (29%) developed DCI. Hyponatremia occurred significantly more often in DCI patients compared with no-DCI patients (77% vs. 48%). Sodium levels, hyponatremia, hypernatremia, and sodium fluctuations did not predict DCI. However, higher sodium levels were significantly associated with poor outcome in DCI patients (DCI onset -7, DCI +0, +1, +2, +4, +5, +8, +9 d), and in no-DCI patients (postbleed day 6-10 and 12-14). Also, hypernatremia and greater sodium fluctuations were significantly associated with poor outcome in both DCI and no-DCI patients. CONCLUSIONS: Sodium levels, hyponatremia, and sodium fluctuations were not associated with the occurrence of DCI. However, higher sodium levels, hypernatremia, and greater sodium fluctuations were associated with poor outcome after aSAH irrespective of the presence of DCI. Therefore, sodium levels, even with mild changes in levels, warrant close attention.

Predictive value of the five-repetition sit-to-stand test for outcomes after surgery for lumbar disc herniation: prospective study.

OBJECTIVE: It is unknown whether presence of pre-operative objective functional impairment (OFI) can predict post-operative outcomes in patients with lumbar disc herniation (LDH). We aimed to determine whether pre-operative OFI measured by the five-repetition sit-to-stand test (5R-STS) could predict outcomes at 12-months post-discectomy. METHODS: Adult patients with LDH scheduled for surgery were prospectively recruited from a Dutch short-stay spinal clinic. The 5R-STS time and patient reported outcome measures (PROMs) including Oswestry Disability Index, Roland-Morris Disability Questionnaire, Visual Analogue Scale (VAS) for back and leg pain, EQ-5D-3L health-related quality of life, EQ5D-VAS and ability to work were recorded pre-operatively and at 12-months. A 5R-STS time cut-off of ≥ 10.5 s was used to determine OFI. Mann-Whitney and Chi-square tests were employed to determine significant differences in post-operative outcomes between groups stratified by presence of pre-operative OFI. RESULTS: We recruited 134 patients in a prospective study. Twelve-month follow-up was completed by 103 (76.8%) patients. Mean age was 53.2 ± 14.35 years and 50 (48.5%) patients were female. Pre-operatively, 53 (51.5%) patients had OFI and 50 (48.5%) did not. Post-operatively, patients with OFI experienced a significantly greater mean change (p < 0.001) across all PROMs compared to patients without OFI, except leg pain (p = 0.176). There were no significant differences in absolute PROMs between groups at 12-months (all p > 0.05). CONCLUSIONS: The presence of OFI based on 5R-STS time does not appear to decrease a patient's likelihood of experiencing satisfactory post-operative outcomes. The 5R-STS cannot predict how a patient with LDH will respond to surgery at 12-month follow-up.

Identifying clusters of objective functional impairment in patients with degenerative lumbar spinal disease using unsupervised learning.

OBJECTIVES: The five-repetition sit-to-stand (5R-STS) test was designed to capture objective functional impairment (OFI), and thus provides an adjunctive dimension in patient assessment. It is conceivable that there are different subsets of patients with OFI and degenerative lumbar disease. We aim to identify clusters of objectively functionally impaired individuals based on 5R-STS and unsupervised machine learning (ML). METHODS: Data from two prospective cohort studies on patients with surgery for degenerative lumbar disease and 5R-STS times of ≥ 10.5 s-indicating presence of OFI. K-means clustering-an unsupervised ML algorithm-was applied to identify clusters of OFI. Cluster hallmarks were then identified using descriptive and inferential statistical analyses. RESULTS: We included 173 patients (mean age [standard deviation]: 46.7 [12.7] years, 45% male) and identified three types of OFI. OFI Type 1 (57 pts., 32.9%), Type 2 (81 pts., 46.8%), and Type 3 (35 pts., 20.2%) exhibited mean 5R-STS test times of 14.0 (3.2), 14.5 (3.3), and 27.1 (4.4) seconds, respectively. The grades of OFI according to the validated baseline severity stratification of the 5R-STS increased significantly with each OFI type, as did extreme anxiety and depression symptoms, issues with mobility and daily activities. Types 1 and 2 are characterized by mild to moderate OFI-with female gender, lower body mass index, and less smokers as Type I hallmarks. CONCLUSIONS: Unsupervised learning techniques identified three distinct clusters of patients with OFI that may represent a more holistic clinical classification of patients with OFI than test-time stratifications alone, by accounting for individual patient characteristics.

Aneurysm Prevalence and Quality of Life During Screening in Relatives of Patients With Unruptured Intracranial Aneurysms: A Prospective Study.

BACKGROUND AND OBJECTIVES: Screening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives (FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether screening is also effective for FDRs of patients with UIA is unknown. We determined the yield of screening in such FDRs, assessed rupture risk and treatment decisions of aneurysms that were found, identified potential high-risk subgroups, and studied the effects of screening on quality of life (QoL). METHODS: In this prospective cohort study, we included FDRs, aged 20-70 years, of patients with UIA without a family history of aSAH who visited the Neurology outpatient clinic in 1 of 3 participating tertiary referral centers in the Netherlands. FDRs were screened for UIA with magnetic resonance angiography between 2017 and 2021. We determined UIA prevalence and developed a prediction model for UIA risk at screening using multivariable logistic regression. QoL was evaluated with questionnaires 6 times during the first year after screening and assessed with a linear mixed-effects model. RESULTS: We detected 24 UIAs in 23 of 461 screened FDRs, resulting in a 5.0% prevalence (95% CI 3.2-7.4). The median aneurysm size was 3 mm (interquartile range [IQR] 2-4 mm), and the median 5-year rupture risk assessed with the PHASES score was 0.7% (IQR 0.4%-0.9%). All UIAs received follow-up imaging, and none were treated preventively. After a median follow-up of 24 months (IQR 13-38 months), no UIA had changed. Predicted UIA risk at screening ranged between 2.3% and 14.7% with the highest risk in FDRs who smoke and have excessive alcohol consumption (c-statistic: 0.76; 95% CI 0.65-0.88). At all survey moments, health-related QoL and emotional functioning were comparable with those in a reference group from the general population. One FDR with a positive screening result expressed regret about screening. DISCUSSION: Based on the current data, we do not advise screening FDRs of patients with UIA because all identified UIAs had a low rupture risk. We observed no negative effect of screening on QoL. A longer follow-up should determine the risk of aneurysm growth requiring preventive treatment.

Clinical response following hypertension induction for clinical delayed cerebral ischemia following subarachnoid hemorrhage: A retrospective, multicenter, cohort study.

BACKGROUND: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of HTI in aSAH patients with clinical DCI. METHODS: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI-related cerebral infarction, in-hospital mortality, and poor clinical outcome [modified Rankin Scale 4-6] assessed at 3 or 6 months), using the intention-to-treat principle. We also performed as-treated and per-protocol analyses. RESULTS: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17-2.27) and at day 5 after DCI 1.04 (95% CI 0.84-1.29). Secondary outcomes were comparable between the groups. The as-treated and per-protocol analyses yielded similar results. CONCLUSIONS: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3-/6-month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI.

Explaining Blood-Brain Barrier Permeability of Small Molecules by Integrated Analysis of Different Transport Mechanisms.

The blood-brain barrier (BBB) represents a major obstacle to delivering drugs to the central nervous system (CNS), resulting in the lack of effective treatment for many CNS diseases including brain cancer. To accelerate CNS drug development, computational prediction models could save the time and effort needed for experimental evaluation. Here, we studied BBB permeability focusing on active transport (influx and efflux) as well as passive diffusion using previously published and self-curated data sets. We created prediction models based on physicochemical properties, molecular substructures, or their combination to understand which mechanisms contribute to BBB permeability. Our results show that features that predicted passive diffusion over membranes overlap with features that explain endothelial permeation of approved CNS-active drugs. We also identified physical properties and molecular substructures that positively or negatively predicted BBB transport. These findings provide guidance toward identifying BBB-permeable compounds by optimally matching physicochemical and molecular properties to BBB transport mechanisms.

A Systematic Review of Viscoelastic Testing in Patients with Subarachnoid Hemorrhage.

OBJECTIVE: Bleeding and thromboembolic complications frequently occur after subarachnoid hemorrhage (SAH) and substantially contribute to poor outcome. Viscoelastic testing could be used for detection of coagulopathies after SAH. This review summarizes literature on the usefulness of viscoelastic testing to detect coagulopathy in patients with SAH and explores whether viscoelastic parameters are associated with SAH-related complications and clinical outcome. METHODS: PubMed, Embase, and Google Scholar were systematically searched on August 18, 2022. Two authors independently selected studies that reported viscoelastic testing in patients with SAH and assessed the quality of studies using the Newcastle-Ottawa Scale or a previously reported framework for quality assessment. Data were meta-analyzed if methodologically possible. RESULTS: The search yielded 19 studies (1160 patients with SAH). Pooling of data including all relevant studies was not possible for any of the outcome measurements because of methodological differences. Thirteen of 19 studies evaluated the association of coagulation profiles and SAH, of which 11 studies showed a hypercoagulable profile. Rebleeding was associated with platelet dysfunction, deep venous thrombosis was associated with faster clot initiation, and both delayed cerebral ischemia and poor outcome were associated with increased clot strength. CONCLUSIONS: This explorative review shows that patients with SAH frequently have a hypercoagulable profile. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) parameters are associated with rebleeding, delayed cerebral ischemia, deep venous thrombosis, and poor clinical outcome after SAH; however, more research on the subject is needed. Future studies should focus on determining the optimal time frame and cutoff values for TEG or ROTEM to predict these complications.

Laboratory biomarkers of delayed cerebral ischemia following subarachnoid hemorrhage: A systematic review.

Delayed cerebral ischemia (DCI) substantially contributes to disability and death in subarachnoid hemorrhage (SAH) patients; however, its pathophysiology is incompletely understood and diagnostic and therapeutic strategies are lacking. Biomarkers may help to elucidate the pathophysiology, optimize early diagnosis, or provide treatment targets. We systematically searched PubMed and Embase on October 13, 2021, for studies that evaluated at least one laboratory biomarker in patients with DCI, using the most up-to-date definition of DCI as proposed by a panel of experts in 2010. Quality of studies was assessed using the Newcastle-Ottawa Scale or Cochrane Collaboration's risk of bias assessment tool. Biomarkers of clinical and radiological DCI were analyzed separately. Results were meta-analyzed if possible, otherwise narratively reviewed. Biomarkers were classified as significant, inconclusive, or nonsignificant. We defined validated biomarkers as those with significant results in meta-analyses, or in at least two studies using similar methodologies within the same time interval after SAH. The search yielded 209 articles with 724 different biomarkers; 166 studies evaluated 646 biomarkers of clinical DCI, of which 141 were significant and 7 were validated biomarkers (haptoglobulin 2-1 and 2-2, ADAMTS13, vWF, NLR, P-selectin, F2-isoprostane); 78 studies evaluated 165 biomarkers of radiological DCI, of which 63 were significant and 1 was a validated biomarker (LPR). Hence, this review provides a selection of seven biomarkers of clinical DCI and one biomarker of radiological DCI as most promising biomarkers of DCI. Future research should focus on determining the exact predictive, diagnostic, and therapeutic potentials of these biomarkers.

Safety and technical efficacy of early minimally invasive endoscopy-guided surgery for intracerebral haemorrhage: the Dutch Intracerebral haemorrhage Surgery Trial pilot study.

BACKGROUND: Previous randomised controlled trials could not demonstrate that surgical evacuation of intracerebral haemorrhage (ICH) improves functional outcome. Increasing evidence suggests that minimally invasive surgery may be beneficial, in particular when performed early after symptom onset. The aim of this study was to investigate safety and technical efficacy of early minimally invasive endoscopy-guided surgery in patients with spontaneous supratentorial ICH. METHODS: The Dutch Intracerebral Haemorrhage Surgery Trial pilot study was a prospective intervention study with blinded outcome assessment in three neurosurgical centres in the Netherlands. We included adult patients with spontaneous supratentorial ICH ≥10mL and National Institute of Health Stroke Scale (NIHSS) score ≥2 for minimally invasive endoscopy-guided surgery within 8 h after symptom onset in addition to medical management. Primary safety outcome was death or increase in NIHSS ≥4 points at 24 h. Secondary safety outcomes were procedure-related serious adverse events (SAEs) within 7 days and death within 30 days. Primary technical efficacy outcome was ICH volume reduction (%) at 24 h. RESULTS: We included 40 patients (median age 61 years; IQR 51-67; 28 men). Median baseline NIHSS was 19.5 (IQR 13.3-22.0) and median ICH volume 47.7mL (IQR 29.4-72.0). Six patients had a primary safety outcome, of whom two already deteriorated before surgery and one died within 24 h. Sixteen other SAEs were reported within 7 days in 11 patients (of whom two patients that already had a primary safety outcome), none device related. In total, four (10%) patients died within 30 days. Median ICH volume reduction at 24 h was 78% (IQR 50-89) and median postoperative ICH volume 10.5mL (IQR 5.1-23.8). CONCLUSIONS: Minimally invasive endoscopy-guided surgery within 8 h after symptom onset for supratentorial ICH appears to be safe and can effectively reduce ICH volume. Randomised controlled trials are needed to determine whether this intervention also improves functional outcome. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03608423, August 1st, 2018.

ALL-tRNAseq enables robust tRNA profiling in tissue samples.

Transfer RNAs (tRNAs) are small adaptor RNAs essential for mRNA translation. Alterations in the cellular tRNA population can directly affect mRNA decoding rates and translational efficiency during cancer development and progression. To evaluate changes in the composition of the tRNA pool, multiple sequencing approaches have been developed to overcome reverse transcription blocks caused by the stable structures of these molecules and their numerous base modifications. However, it remains unclear whether current sequencing protocols faithfully capture tRNAs existing in cells or tissues. This is specifically challenging for clinical tissue samples that often present variable RNA qualities. For this reason, we developed ALL-tRNAseq, which combines the highly processive MarathonRT and RNA demethylation for the robust assessment of tRNA expression, together with a randomized adapter ligation strategy prior to reverse transcription to assess tRNA fragmentation levels in both cell lines and tissues. Incorporation of tRNA fragments not only informed on sample integrity but also significantly improved tRNA profiling of tissue samples. Our data showed that our profiling strategy effectively improves classification of oncogenic signatures in glioblastoma and diffuse large B-cell lymphoma tissues, particularly for samples presenting higher levels of RNA fragmentation, further highlighting the utility of ALL-tRNAseq for translational research.

Predictors of five-repetition sit-to-stand test performance in patients with lumbar degenerative disease.

BACKGROUND: The five-repetition sit-to-stand test (5R-STS) has recently been validated as an objective measure of functional impairment in patients with lumbar degenerative disease (LDD). Knowledge of factors influencing 5R-STS performance is useful to correct for confounders, create personalized adjusted test times, and potentially identify prognostic subgroups. We evaluate factors predicting the 5R-STS performance in patients with LDD. METHODS: Patients with LDD requiring surgery were included. Each participant performed the 5R-STS and completed a questionnaire that included their age, gender, weight, height, body mass index (BMI), smoking status, education level, employment type, ability to work, analgesic drug usage, history of previous spinal surgery, and EQ5D depression and anxiety domain. Surgical indication and index level of the spinal pathology were also recorded. Predictors of 5R-STS were identified through multivariable linear regression. RESULTS: The cohort consisted of 240 patients, 47.9% being female (mean age, 47.7 ± 13.6 years). In the final multivariable model incorporating confounders, height (regression coefficient (RC), 0.08; 95% confidence interval (CI), 0.003/0.16, p = 0.042) and being an active smoker (RC, 2.44; 95%CI, 0.56/4.32, p = 0.012) were significant predictors of worse 5R-STS performance. Full ability to work (RC, - 2.39; 95%CI, - 4.39/ - 0.39, p = 0.020) was associated with a better 5R-STS performance. Age, height, surgical indication, index level of pathology, history of previous spine surgery, history of pain, analgesic drug use, employment type, and severity of anxiety and depression symptoms demonstrated confounding effect on the 5R-STS time. CONCLUSIONS: Greater height, being an active smoker, and inability to work are significant predictors of worse 5R-STS performance in patients with LDD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03303300 and NCT03321357.

[Ventriculoperitoneal shunt dysfunction in children: various clinical presentations]. / Ventriculoperitoneale-shuntdisfunctie bij kinderen.

The clinical presentation of a ventriculoperitoneal shunt (VP-shunt) dysfunction depends on whether the cranial sutures are still unfused, and on the cause and severity of the VP-shunt obstruction. A suspicion of a VP-shunt dysfunction is always reason to consult with a neurosurgeon. A patient with a suspected VP-shunt dysfunction that presents with elevated intracranial pressure should be urgently assessed at the emergency department of a neurosurgical center. Conclusions about whether the ventricular system is enlarged should be based on comparison between the imaging made to demonstrate the VP-shunt dysfunction and a reference scan of the brain, made when the patient was in a good clinical condition. In a patient with small ventricles, but clinical indications of elevated intracranial pressure, a VP-shunt dysfunction can't be ruled out. In that case fundoscopy may be very valuable to rule out papilledema.

Multidisciplinary integrated care pathway for von Hippel-Lindau disease.

BACKGROUND: Clinical pathways are care plans established to describe essential steps in the care of patients with a specific clinical problem. They translate (inter)national guidelines into local applicable protocols and clinical practice. The purpose of this article is to establish a multidisciplinary integrated care pathway for specialists and allied health care professionals in caring for individuals with von Hippel-Lindau (VHL) disease. METHODS: Using a modified Delphi consensus-making process, a multidisciplinary panel from 5 Dutch University Medical Centers produced an integrated care pathway relating to the provision of care for patients with VHL by medical specialists, specialized nurses, and associated health care professionals. Patient representatives cocreated the pathway and contributed quality criteria from the patients' perspective. RESULTS: The panel agreed on recommendations for the optimal quality of care for individuals with a VHL gene mutation. These items were the starting point for the development of a patient care pathway. With international medical guidelines addressing the different VHL-related disorders, this article presents a patient care pathway as a flowchart that can be incorporated into VHL expertise clinics or nonacademic treatment clinics. CONCLUSIONS: Medical specialists (internists, urologists, neurosurgeons, ophthalmologists, geneticists, medical oncologists, neurologists, gastroenterologists, pediatricians, and ear-nose-throat specialists) together with specialized nurses play a vital role alongside health care professionals in providing care to people affected by VHL and their families. This article presents a set of consensus recommendations, supported by organ-specific guidelines, for the roles of these practitioners in order to provide optimal VHL care. This care pathway can form the basis for the development of comprehensive, integrated pathways for multiple neoplasia syndromes.

Interventions in Acute Intracranial Surgery: An Evidence-Based Perspective.

From a pathophysiological point of view, early neurosurgical treatment seems essential to prevent secondary brain injury and has been stated as the "time-is-brain" concept. However, the question immediately rises: "Is there an optimal time window for acute intracranial neurosurgical interventions?" In neurosurgery, treatment modality has been studied far more extensively than timing to surgery ("time-to-surgery"). The majority of acute intracranial neurosurgical interventions are carried out for traumatic brain injury and hemorrhagic or ischemic stroke. Current guidelines for traumatic brain injury, spontaneous intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and middle cerebral artery infarction are reviewed and lessons learned from the randomized controlled trials mentioned are discussed. In acute intracranial neurosurgical interventions, "delayed consent" procedures could play an important role for this field of research. Whether there is an optimal time window for acute intracranial neurosurgical interventions seems difficult to be answered with randomized controlled trials referred to in the current guidelines. Observational designs, such as comparative effectiveness research, and special statistical techniques, may provide a better understanding in the optimal "time-to-surgery."