Marianne Juhler

This pilot observational study evaluated whether frequent overnight sampling of ventricular cerebrospinal fluid could clarify how sleep, hypocretin and lactate relate to amyloid‐β42 dynamics in adults with hydrocephalus. Seven participants underwent hourly ventricular cerebrospinal fluid sampling from early evening to late morning during inpatient monitoring, combined with full polysomnography. Concentrations of amyloid‐β42, hypocretin, lactate, melatonin and electrolytes were measured and normalised to each individual's mean. Relationships with sleep stage and circadian patterns were examined using correlation analysis and cosinor modelling. Sleep was markedly disrupted, with obstructive sleep apnea common and analysable sleep data available for six participants. Non‐rapid eye movement sleep peaked at approximately 4 AM Amyloid‐β42 rose in the evening, plateaued during peak non‐rapid eye movement sleep and increased sharply after 8 AM Hypocretin and lactate were positively correlated and each preceded and correlated with amyloid‐β42 surges. Melatonin peaked near 6 AM and was associated with non‐rapid eye movement sleep. Intracranial pressure displayed a strong circadian rhythm, peaking during non‐rapid eye movement sleep, whereas hypocretin and amyloid‐β42 exhibited only modest rhythmicity. These findings demonstrate that overnight ventricular cerebrospinal fluid sampling is feasible in adults with hydrocephalus. Preliminary evidence suggests that processes linked to wakefulness, rather than sleep or intrinsic circadian timing, may be the primary drivers of overnight amyloid‐β42 variation. Hypocretin pathways may represent potential therapeutic targets in Alzheimer's disease, but conclusions are limited by abnormal sleep architecture and underlying neurological disease. Validation in larger and more representative populations is warranted.

Endoscopic procedures, especially ventriculocystostomy (VC) and ventriculocystocisternostomy (VCC), are preferred treatments for suprasellar arachnoid cysts (SACs). Yet, results from current studies on their effects are varied. This study offers a comprehensive systematic review on surgical and clinical outcomes after VC and VCC and the risk of reoperation is compared by a meta-analysis. We conducted a literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical articles evaluating endoscopic treatment modalities for SAC using PubMed/Medline and Embase. The primary outcome was the risk of reoperation with a subgroup analysis among infants < 1 years of age. Postoperative complications were described to the extend they were reported in the literature. The risk of bias was assessed using the Newcastle-Ottawa scoring system. The meta-analysis was performed using RevMan 5.0 to compare the reoperation rates for VC and VCC as a risk ratio from a Forest plot with 95% confidence intervals in a fixed-effects model. Publication bias was assessed visually using a funnel plot. Nineteen observational studies were eligible for inclusion, comprising 94 patients who underwent VCC and 427 patients who underwent VC. Patients who underwent VCC had a significantly lower risk of reoperation of 0.33 (95% CI 0.17–0.65; p < 0.002). However, the risk of postoperative complications was considerable for both VCC (16.7%) and VC (12.7%), yet not significantly different (p = 0.915). Within the subgroup of infants age < 1 year, the risk of reoperation was significantly higher (29.4%) compared to older children (5.7%) (95% CI 1.96–42.07; p < 0.002). The results support VCC as an effective and long-lasting treatment for symptomatic SACs with significantly lower reoperation rates, compared to VC.

Background: Postoperative speech impairment (POSI) and cranial nerve deficits (CND) are common complications of pediatric posterior fossa (PF) tumor surgery. Intraoperative MRI (ioMRI) has proven a useful tool in achieving gross total resection. The risk of POSI and CND with ioMRI remains unclear, making it the primary scope of this study. Additionally, we assessed whether POSI was associated with CND. Methods: We prospectively included pediatric patients undergoing PF tumor surgery in 36 centers across 15 European countries. Neurological status and speech were assessed preoperatively and 1–4 weeks postoperatively. Surgical details, including tumor location and use of ioMRI, were recorded within 72 h of surgery. Postoperative CND were categorized as 0, 1, 2, or ≥ 3 nerves affected; POSI as habitual, reduced speech, or mutism. Proportional odds models estimated odds ratios (OR) for 1) POSI with stepwise adjustment for tumor location and age, and 2) CND with adjustment for preoperative CND and tumor location. Subgroup analyses assessed systematic differences, missing data, center-level effects, and histology adjustment. Results: Of 790 primary PF tumor surgeries, 141 (18%) involved ioMRI. POSI occurred in 183/790 (23%) and postoperative CND in 213/790 (27%). POSI-risk with ioMRI showed non-significant unadjusted OR (95% CI) 0.83 (0.53;1.30); adjusted OR 0.76 (0.43;1.35). Fewer CNDs were observed with ioMRI (unadjusted OR 0.63 (0.40;1.00), adjusted OR 0.58 (0.33;0.94), p = 0.03). POSI-risk was associated with more CNDs (adjusted OR for 1 CND: 2.06 (1.15;3.68); 2 CND: 2.13 (1.02;4.42); ≥ 3 CND: 4.15 (1.98;8.70), p < 0.05). Conclusions: ioMRI was not associated with increased risk of postoperative complications in this multicenter cohort. The reduction in CND among ioMRI cases may reflect derived effects on surgical decision-making, expertise, case-load and case-mix. Results should be interpreted with caution due to limited intraoperative data. The association between POSI-risk and cumulative CND may indicate extensive brainstem involvement. Our findings highlight the need to further explore how ioMRI-guided strategies affect functional outcomes in pediatric PF tumour surgery. Clinical Trials ID: NCT02300766 (October 2014)

BACKGROUND: Ventriculoatrial (VA) shunt placement is an alternative treatment for hydrocephalus when ventriculoperitoneal shunt placement is not feasible. While shunt obstruction and infection are well-known complications, elevated systemic venous pressure is likely an underrecognized cause of dysfunction. Elevated right atrial pressure can reduce the pressure gradient for CSF drainage, leading to intracranial hypertension despite a mechanically functional shunt. OBSERVATIONS: A 19-year-old female with a VA shunt developed refractory intracranial hypertension despite multiple valve adjustments and a mechanically functional shunt. Venography with pressure measurement revealed elevated systemic venous pressure, with jugular venous pressures elevated to 12–13 mm Hg. Shunt revision confirmed high outflow resistance at the atrial end (20 cm H ₂ O = approximately 15 mm Hg), suggesting impaired CSF drainage due to elevated right atrial pressure. Nitroglycerin reduced intracranial pressure but was discontinued due to headache exacerbation. Subsequently, acetazolamide provided symptomatic relief. LESSONS: Elevated systemic venous pressure can impair VA shunt function and cause intracranial hypertension. Preoperative central venous pressure measurement may help identify patients at risk. Nitroglycerin may serve as a diagnostic tool for VA shunt dysfunction related to elevated venous pressure. Awareness of increased systemic venous pressure as a factor in VA shunt dysfunction is warranted. https://thejns.org/doi/10.3171/CASE25226

Purpose: Postoperative speech impairment (POSI) is a core symptom of cerebellar mutism syndrome (CMS) and is a common complication after the resection of paediatric posterior fossa (PF) tumours. Preoperative glucocorticoids (pGC) are considered standard treatment to reduce tumour oedema; in addition, glucocorticoids are often administered intraoperatively (iGC) to reduce both postoperative nausea and vomiting. The study aims to investigate whether the occurrence of POSI may be associated with pGC and iGC. Methods: In a prospective observational multicentre study, we included children with a PF tumour requiring either resection or open biopsy. The use of pGC and iGC, including drug type and dose, was registered. Postoperative speech status was classified as mutism, reduced speech, or habitual speech, where mutism and reduced speech were considered POSI of higher and lower severity, respectively. Proportional odds logistic regression with adjustment for tumour type, tumour location, and age was used to analyse the occurrence of POSI associated with glucocorticoids (GC). Results: From August 2014 to November 2024, we recruited 810 children, of whom 605 were included in the primary analysis. We found no association between the use of GC (pGC nor iGC) and the occurrence of POSI. The result did not change when adjusting for tumour type, tumour location, and age. The analysis included both a comparison between using and not using pGC (OR 1.06 [95% CI 0.46 –2.49], reference level: use of pGC) and/or iGC (1.28 [0.58–2.82], reference level: use of iGC), and a dose–response analysis of the occurrence of POSI in relation to doubling the dose of GC (pGC OR 1.28 [0.84–1.98]; iGC OR 1.07 [0.62–1.82]). Conclusion: Our study did not find evidence of a significant change in the occurrence of POSI with the use of pGC or iGC, but our results alone cannot rule out that the administration of pGC or iGC may have some effect. Therefore, our data do not call for a change in recommendations for the use of GC as protection against the development of POSI. Trial registration number: Clinicaltrials.gov (NCT02300766). Date of registration: November 25, 2014

Background: Cerebellar Mutism Syndrome (CMS) is a neurological complication of posterior fossa (PF) tumour surgery in children, and postoperative speech impairment (POSI) is the cardinal symptom of CMS. The role of tumour volume on the risk of POSI remains unexplored. This study investigates the association between tumour volume and the risk of POSI. Methods: We included 360 patients from the European CMS study with available preoperative T1-weighted contrast-enhanced brain MRI. Speech status was assessed within two weeks postoperatively and categorised into three levels: habitual speech, severely reduced speech, and mutism. Tumour volumes were calculated using the BrainLab Elements SmartBrush™, a semi-automated segmentation tool. We used proportional odds models to estimate the odds ratio (OR) with adjustments for tumour location, pathology, and age. Based on the primary analysis, a risk stratification model for medulloblastoma patients was constructed, and the optimal volume cut-off was determined with Youden’s Index. Results: We found no effect of the overall tumour volume on the risk of POSI. This result did not change when adjusted for tumour location, pathology, and age. We found an association between tumour volume of medulloblastoma and the risk of POSI (unadjusted OR of 1.04 per increase in cm³ (95% CI 1.01;1.07, p = 0.01)), which did not change when adjusting for tumour location and age. The risk stratification cut-off for the tumour volume of medulloblastoma was calculated to be 16,5 cm³. Patients with medulloblastoma and preoperative tumour volumes below 16,5 cm³ had an absolute risk of 13% for POSI (low-risk group), whereas patients with preoperative tumour volumes above 16,5 cm³ had an absolute risk of 50% for POSI (high-risk group). Conclusion: Our data showed an association between preoperative tumour volume and the risk of POSI in children with medulloblastoma, while no association was found for the volume of other tumour types. We suggest a straightforward cut-off risk model for assessing the risk of POSI in children with medulloblastoma based on preoperative tumour volume. This approach can aid clinicians in informing patients and parents about the complications related to CMS following PF tumour surgery in children. Clinical Trials: ID NCT02300766 (October 2014).

Despite being a common, well-recognized and important complication to External Ventricular Drainage (EVD), a consensus definition for Ventriculostomy Related Infections (VRI) has not yet been established. We conducted a review to qualitatively assess definition heterogeneity and objectivity among Randomized Controlled Trials (RCTs); and investigated systematic reviews, meta-analyses, and reviews of the literature for definition citation accuracy and common methodological approaches and points of discussion related to VRI definitions. RCTs were grouped into arbitrarily chosen infection rate brackets to examine the hypothesized correlation between broader definitions and higher infection rates in RCTs. A literature search was conducted via Ovid in the Embase, MedLine and Cochrane databases from all years until the 8th of January 2025. Using Covidence, two authors (MH, AA) independently evaluated records, including studies that had ≥ 1 VRI definitions and numerical VRI rates. We identified 12 definitions in 13 RCTs, documenting pronounced disagreement. Cumulative rates for “definitive” VRI (8.4%) were lower than “suspected” VRI (13.5%). Qualitatively assessed, studies with narrow definitions presented lower VRI rates. All 17/17 meta-analyses and systematic reviews, and 15/19 literature reviews cited ≥ 1 definition inaccurately. Trial results may change based on definition choice. Definition heterogeneity was not sufficiently accounted for in meta-analyses. All literature-based studies were confounded by definition heterogeneity. Previously reported findings based on meta-analytical methodologies may be invalid, and inaccurately presented definitions could give a false impression of trial comparability. A consensus set of definitions are necessary to allow comparison between studies, and should be constructed to account for the intended use since sensitivity and specificity may have different weight depending on the context.

Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis. Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19). Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool. Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.