Assessing the effects of spontaneous intracranial hypotension on quality of life, work ability and disability.

BACKGROUND: Spontaneous intracranial hypotension (SIH), characterized by headaches due to cerebrospinal fluid leaks or low pressure, is a challenging condition to diagnose and treat and affects the quality of life. METHODS: An 8­week online survey was conducted to assess the impact of SIH on symptoms, sociodemographics and quality of life. The cohort was comprised of patients who had a self-reported diagnosis of SIH and were divided into two groups: those with radiological evidence of SIH and those with clinical suspicion but no radiological evidence. Mental health and disability were evaluated using the Depression, Anxiety and Stress Scale-21 (DASS-21) and the Henry Ford Hospital Headache Disability Inventory (HDI). RESULTS: A total of 86 participants were included in the study, 59 with radiological evidence and 27 without. Most participants were female (84.9%) with a mean age of 44.8 years. Orthostatic headache was more common in participants without radiological evidence (74.1% vs. 42.4%). The severity in those with radiological evidence was 27.1% mild, 27.1% moderate, 30.5% severe and 15.3% extremely severe, while those without had 7.4% mild, 18.5% moderate, 63.0% severe and 11.1% extremely severe headaches. Mental health assessment using the DASS-21 scale showed that 77.9% of all participants reported signs of depression, 96.5% reported anxiety and 89.5% reported stress. The HDI showed 2.3% total disability, 40.7% severe, 19.8% moderate and 37.2% mild. The impact on employment was significant: 15.1% were able to work full-time, 48.8% part-time, 30.2% were unable to work and 5.8% retired early due to SIH. CONCLUSION: The study demonstrates the broad impact of SIH affecting physical health, mental well-being, and socioeconomic status, and calls for multifaceted and robust management approaches to address its complex effects on patients.

Incidental durotomy during tubular microdiscectomy does not preclude same-day discharge.

PURPOSE: One of the major advantages of a minimally invasive microdiscectomy is that when CSF leak occurs, there is minimal anatomic dead space for ongoing leakage following removal of the tubular retractor. However, there are no published reports that address the safety and long-term outcomes of same-day discharge for CSF leak after tubular microdiscectomy. METHODS: This is a retrospective compartive study of 30 patients with incidental durotomy during minimally invasive tubular microdiscectomy occurring between January 1, 2009 to August 31, 2023 at our institution. RESULTS: There were 16 patients (53%) admitted to hospital and 14 (47%) patients discharged home the same day following CSF leak. There were no differences in patient demographics between the two groups at baseline. Twenty-nine out of 30 (97%) of the patients had onlay duraplasty, and one (3%) patient was repaired using sutures through the tubular retractor. None were converted to an open approach. The hospitalized group was kept on bed rest overnight or for 24 h. The discharge group was kept on best rest for 2 h or mobilized immediately after surgery. No patients in either group required readmission or revision surgery for CSF leak. The average length of admission for the hospitalized group was 2.4 ± 4.0 days. CONCLUSION: Patients with CSF leak during minimally invasive tubular microdiscectomy can be safely discharged home the same day.

Coupled pulsatile vascular and paravascular fluid dynamics in the human brain.

BACKGROUND: Cardiac pulsation propels blood through the cerebrovascular network to maintain cerebral homeostasis. The cerebrovascular network is uniquely surrounded by paravascular cerebrospinal fluid (pCSF), which plays a crucial role in waste removal, and its flow is suspected to be driven by arterial pulsations. Despite its importance, the relationship between vascular and paravascular fluid dynamics throughout the cardiac cycle remains poorly understood in humans. METHODS: In this study, we developed a non-invasive neuroimaging approach to investigate the coupling between pulsatile vascular and pCSF dynamics within the subarachnoid space of the human brain. Resting-state functional MRI (fMRI) and dynamic diffusion-weighted imaging (dynDWI) were retrospectively cardiac-aligned to represent cerebral hemodynamics and pCSF motion, respectively. We measured the time between peaks (∆TTP) in d d ϕ f M R I and dynDWI waveforms and measured their coupling by calculating the waveforms correlation after peak alignment (correlation at aligned peaks). We compared the ∆TTP and correlation at aligned peaks between younger [mean age: 27.9 (3.3) years, n = 9] and older adults [mean age: 70.5 (6.6) years, n = 20], and assessed their reproducibility within subjects and across different imaging protocols. RESULTS: Hemodynamic changes consistently precede pCSF motion. ∆TTP was significantly shorter in younger adults compared to older adults (-0.015 vs. -0.069, p < 0.05). The correlation at aligned peaks were high and did not differ between younger and older adults (0.833 vs. 0.776, p = 0.153). The ∆TTP and correlation at aligned peaks were robust across fMRI protocols (∆TTP: -0.15 vs. -0.053, p = 0.239; correlation at aligned peaks: 0.813 vs. 0.812, p = 0.985) and demonstrated good to excellent within-subject reproducibility (∆TTP: intraclass correlation coefficient = 0.36; correlation at aligned peaks: intraclass correlation coefficient = 0.89). CONCLUSION: This study proposes a non-invasive technique to evaluate vascular and paravascular fluid dynamics. Our findings reveal a consistent and robust cardiac pulsation-driven coupling between cerebral hemodynamics and pCSF dynamics in both younger and older adults.

Thrombospondin-4 as potential cerebrospinal fluid biomarker for therapy response in pediatric spinal muscular atrophy.

BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) as the second most common neurodegenerative disorder in childhood is characterized by the deficiency of survival of motor neuron (SMN) protein leading predominantly to degeneration of alpha motor neurons and consequently to progressive muscle weakness and atrophy. Besides some biomarkers like SMN2 copy number therapeutic biomarkers for SMA with known relevance for neuromuscular transmission are lacking. Here, we examined the potential of Thrombospondin-4 (TSP4) to serve as a cerebrospinal fluid (CSF) biomarker, which may also indicate treatment response. METHODS: We used untargeted proteomic analyses to determine biomarkers in CSF samples derived from pediatric pre-symptomatic (n = 6) and symptomatic (n = 4) SMA patients. The identified biomarker TSP4 was then validated in additional 68 CSF samples (9 adult and 24 pediatric SMA patients, 5 adult and 13 pediatric non-disease controls in addition to 17 pediatric disease controls) by enzyme-linked immunosorbent assay (ELISA) as an additional analytical approach. RESULTS: Untargeted proteomic analyses of CSF identified a dysregulation of TSP4 and revealed a difference between pre-symptomatic SMA patients and patients identified after the onset of first symptoms. Subsequent ELISA-analyses showed that TSP4 is decreased in pediatric but not adult SMA patients. CSF of pediatric patients with other neurological disorders demonstrated no alteration of TSP4 levels. Furthermore, CSF TSP4 levels of pediatric SMA patients increased after first dose of Nusinersen. CONCLUSIONS: We found that TSP4 levels are exclusively reduced in CSF of pediatric SMA patients and increase after treatment, leading us to the hypothesis that TSP4 could serve as a CSF biomarker with the potential to monitor treatment response in pediatric SMA patients. Moreover, TSP4 enable to distinguish pre-symptomatic and symptomatic patients suggesting a potential to serve as a stratification marker.

Upright CT-based evaluation of the effects of posture on skull-base reconstruction after endoscopic endonasal surgery.

Cerebrospinal fluid (CSF) leakage is a common complication associated with endoscopic endonasal skull-base surgery (EESBS). Postoperative mobilization-associated postural changes are considered to cause CSF leakage. However, no study has demonstrated a robust relationship between postural changes and CSF leakage. We used upright computed tomography (CT) to clarify the effects of postural changes on the reconstructed skull base (RSB) after EESBS. Thirty patients who underwent EESBS at our institution were prospectively included, and their upright and supine CTs were compared to measure morphological changes in the RSB. Patient clinical data were also collected from medical charts and surgical videos, and their relationships with morphological changes were assessed. In upright CTs, the RSB shifted intracranially by 0.94 (0.0-2.9) mm on average. This shift was larger in cases with lesions extending to the sphenoid sinus, dural defects, intraoperative pulsation of the RSB, and large bone windows. The direction of the change was opposite to intuitive movement driven by gravity because of reduced intracranial pressure in the sitting position. Thus, these shifts can be directly associated with postoperative CSF leakage caused by reconstruction material displacement. Skull-base reconstruction and postoperative postural management accounting for these morphological changes may be necessary for preventing CSF leakage.

Use of Subfascial Passive Bile Bag Drainage for the Management of Durotomies in Spine Surgery.

INTRODUCTION: Historically, the use of subfascial drains for the management of durotomies was avoided due to concerns about the creation of cerebrospinal fluid (CSF) fistulas. Currently, there are limited series utilizing subfascial drainage for CSF leak management, many of which utilize suction drainage. We report our experience with the use of subfascial passive drainage in the management of such leaks. OBJECTIVE: To demonstrate the efficacy of a passive subfascial bile bag for diversion of CSF post-operatively in concert with a post-operative head of bed (HOB) protocol for the management of durotomies in spine surgery. METHODS: We performed a retrospective chart review of patients who underwent spinal surgery at a single institution performed by one surgeon. Cases utilizing a passive subfascial bile bag for durotomies were identified. A total of 1,882 consecutive surgeries were reviewed, and 108 met the inclusion criteria. The primary outcome was return to the operating room (OR) and/or the need for lumbar drain placement. Patient sociodemographic information and pre-, intra-, and post-operative clinical characteristics were reviewed. RESULTS: A total of 108 patients underwent subfascial bile bag CSF diversion after intra-operative durotomy. Four patients (3.7%) experienced post-operative CSF leakage requiring lumbar drain placement, while only two (1.9%) patients required a return to the OR. One patient returned to the OR for symptomatic pseudomeningocele and the other for ongoing CSF drainage from their wound. CONCLUSION:  Durotomies are known to increase complication rates, including reoperation. The use of subfascial passive bile bag drainage in concert with a post-operative HOB protocol is a safe and effective manner to manage durotomies while minimizing the need for reoperation.

CSF-profile and hypocretin levels in children with narcolepsy type 1 and 2.

BACKGROUND: Narcolepsy is a rare neurological disease caused by dysfunction of hypocretin-producing neurons. Hypocretin concentrations in the cerebrospinal fluid (CSF) of less than 110 pg/ml are considered pathological in adults. OBJECTIVES: To compare hypocretin levels of children with narcolepsy type 1, type 2 and disease control groups, in addition to a detailed CSF analysis, clinical and polysomnographic parameters. METHODS: In a retrospective, cross-sectional study, children diagnosed with narcolepsy based on clinical and polysomnographic parameters, who received a CSF analysis and hypocretin measurement, in addition to controls, were included. CSF was analyzed for the presence of cells, total protein, lactate, intrathecal synthesis of antibodies against measles, rubella and/or varicella zoster, and oligoclonal bands. All children had a complete sleep study including a multiple sleep latency test (MSLT). RESULTS: 49 children with narcolepsy type 1, 15 children with type 2 and 37 children with other (suspected) neurological diseases were included. CSF routine analysis did not reveal any differences between the three groups. All children with narcolepsy type 1 had hypocretin levels of less than 110 pg/ml (range: 10-101 pg/ml). Hypocretin levels in type 2 patients ranged from 43 to 436 pg/ml (median 157 pg/ml). The median hypocretin level in the control cohort was 365 pg/ml (range: 153-583 pg/ml). In 4 children with narcolepsy type 2 the diagnosis was changed to narcolepsy level 1 because of a CSF hypocretin level of less than 110 pg/ml according to the recently proposed criteria, which consider the measurement of hypocretin in CSF. CONCLUSION: Children with narcolepsy type 1 showed significantly lower CSF hypocretin levels than children with narcolepsy type 2 and controls. As suggested by the recently published narcolepsy criteria, hypocretin levels of less than 110 pg/ml should be used as an additional criterion for the presence of narcolepsy type 1 in children.

Reuse of Nasoseptal Flaps for Endoscopic Endonasal Skull Base Reconstruction.

Introduction Pedicled nasoseptal flap (NSF) placement is a critical component of skull base reconstruction after endoscopic endonasal approaches (EEAs). The effectiveness of NSF reuse has not been thoroughly studied. Prior reports using flaps harvested at one center and reused at another may have technical variability bias. Methods We identified patients who underwent both their initial and NSF-reused surgeries at Weill Cornell Medical College from 2004 to 2022 using a prospective database of all EEAs. Surgical pathology, intraoperative leak grade, use of cerebrospinal fluid (CSF) diversion and skull base coverage were examined. The primary outcome measure was occurrence of CSF leak. Results Fourteen patients (six women, eight men) underwent 14 first time and 14 revision operations with median age of 36.6 years (interquartile range [IQR]: 23.9-61.3) at the time of the NSF reuse. The median interval between the first NSF use and reuse was 70.6 months (IQR: 16.6-87). Eight patients were operated on for pituitary adenoma. Nonadenomas included three craniopharyngiomas and one case each of epidermoid, ependymoma, and chordoma. There were 16 high-flow, 8 low-flow intraoperative leaks, and 4 with no leak. CSF diversion was used in 24 operations. There were three postoperative leaks, one after a first operation and two after NSF reuse. All postoperative CSF leaks, whether first or second operations, occurred in cases with both high-flow intraoperative CSF leak and incomplete NSF coverage ( p = 0.006). Conclusion NSF reuse is effective at preventing postoperative CSF leak. The primary predictors of leak are high-flow intraoperative leak and inadequate defect coverage with NSF, regardless of the operation number.

Anatomical-Radiological Aspects and Their Influence on the Results of Pituitary Adenomas Endoscopic Endonasal Surgery.

Introduction Endoscopic endonasal surgery has globally improved postoperative results in pituitary adenomas. Material and Methods We retrospectively analyzed 101 patients who underwent endonasal endoscopic surgery for pituitary adenomas in the period from 2016 to 2021. Data on epidemiological variables, preoperative radiological factors including tumor volume, tumor appearance, cavernous sinus invasion (modified Knosp scale), degree of extension according to the SIPAP (stands for the five directions in which a pituitary adenoma can extend: suprasellar, infrasellar, parasellar, anterior, and posterior) classification, and preoperative visualization of the healthy gland on magnetic resonance imaging (MRI) were collected as well as intra- and postoperative cerebrospinal fluid (CSF) leak. As variables of interest, data on the degree of tumoral resection and preservation of hormonal function were collected. Results Among the preoperative factors related to greater tumoral resection, we found a lesser tumoral extension according to the SIPAP scale, and the absence of a postoperative CSF leak had a statistically significant relation with greater hormonal preservation. Conclusion The SIPAP classification is a simple-to-measure preoperative radiological variable that could predict the extent of resection, and, conversely, the occurrence of a postoperative CSF leak has been associated with an inferior endocrinological outcome in this type of surgery.

Giant metastatic mixed-type spinal ependymoma presenting with hydrocephalus.

Ependymomas are rare nervous system tumors that can arise anywhere in the neuraxis. While having a high propensity for leptomeningeal dissemination, retrograde dissemination (from the spine to the CNS) remains infrequent. We describe the case of a 31-year-old female who presented with hydrocephalus secondary to an intracranial leptomeningeal metastasis of a giant spinal ependymoma with mixed (classic and myxopapillary) histopathologic features, successfully treated with surgical resection and radiotherapy of the entire neuraxis. This case highlights the importance of including ependymomas in the differential diagnosis for lesions in atypical extra-axial locations, of systematically obtaining imaging of the entire neuraxis when suspecting it, and of considering retrograde dissemination when both intracranial and spinal lesions are present.

Heat shock on bovine embryos from day 2.5-3 selects the most competent for progression to the blastocyst stage.

Heat shock can impair embryo formation, while growth factors, such as colony-stimulating factor 2 (CSF2), modulate embryonic development. This study evaluated the effect of heat shock between days 2.5 and 3, as well as the impact of CSF2 at day 5 on bovine embryos cultured in a serum-free in vitro medium. The focus was on blastocyst development, the number of blastomeres, DNA fragmentation (TUNEL-positive cells), and mitochondrial activity. Heat shock reduced the proportion of cleaved embryos that developed into blastocysts (P = 0.0603). The resultant blastocysts exhibited a reduced number and proportion of TUNEL-positive cells in the trophectoderm (P = 0.0270 and P = 0.0240, respectively) and in the entire embryo (P = 0.0029 and P = 0.0031, respectively). Additionally, mitochondrial activity was lower in blastocysts derived from heat-shocked embryos (P = 0.0150) and further reduced in embryos exposed to both heat shock and CSF2 (P = 0.0415). In conclusion, the exposure of cleaved embryos to heat shock reduced their development to the blastocyst stage. However, the resulting blastocysts showed decreased DNA fragmentation and mitochondrial activity.

Intracerebroventricular injection of α-synuclein preformed fibrils do not induce motor and olfactory impairment in C57BL/6 mice.

INTRODUCTION: Alpha-synuclein (αSyn) is believed to play a central role in the pathogenesis of Parkinson's disease (PD). Cerebrospinal fluid (CSF) total αSyn were significantly lower in PD patients, whereas the aggregates were higher, and this phenomenon was further exacerbated with longer disease duration. However, whether CSF αSyn can be the cause and/or a consequence in PD is not fully elucidated. METHOD: We administered 2 ng or 200 ng αSyn preformed fibrils (PFFs) by intracerebroventricular injection for consecutive 7 days in C57BL/6 mice. The olfactory function was assessed by the olfactory discrimination test and buried food-seeking test. The locomotor function was assessed by the rotarod test, pole test, open field test and CatWalk gait analysis. Phosphorylated αSyn at serine 129 was detected by the immunohistochemistry staining. Iron levels was determined by Perl's-DAB iron staining and synchrotron-based X-ray fluorescence. RESULTS: The mice did not exhibit any diffuse synucleinopathy in the brain for up to 30 weeks, although αSyn PFFs induced aggregation in SH-SY5Y cells and in the substantia nigra and striatum of mice with stereotactic injection. No impairment of motor behaviors or olfactory functions were observed, although there was a temporary motor enhancement at 1 week. We then demonstrated iron levels were comparable in certain brain regions, suggesting there was no iron deposition/redistribution occurred. CONCLUSION: The intraventricular injection of αSyn PFFs does not induce synucleinopathy or behavioral symptoms. These findings have implications that CSF αSyn aggregates may not necessarily contribute to the onset or progression in PD.

Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration.

BACKGROUND: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking. METHODS: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing. RESULTS: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. CONCLUSION: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.

Increases in amyloid-ß42 slow cognitive and clinical decline in Alzheimer's disease trials.

Positive effects of new anti-amyloid-ß (Aß) monoclonal antibodies in Alzheimer's disease (AD) have been attributed to brain amyloid reduction. However, most anti-Aß antibodies also increase the CSF levels of the 42-amino acid isoform (Aß42). We evaluated the associations of changes in CSF Aß42 and brain Aß-PET with cognitive and clinical end points in randomized trials of anti-Aß drugs that lowered (ß- and γ-secretase inhibitors) or increased CSF Aß42 levels (anti-Aß monoclonal antibodies) to test the hypothesis that post-treatment increases in CSF Aß42 levels are independently associated with cognitive and clinical outcomes. From long-term (≥12 months) randomized placebo-controlled clinical trials of anti-Aß drugs published until November 2023, we calculated the post-treatment versus baseline difference in ADAS-Cog (cognitive subscale of the Alzheimer's Disease Assessment Scale) and CDR-SB (Clinical Dementia Rate-Sum of Boxes) and z-standardized changes in CSF Aß42 and Aß-PET Centiloids (CL). We estimated the effect size [regression coefficients (RCs) and confidence intervals (CIs)] and the heterogeneity (I2) of the associations between AD biomarkers and cognitive and clinical end points using random-effects meta-regression models. We included 25 966 subjects with AD from 24 trials. In random-effects analysis, increases in CSF Aß42 were associated with slower decline in ADAS-Cog (RC: -0.55; 95% CI: -0.89, -0.21, P = 0.003, I2 = 61.4%) and CDR-SB (RC: -0.16; 95% CI: -0.26, -0.06, P = 0.002, I2 = 34.5%). Similarly, decreases in Aß-PET were associated with slower decline in ADAS-Cog (RC: 0.69; 95% CI: 0.48, 0.89, P < 0.001, I2 = 0%) and CDR-SB (RC: 0.26; 95% CI: 0.18, 0.33, P < 0.001, I2 = 0%). Sensitivity analyses yielded similar results. Higher CSF Aß42 levels after exposure to anti-Aß drugs are independently associated with slowing cognitive impairment and clinical decline. Increases in Aß42 may represent a mechanism of potential benefit of anti-Aß monoclonal antibodies in AD.

Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of Frontotemporal Dementia.

Diagnosis of Frontotemporal dementia (FTD) and the specific underlying neuropathologies (frontotemporal lobar degeneration; FTLD- Tau and FTLD-TDP) is challenging, and thus fluid biomarkers are needed to improve diagnostic accuracy. We used proximity extension assays to analyze 665 proteins in cerebrospinal fluid (CSF) samples from a multicenter cohort including patients with FTD (n = 189), Alzheimer's Disease dementia (AD; n = 232), and cognitively unimpaired individuals (n = 196). In a subset, FTLD neuropathology was determined based on phenotype or genotype (FTLD-Tau = 87 and FTLD-TDP = 68). Forty three proteins were differentially regulated in FTD compared to controls and AD, reflecting axon development, regulation of synapse assembly, and cell-cell adhesion mediator activity pathways. Classification analysis identified a 14- and 13-CSF protein panel that discriminated FTD from controls (AUC: 0.96) or AD (AUC: 0.91). Custom multiplex panels confirmed the highly accurate discrimination between FTD and controls (AUCs > 0.96) or AD (AUCs > 0.88) in three validation cohorts, including one with autopsy confirmation (AUCs > 0.90). Six proteins were differentially regulated between FTLD-TDP and FTLD-Tau, but no reproducible classification model could be generated (AUC: 0.80). Overall, this study introduces novel FTD-specific biomarker panels with potential use in diagnostic setting.

The cerebrospinal fluid (CSF)-contacting raphe nucleus (CsfR) in mice.

A unique nucleus, the cerebrospinal fluid-contacting nucleus (CsfR), has been identified in the brain parenchyma. This nucleus features neurons with somas located within the parenchyma and processes extending into the cerebrospinal fluid (CSF). This anatomical configuration suggests that the CsfR may serve as a crucial interface between the nervous and body fluid regulatory systems, potentially playing a significant role in overall physiological modulation. Despite its importance, the precise biological significance of the CsfR remains to be fully elucidated. Previous research has characterized the CsfR, providing detailed information on its position, neighboring structures, neuron distribution, and 3D reconstruction in both rats and non-human primates, with stereotaxic coordinates specifically provided for the rat model. Given the relevance of mice as a model organism, especially the C57BL/6J strain, this study aims to explore the existence and morphology of the CsfR in mice. Our findings confirm the presence of the CsfR, consistently located in the ventral gray area of the lower part of the aqueduct and the upper part of the fourth ventricle floor. It is bilaterally symmetrical and heart-shaped in the coronal plane, which differs slightly from the Y-shape observed in coronal sections of rats. This study provides significant references for researchers investigating this specialized nucleus.

Case report: CSF hypotension secondary to a free syringo-subarachnoid-peritoneal shunt.

INTRODUCTION: Syringomyelia is present in 40% of pediatric patients with Chiari malformation. Typically treated with posterior fossa decompression, some cases require further intervention such as syrinx shunting. CASE REPORT: We report a 16-year-old female with Chiari type 1 malformation and syringomyelia who underwent posterior fossa decompression and subsequent free syringo-subarachnoid-peritoneal shunting. The patient developed symptoms of CSF overdrainage, and imaging indicated CSF hypotension. A distal catheter ligation temporarily improved symptoms, but eventually, a programmable ventricular shunt was necessary due to shunt dependence. CONCLUSION: This case highlights the rare complication of CSF overdrainage from syrinx shunting and the importance of shunt selection considerations.

Combined Lactate Glucose Ratio (CLGR) as a novel marker for rapid diagnosis of CSF bacterial infection in neurosurgical patients: diagnostic accuracy study and benchtop analyzer correlation.

OBJECTIVE: This study aimed to assess the diagnostic accuracy of a novel marker, the combined lactate-to-glucose ratio (CLGR), in identifying cerebrospinal fluid (CSF) bacterial infection (CBI) in neurosurgical patients. Additionally, it seeks to establish cut-off values for CLGR and evaluate the reliability of measurement using blood gas analyzer (BGA). METHODS: CSF samples were collected from two neurosurgical centers in Kuala Lumpur, Malaysia, between January 2022 and October 2023. Conventional markers and CLGR were quantified using standard laboratory methods, with BGA utilized for measurement when feasible. Samples were categorized into confirmed CBI-positive (CBI+) and CBI-negative (CBI-) groups. Marker performance was compared, and receiver operating characteristic analysis conducted. Pearson's correlation assessed the agreement between BGA and laboratory measurements. RESULTS: Among the 130 CSF samples, 11 were CBI+. Both cLac and CLGR were significantly elevated in the CBI+ group (p<0.001). The area under the curve (AUC) for cLac and CLGR was 0.990 and 0.994, respectively. Using a cut-off of 6.0mmol/L, cLac demonstrated sensitivity of 100%, specificity of 93.3%, positive predictive value (PPV) of 57.9%, negative predictive value (NPV) of 100%, and diagnostic accuracy of 93.9%. CLGR ≥20.0 showed even higher accuracy: 100.0% sensitivity, 98.6% specificity, 84.6% PPV, 100% NPV, and overall accuracy of 98.5%. Both markers maintained excellent performance in blood-stained CSF. BGA measurements correlated well with laboratory results (r=0.980 & 0.999, respectively, p<0.001). CONCLUSIONS: CLac levels ≥6.0mmol/L and CLGR ≥20.0 accurately identified CBI in neurosurgical patients, with CLGR exhibiting superior efficacy. The potential for instant BGA measurement suggests promise for point-of-care testing.

Carotid artery vascular stenosis causes the blood-CSF barrier damage and neuroinflammation.

BACKGROUND: The choroid plexus (ChP) helps maintain the homeostasis of the brain by forming the blood-CSF barrier via tight junctions (TJ) at the choroid plexus epithelial cells, and subsequently preventing neuroinflammation by restricting immune cells infiltration into the central nervous system. However, whether chronic cerebral hypoperfusion causes ChP structural damage and blood-CSF barrier impairment remains understudied. METHODS: The bilateral carotid stenosis (BCAS) model in adult male C57BL/6 J mice was used to induce cerebral hypoperfusion, a model for vascular contributions to cognitive impairment and dementia (VCID). BCAS-mediated changes of the blood-CSF barrier TJ proteins, apical secretory Na+-K+-Cl- cotransporter isoform 1 (NKCC1) protein and regulatory serine-threonine kinases SPAK, and brain infiltration of myeloid-derived immune cells were assessed. RESULTS: BCAS triggered dynamic changes of TJ proteins (claudin 1, claudin 5) accompanied with stimulation of SPAK-NKCC1 complex and NF-κB in the ChP epithelial cells. These changes impacted the integrity of the blood-CSF barrier, as evidenced by ChP infiltration of macrophages/microglia, neutrophils and T cells. Importantly, pharmacological blockade of SPAK with its potent inhibitor ZT1a in BCAS mice attenuated brain immune cell infiltration and improved cognitive neurological function. CONCLUSIONS: BCAS causes chronic ChP blood-CSF damage and immune cell infiltration. Our study sheds light on the SPAK-NKCC1 complex as a therapeutic target in neuroinflammation.