Continuous Cerebrospinal Fluid Research Articles

331 Validation of a Novel CSF-Based Biomarker of Mitochondrial Function

OBJECTIVES/GOALS: Determine the exosome mitochondrial DNA (mtDNA) copy number in cerebrospinal fluid (CSF) as a measure of neuronal mitochondrial integrity in patients with subarachnoid hemorrhage (SAH). Determine the patterns of beta amyloid and tau protein biology in CSF of SAH patients and correlate those measures with the clinical status of the SAH patients. METHODS/STUDY POPULATION: The CSF is collected from SAH patients undergoing ventriculostomy-based continuous CSF drainage. Adults from all ethnicities and sex are included in this study. The exosomes are isolated from CSF samples using a precipitation method and particle count and size are measured using NanoSight. The DNA is extracted using an exosomal DNA isolation kit (XCF kit). The CSF mtDNA copy number is measured using digital drop PCR with mitochondrial DNA primers. The levels of beta-amyloid (a-beta-40 and -42) and tau protein in CSF are measured using a sensitive ELISA-based assay. A quantitative evaluation of mitochondrial DNA copy number, clinical status of the SAH patients and beta amyloid, and tau protein levels will be conducted and reported. RESULTS/ANTICIPATED RESULTS: Preliminary results of four CSF samples showed similar patterns in CSF exosome particle number, particle size and exosomal mtDNA copy number in relation to samples from the admission day. Particle number decreased with time while particle size increased. More patient samples will be analyzed to confirm the patterns. We anticipate that mtDNA copy number will correlate with brain beta-amyloid and tau protein levels. Moreover, we anticipate that the clinical status of the SAH patients will associate with the mtDNA copy number. We specifically predict that higher mtDNA copy number levels will correlate with better clinical outcomes. DISCUSSION/SIGNIFICANCE: Mitochondrial function is critical to brain health, but we lack effective ways to monitor this parameter. Here we focus on a CSF based biomarker, exosome-derived mtDNA, which is intended to reflect the integrity of brain mitochondria. As bioenergetic metabolism influences beta amyloid and tau biology, predicting those levels are important.

Management of Cerebrospinal Fluid Leakage by Pump-Regulated Volumetric Continuous Lumbar Drainage Following Anterior Cervical Decompression and Fusion for Ossification of the Posterior Longitudinal Ligament.

Cerebrospinal fluid (CSF) leakage is a major concern related to anterior cervical decompression and fusion for ossification of the posterior longitudinal ligament (OPLL). We propose a management algorithm for CSF leakage following anterior cervical decompression and fusion for OPLL involving the use of pump-regulated volumetric continuous lumbar drainage. We retrospectively reviewed patients who underwent anterior cervical decompression and fusion for OPLL and were managed with the proposed algorithm between March 2018 and July 2022. The proposed management algorithm for CSF leakage by pump-regulated volumetric continuous lumbar drainage was as follows. On exposure of the arachnoid membrane with or without CSF leakage, a dural sealant patch was applied to manage the dural defect. In case of persistent CSF leakage despite application of the dural sealant patch, patients underwent pump-regulated volumetric continuous lumbar drainage. Fifty-one patients were included in the study. CSF leakage occurred in 14 patients. Of these 14 patients, 9 patients underwent lumbar drain insertion according to the proposed management algorithm. Successful resolution of CSF leakage was observed in 8 of the 9 patients who underwent lumbar drainage. All patients were encouraged to ambulate without concern of CSF overdrainage due to gravity, because it could be avoided with pump-regulated volumetric continuous CSF drainage. Therefore, complications associated with absolute bed rest or CSF overdrainage were not observed. The proposed management algorithm with pump-regulated volumetric continuous lumbar drainage showed safety and efficacy for management of CSF leakage following anterior decompression and fusion for OPLL.

Preventive effect of intermittent cerebrospinal fluid drainage for secondary chronic hydrocephalus after aneurysmal subarachnoid hemorrhage

BackgroundThe efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH.MethodsOverall, 204 patients (69 men and 135 women) treated for aneurysmal SAH between 2007 and 2022 were included in this study. Following SAH onset, 136 patients were managed with continuous CSF drainage, whereas 68 were managed with intermittent CSF drainage. Logistic regression analyses were used to calculate the age-adjusted and multivariate odds ratios for the development of sCH. The Cox proportional hazards regression model were used to compare the effects of intermittent and continuous CSF drainage on sCH development.ResultsOverall, 96 patients developed sCH among the 204 patients with SAH. In total, 74 (54.4%) of the 136 patients managed with continuous CSF drainage developed sCH, whereas 22 (32.4%) of the 68 patients managed with intermittent CSF drainage developed sCH. This demonstrated that the rate of sCH development was significantly lower among patients managed with intermittent CSF drainage. Compared with continuous CSF drainage, intermittent CSF drainage exhibited a multivariate odds ratio (95% confidential interval) of 0.25 (0.11–0.57) for sCH development. Intermittent CSF drainage was more effective (0.20, 0.04–0.95) in patients with severe-grade SAH than in those with mild-grade SAH (0.33, 0.12–0.95). Intermittent CSF drainage was ineffective in patients with acute hydrocephalus (8.37, 0.56–125.2), but it was effective in patients without acute hydrocephalus (0.11, 0.04–0.31).ConclusionsCompared with continuous CSF drainage, intermittent drainage is more effective in reducing sCH after aneurysmal SAH. Although intermittent drainage was ineffective in cases of co-occurrence of acute hydrocephalus, it was effective in reducing sCH development regardless of the severity of initial symptoms at SAH onset.

Successful Cervical Epidural Blood Patch as a Treatment of Spontaneous Intracranial Hypotension - A Case Report

Background: Spontaneous intracranial hypotension can be a source of headache due to a continuous cerebrospinal fluid leakage. Case: A 33-year-old male patient with unremarkable history was presented with a headache, accompanying posterior neck stiffness and tinnitus lasting for 4 days. The opening pressure from cerebrospinal fluid tapping was 60mmH2O. Magnetic resonance imaging of the neck showed fluid collection at right C1-2 level, suggesting spontaneous intracranial hypotension. The headache did not respond to conservative treatments. Epidural blood patch was performed at C4-5 level. On postoperative day 1, remnant headache was only 20 percent and patient was discharged the day after. Conclusions: In spontaneous intracranial hypotension with leakage site at high cervical level, an epidural blood patch at a different cervical level can be safely performed to relieve the symptoms.

Choroid Plexus Aquaporins in CSF Homeostasis and the Glymphatic System: Their Relevance for Alzheimer’s Disease

The glymphatic system, a fluid-clearance pathway involved in brain waste clearance, is known to be impaired in neurological disorders, including Alzheimer's disease (AD). For this reason, it is important to understand the specific mechanisms and factors controlling glymphatic function. This pathway enables the flow of cerebrospinal fluid (CSF) into the brain and subsequently the brain interstitium, supported by aquaporins (AQPs). Continuous CSF transport through the brain parenchyma is critical for the effective transport and drainage of waste solutes, such as toxic proteins, through the glymphatic system. However, a balance between CSF production and secretion from the choroid plexus, through AQP regulation, is also needed. Thus, any condition that affects CSF homeostasis will also interfere with effective waste removal through the clearance glymphatic pathway and the subsequent processes of neurodegeneration. In this review, we highlight the role of AQPs in the choroid plexus in the modulation of CSF homeostasis and, consequently, the glymphatic clearance pathway, with a special focus on AD.

Continuous lumbar drainage after aneurysmal subarachnoid hemorrhage decreased malondialdehyde in cerebrospinal fluid and improved outcome

The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH. Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured. There were 41 patients in non-LD group (age: 58.7±13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3±10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p=0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (>60 years) (p=0.0293), higher MDA level in the CSF (p=0.0208), and delayed ischemic neurological deficit (p=0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p<0.001). The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

Review/Perspective On the Diagnosis and Surgical Management of Spinal Arachnoid Cysts.

Background: Spinal arachnoid cysts (SAC) are typically congenital, spontaneous, traumatic (i.e., including iatrogenic/surgical), or inflammatory in origin. In descending order, they occur in the thoracic, lumbar, and cervical spine, and originate from focal entrapment of the arachnoid membrane. Arachnoid cysts represent 1–2% of all cystic spinal masses/tumors. The majority are extradural arachnoid cysts (EDAC) while 10% of all arachnoid cysts are intradural (IDAC) including subarachnoid, or extra-arachnoidal/subdural. Only rarely are they intramedullary in location. The clinical symptoms/signs of IDAC/EDAC include; intracranial hypotension (i.e., due to continued cerebrospinal fluid drainage), radiculopathy, and/or myelopathy.Methods: Magnetic Resonance Images (MR) and Myelo-Computed Tomography (Myelo-CT) studies classically document the predominant dorsal location of IDAC/EDAC. They also show their extent and severity contributing to root, cord, and/or cauda equina compression. In the cervical/thoracic spine, MR/Myelo-CT studies classically show the “double cord” or “windsock” signs, while the “fake arachnoiditis sign” may be seen in the lumbar spine. The latter sign signals the presence of a circumferential extra-arachnoidal-subdural cyst that centrally “traps” the cauda equina. Note, that this resembles and is often misinterpreted as adhesive archnoiditis.Results: Patients with significant SAC-related neurological deficits typically warrant early surgery. That surgery includes; partial/total resection/fenestration of cyst walls, and occlusion of communicating fistulas with or without accompanying shunts.Conclusion: It is critical to recognize the clinical (i.e., intracranial hypotension, radiculopathy, and/or myelopathy) and radiographic MR/Myelo-CT signs (i.e., “double cord,” “windsock signs”, or “fake arachnoiditis sign”) of IDAC, EDAC, or intramedullary spinal arachnoid cysts to appropriately offer treatment. For those with significant neurological deficits, early surgery (i.e. optimally 0-< 24 hours after the onset of symptoms/signs consisting of laminectomies, partial/total cyst resection/fenestration, and ligation/occlusion of the subarachnoid-cyst fistula with or without shunt placement), is essential to avoid significant permanent neurological sequelae.

Treatment of Secondary Hydrocephalus after Subarachnoid Hemorrhage

Hydrocephalus is one of the major complications secondly occurring with or after subarachnoid hemorrhage(SAH). Hydrocephalus can be classified into acute(≦ 48 h), subacute(3-14 days), or chronic phases(≧ 2 weeks)in which a cerebrospinal fluid(CSF)shunt is required as the curative treatment at the rate of approximately 30%. On the mechanism of hydrocephalus development, it is generally accepted that an inflammatory reaction and the ensuing fibrosis process impede continuous CSF flow outward to the sinus, terminally from arachnoid granulation, leptomeninges, or ventricle walls, in addition to the mechanical blockage due to SAH clots. Several factors associated with the severity of SAH, such as a high Hunt and Hess grade, intraventricular hemorrhage, and a ruptured aneurysm in the posterior circulation also predict the development of shunt-dependent hydrocephalus. The predictive scoring system is available. Effective treatment of hydrocephalus still involves the use of CSF shunts. No superiority between ventriculoperitoneal and lumboperitoneal shunts has been established. Even during oral, single antiplatelet treatment after coil embolization for ruptured aneurysms, curative shunt operation is possible with low frequency of hemorrhagic complications. Hydrocephalus should be diagnosed early and treated appropriately to improve the functional outcome of the patients after SAH.

Intraoperative Monitoring of CSF Pressure in Patients with Degenerative Cervical Myelopathy (COMP-CORD Study): A Prospective Cohort Study.

Degenerative cervical myelopathy (DCM) is hallmarked by spinal canal narrowing and related cord compression and myelopathy. Cerebrospinal fluid (CSF) pressure dynamics are likely disturbed due to spinal canal stenosis. The study aimed to investigate the diagnostic value of continuous intraoperative CSF pressure monitoring during surgical decompression. This prospective single center study (NCT02170155) enrolled DCM patients who underwent surgical decompression between December 2019 and May 2021. Data from n = 17 patients were analyzed and symptom severity graded with the modified Japanese Orthopedic Score (mJOA). CSF pulsations were continuously monitored with a lumbar intrathecal catheter during surgical decompression. Mean patient age was 62 ± 9 years (range 38-73; 8 female), symptoms were mild-moderate in most patients (mean mJOA 14 ± 2, range 10-18). Measurements were well tolerated without safety concerns. In 15/16 patients (94%), CSF pulsations increased at the time of surgical decompression. In one case, responsiveness could not be evaluated for technical reasons. Unexpected CSF pulsation decrease was related to adverse events (i.e., CSF leakage). Median CSF pulsation amplitudes increased from pre-decompression (0.52 mm Hg, interquartile range [IQR] 0.71) to post-decompression (0.72 mm Hg, IQR 0.96; p = 0.001). Mean baseline CSF pressure increased with lower magnitude than pulsations, from 9.5 ± 3.5 to 10.3 ± 3.8 mm Hg (p = 0.003). Systematic relations of CSF pulsations were confined to surgical decompression, independent of arterial blood pressure (p = 0.927) or heart rate (p = 0.102). Intraoperative CSF pulsation monitoring was related to surgical decompression while in addition adverse events could be discerned. Further investigation of the clinical value of intraoperative guidance for decompression in complex DCM surgery is promising.

Systematic review and meta-analysis of the effect of continuous cerebrospinal fluid drainage on keyhole surgery during the perioperative period.

Lumbar continuous drainage of fluid (LCDF) has become more widely used in the diagnosis and treatment of neurological diseases in recent years. The use of LCDF can enable a better understanding of the patient's condition and reduce the incidence of related complications. LCDF can also affect complications of perforation surgery, including mortality during hospitalization, cerebral vasospasm (CVS), bleeding, and aneurysmal subarachnoid hemorrhage (aSAH). Articles published from library construction to April 2021 were searched for in the English-language databases PubMed, Cochrane Library, and Embase. All randomized controlled trials (RCTs) with LCDF and hole locking surgery were meta-analyzed using the Cochrane Collaboration's RevMan 5.3 software. Ten RCTs involving 1,092 patients (continuous drainage group, n=585; control group, n=507) were included in the meta-analysis. For the statistical different in incidence of perioperative cerebral infarction in the two groups, the odds ratio (OR) was 5.42 [95% confidence interval (CI): (2.71, 10.83); P<0.00001], and for the statistical difference in the incidence of cerebral hemorrhage, the OR was 4.76 [95% CI: (2.11, 10.76); P=0.0002]. Perioperative complications were fewer in the LCDF-treated drainage group than in the conventional group. This meta-analysis of 10 RCTs confirmed that LCDF compared with other treatments is associated with a lower incidence of perioperative complications, such as cerebral hemorrhage, hydrocephalus, and cerebral infarction, as well as increased Glasgow Outcome Scale (GOS).

Acute Spinal Subarachnoid Hemorrhage: Case Report Cured by Continuous Cerebrospinal Fluid Drainage by Lumbar Puncture

Background: Spinal subarachnoid hemorrhage (SSH) is a rare condition that can lead to severe neurological deficits. Clinicians should consider SSH when neurological deficits such as low back pain, pain hyperalgesia, paraplegia, and urinary and fecal incontinence are present. There is much debate as to whether SSH should be treated surgically or conservatively. There are few reports in the literature about this disease. In this paper, we report a case of SSH in terms of etiology, clinical manifestations, diagnosis and treatment. Methods: A case of SSH in our hospital was retrospectively analyzed in terms of etiology, pathogenesis, clinical manifestations, diagnosis and treatment. Results: The possible etiology of SSH in this case was due to rapid changes in intra-thoracic and intra-abdominal pressure due to prolonged bending, which caused tearing of the blood vessels in the subarachnoid space. The patient has returned to normal life with continuous lumbar puncture for cerebrospinal fluid drainage. Conclusion: We report a case of SSH with typical symptoms of back pain, sensory, motor and autonomic dysfunction. MRI is used as the method of choice to diagnose SSH, which is typically characterized by the lumbar sedimentation sign. Lumbar puncture for continuous drainage of cerebrospinal fluid is simple and less invasive, and may be considered by neurosurgeons as the treatment of choice for SSH, with further surgical treatment considered if results are poor.

Safety of Early Mobilization in Patients With Intraoperative Cerebrospinal Fluid Leak in Minimally Invasive Spine Surgery: A Case Series

Cerebrospinal fluid (CSF) leak is a common complication in spine surgery. Repairing durotomy is more difficult in the setting of minimally invasive spine surgery (MISS). Efficacy of postoperative bed rest in case of dural tear in MISS is not clear. To assess the safety and efficacy of our protocol of dura closure without changing access, early mobilization, and discharge in cases of intraoperative CSF leak in MISS. A retrospective review from 2006 to 2018 of patients who underwent MISS for degenerative and neoplastic diseases with documented accidental or intentional durotomy was conducted. The primary outcome of interest was readmission rate for repair of persistent CSF leak. Secondary outcomes captured included development of pseudomeningocele, positional headache, and subdural hematoma. A total of 80 patients were identified out of 527 patients. Of these, intentional durotomy was performed in 28 patients and unintentional durotomy occurred in 52 patients. Mean follow-up period was 80.6 mo. Most of the patients were discharged on postoperative day 0 (within 4 h of surgery) without activity restrictions. A total of 2 (2.5%) patients required readmission and dural repair for continuous CSF leak and 3 patients (3.75%) developed pseudomeningocele. No lumbar drain insertion, meningitis, or subdural hematoma was reported. Early mobilization and discharge in cases of intraoperative CSF leak in MISS appear to be safe and not associated with higher rate of complications than that of reported literature.

Evaluating the Role of Pre-operative Cerebrospinal Fluid Diversion by Lumbar Drain in Transnasal Transsphenoidal Tumor Surgeries

Background and Aim: The major concerns related to the Endoscopic Endonasal Transsphenoidal (EET) surgery for sellar and suprasellar tumors include the risks of post-operative Cerebrospinal Fluid (CSF) leak, leading to morbidity and at times mortality, due to severe meningitis. Time is required to develop possible preventive measures that can reduce the risk of post-operative CSF rhinorrhea. The present study aimed to evaluate the effects of pre-operative CSF diversion by lumbar drainage in EET tumor surgeries on preventing post-operative CSF leak and its effect on the length of hospital stay. Methods and Materials/Patients: We conducted a prospective study on 20 patients with a pituitary tumor that underwent EET surgery between October 2018 and December 2019. Preoperative Lumbar Drain (LD) was inserted after induction in all explored patients. The tumor was excised with continuous intraoperative CSF drainage. Post-operatively, the LD was kept for 3 days and clamped for the next 24 hours. If no evidence of CSF rhinorrhea was present, it was removed. Complications related to CSF drainage, CSF leak, and hospital stays were evaluated. Results: Our study population consisted of 13(65%) men and 7(35%) women, with Mean±SD age of 39.8±10.71 years. The most commonly presented complaint was visual disturbance (60%) and the least common symptom was urinary disturbance (5%). The intra-operative leak was detected in 9(45%) patients, while the post-operative leak was present in only 1(5%) patient. LD blockage significantly contributed to post-operative CSF leak (P=0.001). The Mean±SD hospital stay in the post-operative period was 8.85±3.22 days with 65% of patients having a hospital stay of &lt;7 days. Other post-operative complications (e.g. diabetes insipidus, electrolyte imbalance, and hormonal disturbances) were mainly responsible for prolonged post-operative hospital stay (P=0.001). Conclusion: Pre-operative LD, apart from helping to reduce the incidence of post-operative CSF leak, is not associated with an overall increased post-operative hospital stay.

Reconstructive Outcomes of Multilayered Closure of Large Skull Base Dural Defects Following Open Anterior Craniofacial Resection.

Introduction Standardized reconstruction protocols for large open anterior skull base defects with dural resection are not well described. Here we report the outcomes and technique of a multilayered reconstructive algorithm utilizing local tissue, dural graft matrix, and microvascular free tissue transfer (MVFTT) for reconstruction of these deformities. Design This study is a retrospective review. Results Eleven patients (82% males) met inclusion criteria, with five (45%) having concurrent orbital exenteration and eight (73%) requiring maxillectomy. All patients required dural resection with or without intracranial tumor resection, with the average dural defect being 36.0 ± 25.9 cm 2 . Dural graft matrices and pericranial flaps were used for primary reconstruction of the dural defects, which were then reinforced with free fascia or muscle overlay by means of MVFTT. Eight (73%) patients underwent anterolateral thigh MVFTT, with the radial forearm, fibula, and vastus lateralis comprising the remainder. Average total surgical time of tumor resection and reconstruction was 14.9 ± 3.8 hours, with median length of hospitalization being 10 days (IQR: 9.5, 14). Continuous cerebrospinal fluid drainage through a lumber drain was utilized in 10 (91%) patients perioperatively, with an average length of indwelling drain of 5 days. Postoperative complications occurred in two (18%) patients who developed asymptomatic pneumocephalus that resolved with high-flow oxygen therapy. Conclusion A standardized multilayered closure technique of dural graft matrix, pericranial flap, and MVFTT overlay in the reconstruction of large open anterior craniofacial dural defects can assist the reconstructive team in approaching these complex deformities and may help prevent postoperative complications.

A Western‐style dietary pattern is associated with cerebrospinal fluid biomarker levels for preclinical Alzheimer's disease—A population‐based cross‐sectional study among 70‐year‐olds

BackgroundDiet may be a modifiable factor for reducing the risk of Alzheimer's disease (AD). Western‐style dietary patterns are considered to increase the risk, whereas Mediterranean‐style dietary patterns are considered to reduce the risk. An association between diet and AD‐related biomarkers have been suggested, but studies are limited.AimTo investigate potential relations between dietary patterns and cerebrospinal fluid (CSF) biomarkers for AD among dementia‐free older adults.MethodsData were derived from the population‐based Gothenburg H70 Birth Cohort Studies, Sweden. A total of 269 dementia‐free 70‐year‐olds with dietary and cerebrospinal fluid (CSF) amyloid beta (Aβ42 and Aβ40), total tau (t‐tau), and phosphorylated tau (p‐tau) data were investigated. Dietary intake was determined by the diet history method, and four dietary patterns were derived by principal component analysis. A Western dietary pattern, a Mediterranean/prudent dietary pattern, a high‐protein and alcohol pattern, and a high‐total and saturated fat pattern. Logistic regression models, with CSF biomarker pathology (yes/no) as dependent variables, and linear regression models with continuous CSF biomarker levels as dependent variables were performed. The analyses were adjusted for sex, energy intake, body mass index (BMI), educational level, and physical activity level.ResultsThe odds ratio for having total tau pathology (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.02 to 2.01) and preclinical AD (Aβ42 and tau pathology; OR 1.79; 95% CI 1.03 to 3.10) was higher among those with a higher adherence to a Western dietary pattern. There were no other associations between the dietary patterns and CSF biomarkers that remained significant in both unadjusted and adjusted models.DiscussionOur findings suggest that higher adherence to a Western dietary pattern may be associated with pathological levels of AD biomarkers in the preclinical phase of AD. These findings can be added to the increasing amount of evidence linking diet with AD and may be useful for future intervention studies investigating dietary intake in relation to AD.

Primary Repair of Posteriorly Located Anterior Skull Base Dural Defects Using Nonpenetrating Titanium Clips in Cranial Trauma.

Objective Primary repair of posteriorly located anterior skull base (ASB) dural defects following cranial trauma is made difficult by narrow operative corridors and adherent dura mater. Inadequate closure may result in continued cerebrospinal fluid (CSF) leak and infectious sequelae. Here, we report surgical outcomes following the use of nonpenetrating titanium microclips as an adjunctive repair technique in traumatic anterior skull base dural defects extending from the olfactory groove to the tuberculum sellae. Methods All trauma patients who underwent a bifrontal craniotomy from January 2013 to October 2019 were retrospectively reviewed. Patients with ASB defects located at posterior to the olfactory groove were analyzed. Patients with isolated frontal sinus fractures were excluded. All patients presented with CSF leak or radiographic signs of dural compromise. Patients were divided according to posterior extent of injury. Patient characteristics, imaging, surgical technique, and outcomes are reported. Results A total of 19 patients who underwent a bifrontal craniotomy for repair of posteriorly located ASB dural defects using nonpenetrating titanium microclips were included. Defects were divided by location: olfactory groove (10/19), planum sphenoidale (6/19), and tuberculum sellae (3/19). No patients demonstrated a postoperative CSF leak. No complications related to the microclip technique was observed. Clip artifact did not compromise postoperative imaging interpretation. Conclusion Primary repair of posteriorly located ASB dural defects is challenging due to narrow working angles and thin dura mater. Use of nonpenetrating titanium microclips for primary repair of posteriorly located dural defects is a reasonable adjunctive repair technique and was associated with no postoperative CSF leaks in this cohort.

Cerebrospinal fluid Aβ42 moderates the relationship between brain functional network dynamics and cognitive intraindividual variability

As Alzheimer’s disease (AD) pathology accumulates, resting-state functional connectivity (rs-fc) within and between brain networks decreases, and fluctuations in cognitive performance known as intraindividual variability (IIV) increase. Here, we assessed the relationship between IIV and anticorrelations in rs-fc between the default mode network (DMN)-dorsal attention network (DAN) in cognitively normal older adults and symptomatic AD participants. We also evaluated the relationship between cerebrospinal fluid (CSF) biomarkers of AD (amyloid-beta [Aβ42] and tau) and IIV-anticorrelation in rs-fc. We observed that cognitive IIV and anticorrelations between DMN × DAN were higher in individuals with AD compared with cognitively normal participants. As DMN × DAN relationship became more positive, cognitive IIV increased, indicating that stronger anticorrelations between networks support more consistent cognitive performance. Moderation analyses indicated that continuous CSF Aβ42, but not CSF total tau, moderated the relationship between cognitive IIV and DMN × DAN, collectively demonstrating that greater amyloid burden and alterations in functional network dynamics are associated with cognitive changes seen in AD. These findings are valuable, as they suggest that amyloid affects cognitive functioning during the early stages of AD.

Ultrasound increases the success rate of spinal needle placement through the epidural needle during combined spinal-epidural anaesthesia: A randomised controlled study.

Combined spinal-epidural anaesthesia (CSEA) using a needle-through-needle technique is currently widely used. However, successful epidural needle placement does not mean a successful spinal needle placement during CSEA. Whether ultrasound assistance could increase the first-pass success rate of spinal needle placement for CSEA remains unknown. The aim of this study was to investigate if ultrasound assistance could increase the first-pass success rate of spinal needle placement through the epidural needle during CSEA performed by experienced anaesthesiologists in patients undergoing caesarean section. A prospective, randomised, double-blind study. Single centre, Department of Anaesthesiology, Shengjing Hospital, China Medical University, China, from June 2019 to September 2019. A total of 185 patients (aged 24 years to 52 years, American Society of Anesthesiologists grade (ASA) II-III, 38 to 40 weeks gestation) scheduled to undergo elective caesarean section under CSEA were enrolled. The patients were randomised to either an ultrasound group (patients received a preprocedural ultrasound scan, and the puncture site was identified by ultrasound imaging) and a palpation group (patients received a sham procedural ultrasound scan, and the puncture site was identified by conventional palpation). The primary outcome measure was the first-pass success rate for spinal needle placement through the epidural needle. Secondary outcome measures were total duration of CSEA, time required for successful epidural needle and spinal needle placement, number of epidural needle redirections and complications. Preprocedural ultrasound imaging significantly increased the first-pass success rate of spinal needle placement through the epidural needle compared with conventional palpation (93.8 vs. 68.8%, P < 0.001). Preprocedural ultrasound imaging also decreased the total duration of CSEA (186.9 ± 37.1 vs. 213 ± 60.4 s, P = 0.0015) and the time required for successful spinal needle placement (78.3 ± 22.9 vs. 100.1 ± 53.7 s, P < 0.01) compared with conventional palpation. Fewer patients in the ultrasound group needed epidural needle redirections during the spinal needle placement procedure than in the palpation group (four patients vs. 20 patients, P < 0.01). For experienced anaesthesiologists, preprocedural ultrasound imaging significantly increased the first-pass success rate of spinal needle placement through the epidural needle for obstetric patients undergoing caesarean section under CSEA. chictr.org.cn, identifier: ChiCTR1900024132.

Worsening CSF parameters after the start of anti-tuberculosis treatment predicts intracerebral tuberculoma development

ObjectivesWe investigated whether early worsening of cerebrospinal fluid (CSF) predicts the later paradoxical tuberculomas and is a potential predictive biomarker. MethodsPatients of HIV-negative tuberculous meningitis fulfilling the inclusion criteria(n = 98) underwent clinical and CSF evaluation, together with repeated neuroimaging. We compared the baseline clinical data and continuous CSF of patients who did (n = 36) and did not (n = 62) develop paradoxical tuberculomas, and reported the changes associated with symptomatic tuberculomas. A logistic regression analysis was developed to reveal predictors for paradoxical tuberculomas. ResultsThe proportion of worsening CSF parameters (WBC count and percent neutrophils) in the paradoxical tuberculomas group (27/36, 75.0%) was significantly higher than the non-paradoxical tuberculomas group (15/62, 24.2%). The logistic regression analysis revealed that worsening CSF parameters was the highest risk predictor for paradoxical tuberculomas. Most worsening CSF parameters (81.0%) occurred within two weeks after treatment (2–24 days, median 7 days), and paradoxical tuberculomas commonly happened two weeks later (12 days to 13 months, median 22 days). The period between worsening CSF parameters and paradoxical tuberculomas ranged from 6 to 383 days (median 21days). There were no significant differences in mortality and prognosis between the two groups. ConclusionsEarly worsening of CSF parameters predicts subsequent development or progression of tuberculomas.

Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity

BackgroundStage 1 of the National Institute on Aging–Alzheimer’s Association’s proposed Alzheimer’s disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ. MethodsWe examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer’s Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology. ResultsForty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level). ConclusionsThe possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels.