Lateral Spinal CSF Leaks in Patients with Spontaneous Intracranial Hypotension: Radiologic-Anatomic Study of Different Variants.

BACKGROUND AND PURPOSE: Spinal CSF leaks cause spontaneous intracranial hypotension. Several types of leaks have been identified, and one of these types is the lateral dural tear. Performing myelography with the patient in the decubitus position allows precise characterization of these leaks. The purpose of the current study was to describe the different variants of spontaneous lateral CSF leaks. MATERIALS AND METHODS: This retrospective cohort study included a consecutive group of patients with spontaneous intracranial hypotension and lateral CSF leaks who underwent digital subtraction myelography in the decubitus position and underwent surgery to repair the CSF leak between July 2018 and June 2023. RESULTS: The mean age of the 53 patients (37 women and 16 men) was 35.5 years. Three different variants of lateral CSF leak could be identified. Forty-nine patients (92.5%) had a lateral dural tear associated with the nerve root sleeve. The dural tear was at the axilla of the nerve root sleeve in 36 patients (67.9%) and at the shoulder in 13 patients (24.5%). Four patients (7.5%) had a lateral dural tear at the level of the pedicle that was not associated with the nerve root sleeve. Findings on digital subtraction myelography were concordant with intraoperative findings in all patients. An extradural CSF collection was seen in all patients with a lateral dural tear associated with the nerve root sleeve but in only 2 of the 4 patients with the pedicular variant of a lateral dural tear. CONCLUSIONS: We identified 3 variants of spontaneous lateral dural tears. Most lateral dural tears are associated with extradural CSF collections and arise from either the axilla (67.9%) or the shoulder (24.5%) of the nerve root sleeve. Lateral dural tears at the level of the pedicle (7.5%) not associated with the nerve root sleeve are uncommon and may require specialized imaging for their detection.

Altered brain expression and cerebrospinal fluid levels of TIMP4 in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a highly prevalent and progressive pathology, involving amyloid-ß (Aß) deposition in the cerebral blood vessel walls. CAA is associated with an increased risk for intracerebral hemorrhages (ICH). Insight into the molecular mechanisms associated with CAA pathology is urgently needed, to develop additional diagnostic tools to allow for reliable and early diagnosis of CAA and to obtain novel leads for the development of targeted therapies. Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) is associated with cardiovascular functioning and disease and has been linked to vascular dementia. Using immunohistochemistry, we studied occipital brain tissue samples of 57 patients with CAA (39 without ICH and 18 with ICH) and 42 controls, and semi-quantitatively assessed expression levels of TIMP4. Patients with CAA had increased vascular expression of TIMP4 compared to controls (p < 0.001), and in these patients, TIMP4 expression correlated with CAA severity (τb = 0.38; p = 0.001). Moreover, TIMP4 expression was higher in CAA-ICH compared to CAA-non-ICH cases (p = 0.024). In a prospective cross-sectional study of 38 patients with CAA and 37 age- and sex-matched controls, we measured TIMP4 levels in cerebrospinal fluid (CSF) and serum using ELISA. Mean CSF levels of TIMP4 were decreased in patients with CAA compared to controls (3.36 ± 0.20 vs. 3.96 ± 0.22 ng/ml, p = 0.033), whereas median serum levels were increased in patients with CAA (4.51 ng/ml [IQR 3.75-5.29] vs 3.60 ng/ml [IQR 3.11-4.85], p-9.013). Moreover, mean CSF TIMP4 levels were lower in CAA patients who had experienced a symptomatic hemorrhage compared to CAA patients who did not (2.13 ± 0.24 vs. 3.57 ± 0.24 ng/ml, p = 0.007). CSF TIMP4 levels were associated with CSF levels of Aß40 (spearman r (rs) = 0.321, p = 0.009). In summary, we show that TIMP4 is highly associated with CAA and CAA-related ICH, which is reflected by higher levels in the cerebral vasculature and lower levels in CSF. With these findings we provide novel insights into the pathophysiology of CAA, and more specifically in CAA-associated ICH.

Persistent activity of aerobic methane-oxidizing bacteria in anoxic lake waters due to metabolic versatility.

Lacustrine methane emissions are strongly mitigated by aerobic methane-oxidizing bacteria (MOB) that are typically most active at the oxic-anoxic interface. Although oxygen is required by the MOB for the first step of methane oxidation, their occurrence in anoxic lake waters has raised the possibility that they are capable of oxidizing methane further anaerobically. Here, we investigate the activity and growth of MOB in Lake Zug, a permanently stratified freshwater lake. The rates of anaerobic methane oxidation in the anoxic hypolimnion reached up to 0.2 µM d-1. Single-cell nanoSIMS measurements, together with metagenomic and metatranscriptomic analyses, linked the measured rates to MOB of the order Methylococcales. Interestingly, their methane assimilation activity was similar under hypoxic and anoxic conditions. Our data suggest that these MOB use fermentation-based methanotrophy as well as denitrification under anoxic conditions, thus offering an explanation for their widespread presence in anoxic habitats such as stratified water columns. Thus, the methane sink capacity of anoxic basins may have been underestimated by not accounting for the anaerobic MOB activity.

Prevalence of Cerebral Amyloid Angiopathy Pathology and Strictly Lobar Microbleeds in East-Asian Versus Western Populations: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer's disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH). METHODS: We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models. RESULTS: We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts. CONCLUSION: The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-ß immunotherapy as treatment for AD in East-Asian and Western countries alike.

Pediatric post-dural puncture headache and paraplegia.

A cerebrospinal fluid (CSF) leak developed in a 14-year-old girl and a 12-year-old boy following a diagnostic lumbar puncture. Two days and sixteen years later, respectively, paraplegia developed due to a functional disorder. Imaging revealed an extensive extradural CSF collection in both patients and digital subtraction myelography was required to pinpoint the exact site of a ventral dural puncture hole where the lumbar spinal needle had gone "through and through" the dural sac. The CSF leak was complicated by cortical vein thrombosis in one patient. Both patients underwent uneventful surgical repair of the ventral dural puncture hole with prompt resolution of the paraplegia. Iatrogenic ventral CSF leaks may become exceptionally long standing and may be complicated by paraplegia on a functional basis both in the acute and chronic phases.

Rhizobia-diatom symbiosis fixes missing nitrogen in the ocean.

Nitrogen (N2) fixation in oligotrophic surface waters is the main source of new nitrogen to the ocean1 and has a key role in fuelling the biological carbon pump2. Oceanic N2 fixation has been attributed almost exclusively to cyanobacteria, even though genes encoding nitrogenase, the enzyme that fixes N2 into ammonia, are widespread among marine bacteria and archaea3-5. Little is known about these non-cyanobacterial N2 fixers, and direct proof that they can fix nitrogen in the ocean has so far been lacking. Here we report the discovery of a non-cyanobacterial N2-fixing symbiont, 'Candidatus Tectiglobus diatomicola', which provides its diatom host with fixed nitrogen in return for photosynthetic carbon. The N2-fixing symbiont belongs to the order Rhizobiales and its association with a unicellular diatom expands the known hosts for this order beyond the well-known N2-fixing rhizobia-legume symbioses on land6. Our results show that the rhizobia-diatom symbioses can contribute as much fixed nitrogen as can cyanobacterial N2 fixers in the tropical North Atlantic, and that they might be responsible for N2 fixation in the vast regions of the ocean in which cyanobacteria are too rare to account for the measured rates.

The relation of a cerebrospinal fluid profile associated with Alzheimer's disease with cognitive function and neuropsychiatric symptoms in sporadic cerebral amyloid angiopathy.

BACKGROUND: Patients with sporadic cerebral amyloid angiopathy (sCAA) frequently report cognitive or neuropsychiatric symptoms. The aim of this study is to investigate whether in patients with sCAA, cognitive impairment and neuropsychiatric symptoms are associated with a cerebrospinal fluid (CSF) biomarker profile associated with Alzheimer's disease (AD). METHODS: In this cross-sectional study, we included participants with sCAA and dementia- and stroke-free, age- and sex-matched controls, who underwent a lumbar puncture, brain MRI, cognitive assessments, and self-administered and informant-based-questionnaires on neuropsychiatric symptoms. CSF phosphorylated tau, total tau and Aß42 levels were used to divide sCAA patients in two groups: CAA with (CAA-AD+) or without a CSF biomarker profile associated with AD (CAA-AD-). Performance on global cognition, specific cognitive domains (episodic memory, working memory, processing speed, verbal fluency, visuoconstruction, and executive functioning), presence and severity of neuropsychiatric symptoms, were compared between groups. RESULTS: sCAA-AD+ (n=31; mean age: 72 ± 6; 42%, 61% female) and sCAA-AD- (n=23; 70 ± 5; 42% female) participants did not differ with respect to global cognition or type of affected cognitive domain(s). The number or severity of neuropsychiatric symptoms also did not differ between sCAA-AD+ and sCAA-AD- participants. These results did not change after exclusion of patients without prior ICH. CONCLUSIONS: In participants with sCAA, a CSF biomarker profile associated with AD does not impact global cognition or specific cognitive domains, or the presence of neuropsychiatric symptoms.

Decreased microvascular claudin-5 levels in cerebral amyloid angiopathy associated with intracerebral haemorrhage.

Decreased microvascular levels of claudin-5 in the occipital and temporal lobe of patients with cerebral amyloid angiopathy are associated with intracerebral haemorrhage.

Proximity extension assay in cerebrospinal fluid identifies neurofilament light chain as biomarker of neurodegeneration in sporadic cerebral amyloid angiopathy.

BACKGROUND: Sporadic cerebral amyloid angiopathy (sCAA) is a disease characterised by the progressive deposition of the amyloid beta (Aß) in the cerebral vasculature, capable of causing a variety of symptoms, from (mild) cognitive impairment, to micro- and major haemorrhagic lesions. Modern diagnosis of sCAA relies on radiological detection of late-stage hallmarks of disease, complicating early diagnosis and potential interventions in disease progression. Our goal in this study was to identify and validate novel biomarkers for sCAA. METHODS: We performed a proximity extension assay (PEA) on cerebrospinal fluid (CSF) samples of sCAA/control participants (n = 34/51). Additionally, we attempted to validate the top candidate biomarker in CSF and serum samples (n = 38/26) in a largely overlapping validation cohort, through analysis with a targeted immunoassay. RESULTS: Thirteen proteins were differentially expressed through PEA, with top candidate NFL significantly increased in CSF of sCAA patients (p < 0.0001). Validation analyses using immunoassays revealed increased CSF and serum NFL levels in sCAA patients (both p < 0.0001) with good discrimination between sCAA and controls (AUC: 0.85; AUC: 0.79 respectively). Additionally, the CSF: serum NFL ratio was significantly elevated in sCAA (p = 0.002). DISCUSSION: Large-scale targeted proteomics screening of CSF of sCAA patients and controls identified thirteen biomarker candidates for sCAA. Orthogonal validation of NFL identified NFL in CSF and serum as biomarker, capable of differentiating between sCAA patients and controls.

Divergent Associations of Slow-Wave Sleep versus Rapid Eye Movement Sleep with Plasma Amyloid-Beta.

OBJECTIVE: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood. METHODS: We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20-68 years. Nocturnal plasma concentrations of amyloid-beta-40, amyloid-beta-42, cortisol, and growth hormone were assessed every 20 minutes. Amyloid-beta fluctuations were modeled with sleep stages, (non)oscillatory power, and hormones as predictors while controlling for age and participant-specific random effects. RESULTS: Amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, and slow-wave (0.3-4Hz) oscillatory and high-band (30-48Hz) nonoscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40-100 minutes previously (all t values > |3|, p values < 0.003). Older participants showed higher amyloid-beta-40 levels. INTERPRETATION: Slow-wave oscillations are associated with higher plasma amyloid-beta levels, whereas REM sleep is related to decreased amyloid-beta plasma levels, possibly representing changes in central amyloid-beta production or clearance. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40 may indicate that peripheral clearance becomes less efficient with age. ANN NEUROL 2024;96:46-60.

Evaluation of 100 Dutch cases with 16p11.2 deletion and duplication syndromes; from clinical manifestations towards personalized treatment options.

The 16p11.2 deletion syndrome is a clinically heterogeneous disorder, characterized by developmental delay, intellectual disability, hyperphagia, obesity, macrocephaly and psychiatric problems. Cases with 16p11.2 duplication syndrome have similar neurodevelopmental problems, but typically show a partial 'mirror phenotype' with underweight and microcephaly. Various copy number variants (CNVs) of the chromosomal 16p11.2 region have been described. Most is known about the 'typical' 16p11.2 BP4-BP5 (29.6-30.2 Mb; ~600 kb) deletions and duplications, but there are also several published cohorts with more distal 16p11.2 BP2-BP3 CNVs (28.8-29.0 Mb; ~220 kb), who exhibit clinical overlap. We assessed 100 cases with various pathogenic 16p11.2 CNVs and compared their clinical characteristics to provide more clear genotype-phenotype correlations and raise awareness of the different 16p11.2 CNVs. Neurodevelopmental and weight issues were reported in the majority of cases. Cases with distal 16p11.2 BP2-BP3 deletion showed the most severe obesity phenotype (73.7% obesity, mean BMI SDS 3.2). In addition to the more well defined typical 16p11.2 BP4-BP5 and distal 16p11.2 BP2-BP3 CNVs, we describe the clinical features of five cases with other, overlapping, 16p11.2 CNVs in more detail. Interestingly, four cases had a second genetic diagnosis and 18 cases an additional gene variant of uncertain significance, that could potentially help explain the cases' phenotypes. In conclusion, we provide an overview of our Dutch cohort of cases with various pathogenic 16p11.2 CNVs and relevant second genetic findings, that can aid in adequately recognizing, diagnosing and counseling of individuals with 16p11.2 CNVs, and describe the personalized medicine for cases with these conditions.

Neuropsychiatric symptoms with focus on apathy and irritability in sporadic and hereditary cerebral amyloid angiopathy.

BACKGROUND: Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. METHODS: We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. RESULTS: We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.ß = 1.4[95%CI:0.6-2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1-2.9]; presymptomatic D-CAA:1.2[0.1-2.2], control median:0[IQR:0-3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.ß=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.ß=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. DISCUSSION: According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.

Basophil activation test in the food allergy clinic: its current use and future applications.

INTRODUCTION: The basophil activation test (BAT) has shown evidence of high sensitivity and high specificity to support the diagnosis of IgE-mediated allergy. It is a functional test that uses live cells analyzed by flow cytometry and thus needs to be performed within 24h of blood collection. BAT has shown to be reproducible and reliable when tested in a clinical diagnostic laboratory with standardized protocols and flow cytometry settings. AREAS COVERED: In this review, we summarize the evidence to support clinical use of BAT and the next steps required for clinical implementation for an improve clinical care for patients with suspected IgE-mediated food allergy. EXPERT OPINION: BAT has recently been included in Clinical Guidelines of Food Allergy Diagnosis and its implementation in clinical practice depends largely on availability. Proposed clinical applications of the BAT include: distinction between food allergy and asymptomatic IgE sensitization; determination of food allergic status to peanut, tree nuts and seeds in polysensitized children; evaluation of tolerance to baked egg and baked milk in egg and milk allergic children; identification of patients at high-risk of severe allergic reactions; monitoring for spontaneous resolution of food allergy; confirmation of eligibility for specific treatments of food allergy; prediction and monitoring of response to immunomodulatory treatments.

Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy.

BACKGROUND: Neurofilament light chain (NFL) is a biomarker for neuroaxonal damage and glial fibrillary acidic protein (GFAP) for reactive astrocytosis. Both processes occur in cerebral amyloid angiopathy (CAA), but studies investigating the potential of NFL and GFAP as markers for CAA are lacking. We aimed to investigate NFL and GFAP as biomarkers for neuroaxonal damage and astrocytosis in CAA. METHODS: For this cross-sectional study serum and cerebrospinal fluid (CSF) samples were collected between 2010 and 2020 from controls, (pre)symptomatic Dutch-type hereditary (D-CAA) mutation-carriers and participants with sporadic CAA (sCAA) from two prospective CAA studies at two University hospitals in the Netherlands. NFL and GFAP levels were measured with Simoa-assays. The association between NFL and GFAP levels and age, cognitive performance (MoCA), CAA-related MRI markers (CAA-CSVD-burden) and Aß40 and Aß42 levels in CSF were assessed with linear regression adjusted for confounders. The control group was divided in age < 55 and ≥55 years to match the specific groups. RESULTS: We included 187 participants: 28 presymptomatic D-CAA mutation-carriers (mean age 40 years), 29 symptomatic D-CAA participants (mean age 58 years), 59 sCAA participants (mean age 72 years), 33 controls < 55 years (mean age 42 years) and 38 controls ≥ 55 years (mean age 65 years). In presymptomatic D-CAA, only GFAP in CSF (7.7*103pg/mL vs. 4.4*103pg/mL in controls; P<.001) was increased compared to controls. In symptomatic D-CAA, both serum (NFL:26.2pg/mL vs. 12.5pg/mL; P=0.008, GFAP:130.8pg/mL vs. 123.4pg/mL; P=0.027) and CSF (NFL:16.8*102pg/mL vs. 7.8*102pg/mL; P=0.01 and GFAP:11.4*103pg/mL vs. 7.5*103pg/mL; P<.001) levels were higher than in controls and serum levels (NFL:26.2pg/mL vs. 6.7pg/mL; P=0.05 and GFAP:130.8pg/mL vs. 66.0pg/mL; P=0.004) were higher than in pre-symptomatic D-CAA. In sCAA, only NFL levels were increased compared to controls in both serum (25.6pg/mL vs. 12.5pg/mL; P=0.005) and CSF (20.0*102pg/mL vs 7.8*102pg/mL; P=0.008). All levels correlated with age. Serum NFL correlated with MoCA (P=0.008) and CAA-CSVD score (P<.001). NFL and GFAP in CSF correlated with Aß42 levels (P=0.01/0.02). CONCLUSIONS: GFAP level in CSF is an early biomarker for CAA and is increased years before symptom onset. NFL and GFAP levels in serum and CSF are biomarkers for advanced CAA.

DNA methylation episignature and comparative epigenomic profiling for Pitt-Hopkins syndrome caused by TCF4 variants.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by pathogenic variants in TCF4, leading to intellectual disability, specific morphological features, and autonomic nervous system dysfunction. Epigenetic dysregulation has been implicated in PTHS, prompting the investigation of a DNA methylation (DNAm) "episignature" specific to PTHS for diagnostic purposes and variant reclassification and functional insights into the molecular pathophysiology of this disorder. A cohort of 67 individuals with genetically confirmed PTHS and three individuals with intellectual disability and a variant of uncertain significance (VUS) in TCF4 were studied. The DNAm episignature was developed with an Infinium Methylation EPIC BeadChip array analysis using peripheral blood cells. Support vector machine (SVM) modeling and clustering methods were employed to generate a DNAm classifier for PTHS. Validation was extended to an additional cohort of 11 individuals with PTHS. The episignature was assessed in relation to other neurodevelopmental disorders and its specificity was examined. A specific DNAm episignature for PTHS was established. The classifier exhibited high sensitivity for TCF4 haploinsufficiency and missense variants in the basic-helix-loop-helix domain. Notably, seven individuals with TCF4 variants exhibited negative episignatures, suggesting complexities related to mosaicism, genetic factors, and environmental influences. The episignature displayed degrees of overlap with other related disorders and biological pathways. This study defines a DNAm episignature for TCF4-related PTHS, enabling improved diagnostic accuracy and VUS reclassification. The finding that some cases scored negatively underscores the potential for multiple or nested episignatures and emphasizes the need for continued investigation to enhance specificity and coverage across PTHS-related variants.

Aseptic Revision Total Hip Arthroplasty Through an Anterior Approach: Survivorship and Risk Factors for Re-Revision.

BACKGROUND: The utilization of anterior-based approaches for total hip arthroplasty (THA) is increasing. Literature on the outcomes of revision THA (rTHA) through an anterior approach, however, is sparse. This study reports the survivorship and risk factors for re-revision in patients undergoing aseptic rTHA through an anterior approach. METHODS: This was a single-institution, retrospective cohort analysis of patients who underwent aseptic rTHA through an anterior approach (direct anterior, anterior-based muscle sparing) from January 2017 to December 2021, regardless of the original surgical approach. Exclusion criteria were age <18 years, conversion THA, and septic revisions. Patient demographics, complications, and postoperative outcomes were collected. Kaplan-Meier curves were used to measure survivorship while Cox regression analyses were used to identify risk factors for re-revision of THA. RESULTS: We identified 251 total anterior rTHAs, of which 155 were aseptic anterior revisions. There were 111 patients (111 rTHAs; 63 anterior-based muscle sparing and 48 direct anterior) who met criteria and had a mean follow-up of 4.2 years (range, 2.1 to 6.9). There were a total of 54 (49%) anterior-based index approaches and 57 (51%) posterior index approaches. The most common indications for rTHA were femoral loosening (n = 25, 22.5%), followed by instability (n = 16, 14.4%) and wear or osteolysis (n = 16, 14.4%). At 2 years, the survivorship from reoperation and re-revision was 89% (95% confidence interval: 84 to 95) and 91% (95% confidence interval: 86 to 96), respectively. Reoperation occurred in 14 patients (12.6%) at a mean time of 7.8 months (range, 0.5 to 28.6). Re-revision occurred in 12 patients (10.8%) at a mean time of 7.3 months (range, 0.5 to 28.6). Instability was the most common reason for re-revision (4.5%). Neither index approach type, revision approach type, nor any patient-specific risk factors were identified as predictors of re-revision or reoperation in multivariable regression analysis. CONCLUSIONS: This study demonstrates an acceptable rate of re-revision when aseptic rTHA is performed through an anterior approach, with the most common reason for aseptic re-revision being instability.

Use of The Risk Assessment and Prediction Tool to Predict Same-day Discharge After Primary Hip and Knee Arthroplasty.

INTRODUCTION: The Risk Assessment and Prediction Tool (RAPT) is a preoperative screening tool developed to predict discharge disposition after total hip arthroplasty (THA) and total knee arthroplasty (TKA), but its predictive value for same-day discharge (SDD) has not been investigated. The aims of this study were (1) to assess RAPT's ability to predict SDD after primary THA and TKA and (2) to determine a cutoff RAPT score that may recognize patients appropriate for SDD. METHODS: Data were retrospectively collected from patients undergoing primary THA and TKA at a single tertiary care center between February 2020 and May 2021. A receiver operating characteristic curve was generated to choose a cutoff value to screen for SDD. Logistic regression analysis was done to identify factors including age, BMI, or RAPT score that may be associated with SDD. RESULTS: Three hundred sixty-one patients with preoperative RAPT scores were included in the analysis of whom 147 (42.6%) underwent SDD. A cutoff of ≥9 was identified for TKA and ≥11 for THA. RAPT had a predictive accuracy of only 66.7% for SDD, whereas the discharge plan documented in the preoperative note was 91.7% accurate. DISCUSSION: Although there is a positive association between RAPT and SDD, it is not a useful screening tool given its low predictive accuracy.

Optic Nerve Sheath MR Imaging Measurements in Patients with Orthostatic Headaches and Normal Findings on Conventional Imaging Predict the Presence of an Underlying CSF-Venous Fistula.

BACKGROUND AND PURPOSE: Spontaneous spinal CSF leaks typically cause orthostatic headache, but their detection may require specialized and invasive spinal imaging. We undertook a study to determine the value of simple optic nerve sheath MR imaging measurements in predicting the likelihood of finding a CSF-venous fistula, a type of leak that cannot be detected with routine spine MR imaging or CT myelography, among patients with orthostatic headache and normal conventional brain and spine imaging findings. MATERIALS AND METHODS: This cohort study included a consecutive group of patients with orthostatic headache and normal conventional brain and spine imaging findings who underwent digital subtraction myelography under general anesthesia to look for spinal CSF-venous fistulas. RESULTS: The study group consisted of 93 patients (71 women and 22 men; mean age, 47.5 years; range, 17-84 years). Digital subtraction myelography demonstrated a CSF-venous fistula in 15 patients. The mean age of these 8 women and 7 men was 56 years (range, 23-83 years). The mean optic nerve sheath diameter was 4.0 mm, and the mean perioptic subarachnoid space was 0.5 mm in patients with a CSF-venous fistula compared with 4.9 and 1.2 mm, respectively, in patients without a fistula (P < .001). Optimal cutoff values were found at 4.4 mm for optic nerve sheath diameter and 1.0 mm for the perioptic subarachnoid space. Fistulas were detected in about 50% of patients with optic nerve sheath diameter or perioptic subarachnoid space measurements below these cutoff values compared with <2% of patients with optic nerve sheath diameter or perioptic subarachnoid space measurements above these cutoff values. Following surgical ligation of the fistula, optic nerve sheath diameter increased from 4.0 to 5.3 mm and the perioptic subarachnoid space increased from 0.5 to 1.2 mm (P < .001). CONCLUSIONS: Concerns about a spinal CSF leak should not be dismissed in patients with orthostatic headache when conventional imaging findings are normal, and simple optic nerve sheath MR imaging measurements can help decide if more imaging needs to be performed in this patient population.

Metabolite transport across central nervous system barriers.

Metabolomic analysis of cerebrospinal fluid (CSF) is used to improve diagnostics and pathophysiological understanding of neurological diseases. Alterations in CSF metabolite levels can partly be attributed to changes in brain metabolism, but relevant transport processes influencing CSF metabolite concentrations should be considered. The entry of molecules including metabolites into the central nervous system (CNS), is tightly controlled by the blood-brain, blood-CSF, and blood-spinal cord barriers, where aquaporins and membrane-bound carrier proteins regulate influx and efflux via passive and active transport processes. This report therefore provides reference for future CSF metabolomic work, by providing a detailed summary of the current knowledge on the location and function of the involved transporters and routing of metabolites from blood to CSF and from CSF to blood.