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INTRODUCTION: The established cerebrospinal fluid (CSF) phosphorylated tau181 (p‐tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age‐related tauopathy (PART) found in Creutzfeldt–Jakob disease (CJD) at autopsy. METHODS: We investigated CSF N‐terminal p‐tau181, p‐tau217, and p‐tau231 with in‐house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post‐mortem examination performed in patients with CJD 1.3 (0.3–14.3) months after CSF collection revealed no co‐pathology in 10, concomitant AD in 8, PART in 8, and other co‐pathologies in 3 patients. RESULTS: N‐terminal p‐tau was increased in CJD versus SCD (p < 0.0001) and correlated with total tau (t‐tau) in the presence of AD and PART co‐pathology (rho = 0.758–0.952, p ≤ 001). Concentrations in CJD+AD were indistinguishable from AD dementia, with the largest fold‐change in p‐tau217 (11.6), followed by p‐tau231 and p‐tau181 (3.2–4.5). DISCUSSION: Variable fold‐changes and correlation with t‐tau suggest that p‐tau closely associates with neurodegeneration and concomitant AD in CJD. Highlights: N‐terminal phosphorylated tau (p‐tau) biomarkers are increased in Creutzfeldt–Jakob disease (CJD) with and without concomitant AD.P‐tau217, p‐tau231, and p‐tau181 correlate with total tau (t‐tau) and increase in the presence of amyloid beta (Aβ) co‐pathology.N‐terminal p‐tau181 and p‐tau231 in Aβ‐negative CJD show variation among PRNP genotypes.Compared to mid‐region–targeting p‐tau181, cerebrospinal fluid (CSF) N‐terminal p‐tau has greater potential to reflect post‐mortem neuropathology in the CJD brain. [ABSTRACT FROM AUTHOR]

• Limited studies address the prognostic value of OCB counts in MS. • Higher OCB counts are associated with more upper cervical and T2 lesions in MS. • No significant association found between OCB count and EDSS or ARR. • Elevated IgG index and OCB positivity correlate with increased disability and relapse rates. • Comprehensive CSF analysis is crucial for effective MS management. Cerebrospinal fluid (CSF) biomarkers provide critical insights into the pathophysiology and progression of multiple sclerosis (MS), as this study aimed to investigate the relationships between CSF oligoclonal band (OCB) counts and the clinical course and short-term prognosis of MS patients. A retrospective cohort analysis covering a five-year period was conducted at two MS centers. Data on demographics, clinical presentation, MRI findings, EDSS scores, annualized relapse rate (ARR) in the first two years, and CSF analyses were analyzed. Among 310 patients, the ages ranged from 19 to 73 years, with a mean age of 38 years. OCBs were detected in 86.5 % (n = 268) of the patients. Those with a greater number of OCB bands had significantly more upper cervical lesions and T2 lesions (p < 0.05). A weak positive correlation was found between OCB and the IgG index score. No significant relationship was observed between band count and the ARR or EDSS score. OCB-positive patients had higher IgG index scores and more upper cervical lesions (p < 0.05). Additionally, patients with elevated IgG index levels (>0.7) exhibited significantly greater EDSS scores and more T2 lesions (p < 0.05). This study highlights the importance of OCB counts as a significant marker for assessing disease activity and progression in MS patients. These findings emphasize the need for a comprehensive approach that integrates CSF analysis with clinical and radiological data to effectively manage MS and tailor treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that is clinically characterized by gait disturbance and balance impairment. Our purpose was to evaluate the effects of cerebrospinal fluid tap test procedures on gait, turning and balance parameters in the first 24 hours following the procedure in patients. Methods: Twenty-eight patients with a median age of 78 years participated in the study. All patients underwent assessment of gait characteristics, turning and balance before and after a tap test. Gait characteristics and turning were measured using the G-walk sensor system. Balance-related issues were assessed using three standardized tests in the Biodex Balance System: postural stability and fall risk tests, and the modified clinical test of sensory integration and balance. Results: The patients' mean walking speed increased after the tap test (p < 0.05), but left stride length, right stride length, and cadence did not show statistically significant improvement (p > 0.05). In the balance assessment, significant differences between pre- and post-scores were found on all tests (p < 0.01), except for the eyes-closed firm test (p > 0.05). Regression analyses revealed that baseline walking speed (p < 0.05) was significantly associated with positive tap test response. Conclusion: The cerebrospinal fluid tap test procedure has positive effects onwalking and turning activities, balance, and the risk of falling in older patients with iNPH in the first 24 hours following the procedure. Slow walking speed may predict positive tap test response. For patients unsuitable for shunt surgery, a tap testmay be an effectivemethod to reduce the risk of falls and improve factors thatmay cause falls. [ABSTRACT FROM AUTHOR]

Objectives Viruses are the most common infectious causes of aseptic meningitis (AM). After the COVID-19 pandemic, AM following the COVID-19 disease and its different vaccines were reported. This study compares some characteristics of patients with AM before and after the COVID-19 pandemic. Materials & Methods This retrospective cross-sectional study analyzed patients' demographic and laboratory data (one month to 14 years old) with AM from March 2018 to March 2022. The first period involves two years before the COVID-19 outbreak (March 2018 to March 2020). The second period starts with the COVID-19 pandemic (from March 2020 until March 2022). Results A significant decrease was observed in the frequency of patients admitted with AM after the COVID-19 pandemic in the referral children's hospital in Qazvin. The incidence of AM in children older than five decreased significantly, and as a result, the average age of patients with this diagnosis decreased, too. A meaningful decline in the prevalence of AM in the summer and fall seasons has been observed. Conclusion After the COVID-19 outbreak, the incidence of AM in children significantly decreased. Implementing the hygienic recommendations for inhibiting COVID-19 virus transmission also protected children from the spread of other viruses. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early‐onset Alzheimer's disease (EOAD). METHODS: We examined single‐cell RNA‐sequencing (scRNA‐seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital polymerase chain reaction (ddPCR) data from CD4 T cells from participants with EOAD and clinically normal controls. RESULTS: We analyzed PBMCs from 16 individuals by scRNA‐seq and discovered increased interferon signaling‐associated gene (ISAG) expression and striking expansion of antiviral‐like ISAGhi T cells in EOAD. Isolating CD4 T cells from 19 individuals, including four cases analyzed by scRNA‐seq, we confirmed increased expression of ISAGhi marker genes. Publicly available cerebrospinal fluid leukocyte scRNA‐seq data from late‐onset mild cognitive impairment and AD also revealed increased expression of interferon‐response genes. DISCUSSION: Antiviral‐like ISAGhi T cells are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted. Highlights: Interferon‐responsive T cells expanded in early‐onset Alzheimer's disease (AD).Increased interferon‐associated gene expression present in early‐ and late‐onset AD.Peripheral immune changes in T and NK cells driven by females with early‐onset AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study delineated the interrelationships between subclinical alterations in the left heart, cerebrospinal fluid (CSF), Alzheimer's disease (AD) biomarkers, and cognition. METHODS: Multiple linear regressions were conducted in 1244 cognitively normal participants (mean age = 65.5; 43% female) who underwent echocardiography (left atrial [LA] and left ventricular [LV] morphologic or functional parameters) and CSF AD biomarkers measurements. Mediating effects of AD pathologies were examined. Differences in cardiac parameters across ATN categories were tested using analysis of variance (ANOVA) and logistic regressions. RESULTS: LA or LV enlargement (characterized by increased diameters and volumes) and LV hypertrophy (increased interventricular septal or posterior wall thickness and ventricular mass) were associated with higher CSF phosphorylated (p)‐tau and total (t)‐tau levels, and poorer cognition. Tau pathologies mediated the heart‐cognition relationships. Cardiac parameters were higher in stage 2 and suspected non‐Alzheimer's pathology groups than controls. DISCUSSION: These findings suggested close associations of subclinical cardiac changes with tau pathologies and cognition. Highlights: Various subclinical alterations in the left heart related to poorer cognition.Subclinical cardiac changes related to tau pathologies in cognitively normal adults.Tau pathologies mediated the heart‐cognition relationships.Subclinical cardiac changes related to the AD continuum, especially to stage 2.The accumulation of cardiac alterations magnified their damage to the brain. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has gained prominence recently. Clinical studies have explored tDCS as an adjunct to neurologic disease rehabilitation, with evidence suggesting its potential in modulating brain clearance mechanisms. The glymphatic system, a proposed brain waste clearance system, posits that cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange aids in efficient metabolic waste removal. While some studies have linked tDCS to astrocytic inositol trisphosphate (IP 3)/Ca2+ signaling, the impact of tDCS on CSF-ISF exchange dynamics remains unclear. tDCS influences the dynamics of CSF-ISF exchange through astrocytic IP 3 /Ca2+ signaling. In this study, we administered tDCS (0.1 mA for 10 min) to C57BL/6N mice anesthetized with ketamine-xylazine (KX). The anode was positioned on the cranial bone above the cortex, and the cathode was inserted into the neck. Following tDCS, we directly assessed brain fluid dynamics by injecting biotinylated dextran amine (BDA) as a CSF tracer into the cisterna magna (CM). The brain was then extracted after either 30 or 60 min and fixed. After 24 h, the sectioned brain slices were stained with Alexa 594-conjugated streptavidin (SA) to visualize BDA using immunohistochemistry. We conducted Electroencephalography (EEG) recordings and aquaporin 4 (AQP4)/CD31 immunostaining to investigate the underlying mechanisms of tDCS. Additionally, we monitored the efflux of Evans blue, injected into the cisterna magna, using cervical lymph node imaging. Some experiments were subsequently repeated with inositol trisphosphate receptor type 2 (IP 3 R2) knockout (KO) mice. Post-tDCS, we observed an increased CSF tracer influx, indicating a modulation of CSF-ISF exchange by tDCS. Additionally, tDCS appeared to enhance the brain's metabolic waste efflux. EEG recordings showed an increase in delta wave post-tDCS. But no significant change in AQP4 expression was detected 30 min post-tDCS. Besides, we found no alteration in CSF-ISF exchange and delta wave activity in IP 3 R2 KO mice after tDCS. Our findings suggest that tDCS augments the glymphatic system's influx and efflux. Through astrocytic IP 3 /Ca2+ signaling, tDCS was found to modify the delta wave, which correlates positively with brain clearance. This study underscores the potential of tDCS in modulating brain metabolic waste clearance. • tDCS increased the CSF-ISF exchange. • tDCS enhanced the efflux of the glymphatic system. • tDCS promoted delta wave power. • tDCS enhanced the clearance of brain metabolic waste by astrocytic IP 3 /Ca2+ signaling. [ABSTRACT FROM AUTHOR]

Purpose: We report a patient with recurrent optic disc pit (ODP) maculopathy after Valsalva's maneuver and discuss its pathophysiology. We also hypothesize the role of Valsalva's maneuver in its genesis. Method: Case report of one patient, male, 12 years old. Results: Serous retinal detachment may occur in association with the ODP, a developmental anomaly of the optic nerve head. Histopathologically, it consists of a dysplastic retina herniation into a pocket extending posteriorly through a defect in the lamina cribrosa into the subarachnoid space. These three different compartments--intraocular space, optic nerve head, and subarachnoid space--and the dynamic interactions among them should be understood as the key factors for the occurrence of ODP-related serous retinal detachment. Conclusion: Based on the possibility that serous retinal detachment secondary to the ODP could be related to the Valsalva's maneuver, we strongly recommend that patients with ODP be advised to avoid intense physical or work activities that may increase abdominal, thoracic, and cerebral pressure and to refrain from playing wind instruments to avoid pretreatment, per treatment, and post-treatment intercurrences. [ABSTRACT FROM AUTHOR]

Leptomeningeal metastasis (LM) is a lethal complication of malignant tumors, with an incidence rate of 3%-5% among patients with non-small cell lung cancer (NSCLC). LM poses significant challenges in diagnosis, has poor prognosis, limited treatment options, and lacks standardized criteria for evaluating therapeutic efficacy, making it a dif- ficult aspect of NSCLC management. Circulating tumor DNA (ctDNA), shed from tumor cells and carrying cancer-related information, holds significant value in precision oncology. Cerebrospinal fluid (CSF), present in the subarachnoid space of the brain, the spinal cord, and the central canal, and in direct contact with meningeal tissues, serves as the fluid medium that best reflects the genetic characteristics of LM. In recent years, CSF ctDNA has become a focal point due to its multi-omics features, playing a crucial role in the management of central nervous system (CNS) metastatic tumors. Its applications span the entire continuum of care, including aiding in diagnosis, assessing treatment response, predicting prognosis, and analyzing resistance mechanisms. This article provides a concise overview of CSF ctDNA detection techniques and their clinical applications in patients with NSCLC-LM. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Lewy body disease (LBD) is a common primary or co‐pathology in neurodegenerative syndromes. An alpha‐synuclein seed amplification assay (αSyn‐SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala‐predominant cases, is not well understood. METHODS: Antemortem CSF from neuropathology‐confirmed LBD cases was tested with αSyn‐SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined. RESULTS: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala‐predominant (6/14, 42.8%) and brainstem‐predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn‐SAA‐positive cases (6/7, 85.7%) than negative (2/13, 15.4%). DISCUSSION: In this behavioral neurology cohort, αSyn‐SAA had excellent diagnostic performance for cortical LBD. In amygdala‐ and brainstem‐predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn‐SAA detects early LBD progression in these cohorts. Highlights: A cerebrospinal fluid alpha‐synuclein assay detects cortical LBD with high sensitivity/specificity.Positivity in prodromal stages of LBD was associated with early cortical spread.The assay provides precision diagnosis of LBD that could support clinical trials.The assay can also identify LBD co‐pathology, which may impact treatment responses. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear. METHODS: The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC‐FID. The MCI subjects were followed up for 58 ± 12.5 months. RESULTS: In controls, CSF has a more neuroprotective LFA than plasma. In CSF, a higher content of docosahexaenoic acid was associated with a reduced risk of MCI‐to‐AD progression. In plasma, higher oleic acid content was associated with lower risk of AD, MCI, and MCI‐to‐AD progression, whereas higher levels of vaccenic acid and docosahexaenoic acid were associated with greater risk of AD and MCI, and higher rate of MCI‐to‐AD progression, respectively. DISCUSSION: The circulating LFA is involved in the pathogenesis and progression of AD. Highlights: The lipidome fatty acid profile in CSF and plasma was markedly different.Higher levels of vaccenic acid and lower levels of oleic acid in plasma were associated with greater risk of Alzheimer's disease.In plasma, higher levels of oleic acid were associated with a reduced risk of MCI‐to‐AD progression.Higher levels of docosahexaenoic acid in CSF were associated with a lower risk of MCI‐to‐AD progression.Higher levels of docosahexaenoic acid in plasma were associated with a greater rate of MCI‐to‐AD progression. [ABSTRACT FROM AUTHOR]

Rationale: Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder caused by persistent measles virus infection. SSPE predominantly affects children and adolescents. The symptoms usually develop 6-15 years after measles infection and ultimately leading to death in many cases. Patient concerns: Patient 1 presented with cognitive decline and myoclonus and the Patient 2 presented with diminution of vision with myoclonic jerks. Diagnosis: Based on the clinical features with a characteristic electroencephalogram pattern and the presence of a high titer of anti-measles IgG in serum and cerebrospinal fluid, these patients were diagnosed as SSPE. Interventions: Antiepileptics were started for controlling myoclonus along with supportive treatment. Outcomes: Both patients were discharged on antiepileptics and supportive care. Lessons: Whenever there are unusual clinical manifestations with unknown vaccination status, SSPE can be suspected and the cerebrospinal fluid should be examined for anti-measles antibodies. Our case study also highlights the importance of universal coverage of measles vaccination. To reduce the incidence of measles and associated deaths, it is important to maintain a high level of immunization coverage for the measles vaccine and to strengthen all the integral components of the national immunization program. [ABSTRACT FROM AUTHOR]

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Lewy body disease, a frequently observed co‐pathology in Alzheimer's disease (AD), can be identified antemortem in cerebrospinal fluid (CSF) by α‐synuclein seed amplification assay (αS‐SAA). The prevalence and clinical impact of CSF αS‐SAA positivity in AD are still unknown. METHODS: αS‐SAA was performed on CSF samples from 240 AD patients (preclinical, prodromal, and dementia stages), 85 controls, 84 patients with Parkinson's disease (PD), and 21 patients with PD with dementia or dementia with Lewy bodies. In AD patients, associations between αS‐SAA positivity and cognitive changes were also evaluated. RESULTS: In agreement with available neuropathological studies, αS‐SAA positivity was observed in 30% of AD patients (vs 9% in controls), and was associated with cognitive decline, visuospatial impairment, and behavioral disturbances. DISCUSSION: αS‐SAA positivity in AD patients reflects the prevalence observed in neuropathological series and is associated with a worse clinical outcome. These data confirm the validity of CSF αS‐SAA positivity as biomarker of synucleinopathy. [ABSTRACT FROM AUTHOR]

The pain-reducing effects of the exercise were exerted through different mechanisms. Knowing more clear mechanisms helps to find more approach that is therapeutic. The objective of the present study is the evaluation of cerebrospinal fluid (CSF) glutamate level alteration in neuropathic pain rats and whether physical activity could modulate it. In the present study 104 male Wistar rats weighing 180–220 g were randomly divided into 4 groups (Sham, Sham + Exe, Neuropathy, and Neuropathy + Exe) which in turn each group subdivided into 4 groups according to time points for behavioral testing and CSF sampling (Baseline, 2 weeks, 3 weeks, and 4 weeks). To induction of neuropathy (by chronic constriction injury,), after anesthetizing with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg), the animal's right sciatic nerve was exposed and was ligated using four movable catgut chromic suture 4/0. The exercise protocol included 25 min of daily swimming, 5 days a week for 4 weeks. Thermal hyperalgesia and mechanical tactile threshold were detected using the plantar test and Von Frey filaments, respectively. CSF glutamate level was determined using high-performance liquid chromatography. Findings indicated that mechanical and thermal thresholds significantly (p < 0.01, p < 0.05 respectively) decreased in the neuropathy group against that in sham groups. On the other hand, exercise significantly increased mechanical tactile threshold (p < 0.0012) and thermal threshold (p < 0.05) compared to the neuropathy group. Moreover, CSF glutamate level prominently (p < 0.01) was increased in the neuropathy group compared to the sham group, and swimming exercise significantly (p < 0.001) reduced it. The present findings provide new evidence showing that medium-intensity swimming exercise attenuates pain-like behaviors in neuropathic pain animals, which is possibly due to decreasing CSF glutamate level and its neurotransmission. [ABSTRACT FROM AUTHOR]

Limited updated literature exists about the prevalence and spectrum of malignancies involving cerebrospinal fluid (CSF). In this multi-institutional study, we review our experience with focus on first time malignancy diagnosis in CSF samples of adults. Institutional databases at 4 academic centers were queried retrospectively for CSFs over a 10-year period. The following data elements were collected: total # of CSFs, total # of CSFs with a malignant diagnosis; for each patient with a first time CSF diagnosis of malignancy: age, gender, diagnosis, prior history of malignancy, and ancillary studies. Twenty-four thousand one hundred forty-two CSFs were collected with a positive for malignancy rate of 2.3% (n = 551). Out of 347 (1.4%) adults with a first-time diagnosis of CSF malignancy 182 (52%) were female (age range: 19-89/mean: 57) and 165 (48%) were male (age range: 20-95/mean: 60). Hematolymphoid malignancies (48%, n = 168) were overall the most common neoplasm. In women, metastatic carcinomas (63%, n = 114) were the leading malignancy, of which the majority were breast primaries. In men, lymphomas/leukemias (64%, n = 106) were the leading malignancy, of which the majority were B-cell lymphomas. Ancillary studies aided the final diagnosis in 110 (32%) cases. For 286 (82%) cases, a prior history of malignancy was available to correlate CSF findings. A malignancy diagnosis in the CSF of adults is rare. The most common malignancies in females and males are metastatic breast carcinoma and hematolymphoid malignancies, respectively. Metastatic neoplasms account for the majority, with primary central nervous system neoplasms being quite uncommon. History of malignancy and ancillary tests can be helpful. [ABSTRACT FROM AUTHOR]

• Physical activity interventions could moderately reduce blood amyloid beta (Aβ), but the results were not statistically significant and should be interpreted with caution. • There were not enough studies in the literature to meta-analyze the effects of physical activity on the brain and cerebrospinal fluid (CSF) Aβ. • In observational studies, the association of physical activity with brain and blood Aβ was not significant. • Higher levels of physical activity were positively associated with Aβ in the CSF. One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is associated with decreased dementia risk, and one potential path could be through Aβ levels modulation. We aimed to explore the relationship between physical activity and Aβ in middle-aged and older adults. A systematic search of PubMed, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, and SPORTDiscus was performed from inception to April 28, 2022. Studies were eligible if they included physical activity and Aβ data in adults aged 45 years or older. Multi-level meta-analyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβ levels. In total, 37 articles were included (8 randomized controlled trials, 3 non-randomized controlled trials, 4 prospective longitudinal studies, and 22 cross-sectional studies). The overall effect size of physical activity interventions on changes in blood Aβ was medium (pooled standardized mean difference = –0.69, 95% confidence interval (95%CI): –1.41 to 0.03; I 2 = 74.6%). However, these results were not statistically significant, and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid (CSF) and brain Aβ. Data from observational studies were examined based on measurements of Aβ in the brain using positron emission tomography scans, CSF, and blood. Higher physical activity was positively associated with Aβ only in the CSF (Estimate r = 0.12; 95%CI: 0.05–0.18; I 2 = 38.00%). Physical activity might moderately reduce blood Aβ in middle-aged and older adults. However, results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies. In observational studies, higher levels of physical activity were positively associated with Aβ only in CSF. Therefore, further research is needed to understand the modulating role of physical activity in the brain, CSF, and blood Aβ, as well as its implication for cognitive health. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study aimed to investigate outcomes following open surgery for extensive skull base ORN. Open surgery through a personalized sequential approach was employed to deal with five cases of extensive skull base ORN. Two patients with mild cases underwent regional debridement and sequestrectomy, and three patients with severe cases underwent extensive resection with reconstruction using free anterolateral thigh (ALT) flap. Biological glues and vascularized flaps were used for obturation of the skull base bony defect to prevent postoperative cerebrospinal fluid (CSF) leakage. The infections were controlled by antibiotic administrations which strictly followed the principles of antimicrobial stewardship (AMS). As results, both regional debridement plus sequestrectomy and extensive resection achieved satisfied outcomes in all patients. No severe complications and delayed hospitalization occurred. During the follow-up period (8–19 months), all patients were alive, pain free, without crusting or purulent discharge, and no sequestration or CSF leakage occurred. In conclusion, a personalized sequential approach including open surgery, pedicled/vascularized free flap reconstruction and AMS was advocated for patients with extensive skull base ORN. [ABSTRACT FROM AUTHOR]

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age‐related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid‐related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA‐related inflammation (CAA‐ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid β (Aβ) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy. [ABSTRACT FROM AUTHOR]

Plasma amyloid beta (Aβ) and tau are emerging as accessible biomarkers for Alzheimer's disease (AD). However, many assays exist with variable test performances, highlighting the need for a comparative assessment to identify the most valid assays for future use in AD and to apply to other settings in which the same biomarkers may be useful, namely, cerebral amyloid angiopathy (CAA). CAA is a progressive cerebrovascular disease characterized by deposition of Aβ40 and Aβ42 in cortical and leptomeningeal vessels. Novel immunotherapies for AD can induce amyloid‐related imaging abnormalities resembling CAA‐related inflammation. Few studies have evaluated plasma biomarkers in CAA. Identifying a CAA signature could facilitate diagnosis, prognosis, and a safer selection of patients with AD for emerging immunotherapies. This review evaluates studies that compare the diagnostic test performance of plasma biomarker techniques in AD and cerebrovascular and plasma biomarker profiles of CAA; it also discusses novel hypotheses and future avenues for plasma biomarker research in CAA. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Does neuropsychiatric symptoms and depression symptoms, Alzheimer disease (AD) biomarkers (cerebrospinal fluid or Positron Emission Tomography imaging) increase the risk of cognitive impairment among cognitively normal older adults? • What is the main finding of this study? Neuropsychiatric symptoms, not depression symptoms, increase the risk of cognitive impairment independently of AD biomarkers. There were no statistically significant interactions between neuropsychiatric symptoms and AD biomarkers. • What is the meaning of the finding? Change in neuropsychiatric symptoms is a significant risk factor for incident cognitive impairment among healthy, community-residing older adults. To investigate the effect of neuropsychiatric symptoms and depression symptoms, respectively, and Alzheimer disease (AD) biomarkers (cerebrospinal fluid [CSF] or Positron Emission Tomography [PET] imaging) on the progression to incident cognitive impairment among cognitively normal older adults. Prospective, observation, longitudinal study. Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine. Older adults aged 65 and above who participated in AD longitudinal studies (n = 286). CSF and PET biomarkers, Clinical Dementia Rating (CDR), Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Participants had an average follow-up of eight years, and 31 progressed from CDR 0 to CDR >0. After adjusting for sex, age, and education in the Cox proportional hazards survival models, neuropsychiatric symptoms as a time-dependent covariate was statistically significant in the three CSF (Aβ 42 /Aβ 40 , t-Tau/Aβ 42 , p-Tau/Aβ 42) PET imaging models (HR = 1.33–1.50). The biomarkers were also significant as main effects (HR = 2.00–4.04). Change in depression symptoms was not significant in any models. The interactions between biomarkers and neuropsychiatric symptoms and depression were not statistically significant. Changes in neuropsychiatric symptoms increase the risk of progression to cognitive impairment among healthy, cognitively normal adults, independent of AD biomarkers. Routine assessment of neuropsychiatric symptoms could provide valuable clinical information about cognitive functioning and preclinical disease state. [ABSTRACT FROM AUTHOR]

This document provides an overview of post-dural puncture headache (PDPH), covering its historical perspective, anatomy and physiology of cerebrospinal fluid (CSF), pathophysiology, risk factors, diagnosis, and treatment options. PDPH is a common complication of dural puncture, characterized by a postural headache due to CSF leakage. The understanding of CSF and dural anatomy has evolved over time, leading to advancements in diagnosing and managing PDPH. Treatment options range from conservative measures to epidural blood patch, intrathecal catheter, and regional techniques like sphenopalatine ganglion block and greater occipital nerve block. Further research is needed to optimize treatment approaches and improve patient outcomes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The kynurenine pathway's (KP) malfunction is closely related to Alzheimer's disease (AD), for antagonistic kynurenic acid (KA) and agonistic quinolinic acid act on the N‐methyl‐D‐aspartate receptor, a possible therapeutic target in treating AD. METHODS: In our longitudinal case–control study, KP metabolites in the cerebrospinal fluid were analyzed in 311 patients with AD and 105 cognitively unimpaired controls. RESULTS: Patients with AD exhibited higher concentrations of KA (β = 0.18, P < 0.01) and picolinic acid (β = 0.20, P < 0.01) than the controls. KA was positively associated with tau pathology (β = 0.29, P < 0.01), and a higher concentration of KA was associated with the slower progression of dementia. DISCUSSION: The higher concentrations of neuroprotective metabolites KA and picolinic acid suggest that the activation of the KP's neuroprotective branch is an adaptive response in AD and may be a promising target for intervention and treatment. Highlights: Patients with Alzheimer's disease (AD) exhibited higher concentrations of kynurenic acid and picolinic acid than controls.Higher concentrations of kynurenic acid were associated with slower progression of AD.Potential neurotoxic kynurenines were not increased among patients with AD.Activation of the kynurenine pathway's neuroprotective branch may be an adaptive response in AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed. METHODS: We measured cerebrospinal fluid (CSF) and plasma concentrations of N‐terminal tau fragments (NTA‐tau), using a novel immunoassay (NTA) in the TRIAD cohort, consisting of 272 individuals assessed with amyloid beta (Aβ) positron emission tomography (PET), tau PET, magnetic resonance imaging (MRI) and cognitive assessments. RESULTS: CSF and plasma NTA‐tau concentrations were specifically increased in cognitively impaired Aβ‐positive groups. CSF and plasma NTA‐tau concentrations displayed stronger correlations with tau PET than with Aβ PET and MRI, both in global uptake and at the voxel level. Regression models demonstrated that both CSF and plasma NTA‐tau are preferentially associated with tau pathology. Moreover, plasma NTA‐tau was associated with longitudinal tau PET accumulation across the aging and Alzheimer's disease (AD) spectrum. DISCUSSION: NTA‐tau is a biomarker closely associated with in vivo tau deposition in the AD continuum and has potential as a tau tangle biomarker in clinical settings and trials. Highlights: An assay for detecting N‐terminal tau fragments (NTA‐tau) in plasma and CSF was evaluated.NTA‐tau is more closely associated with tau PET than amyloid PET or neurodegeneration.NTA‐tau can successfully track in vivo tau deposition across the AD continuum.Plasma NTA‐tau increased over time only in cognitively impaired amyloid‐β positive individuals. [ABSTRACT FROM AUTHOR]

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This retrospective study aimed to investigate the relationship between cerebrospinal fluid (CSF) antibody titers of N-methyl- d -aspartate receptor (NMDAR), and clinical characteristics in pediatric patients with anti-NMDAR encephalitis. The clinical and laboratory characteristics of hospitalized patients with anti-NMDAR encephalitis, stratified by antibody titers in CSF and disease severity, were retrospectively studied. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and prognosis of patients were recorded, and each observed indicator was statistically analyzed. A total of 103 pediatric anti-NMDAR encephalitis patients were enrolled in the study, including 41 males (39.8%) and 62 females (60.2%) with a mean age of 8.0 ± 4.0 years. The proportion of patients with cognitive dysfunction and the positive pathogen was higher in the high-titer group than in the low-titer group (p = 0.023, p = 0.042). Consciousness disturbance that occurred as an initial symptom or during the course in the severe group was higher than in the non-severe group (p = 0.002, p < 0.001). More patients in the high-titer group received plasma exchange (PE) than in the low-titer group (p = 0.022). The cure rate of patients was higher with PE (65.2%) than with Corticosteroids and (or) intravenous immunoglobulin (58.1%). Patients with symptoms of disturbance of consciousness may be severer. The severity in pediatric anti-NMDAR encephalitis patients was not correlated with anti-NMDAR antibody titers. Patients with high CSF antibody titers had a better prognosis after early PE therapy. [ABSTRACT FROM AUTHOR]

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients. [ABSTRACT FROM AUTHOR]

We report the case of a 76-year-old man who was diagnosed with advanced stage hepatocellular carcinoma and was treated with atezolizumab plus bevacizumab therapy. Two weeks after 1st dose, he presented with acute changes in consciousness followed by hypothermia. A cerebrospinal fluid test showed an elevated cell count, total protein, and albumin. Infectious, anatomical, endocrinal, and neoplastic etiologies were ruled out. Based on the findings, atezolizumab-induced encephalitis was suspected, and high dose steroid therapy was administered. The patient's conscious level and hypothermia recovered completely about 9 days after starting the steroids, and he recovered without any neurological sequelae. This case report reminds physicians that prompt administration of steroid treatment after early diagnosis of immune checkpoint inhibitor-related encephalitis is the key for patients to recover without apparent neurological sequelae. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a neurobehavioural disorder, characterized by abnormal affiliative and socio-emotional responses which are generally regulated by certain neuropeptides in the hypothalamus (an anatomic component of the ventral diencephalon (VD)). The use of volumetric MRI for studying VD volume change could provide a novel approach for identification of structural brain changes in ASD; this could assist in understanding the pathophysiology of ASD and would reflect on treatment strategies. The aim of the current work was to investigate the role of MRI volumetric analysis of the ventral diencephalon in young children diagnosed with autism spectrum disorder. Methods: Fifty children diagnosed with ASD underwent volumetric brain analysis, on a fully automated MRI brain volumetry system (volBrain), with voxel-based morphometry of various segmental structures of the brain including the VD, using vol2Brain 1.0 pipeline software analysis suite. Results: There were 48 out of 50 children who demonstrated abnormal VD volume which was found below the normal limits compared with reference standard normalized volume. All cases were normocephalic demonstrating normal intra-cranial cavity volumes. Forty out of fifty cases showed increased total volume of grey matter, and eighteen out of fifty cases showed increased total volume of white matter. Regarding the amygdala and hippocampus, there were only two cases (4.0%) which showed slightly increased relative volume of the total amygdala, and two other cases (4.0%) demonstrated increased relative volume of the total hippocampus. Comparison between the autistic patients and normal references revealed a significant difference regarding the VD volume and total volume of grey matter, whereas no significant differences were found regarding the white matter amygdala and hippocampus. Conclusions: Based on the consistent significant volume decrease in the ventral diencephalon in patients with childhood autism, this study concluded that volumetric MRI analysis could be useful for diagnosis of childhood spectrum disorder and could be utilized as a reliable screening method in the clinically vague cases. Further study with a larger sample size including more age groups is recommended for more validation of the results. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To examine the extent to which positron emission tomography (PET)‐, cerebrospinal fluid (CSF)‐, and plasma‐related amyloid‐β/tau/neurodegeneration (A/T/N) biomarkers are associated with Alzheimer's disease (AD) neuropathology at autopsy. METHODS: A total of 100 participants who respectively underwent antemortem biomarker measurements and postmortem neuropathology were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We examined the associations of PET‐, CSF‐, and plasma‐related A/T/N biomarkers in combinations or alone with AD neuropathological changes (ADNC). RESULTS: PET‐ and CSF‐related A/T/N biomarkers in combination showed high concordance with the ADNC stage and alone showed high accuracy in discriminating autopsy‐confirmed AD. However, the plasma‐related A/T/N biomarkers alone showed better discriminative performance only when combined with apolipoprotein E (APO)E ε4 genotype. DISCUSSION: This study supports that PET‐ and CSF‐related A/T/N profiles can be used to predict accurately the stages of AD neuropathology. For diagnostic settings, PET‐, CSF‐, and plasma‐related A/T/N biomarkers are all useful diagnostic tools to detect the presence of AD neuropathology. HIGHLIGHTS: PET‐ and CSF‐related A/T/N biomarkers in combination can accurately predict the specific stages of AD neuropathology.PET‐ and CSF‐related A/T/N biomarkers alone may serve as a precise diagnostic tool for detecting AD neuropathology at autopsy.Plasma‐related A/T/N biomarkers may need combined risk factors when used as a diagnostic tool.Aβ PET and CSF p‐tau181/Aβ42 were most consistent with Aβ pathology, while tau PET and CSF p‐tau181/Aβ42 were most consistent with tau pathology. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Secernin‐1 (SCRN1) is a neuronal protein that co‐localizes with neurofibrillary tangles in Alzheimer's disease (AD), but not with tau inclusions in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), or Pick's disease. METHODS: We measured SCRN1 concentration in cerebrospinal fluid (CSF) using a novel mass spectrometric parallel reaction monitoring method in three clinical cohorts comprising patients with neurochemically characterized AD (n = 25) and controls (n = 28), clinically diagnosed Parkinson's disease (PD; n = 38), multiple system atrophy (MSA; n = 31), PSP (n = 20), CBD (n = 8), healthy controls (n = 37), and neuropathology‐confirmed AD (n = 47). RESULTS: CSF SCRN1 was significantly increased in AD (P < 0.01, fold change = 1.4) compared to controls (receiver operating characteristic area under the curve = 0.78) but not in CBD, PSP, PD, or MSA. CSF SCRN1 positively correlated with CSF total tau (R = 0.78, P = 1.1 × 10−13), phosphorylated tau181 (R = 0.64, P = 3.2 × 10−8), and Braak stage and negatively correlated with Mini‐Mental State Examination score. DISCUSSION: CSF SCRN1 is a candidate biomarker of AD, reflecting tau pathology. HIGHLIGHTS: We developed a parallel reaction monitoring assay to measure secernin‐1 (SCRN1) in cerebrospinal fluid (CSF).CSF SCRN1 was increased in Alzheimer's disease compared to healthy controls.CSF SCRN1 remained unchanged in Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration compared to controls.CSF SCRN1 correlated strongly with CSF phosphorylated tau and total tau.CSF SCRN1 increased across Braak stages and negatively correlated with Mini‐Mental State Examination score. [ABSTRACT FROM AUTHOR]

Purpose Distinguishing intradural extramedullary (IDEM) spinal ependymoma from myxopapillary ependymoma is challenging due to the location of IDEM spinal ependymoma. This study aimed to investigate the utility of clinical and MR imaging features for differentiating between IDEM spinal and myxopapillary ependymomas. Materials and Methods We compared tumor size, longitudinal/axial location, enhancement degree/pattern, tumor margin, signal intensity (SI) of the tumor on T2-weighted images and T1-weighted image (T1WI), increased cerebrospinal fluid (CSF) SI caudal to the tumor on T1WI, and CSF dissemination of pathologically confirmed 12 IDEM spinal and 10 myxopapillary ependymomas. Furthermore, classification and regression tree (CART) was performed to identify the clinical and MR features for differentiating between IDEM spinal and myxopapillary ependymomas. Results Patients with IDEM spinal ependymomas were older than those with myxopapillary ependymomas (48 years vs. 29.5 years, p < 0.05). A high SI of the tumor on T1W1 was more frequently observed in IDEM spinal ependymomas than in myxopapillary ependymomas (p = 0.02). Conversely, myxopapillary ependymomas show CSF dissemination. Increased CSF SI caudal to the tumor on T1WI was observed more frequently in myxopapillary ependymomas than in IDEM spinal ependymomas (p < 0.05). Dissemination to the CSF space and increased CSF SI caudal to the tumor on T1WI were the most important variables in CART analysis. Conclusion Clinical and radiological variables may help differentiate between IDEM spinal and myxo-papillary ependymomas. [ABSTRACT FROM AUTHOR]

Aim: To explore associations of cerebrospinal fluid biomarkers of neurodegeneration and amyloidosis with caregiver burden, cognition and functionality in dementia with Lewy bodies (DLB) paired with late-onset Alzheimer's disease (AD) and healthy older people. Methods: Consecutive outpatients with DLB were matched with outpatients with AD according to sex, cognitive scores and dementia stage, and with cognitively healthy controls according to age and sex to investigate associations of cerebrospinal fluid amyloid-β (Aβ42,Aβ40,Aβ38), tau, phospho-tau Thr181, ubiquitin, α-synuclein and neurofilament light with caregiver burden, functionality, reverse digit span, a clock drawing test, Mini-Mental State Examination (MMSE) and Severe MMSE, adjusted for sex, age, education, dementia duration and APOE-ε4 alleles. Results: Overall, 27 patients with DLB (78.98 ± 9.0 years-old; eleven APOE-ε4 +) were paired with 27 patients with AD (81.50 ± 5.8 years-old; twelve APOE-ε4 +) and 27 controls (78.98 ± 8.7 years-old; four APOE-ε4 +); two-thirds were women. In AD, Aβ42/Aβ38 and Aβ42 were lower, while tau/Aβ42 and phospho-tau Thr181/Aβ42 were higher; α-synuclein/Aβ42 was lower in DLB and higher in AD. The following corrected associations remained significant: in DLB, instrumental functionality was inversely associated with tau/phospho-tau Thr181 and tau/Aβ42, and reverse digit span associated with α-synuclein; in AD, instrumental functionality was inversely associated with neurofilament light, clock drawing test scores inversely associated with phospho-tau Thr181/Aβ42 and α-synuclein/Aβ42, and Severe MMSE inversely associated with tau/Aβ42 and tau/phospho-tau Thr181. Conclusions: Cerebrospinal fluid phospho-tau Thr181 in DLB was similar to AD, but not Aβ42. In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Accumulating evidence suggests that α‐synuclein (αSyn) can modulate Alzheimer's disease (AD) pathology. The aim of this study was to evaluate the prevalence and clinical features associated with cerebrospinal fluid (CSF) αSyn detected by seed amplification assay (SAA) in AD. METHODS: Eighty AD patients with CSF AT(N) biomarker positivity (mean age 70.3 ± 7.3 years) and 28 non‐AD age‐matched controls were included. All subjects underwent standardized clinical assessment; CSF αSyn aggregates were detected by SAA. RESULTS: CSF was αSyn‐SAA positive (αSyn+) in 36/80 AD patients (45%) and in 2/28 controls (7.1%). AD αSyn+ and αSyn− patients were comparable for age, disease severity, comorbidity profile, and CSF core biomarkers. AD αSyn+ presented a higher prevalence of atypical phenotypes and symptoms. CONCLUSIONS: Our findings demonstrate that concomitant CSF αSyn pathology is present in a significant proportion of AD patients starting in the early stages and can affect clinical presentation. Longitudinal studies are warranted to evaluate the significance for the disease course. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in early and late clinical stages. Methods: We included 100 participants who had ante mortem biomarker measurements and underwent post mortem neuropathological examination. Based on ante mortem clinical diagnosis, participants were divided into non‐dementia and dementia, as early or late clinical stages. Results: Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aβ)42/phosphorylated tau (p‐tau)181 showed excellent performance in differentiating autopsy‐confirmed AD and predicting the risk of neuropathological changes in early and late clinical stages. However, CSF Aβ42 performed better in the early clinical stage, while CSF p‐tau181, CSF t‐tau, and plasma p‐tau181 performed better in the late clinical stage. Discussion: Our findings provide important clinical information that, if using PET, CSF, and plasma biomarkers to detect AD pathology, researchers must consider their differential performances at different clinical stages of AD. Highlights: Amyloid PET and CSF Aβ42/p‐tau181 were the most promising candidate biomarkers for predicting AD pathology.CSF Aβ42 can serve as a candidate predictive biomarker in the early clinical stage of AD.CSF p‐tau181, CSF t‐tau, and plasma p‐tau181 can serve as candidate predictive biomarkers in the late clinical stage of AD.Combining APOE ε4 genotypes can significantly improve the predictive accuracy of AD‐related biomarkers for AD pathology. [ABSTRACT FROM AUTHOR]

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post‐mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. Highlights: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's diseaseParadoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltratesIn Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance [ABSTRACT FROM AUTHOR]

Introduction: Immune dysfunction is important in aging and neurodegeneration; lacking clinically available tools limits research translation. We tested associations of cerebral spinal fluid (CSF) monocyte‐to‐lymphocyte ratio (MLR)—innate immune activation surrogate—with cognition in an aging and dementia cohort, hypothesizing that elevated MLR is associated with poorer executive functioning. Methods: CSF MLR was calculated in well‐characterized, genotyped participants enrolled in studies of aging and dementia at University of California, San Francisco Memory and Aging Center (n = 199, mean age 57.5 years, SD 11.9). Linear models tested associations with episodic memory and executive function (verbal fluency, speeded set‐shifting). Results: Aging was associated with higher CSF monocyte, lower lymphocyte counts, and higher MLRs (p < 0.001). MLR was associated with verbal fluency (p < 0.05) only. Discussion: Using clinical labs, we show an inverse association between CSF MLR and executive function in aging and dementia, supporting the utility of clinical labs in capturing associations between innate immune dysfunction and neurodegeneration. [ABSTRACT FROM AUTHOR]

Introduction: We assessed the use of cerebrospinal fluid (CSF) biomarkers as an alternative to positron emission tomography (PET) for brain amyloid beta (Aβ) pathology confirmation in the EMERGE and ENGAGE clinical trials. Methods: EMERGE and ENGAGE were randomized, placebo‐controlled, Phase 3 trials of aducanumab in participants with early Alzheimer's disease. Concordance between CSF biomarkers (Aβ42, Aβ40, phosphorylated tau 181, and total tau) and amyloid PET status (visual read) at screening was examined. Results: Robust concordance between CSF biomarkers and amyloid PET visual status was observed (for Aβ42/Aβ40, AUC: 0.90; 95% CI: 0.83‐0.97; p < 0.0001), confirming CSF biomarkers as a reliable alternative to amyloid PET in these studies. Compared with single CSF biomarkers, CSF biomarker ratios showed better agreement with amyloid PET visual reads, demonstrating high diagnostic accuracy. Discussion: These analyses add to the growing body of evidence supporting CSF biomarkers as reliable alternatives to amyloid PET imaging for brain Aβ pathology confirmation. Highlights: CSF biomarkers and amyloid PET concordance were assessed in Ph3 aducanumab trials.Robust concordance between CSF biomarkers and amyloid PET was observed.CSF biomarker ratios increased diagnostic accuracy over single CSF biomarkers.CSF Aβ42/Aβ40 demonstrated high concordance with amyloid PET.Results support CSF biomarker testing as a reliable alternative to amyloid PET. [ABSTRACT FROM AUTHOR]

• This is the first reported series of very delayed CSF leak following skull base surgery. • It is important to recognize delayed (greater than 1 year) CSF leak as it is very uncommon and failure to do so could result in bacterial meningitis. • The probable causes of very delayed CSF leak following skull base surgery are absorption of bone wax, faulty in Dural closure and closure without reinforcement with fat or muscle flap. • The diagnosis and management of very delayed CSF leak following skull base surgery as it may result in a life-threatening complication. Cerebrospinal fluid (CSF) leak is a potentially dangerous neurosurgical complication. Delayed CSF leak has already been described after trauma, radiation therapy and endonasal transsphenoidal surgery for Sella turcica pathologies. Still, very few reported cases describe delayed CSF leak after craniotomy for tumors. We present our experience with patients showing delayed CSF leak after skull base tumor resection. Data for all tumors resected from the skull base region from January 2004 to December 2018 was retrieved from the surgeon's prospective database and supplemented with a retrospective file review. Patients who presented CSF leak within the first 12 months after surgery and those with a history of trauma or radiation-based treatment to the skull base region were excluded from the study. Epidemiology, clinical presentation, previous surgical approach, pathology, interval between craniotomy and CSF leak and proposed treatment were analyzed. Overall, more than two thousand patients underwent surgery for resection of skull base tumors during the study period. Six patients (two male, four female; mean age 57.5 years, range 30–80) presented with delayed CSF leak, including five (83%) who presented with bacterial meningitis. After skull base tumor resection, CSF leak developed in a mean of 72 months (range 12–132). Three patients underwent retrosigmoid craniotomy, two for resection of cerebellopontine angle epidermoid cyst and one for resection of a petro tentorial meningioma; one had trans petrosal retrolabyrinthine craniotomy for resection of a petroclival epidermoid cyst; one had far lateral craniotomy for resection of a foramen magnum meningioma; and one had pterional craniotomy for resection of a cavernous sinus meningioma. All patients underwent surgical re-exploration and repair. CSF leak was managed with mastoid obliteration in five patients and skull base reconstruction with fat graft in one. Recognition of very delayed CSF leak as a potential complication after resection of skull base tumors may be useful tool in long-term patient management. In our experience, these patients usually present with bacterial meningitis. Surgical options should be considered as a definitive treatment. [ABSTRACT FROM AUTHOR]

An 11 yr old female French bulldog was presented for acute onset of seizures and a 2 wk history of disorientation. On physical examination, a nodular mass at the fourth mammary gland level was observed. Neurological evaluation showed obtundation and compulsive behavior. Brain MRI study did not reveal any abnormalities. Cerebrospinal fluid (CSF) collected from the cerebellomedullary cistern showed a marked increase of total nucleated cell count (400 cells/μL). Cytological evaluation identified the presence of a monomorphic round cell population characterized by large cell bodies, a single eccentrical located nucleus with high nuclear:cytoplasmatic ratio, and marked atypia with anisocytosis, anisokaryosis, and multiple nucleoli. Leptomeningeal carcinomatosis (LC) was suspected. The dog was euthanatized for worsening of clinical signs. Post-mortem examination identified an anaplastic mammary carcinoma in the nodular mammary mass. Infiltration by neoplastic cells exhibiting the same morphological features was detected along leptomeninges of the telencephalon and cerebellum associated with cortical and subcortical parenchymal micrometastases. To our knowledge, this is the first case of LC in a dog detected by CSF evaluation but without any MRI abnormalities. This finding emphasizes the usefulness of CSF cytology in patients with suspected LC even in the absence of any MRI identifiable lesions. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated the comparability of cerebrospinal fluid (CSF) cutoffs for Elecsys immunoassays for amyloid beta (Aβ)42/Aβ40 or Aβ42/phosphorylated tau (p‐tau)181 and the effects of measurement variability when predicting Alzheimer's disease (AD)‐related outcomes (i.e., Aβ‐positron emission tomography [PET] visual read and AD neuropathology). Methods: We studied 750 participants (BioFINDER study, Alzheimer's Disease Neuroimaging Initiative [ADNI], and University of California San Francisco [UCSF]). Youden's index was used to identify cutoffs and to calculate accuracy (Aβ‐PET visual read as outcome). Using longitudinal variability in Aβ‐negative controls, we identified a gray zone around cut‐points where the risk of an inconsistent predicted outcome was >5%. Results: For Aβ42/Aβ40, cutoffs across cohorts were <0.059 (BioFINDER), <0.057 (ADNI), and <0.058 (UCSF). For Aβ42/p‐tau181, cutoffs were <41.90 (BioFINDER), <39.20 (ADNI), and <46.02 (UCSF). Accuracy was ≈90% for both Aβ42/Aβ40 and Aβ42/p‐tau181 using these cutoffs. Using Aβ‐PET as an outcome, 8.7% of participants fell within a gray zone interval for Aβ42/Aβ40, compared to 4.5% for Aβ42/p‐tau181. Similar findings were observed using a measure of overall AD neuropathologic change (7.7% vs. 3.3%). In a subset with CSF and plasma Aβ42/40, the number of individuals within the gray zone was ≈1.5 to 3 times greater when using plasma Aβ42/40. Discussion: CSF Aβ42/p‐tau181 was more robust to the effects of measurement variability, suggesting that it may be the preferred Elecsys‐based measure in clinical practice and trials. [ABSTRACT FROM AUTHOR]

Introduction: We investigate the CNTN5 rs1461684 G variant and the contactin 5 protein in sporadic Alzheimer's disease (sAD). Methods: Contactin 5, sAD biomarkers, and synaptic markers were measured in the cerebrospinal fluid (CSF). Amyloid and tau deposition were assessed using positron emission tomography. Contactin 5 protein and mRNA levels were measured in brain tissue. Results: CSF contactin 5 increases progressively in cognitively unimpaired individuals and is decreased in mild cognitive impairment and sAD. CSF contactin 5 correlates with sAD biomarkers and with synaptic markers. The rs1461684 G variant associates with faster disease progression in cognitively unimpaired subjects. Cortical full‐length and isoform 3 CNTN5 mRNAs are decreased in the presence of the G allele and as a function of Consortium to Establish a Registry for Alzheimer's Disease stages. Discussion: The newly identified rs1461684 G variant associates with sAD risk, rate of disease progression, and gene expression. Contactin 5 protein and mRNA are affected particularly in the early stages of the disease [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most frequent malignancy in women and is curable in ~70-80% of patients with early-stage detection and without complication. Paraneoplastic neurologic syndrome of breast cancer is one such complication which is often hard to diagnose, severely debilitating, and also challenging to treat. Materials and Methods: A 57-year-old woman with no known co-morbidity presented with sudden onset altered sensorium. She was in status epilepticus when brought to emergency and progressed to super refractory status epilepticus in-spite of our efforts. MRI of the brain with contrast done revealed hyper intense signal in bilateral frontal, parietal, occipital, bilateral thalami, periaqueductal region and dorsal midbrain. Cerebrospinal fluid (CSF) study revealed only increased protein. The comprehensive infective panel of CSF was negative. The vasculitis marker, anti NMO and anti MOG antibody were absent. So, we suspected a possibility of autoimmune aetiology and started methylprednisolone along with intravenous immunoglobulin. Results: Her epileptic discharges settled in an electroencephalogram, and we weaned her off ventilation. We detected a right breast mass on clinical examination. The PET CT scan revealed metastasis in the liver, bones, right axillary lymph nodes, and bone marrow. Conclusion: Our patient, who had the first-time presentation, was diagnosed to have paraneoplastic encephalopathy in the background of breast cancer. The importance of proper clinical examination and whole-body PET CT scan, followed by a trial of immunomodulator therapy, is necessary in all patients with non-infective encephalitis. [ABSTRACT FROM AUTHOR]

La cytologie du liquide céphalorachidien (LCR) ou cérébrospinal (LCS) représente un premier temps diagnostique de pathologies du système nerveux central (SNC). Elle permet d'orienter les étiologies suivantes : pathologies neurodégénératives, infectieuses, inflammatoires et tumorales. Elle reste le gold standard pour le diagnostic de dissémination leptoméningée de cellules tumorales. Moins invasive, de diagnostic rapide avec la possibilité de mise en place thérapeutique, son intérêt clinique est important. Son interprétation est à confronter aux autres données biologiques. Cytology of cerebrospinal fluid (CSF) is an important tool in the diagnosis of Central Nervous System pathologies. In this review, the major etiologies will be discussed, such as neurodegeneratives diseases, infectious and inflam- maroty diseases and tumoral diseases. Cytology remains the reference in the diagnosis of meningeal dissemination of tumor cells. Less invasive and allowing a fast diagnosis with rapid introduction of drugs, it has proven its relevance in routine practice. Its interpretation often requires comparison with clinical and other biological data. [ABSTRACT FROM AUTHOR]

Le dosage des IgG totales sur sérum est un examen courant de biologie médicale. Plus spécialisé, le dosage des sous- classes d'IgG sur sérum trouve sa place en deuxième ligne lors d'un bilan de déficit immunitaire ou pour la maladie associée aux IgG4 (MAG4). Dans le liquide céphalorachidien, leur évaluation permet la distinction entre un transsudat et une synthèse intrathécale. Concernant les sous-classes d'IgG dans le LCR, les laboratoires de biologie médicale commencent à recevoir des demandes, afin de mettre en évidence la présence d'IgG4. Dans le LCR elles seraient liées à la pachyméningite hypertrophique associée à la MAG4 mais, en l'absence d'étude clinique de grande envergure, leur dosage ne semble être pertinent que lorsque la biopsie tissulaire est impossible. La technique de dosage validée sur sérum est quantitative en milieu liquide (néphélémétrie/turbidimétrie). L'utilisation de ces techniques sur LCR doit être validée par chaque laboratoire, en l'absence de validation des kits sur LCR. Cette revue actualisée de la littérature revient sur les différentes indications des dosages d'IgG et des sous-classes d'IgG sur sérum, sur l'intérêt du dosage des sous- classes d'IgG sur le LCR et les techniques associées. Serum total IgG measurement is a common lab act in medical biology. More specialized, serum IgG subclasses measurement plays a key role in IgG4-Re- lated Disease but is also useful for second-line diagnosis in humoral immune deficiencies. In the cerebrospinal fluid (CSF), an index is used as an indicator of the relative amount of CSF IgG compared to serum. Any increase in the index reflects IgG production in the central nervous system. Regarding IgG subclasses in the CSF, medical laboratories are now getting demands, actually to find out if there is any IgG4 subclass. These IgG4 in CSF could be associated with IgG4-related hypertrophic pachymeningitis but without appropriate studies corroborating this, their measurement should be done only when tissue biopsy cannot be performed. Quantitative measurement on serum is validated with nephelometry and turbidimetry assays. Each laboratory has to validate the assays on CSF before giving results. In this mini review, we present the indications of total IgG and IgG subclasses on serum as well as the benefit of IgG subclasses in CSF and the techniques available in a medical laboratory. [ABSTRACT FROM AUTHOR]