Altered CSF Research Articles

CSF dynamics throughout the ventricular system using 4D flow MRI: associations to arterial pulsatility, ventricular volumes, and age

BackgroundCerebrospinal fluid (CSF) dynamics are increasingly studied in aging and neurological disorders. Models of CSF-mediated waste clearance suggest that altered CSF dynamics could play a role in the accumulation of toxic waste in the CNS, with implications for Alzheimer’s disease and other proteinopathies. Therefore, approaches that enable quantitative and volumetric assessment of CSF flow velocities could be of value. In this study we demonstrate the feasibility of 4D flow MRI for simultaneous assessment of CSF dynamics throughout the ventricular system, and evaluate associations to arterial pulsatility, ventricular volumes, and age.MethodsIn a cognitively unimpaired cohort (N = 43; age 41–83 years), cardiac-resolved 4D flow MRI CSF velocities were obtained in the lateral ventricles (LV), foramens of Monro, third and fourth ventricles (V3 and V4), the cerebral aqueduct (CA) and the spinal canal (SC), using a velocity encoding (venc) of 5 cm/s. Cerebral blood flow pulsatility was also assessed with 4D flow (venc = 80 cm/s), and CSF volumes were obtained from T1- and T2-weighted MRI. Multiple linear regression was used to assess effects of age, ventricular volumes, and arterial pulsatility on CSF velocities.ResultsCardiac-driven CSF dynamics were observed in all CSF spaces, with region-averaged velocity range and root-mean-square (RMS) velocity encompassing from very low in the LVs (RMS 0.25 ± 0.08; range 0.85 ± 0.28 mm/s) to relatively high in the CA (RMS 6.29 ± 2.87; range 18.6 ± 15.2 mm/s). In the regression models, CSF velocity was significantly related to age in 5/6 regions, to CSF space volume in 2/3 regions, and to arterial pulsatility in 3/6 regions. Group-averaged waveforms indicated distinct CSF flow propagation delays throughout CSF spaces, particularly between the SC and LVs.ConclusionsOur findings show that 4D flow MRI enables assessment of CSF dynamics throughout the ventricular system, and captures independent effects of age, CSF space morphology, and arterial pulsatility on CSF motion.

Prospective Analysis of Acute Encephalitis Syndrome: Clinical Characteristics and Patient Outcomes in a Tertiary Care Pediatric Setting

Background: One of the most frequent neurological emergencies in pediatrics, central nervous system infections cause a considerable amount of death and morbidity. Especially in newborns, the symptoms are frequently modest, therefore a strong index of suspicion is needed to make the diagnosis. Inadequate or delayed treatment may result in fatalities or other severe consequences.  Objective: To ascertain the frequency, clinical characteristics, and etiological makeup of kids hospitalized in tertiary PICU due to acute encephalitis syndrome. Results of kids referred to tertiary PICUs with acute encephalitis symptoms.  Study Design: Hospital based prospective study.  Participants: Children with AES from one month up to 18 years of age admitted in PICU of hospitals.  Intervention: Thorough clinical assessments were completed, and blood samples will be sent for various baseline biochemical analyses. In every instance, samples of blood and urine were sent for sensitivity and culture while adhering to strict aseptic protocol. In every incidence of fever with altered sensorium, neuroimaging and CSF analysis will be carried out.The history, clinical examination, and pertinent laboratory investigations are used to determine the etiology of AES.  Results: Out of the one hundred cases that were examined, five had J.E., thirty had rickettsia, twenty had dengue, one had varicella, twelve had COVID-19, five had measles, four were pyogenic, one had tuberculosis, twelve had ADEM, and nine were undiagnosed. A total of 45 patients were lost to follow-up throughout the follow-up period. Of the patients, 16 had hearing loss, 10 had speech loss, 15 had extra pyramidal abnormality, 21 had behavioral abnormality, and 21 had cranial nerve impairments.  Conclusion: AES is a persistent public health issue that requires immediate attention, as well as cooperation and support from other sectors. Strengthening primary health care is urgently needed to provide access to both routine and emergency care, both of which are essential for better results.

Curious Case of Altered CSF Dynamics.

Curious Case of Altered CSF Dynamics.

The clinical characteristics and therapeutic outcomes of adult patients with community-acquired spontaneous bacterial meningitis with a fulminant clinical course in Taiwan

PurposeTo examine the clinical characteristics of adult patients with community-acquired spontaneous bacterial meningitis (CASBM) with a fulminant clinical course.Materials and methodsThe clinical features and therapeutic outcomes of 127 adult CASBM patients were analyzed. The patients were divided into two groups as those with and without a fulminant clinical course. Fulminant clinical course was defined as meningitis presenting initially with marked consciousness disturbance (Glasgow Coma Scale score < 8) or a rapid deterioration in consciousness level within 48 h of hospitalization.ResultsAmong the 127 enrolled patients, 69 had a fulminant clinical course (47 men and 22 women) and 58 did not. The patients with a fulminant clinical course had a significantly higher incidence of end-stage renal disease (ESRD), severe clinical manifestations and higher mortality rate, and the survivors had significantly worse therapeutic outcomes. Klebsiella (K.) pneumoniae (50 strains) was the most important pathogen for the development of a fulminant clinical course, and all strains were susceptible to ceftriaxone and ceftazidime. With treatment, 50.7% (35/69) of the patients with a fulminant clinical course died, and the presence of K. pneumoniae infection was significant prognostic factor.ConclusionsThe presence of ESRD, initial presentation of altered consciousness, septic shock, seizures and CSF total protein level and K. pneumoniae infection were significantly associated with a fulminant clinical course of adult CASBM, and patients with this specific infectious syndrome had high mortality and morbidity rates. The presence of K. pneumoniae infection is a significant prognostic factor.

Impaired glucose utilization in the brain of patients with delirium following hip fracture.

Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and β-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, β-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.

655 Survival and Quality of Life Following CSF Diversion in Adult Patients with Leptomeningeal Metastases-Associated Hydrocephalus - a Systematic Review &amp; Meta-Analysis

Abstract Aim Leptomeningeal Metastases (LM) is associated with altered CSF flow dynamics (50-70%), and 1-5% of patients will develop communicating hydrocephalus, adversely impacting quality of life (QoL), functional status, and overall survival (OS). There is equipoise for CSF diversion in LM-associated hydrocephalus (LM-H). This systematic review and meta-analysis aims to assess the effect of CSF diversion on OS and QoL in this context. Method This systematic review was conducted in accordance with PRISMA guidelines. Pubmed/MEDLINE, EMBASE, Web of Science, and Scopus were searched for articles evaluating the role of CSF diversion in adult patients with systemic cancer LM-H. A meta-analysis was conducted using random effects models, mean differences, and 95% confidence intervals (CI). Bias was assessed using the ROBINS-I tool. Results Ten eligible studies with a total of 494 patients were included. Two studies reported multivariate hazard ratios for median OS, suggesting no significant effect of shunting on OS (pooled HR = 0.42; p = 0.27; 95% CI 0.09-1.94). A pre-operative and post-operative Karnofsky Performance Status (KPS) mean difference of 17.6 points (CI 10.44-24.68; p&amp;lt;0.0001) was calculated from 4 studies. Across all studies, a symptomatic improvement rate of 67-100% was observed, with high rates of improvement of headaches and nausea and lower rates for cranial nerve palsies. Complication rates across nine studies ranged from 0-21.1%. Conclusions The present findings prompt the generation of a standardised decision-making tool, a critical analysis of individual patient risk-benefit ratios, and systematic measurements for QoL for these patients. Implementation of these will facilitate and optimise surgical management for LM-H patients.

Survival and quality of life after CSF diversion in adult patients with leptomeningeal metastasis-associated hydrocephalus: a systematic review and meta-analysis.

Leptomeningeal metastasis (LM) is associated with altered CSF flow dynamics in 50%-70% of patients. Approximately 1%-5% of patients develop symptomatic LM-associated hydrocephalus (LM-H), which adversely impacts quality of life (QOL), functional status, and overall survival (OS). There is equipoise for CSF diversion procedures in LM-H. This systematic review and meta-analysis aimed to assess the effect of CSF diversion on OS and QOL in this context. This systematic review was conducted according to the PRISMA guidelines. PubMed/Medline, Embase, Web of Science, and Scopus were searched for articles that evaluated the role of CSF diversion for LM-H due to systemic cancer in adult patients. A meta-analysis was conducted using random effects models, with mean differences and 95% CIs reported. Bias was assessed using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. Ten eligible studies with a total of 494 patients were included. Two studies reported multivariate HRs for median OS, suggesting no significant effect of shunting on OS (pooled HR 0.42, 95% CI 0.09-1.94, p = 0.27). A difference between preoperative and postoperative Karnofsky Performance Status of mean 17.6 points (95% CI 10.44-24.68, p < 0.0001) was calculated from 4 studies. Across all studies, a symptomatic improvement rate of 67%-100% was observed, with high rates of improvement for headaches and nausea and lower rates for cranial nerve palsies. Complication rates across 9 studies ranged from 0% to 21.1%. Based on the present findings, shunting does not improve OS but does relieve symptoms, suggesting that individuals who exhibit certain symptoms should be considered for CSF diversion. The present findings prompt the generation of a standardized decision-making tool and a critical analysis of the individual patient risk-benefit ratio. Implementation of these will optimize surgical management of LM-H patients.

Dynamic Fluoroscopic Myelography in the Evaluation of Spinal Dorsal Arachnoid Web

Dorsal arachnoid web is a challenging condition to diagnose on MR imaging. MR imaging flow studies have shown altered CSF flow dynamics near the web. We describe the findings of an arachnoid web with dynamic fluoroscopic myelography in a 77-year-old man. Dynamic myelography revealed functional CSF flow obstruction and focal dorsal thecal sac enlargement with a dynamic change in size at the T6 level.

Choroid plexus mis-splicing and altered cerebrospinal fluid composition in myotonic dystrophy type 1.

Myotonic dystrophy type 1 is a dominantly inherited multisystemic disease caused by CTG tandem repeat expansions in the DMPK 3' untranslated region. These expanded repeats are transcribed and produce toxic CUG RNAs that sequester and inhibit activities of the MBNL family of developmental RNA processing factors. Although myotonic dystrophy is classified as a muscular dystrophy, the brain is also severely affected by an unusual cohort of symptoms, including hypersomnia, executive dysfunction, as well as early onsets of tau/MAPT pathology and cerebral atrophy. To address the molecular and cellular events that lead to these pathological outcomes, we recently generated a mouse Dmpk CTG expansion knock-in model and identified choroid plexus epithelial cells as particularly affected by the expression of toxic CUG expansion RNAs. To determine if toxic CUG RNAs perturb choroid plexus functions, alternative splicing analysis was performed on lateral and hindbrain choroid plexi from Dmpk CTG knock-in mice. Choroid plexus transcriptome-wide changes were evaluated in Mbnl2 knockout mice, a developmental-onset model of myotonic dystrophy brain dysfunction. To determine if transcriptome changes also occurred in the human disease, we obtained post-mortem choroid plexus for RNA-seq from neurologically unaffected (two females, three males; ages 50-70 years) and myotonic dystrophy type 1 (one female, three males; ages 50-70 years) donors. To test that choroid plexus transcriptome alterations resulted in altered CSF composition, we obtained CSF via lumbar puncture from patients with myotonic dystrophy type 1 (five females, five males; ages 35-55 years) and non-myotonic dystrophy patients (three females, four males; ages 26-51 years), and western blot and osmolarity analyses were used to test CSF alterations predicted by choroid plexus transcriptome analysis. We determined that CUG RNA induced toxicity was more robust in the lateral choroid plexus of Dmpk CTG knock-in mice due to comparatively higher Dmpk and lower Mbnl RNA levels. Impaired transitions to adult splicing patterns during choroid plexus development were identified in Mbnl2 knockout mice, including mis-splicing previously found in Dmpk CTG knock-in mice. Whole transcriptome analysis of myotonic dystrophy type 1 choroid plexus revealed disease-associated RNA expression and mis-splicing events. Based on these RNA changes, predicted alterations in ion homeostasis, secretory output and CSF composition were confirmed by analysis of myotonic dystrophy type 1 CSF. Our results implicate choroid plexus spliceopathy and concomitant alterations in CSF homeostasis as an unappreciated contributor to myotonic dystrophy type 1 CNS pathogenesis.

Spinal cord motion assessed by phase-contrast MRI - An inter-center pooled data analysis

BackgroundPhase-contrast MRI of CSF and spinal cord dynamics has evolved among diseases caused by altered CSF volume (spontaneous intracranial hypotension, normal pressure hydrocephalus) and by altered CSF space (degenerative cervical myelopathy (DCM), Chiari malformation). While CSF seems to be an obvious target for possible diagnostic use, craniocaudal spinal cord motion analysis offers the benefit of fast and reliable assessments. It is driven by volume shifts between the intracranial and the intraspinal compartments (Monro-Kellie hypothesis). Despite promising initial reports, comparison of spinal cord motion data across different centers is challenged by reports of varying value, raising questions about the validity of the findings. ObjectiveTo systematically investigate inter-center differences between phase-contrast MRI data. MethodsAge- and gender matched, retrospective, pooled-data analysis across two centers: cardiac-gated, sagittal phase-contrast MRI of the cervical spinal cord (segments C2/C3 to C7/T1) including healthy participants and DCM patients; comparison and analysis of different MRI sequences and processing techniques (manual versus fully automated). ResultsA genuine craniocaudal spinal cord motion pattern and an increased focal spinal cord motion among DCM patients were depicted by both MRI sequences (p < 0.01). Higher time-resolution resolved steeper and larger peaks, causing inter-center differences (p < 0.01). Comparison of different processing methods showed a high level of rating reliability (ICC > 0.86 at segments C2/C3 to C6/C7). DiscussionCraniocaudal spinal cord motion is a genuine finding. Differences between values were attributed to time-resolution of the MRI sequences. Automated processing confers the benefit of unbiased and consistent analysis, while data did not reveal any superiority.

A chronic post dural puncture syndrome without low opening pressure or altered CSF dynamics

A chronic post dural puncture syndrome without low opening pressure or altered CSF dynamics

Compromised Cranio-Spinal Suspension in Chiari Malformation Type 1: A Potential Role as Secondary Pathophysiology.

In Chiari Malformation Type I (CM1), low-lying tonsils obstruct the cisterna magna at the foramen magnum, thereby compromising the essential juncture between the cranial and spinal compartments. The anatomical obstruction of the cisterna magna inhibits bi-directional CSF flow as well as CSF pulse pressure equilibration between the intracranial compartment and the intraspinal compartment in response to instances of increased intracranial pressure. Less understood, however, are the roles of the spinal cord suspension structures at the craniocervical junction which lend viscoelastic support to the spinal cord and tonsils, as well as maintain the anatomical integrity of the cisterna magna and the dura. These include extradural ligaments including the myodural bridges (MDBs), as well as intradural dentate ligaments and the arachnoid framework. We propose that when these elements are disrupted by the cisterna magna obstruction, tonsillar pathology, and altered CSF dynamics, there may arise a secondary pathophysiology of compromised and dysfunctional cranio-spinal suspension in CM1. We present intraoperative images and videos captured during surgical exposure of the craniocervical junction in CM1 to illustrate this proposal.

Determining Etiologic Diagnoses in Patients with Rapidly Progressive Dementia

AbstractBackgroundOverlap in the presenting clinical features and test results in patients with rapidly progressive dementia (RPD) confounds the etiologic diagnoses of RPD, contributing to diagnostic delays, missed treatment opportunities, and poorer outcomes. There is a need to improve diagnostic accuracy in patients with RPD, with particular emphasis on identifying patients with potentially treatment‐responsive causes of RPD early in the symptomatic course.MethodPatients with RPD were prospectively enrolled and evaluated in inpatient settings and outpatient subspecialty (memory) clinics at Washington University (Saint Louis, MO; 2016–2019) and Mayo Clinic (Jacksonville, FL; 2020–2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of widely accessible diagnostic testing and referencing established diagnostic criteria. Diagnostic disagreements were resolved via blinded review by a third specialist. Clinicopathologic correlation was evaluated using neuropathological and genetic data when available.Result160 patients with RPD were assessed, with average age‐at‐symptom onset 60.0±15.9 years; 50% were female. Diagnostic inter‐rater reliability (91% agreement; Cohen’s κ = 0.88, p&lt;0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic or genetic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%—i.e., frontotemporal dementia, Lewy body dementia, vascular cognitive impairment), Creutzfeldt‐Jakob disease (15%), and other causes (15%—e.g., neurosarcoid, metabolic disruptions, neoplastic disease). The average age of patients with potentially treatable causes (AE and selected “other” causes; 54.4±18.2) was younger than those with neurodegenerative dementing illnesses (67.3±9.5) or CJD (67.4±7.9; p&lt;0.001). Patients with potentially treatable causes were more likely to present with altered level of consciousness and seizures (p&lt;0.05). CSF pleocytosis (&gt;5 WBC/hpf) was more common in AE patients (p&lt;0.05).ConclusionEtiologic diagnoses can be reliably established in RPD patients using available clinical data. Treatment‐responsive causes of RPD are common warranting consideration, particularly in younger patients with altered consciousness, seizures, and CSF pleocytosis.

Tandem Mass Tag Proteomic and Untargeted Metabolomic Profiling Reveals Altered Serum and CSF Biochemicals In Iron Deficient Monkeys

Tandem Mass Tag Proteomic and Untargeted Metabolomic Profiling Reveals Altered Serum and CSF Biochemicals In Iron Deficient Monkeys

Cervical cerebrospinal fluid venous fistula with syringomyelia treated with suboccipital decompression: illustrative case.

BACKGROUNDCerebrospinal fluid (CSF) venous fistulas are a recently discovered and underdiagnosed cause of spontaneous spinal CSF leak, which may lead to spontaneous intracranial hypotension. Most cases occur in the thoracic spine, and only 2 cases were reported in the cervical spine. Treatments include the epidural blood patch, fibrin glue injection, and surgical ligation of the fistula.OBSERVATIONSThe authors report the treatment of a C6–7 CSF venous fistula, for which direct ligation was not feasible, with suboccipital decompression, leading to the complete resolution of the symptoms. Based on the clinical course and outcome in our patient, the authors summarize the previous theory and propose a hypothesis for the pathophysiology of headache and other symptoms in patients with CSF venous fistulas.LESSONSThe symptoms of CSF venous fistulas may be linked not only to intracranial hypotension but also to the altered CSF dynamics induced by tonsillar herniation. Suboccipital decompression should be considered as a potential treatment option, especially in patients with Valsalva-induced headache who show a poor response to surgical ligation, patients in whom surgical ligation is not feasible, and patients with foramen magnum obstruction. Further investigation of the pathophysiology of CSF venous fistulas is warranted and should be performed in the future.

Epidemiological, clinical and laboratory aspects of Angiostrongylus cantonensis infection: an integrative review.

This integrative literature review study analyzes the findings of the last 5 years of the parasite Angiostrongylus cantonensis. It is known that this nematode is found in the pulmonary arteries of rats, where it remains as a definitive host. From mice, the cycle spreads to animals, such as snails, which in contact with humans can trigger the disease. In humans, the parasite causes several neurological, abdominal manifestations and mainly meningitis. Based on the review of studies, its epidemiology shows worldwide distribution, although there are endemic cases for this parasite, such as asian countries. Laboratory findings generally showed altered CSF with turbidity, increased protein and eosinophilia, which generated meningeal signs in the patient, moreover MRI exams showed multiple alterations. Rare findings of the nematode in the eyeball, lung and signs of peritoneal inflammation were reported, which requires further studies to understand the whole pathophysiology. Finally, conservative treatment based on anthelmintics and anti-inflammatories brought good responses, although there are reports of deaths, which demonstrates the importance in the prevention and therapy of this disease.

Effects of 6 months of multicomponent exercise on DTI parameters of MCI in the AD continuum

AbstractBackgroundThe cognitive changes in Mild Cognitive Impairment (MCI) can be associated to the neurodegeneration of Alzheimer´s pathology, such as white matter atrophy. Increasing evidence demonstrates that physical activity is an important modifiable factor not only for cardiovascular fitness, but also for brain health. Therefore, the aim of this study was to analyze possible effects of 6 months of multicomponent exercise (MEP) on structural connectivity of MCI in the AD continuum.Method19 MCI subjects were diagnosed using the core criteria of the NIA/AA for MCI and altered CSF amyloid. All of them underwent MRI on a 3.0T Philips Achieva scanner. They were divided into MEP group (3x/week for 6 months) and control group (CG, were stimulated to continue with their normal routine). Aerobic fitness was assessed by graded maximal exercise testing on a motor‐driven treadmill. For WM analysis, we used the Tract‐based‐spatial‐statistics (TBSS) method (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS) to compare the diffusion parameters maps (fractional anisotropy FA, medial diffusivity MD, radial diffusivity RD, axial diffusivity AxD) between times (p‐value&lt;0.05).ResultRepeated measures Anova indicated significant differences between groups and within groups (p=0.008 and p=0,011, respectively), while MEP showed higher values of VO2max (from 24.0 (4.3) to 27.3 (4.4) ml/kg/min‐1), CG reduced (21.0 (3.8) to 19.7 (2.3) ml/kg/min‐1) after 6 months. TBSS demonstrated an increase in FA and AxD values for MEP while FA and AxD values decreased in CG, in the following areas: corpus callosum, forceps major, corticospinal tract, inferior fronto‐occipital fasciculus, inferior and superior longitudinal fasciculus and cingulum. In the same areas mentioned above, MD and RD values decreased for MEP group and increased for CG after the intervention period.ConclusionWe found a positive influence of multicomponent exercise under supervision on aerobic fitness and in the DTI parameters of the participants. Six months of MEP seems to increase the white matter integrity of MCI due to AD.

CSF Aβ42 and Aβ40 and their relation to brain soluble and insoluble Aβ in the 5xFAD mouse model of Alzheimer's disease.

In patients with AD, CSF Aβ42 is reduced while Aβ40 remains unchanged. It has been suggested that altered CSF Aβ42 is due to aggregation of this peptide into insoluble plaques, resulting in less soluble Aβ42 available for secretion to the CSF. However, the relations between soluble and insoluble Aβ42 and Aβ40 in the brain and the concentrations of these Aβ peptides in CSF are not well studied. CSF and cortical brain tissue was collected from 2, 4, 6, and 12 months old male and female 5xFAD mice (n=45). CSF Aβ42 and Aβ40 concentrations were measured using Single molecule array (Simoa) technology. Brain sections were prepared and immunohistochemically (IHC) stained using antibodies specific for Aβ42 and Aβ40. The concentrations of Aβ42 and Aβ40 in soluble (extracted with TBS) and insoluble (extracted with formic acid) cortical brain fractions were determined by the Meso Scale Discovery technique. CSF Aβ42 was decreased over time whereas CSF Aβ40 remained unaltered (Fig 1). In the same mice, IHC revealed an age-related increased deposition of both Aβ42 and Aβ40 in insoluble plaques from 2 months of age (Fig 2). Moreover, measurements of Aβ42 and Aβ40 in soluble and insoluble cortical brain fractions showed increased concentrations of both peptides over time (Fig 3). CSF Aβ42 correlated inversely with cortical deposition of Aβ42 determined with IHC and the concentrations of Aβ42 in soluble and insoluble brain fractions. In contrast, no such correlations were found for Aβ40 (Fig 4). Although cortical levels of the two Aβ peptides were higher in females than in males, these sex differences were not reflected in CSF (Fig 5). Although significant depositions of both Aβ42 and Aβ40 were found in the brain, only Aβ42 was altered in CSF. Together with the finding that Aβ42 was increased, and not reduced, in soluble cortical brain fractions, this may suggest that mechanisms other than aggregation of Aβ42 into insoluble plaques contribute to decreased CSF concentrations of this Aβ peptide in 5xFAD mice. However, additional characterization of Aβ in the soluble brain fraction is needed to further understand its relation to the concentrations in CSF.

The Role of Altered CSF Dynamics in Remote Cerebellar Hemorrhage

Wu, Esther BA; Anderson, Matthew MD; Thompson, Bradford; Klinge, Petra M MD Author Information

Insights into the natural history of spontaneous intracranial hypotension from infusion testing.

To assess the pathophysiologic changes in patients with spontaneous intracranial hypotension (SIH) based on measures of CSF dynamics, and on the duration of symptoms, in a retrospective case-controlled study. We included consecutive patients investigated for SIH at our department from January 2012 to February 2018. CSF leak was considered confirmed if extrathecal contrast spillage was seen on imaging (CT or MRI) after intrathecal contrast application, or dural breach was detected by direct intraoperative visualization. We divided patients with a confirmed CSF leak into 3 groups depending on the symptom duration, as follows: ≤10, 11-52, and >52 weeks. Clinical characteristics and measures of CSF fluid dynamics obtained by computerized lumbar infusion testing were analyzed over time and compared with a reference population. Among the 137 patients included, 69 had a confirmed CSF leak. Whereas 93.1% with <10 weeks of symptoms displayed typical orthostatic headache, only 62.5% with >10 weeks of symptoms did (p = 0.004). Analysis of infusion tests revealed differences between groups with different symptom duration for CSF outflow resistance (p < 0.001), lumbar baseline pressure (p = 0.013), lumbar plateau pressure (p < 0.001), baseline pressure amplitude (p = 0.021), plateau pressure amplitude (p = 0.001), pressure-volume index (p = 0.001), elastance (p < 0.001), and CSF production rate (p = 0.001). Compared to the reference population, only patients with acute symptoms showed a significantly altered CSF dynamics profile. A CSF leak dramatically alters CSF dynamics acutely, but the pattern changes over time. There is an association between the clinical presentation and changes in CSF dynamics.