Cerebrospinal Fluid Space Research Articles

The predictive value of a novel site-specific MRI-based bone quality assessment, endplate bone quality (EBQ), for severe cage subsidence among patients undergoing standalone lateral lumbar interbody fusion

BACKGROUND CONTEXTStudies have shown that site-specific bone density measurements had more predictive value for complications than standard whole-region measurements. Recently, MRI-based assessments of vertebral bone quality (VBQ) were introduced. However, there have been few studies that investigate the association between site-specific MRI bone assessment and osteoporosis-related complications in patients undergoing lumbar interbody fusion. In this work, we created a novel site-specific MRI-based assessment of the endplate bone quality (EBQ) and assessed its predictive value for severe cage subsidence following standalone lateral lumbar interbody fusion (SA-LLIF). PURPOSETo investigate the predictive value of a novel MRI-based bone assessment for severe cage subsidence after SA-LLIF. STUDY DESIGN/SETTINGRetrospective cohort study. PATIENT SAMPLEPatients who underwent SA-LLIF from 2008 to 2019 at a single, academic institution with available preoperative lumbar CT and T1-weighted MRIs. OUTCOME MEASURESAssociation between EBQ and severe subsidence after SA-LLIF. METHODSWe retrospectively reviewed the records of SA-LLIF patients treated between 2008 and 2019. EBQ was measured using preoperative non-contrast T1-weighted MRIs of the lumbar spine. EBQ was defined as the average value of signal intensity of both endplates divided by that of the cerebrospinal fluid space at the level of L3. Bivariate and multivariable analyses with generalized linear mixed models were performed and set binary severe subsidence as the outcome. RESULTSTwo hundred five levels in 89 patients were included. Fifty levels (24.4%) demonstrated severe subsidence. Bone mineral density measured by quantitative computed tomography was significantly lower in the subsidence group. Both VBQ and EBQ were significantly higher in the subsidence group. The EBQ plus Modic change (MC) model demonstrated that the effect of EBQ was independent of MC. In multivariate analyses adjusted with QCT-vBMD, EBQ showed a significant association with cage subsidence whereas VBQ only showed a marginal trend. The EBQ-based prediction model for severe subsidence showed better goodness of fit compared to the VBQ-based model. CONCLUSIONSHigh EBQ was an independent factor for severe cage subsidence after SA-LLIF and the EBQ-based model showed better goodness of fit compared to VBQ- or MC-based models. EBQ assessment before SA-LLIF may provide insight into a patient's risk for severe subsidence.

Improving the diagnosis of radiation necrosis after stereotactic radiosurgery to intracranial metastases with conventional MRI features: a case series

BackgroundThe distinction between true disease progression and radiation necrosis after stereotactic radiosurgery to intracranial metastases is a common, but challenging, clinical scenario. Improvements in systemic therapies are increasing the importance of this distinction. A variety of imaging techniques have been investigated, but the value of any individual technique is limited.Case presentationAssessment should extend beyond simply the appearances of the lesion at a given timepoint, but also consider local anatomy and lesion evolution. Firstly, enlargement of a metastasis is affected by local anatomical boundaries, such as the dural reflections or cerebrospinal fluid spaces. In contrast, the radiation dose administered with stereotactic radiosurgery does not respect these anatomical boundaries and is largely concentric around the treated lesion. Therefore, new, non-contiguous enhancement across such a boundary can be confidently attributed to radiation necrosis. Secondly, the dynamic nature of radiation necrosis may result in a change in lesion shape, with different portions of the lesion simultaneously enlarging and regressing. Regression of part of a lesion indicates radiation necrosis, even if the overall lesion enlarges. This case series describes these two features and provides illustrative clinical examples in which these features allowed a confident diagnosis of radiation necrosis.ConclusionsThe distinction between true disease progression and radiation necrosis should extend beyond just the appearances of the lesion. More nuanced interpretation incorporating a relationship to anatomical boundaries and a change in shape can improve accurate diagnosis of radiation necrosis.

Long-Term Changes in Thecal Sac Compression and Decreased Cerebrospinal Fluid Space Following Paddle Lead Spinal Cord Stimulation at T9: A Long-Term Follow-Up via Three-Dimensional Myelographic Computed Tomography

ObjectivesTo investigate the long-term changes in thecal sac compression following T9 paddle lead spinal cord stimulation (SCS) using three-dimensional myelographic computed tomography (CT). Materials and MethodsSeventeen patients with five-column paddle lead SCS at T9 underwent three-dimensional myelographic CT scans preoperatively, immediately after surgery, and after an average of 11 months. The cross-sectional areas of thecal sac and spinal cord and the widths of anterior and posterior cerebrospinal fluid (CSF) spaces were repeatedly measured and compared. The contact angle of the lead with long-term pain relief was assessed. ResultsThe cross-sectional areas of thecal sac and spinal cord decreased significantly after lead placement (30.47 ± 9.21% and 4.71 ± 9.84%, respectively). Even after 11 months, a significant reduction was found with the preoperative values (17.97 ± 12.32% and 2.88 ± 7.09%). The widths of anterior and posterior CSF spaces decreased significantly after surgery (43.53 ± 13.17% and 57.13 ± 13.17%, respectively) and the severe decrease persisted long-term (29.13 ± 21.54% and 50.99 ± 16.07%). The average pain relief was 42.27 ± 17.50% with no correlation between the rate of reduction in cross-sectional areas of thecal sac and the widths of CSF spaces. ConclusionsSignificant early reduction and late partial restoration occurred in the thecal sac and spinal cord and the width of the anterior and posterior CSF spaces in the T9 5-column paddle lead SCS. Thecal sac compromise was expected to some extent after paddle lead implantation, but the degree is significant, and the cross-sectional area of the spinal cord as well as the thecal sac is affected. Fortunately, these anatomical changes did not cause any clinical problems except for intercostal root irritation. The shape and flat contours of the five-column paddle leads clearly affected the results.

Radiological hints for differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia

Differentiation cerebellar multiple systemic atrophy (MSA-C) from spinocerebellar ataxia (SCA) is important. The “hot cross bun” sign (HCBS) at pons and magnetic resonance spectroscopy (MRS) are helpful. However, the prevalence of HCBS and the alteration of cerebellar MRS parameters are evolving with disease progression. We hypothesized that since the HCBS and MRS are evolving with time, different parameters for differentiation of MSA-C and SCA are required at different disease stages. The aim of this study was to evaluate the HCBS and MRS changes in patients with MSA-C and SCA at different disease stages. A total of 398 patients with molecularly confirmed SCA (SCA1, 2, 3, 6, 17) and 286 patients diagnosed with probable MSA-C (without mutations in SCA1, 2, 3, 6, 17 genes), who had received brain magnetic resonance imaging (MRI) and MRS from January 2000 to January 2020, were recruited. Twenty-five patients were molecularly identified as having SCA1, 68 as SCA2, 253 as SCA3, 34 as SCA6, and 18 as SCA17. We compared their clinical parameters and neuroimaging features at different disease stages. The presence of HCBS was assessed using an axial T2 fast spin-echo or FLAIR sequence. Proton MRS was recorded with voxel of interest focusing on cerebellar hemispheres and cerebellar vermis and avoiding cerebrospinal fluid spaces space using a single-voxel stimulated echo acquisition mode sequence. We found that patients with MSA-C tend to have a higher prevalence of pontine HCBS, worse Scale for the Assessment and Rating of Ataxia scores, lower cerebellar N-acetyl aspartate (NAA)/creatinine (Cr), and choline (Cho)/Cr, compared to patients with SCA at corresponding disease stages. In MSA-C patients with a disease duration < 1 year and without pontine HCBS, a cerebellar NAA/Cr ≤ 0.79 is a good indicator of the possibility of MSA-C. By using the pontine HCBS and cerebellar MRS, discerning MSA-C from SCA became possible. This study provides cutoff values of MRS to serve as clues in differentiating MSA-C from SCAs.

Impedance Characteristics of Stimulation Contacts in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus and Its Relationship to Seizure Outcome in Patients With Refractory Epilepsy

BackgroundDeep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an emerging form of adjunctive therapy in focal refractory epilepsy. Unlike conventional DBS targets, the ANT is both encapsulated by white matter layers and located immediately adjacent to the cerebrospinal fluid (CSF) space. Owing to the location of the ANT, implantation has most commonly been performed using a transventricular trajectory. Previous studies suggest different electrical conductivity between gray matter, white matter, and CSF. ObjectivesIn this study, we asked whether therapeutic impedance values from a fully implanted DBS device could be used to deduce the actual location of the active contact to optimize the stimulation site. Secondly, we tested whether impedance values correlate with patient outcomes. Materials and MethodsA total of 16 patients with ANT-DBS for refractory epilepsy were evaluated in this prospective study. Therapeutic impedance values were recorded on regular outpatient clinic visits. Contact locations were analyzed using delayed contrast-enhanced postoperative computed tomography–3T magnetic resonance imaging short tau inversion recovery fusion images previously shown to demonstrate anatomical details around the ANT. ResultsTransventricularly implanted contacts immediately below the CSF surface showed overall lower and slightly decreasing impedances over time compared with higher and more stable impedances in contacts with deeper parenchymal location. Impedance values in transventricularly implanted contacts in the ANT were significantly lower than those in transventricularly implanted contacts outside the ANT or extraventricularly implanted contacts that were typically at the posterior/inferior/lateral border of the ANT. Increasing contact distance from the CSF surface was associated with a linear increase in therapeutic impedance. We also found that therapeutic impedance values were significantly lower in contacts with favorable therapy response than in nonresponding contacts. Finally, we observed a significant correlation between the left- and right-side averaged impedance and the reduction of the total number of seizures. ConclusionsValuable information can be obtained from the noninvasive measurement of therapeutic impedances. The selection of active contacts to target stimulation to the anterior nucleus may be guided by therapeutic impedance measurements to optimize outcome.

Why don't ventricles dilate in pseudotumor cerebri? A circuit model of the cerebral windkessel.

Pseudotumor cerebri is a disorder of intracranial dynamics characterized by elevated intracranial pressure (ICP) and chronic cerebral venous hypertension without structural abnormalities. A perplexing feature of pseudotumor is the absence of the ventriculomegaly found in obstructive hydrocephalus, although both diseases are associated with increased resistance to cerebrospinal fluid (CSF) resorption. Traditionally, the pathophysiology of ventricular dilation and obstructive hydrocephalus has been attributed to the backup of CSF due to impaired absorption, and it is unclear why backup of CSF with resulting ventriculomegaly would not occur in pseudotumor. In this study, the authors used an electrical circuit model to simulate the cerebral windkessel effect and explain the presence of ventriculomegaly in obstructive hydrocephalus but not in pseudotumor cerebri. The cerebral windkessel is a band-stop filter that dampens the arterial blood pressure pulse in the cranium. The authors used a tank circuit with parallel inductance and capacitance to model the windkessel. The authors distinguished the smooth flow of blood and CSF and the pulsatile flow of blood and CSF by using direct current (DC) and alternating current (AC) sources, respectively. The authors measured the dampening notch from ABP to ICP as the band-stop filter of the windkessel. In obstructive hydrocephalus, loss of CSF pathway volume impaired the flow of AC power in the cranium and caused windkessel impairment, to which ventriculomegaly is an adaptation. In pseudotumor, venous hypertension affected DC power flow in the capillaries but did not affect AC power or the windkessel, therefore obviating the need for adaptive ventriculomegaly. In pseudotumor, the CSF spaces are unaffected and the windkessel remains effective. Therefore, ventricles remain normal in size. In hydrocephalus, the windkessel, which depends on the flow of AC power in patent CSF spaces, is impaired, and the ventricles dilate as an adaptive process to restore CSF pathway volume. The windkessel model explains both ventriculomegaly in obstructive hydrocephalus and the lack of ventriculomegaly in pseudotumor. This model provides a novel understanding of the pathophysiology of disorders of CSF dynamics and has significant implications in clinical management.

MRI-Based Demonstration of the Normal Glymphatic System in a Human Population: A Systematic Review

BackgroundThe glymphatic system has been described as one that facilitates the exchange between the cerebrospinal fluid (CSF) and interstitial fluid, and many recent studies have demonstrated glymphatic flow based on magnetic resonance imaging (MRI). We aim to systematically review the studies demonstrating a normal glymphatic flow in a human population using MRI and to propose a detailed glymphatic imaging protocol.MethodsWe searched the MEDLINE and EMBASE databases to identify studies with human participants involving MRI-based demonstrations of the normal glymphatic flow. We extracted data on the imaging sequence, imaging protocol, and the targeted anatomical structures on each study.ResultsAccording to contrast-enhanced MRI studies, peak enhancement was sequentially detected first in the CSF space, followed by the brain parenchyma, the meningeal lymphatic vessel (MLV), and, finally, the cervical lymph nodes, corresponding with glymphatic flow and explaining the drainage into the MLV. Non-contrast flow-sensitive MRI studies revealed similar glymphatic inflow from the CSF space to the brain parenchyma and efflux of exchanged fluid from the brain parenchyma to the MLV.ConclusionWe may recommend T1-weighted contrast-enhanced MRI for visualizing glymphatic flow. Our result can increase understanding of the glymphatic system and may lay the groundwork for establishing central nervous system fluid dynamic theories and developing standardized imaging protocols.

Practical Aspects of novel MRI Techniques in Neuroradiology: Part 1–3D Acquisitions, Dixon Techniques and Artefact Reduction

Recently introduced MRI techniques offer improved image quality and facilitate examinations of patients even when artefacts are expected. They pave the way for novel diagnostic imaging strategies in neuroradiology. These methods include improved 3D imaging, movement and metal artefact reduction techniques as well as Dixon techniques. Narrative review with an educational focus based on current literature research and practical experiences of different professions involved (physicians, MRI technologists/radiographers, physics/biomedical engineering). Different hardware manufacturers are considered. 3D FLAIR is an example of a versatile 3D Turbo Spin Echo sequence with broad applicability in routine brain protocols. It facilitates detection of smaller lesions and more precise measurements for follow-up imaging. It also offers high sensitivity for extracerebral lesions. 3D techniques are increasingly adopted for imaging arterial vessel walls, cerebrospinal fluid spaces and peripheral nerves. Improved hybrid-radial acquisitions are available for movement artefact reduction in a broad application spectrum. Novel susceptibility artefact reduction techniques for targeted application supplement previously established metal artefact reduction sequences. Most of these techniques can be further adapted to achieve the desired diagnostic performances. Dixon techniques allow for homogeneous fat suppression in transition areas and calculation of different image contrasts based on a single acquisition. · 3D FLAIR can replace 2 D FLAIR for most brain imaging applications and can be a cornerstone of more precise and more widely applicable protocols.. · Further 3D TSE sequences are increasingly replacing 2D TSE sequences for specific applications.. · Improvement of artefact reduction techniques increase the potential for effective diagnostic MRI exams despite movement or near metal implants.. · Dixon techniques facilitate homogeneous fat suppression and simultaneous acquisition of multiple contrasts.. · Sundermann B, Billebaut B, Bauer J et al. Practical Aspects of novel MRI Techniques in Neuroradiology: Part 1-3D Acquisitions, Dixon Techniques and Artefact Reduction. Fortschr Röntgenstr 2022; 194: 1100 - 1108.

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts both during and after long-duration spaceflight and is characterized by the development of optic disc edema, globe flattening, choroidal folds, and hyperopic refractive error shifts. The exact mechanisms underlying these ophthalmic abnormalities remain unclear. New findings regarding spaceflight-associated alterations in cerebrospinal fluid spaces, specifically perivascular spaces, may shed more light on the pathophysiology of SANS. The preliminary results of a recent brain magnetic resonance imaging study show that perivascular spaces enlarge under prolonged microgravity conditions, and that the amount of fluid in perivascular spaces is linked to SANS. The exact pathophysiological mechanisms underlying enlargement of perivascular spaces in space crews are currently unclear. Here, we speculate that the dilation of perivascular spaces observed in long-duration space travelers may result from impaired cerebral venous outflow and compromised cerebrospinal fluid resorption, leading to obstruction of glymphatic perivenous outflow and increased periarterial cerebrospinal fluid inflow, respectively. Further, we provide a possible explanation for how dilated perivascular spaces can be associated with SANS. Given that enlarged perivascular spaces in space crews may be a marker of altered venous hemodynamics and reduced cerebrospinal fluid outflow, at the level of the optic nerve and eye, these disturbances may contribute to SANS. If confirmed by further studies, brain glymphatic dysfunction in space crews could potentially be considered a risk factor for the development of neurodegenerative diseases, such as Alzheimer’s disease. Furthermore, long-duration exposure to microgravity might contribute to SANS through dysregulation of the ocular glymphatic system. If prolonged spaceflight exposure causes disruption of the glymphatic systems, this might affect the ability to conduct future exploration missions, for example, to Mars. The considerations outlined in the present paper further stress the crucial need to develop effective long-term countermeasures to mitigate SANS-related physiologic changes during long-duration spaceflight.

P 68 Unintentional maladjustment of a shunt valve due to electromagnetic door locks – A case report

Normal-pressure hydrocephalus is caused by dilatation of the internal cerebrospinal fluid spaces at normal intracranial pressure. The resulting progressive accumulation of CSF in the brain space can cause permanent damage and, if left untreated, complete loss of brain tissue [2, 4]. The standard treatment for hydrocephalus in children and adults is the implantation of a ventriculo-peritoneal shunt (VP shunt). Most of the currently used shunt systems have a valve to control pressure and drain CSF if necessary [4]. In recent years, malfunction of programmable VP shunts has been reported in patients exposed to strong electromagnetic fields, such as those generated during magnetic resonance imaging (MRI) [1, 3]. However, little is known about the effects of weak magnetic fields on VP shunts. We present the case of a 53 -year-old forensic psychiatric patient in whom the pressure setting of an implanted Codman-Hakim programmable shunt valve changed during passage through various ward doors, leading to the onset of psychiatric symptoms. During the inpatient stay, the valve's pressure setting changed at least six times randomly despite frequent reprogramming and monitoring. References 1 Akbar M, Aschoff A, Georgi JC, Nennig E, Heiland S, Abel R, Stippich C (2010) Adjustable Cerebrospinal Fluid Shunt Valves in 3.0-Tesla MRI: a Phantom Study using Explanted Devices. Rofo 182(7):594-602 2 Kahle KT, Kulkarni AV, Limbrick DD, Warf BC (2016) Hydrocephalus in children. Lancet 387(10020):788–799 3 Mirzayan MJ, Klinge PM, Samii M, Goetz F, Krauss JK (2012) MRI safety of a programmable shunt assistant at 3 and 7 Tesla. Br J Neurosurg 26(3):397-400 4 Portillo Medina SA, Franco JVA, Ciapponi A, Garotte V, Vietto V (2017) Ventriculo-peritoneal shunting devices for hydrocephalus. Cochrane Database Syst Rev. 2017(7): CD012726 Figure 1. Scetch of a Codman-Hakim shunt valve. Figure 2. Image of a Codman-Hakim VP shunt before and after passing a door.

Intrathecal Contrast-Enhanced Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics and Glymphatic Enhancement in Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease, characterized by cerebrospinal fluid (CSF) flow disturbance. Today, the only available treatment is CSF diversion surgery (shunt surgery). While traditional imaging biomarkers typically assess CSF space anatomy, recently introduced imaging biomarkers of CSF dynamics and glymphatic enhancement, provide imaging of CSF dynamics and thereby more specifically reveal elements of the underlying pathophysiology. The biomarkers address CSF ventricular reflux grade as well as glymphatic enhancement and derive from intrathecal contrast-enhanced MRI. However, the contrast agent serving as CSF tracer is administered off-label. In medicine, the introduction of new diagnostic or therapeutic methods must consider the balance between risk and benefit. To this end, we performed a prospective observational study of 95 patients with iNPH, comparing different intrathecal doses of the MRI contrast agent gadobutrol (0.10, 0.25, and 0.50 mmol, respectively), aiming at the lowest reasonable dose needed to retrieve diagnostic information about the novel MRI biomarkers. The present observations disclosed a dose-dependent enrichment of subarachnoid CSF spaces (cisterna magna, vertex, and velum interpositum) with dose-dependent ventricular reflux of tracer in iNPH, as well as dose-dependent glymphatic tracer enrichment. The association between tracer enrichment in CSF and parenchymal compartments were as well dose-related. Intrathecal gadobutrol in a dose of 0.25 mmol, but not 0.10 mmol, was at 1.5T MRI considered sufficient for imaging altered CSF dynamics and glymphatic enhancement in iNPH, even though 3T MRI provided better sensitivity. Tracer enrichment in CSF at the vertex and within the cerebral cortex and subcortical white matter was deemed too low for maintaining diagnostic information from a dose of 0.10 mmol. We conclude that reducing the intrathecal dose of gadobutrol from 0.50 to 0.25 mmol gadobutrol improves the safety margin while maintaining the necessary diagnostic information about disturbed CSF homeostasis and glymphatic failure in iNPH.

Shunt freedom in slit ventricle syndrome: using paradoxical ventriculomegaly following lumbar shunting to our advantage. Illustrative cases.

BACKGROUNDThe authors present two cases of paradoxical ventriculomegaly after lumboperitoneal (LP) shunting in patients with slit ventricle syndrome (SVS).OBSERVATIONSAfter placement of an LP shunt, both patients rapidly developed radiographic and clinically symptomatic ventricular enlargement. The then generous ventricular corridors allowed both patients to be treated by endoscopic third ventriculostomy (ETV) with concurrent removal of their LP shunt. The patients then underwent staged increases in their shunt resistance to the maximum setting and remain asymptomatic.LESSONSThe authors suggest that this paradoxical ventriculomegaly may have resulted from a pressure gradient between the shunt systems in the intra- and extraventricular spaces due to a noncommunicating etiology of their hydrocephalus. ETV may successfully exploit this newfound obstructive hydrocephalus and provide resolution of the radiographic and clinical hydrocephalus through allowing for improved communication between the cranial and lumbar cerebrospinal fluid spaces in SVS.

The expansion and severity of chronic MS lesions follows a periventricular gradient

Background and Objectives: Expansion of chronic lesions in multiple sclerosis (MS) patients and recently described cerebrospinal fluid (CSF)-related gradient of tissue damage are linked to microglial activation. The aim of this study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces. Methods: Pre- and post-gadolinium three-dimensional (3D)-T1, 3D FLAIR and diffusion tensor images were acquired from 36 relapsing-remitting MS (RRMS) patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1 mm thick concentric bands radiating from the ventricles. Results: Voxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue destruction at baseline that significantly increased during follow-up in bands close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone. Discussion: Our data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.

Differential diagnosis of pneumonia as a complication of nasal liquorrhea in the context of the COVID-19 pandemic: Case report

Nasal liquorrhea the outflow of cerebrospinal fluid from the cerebrospinal fluid spaces of the cranial cavity into the nasal cavity or paranasal sinuses due to the presence of a congenital or acquired defect in the bones of the skull base and meninges of various etiologies. Nasal liquorrhea leads to potentially fatal complications: meningitis, meningoencephalitis, pneumocephalus, brain abscess. Also, with nasal liquorrhea, less dangerous complications may occur: aspiration bronchopneumonia and gastritis. The article presents a case of aspiration pneumonia in two patients with nasal liquorrhea treated at the Burdenko National Medical Research Center for Neurosurgery during the COVID-19 pandemic. Both patients noted the profuse nature of the nasal liquorrhea, complained of coughing in a horizontal position. In both cases, no RNA virus (SARS-CoV-2) was detected during the polymerase chain reaction. Antibodies (IgG, M) to coronavirus were not detected. Computed tomography of the chest organs in both cases revealed areas of frosted glass darkening. Since no data was obtained for coronavirus infection (negative tests for coronavirus, lack of antibodies), changes in the lungs were interpreted as a consequence of constant aspiration of CSF. The patients were admitted to a separate ward. Both patients underwent endoscopic endonasal plasty of the skull base defect. The postoperative period in both cases was uneventful. In both cases, the patients underwent computer tomography scan of the chest organs one month later. On the photographs, the signs of pneumonia completely regressed.

430 Trans-cerebellar Stereotactic-guided Cisternoperitoneal Shunt Placement for Idiopathic Intracranial Hypertension

INTRODUCTION: Idiopathic intracranial hypertension (IIH, pseudotumor cerebri) mainly affects young, obese females and can cause debilitating symptoms as well as optic nerve ischemia if not treated. Cerebrospinal fluid (CSF) diversion is often necessary to reduce intracranial pressure (ICP). Ventriculoperitoneal shunts (VPS) and lumboperitoneal shunts (LPS) are the main methods of CSF diversion but both are fraught with high rates of shunt failures in IIH patients. We propose the novel trans-cerebellar stereotactic-guided cisternoperitoneal shunt (TCSG-CPS) technique, which places the proximal shunt catheter in the posterior cisterna magnum, which is a non-collapsible CSF space. METHODS: Retrospective data regarding perioperative and postoperative data from all patients who underwent TCSG-CPS placement from 2015-2020 for IIH were collected. Intraoperatively, patients are positioned as for VPS but with the head turned further laterally to adequately expose the retrosigmoid space. Using neuronavigation, the transverse and sigmoid sinuses are located and an opening is made at the transverse-sigmoid junction. The proximal catheter is then inserted transcerebellarly into the posterior foramen magnum using electromagnetic neuronavigation to accurately track the catheter tip. RESULTS: Thirty-two patients underwent TCSG-CPS placement. 91% were female, with a mean BMI of 36.0 ± 7.5. Fourteen patients had undergone prior VPS or LPS placement with shunt failures. Shunt placement, including removal of prior shunts when applicable, took an average of 150 minutes. There were no intraoperative complications and patients were discharged uneventfully after mean 1.7 days. On follow-up visits at 6 months, 81% had relief of their presenting symptoms. Shunt survival without revision at 1 and 3 year were 86% and 67%, respectively. Overall infection rate was 0% in the study period. CONCLUSION: The TCSG-CPS offers an alternative solution to VPS and LPS for CSF diversion in patients with IIH and demonstrates a lower failure rate and more durable symptom relief compared to historical data on VPS and LPS. Using the proper techniques and equipment promotes safe and facile placement of the proximal catheter.

194 Why Do Ventricles Not Dilate in Pseudotumor Cerebri? A Circuit Model of Cerebral Windkessel

INTRODUCTION: Pseudotumor cerebri is characterized by elevated intracranial pressure (ICP) without ventricular dilation. The pathophysiology of pseudotumor is traditionally viewed as chronic cerebrovenous hypertension which causes impaired cerebrospinal fluid (CSF) resorption. Increased resistance to CSF absorption results in ventriculomegaly in obstructive hydrocephalus. In pseudotumor, however, lack of ventriculomegaly cannot be explained by this mechanism. In this study, we model the cerebral windkessel as a CSF pulsation absorber. We hypothesize that inability to absorb CSF pulsation diverts pulsatile energy to ventricles, causing ventriculomegaly, whereas effective CSF pulsation absorption leaves ventricles normal in size. METHODS: Cerebral windkessel is a band-pass filter considering arterial blood pressure (ABP) as input and ICP as output. We used a tank circuit with parallel inductance and capacitance to model windkessel and compare with the transfer function between ABP and ICP in normal dogs. Normal CSF dynamics were simulated by setting circuit parameters to correlate physiological recordings from dogs: frequency for heart rate, input and output voltages for ABP and ICP, and CSF and capillary resistance for resistance to pulsatile and pulseless flow, respectively. CSF path resistance was increased to simulate CSF space narrowing in hydrocephalus. Capillary resistance was increased to simulate impaired venous flow in pseudotumor. RESULTS: The circuit output shows agreement with physiological recordings, in which ICP pulse precedes ABP pulse. Windkessel is most effective at a given pulse frequency. In hydrocephalus, increased resistance to CSF flow disrupts cerebral windkessel, leading to ineffective pulse dampening and increased ICP phase lead. In pseudotumor, increased capillary resistance does not change cerebral windkessel effectiveness or ICP phase lead. CONCLUSION: The cerebral windkessel is a CSF pulsation absorber. An ineffective windkessel in hydrocephalus inhibits CSF pulsation absorption and diverts pulsatile energy to dilate ventricles, whereas an effective one in pseudotumor leaves ventricles normal. Our model of CSF dynamics emphasizes that ventricular dilation is a result of ineffective windkessel and decreased CSF pulsation absorption. This model provides a novel perspective on the pathophysiology of abnormal CSF dynamics and offers new directions for future research.

Cerebrospinal fluid metabolic profiling reveals divergent modulation of pentose phosphate pathway by midazolam, propofol and dexmedetomidine in patients with subarachnoid hemorrhage: a cohort study

BackgroundAgitation is common in subarachnoid hemorrhage (SAH), and sedation with midazolam, propofol and dexmedetomidine is essential in agitation management. Previous research shows the tendency of dexmedetomidine and propofol in improving long-term outcome of SAH patients, whereas midazolam might be detrimental. Brain metabolism derangement after SAH might be interfered by sedatives. However, how sedatives work and whether the drugs interfere with patient outcome by altering cerebral metabolism is unclear, and the comprehensive view of how sedatives regulate brain metabolism remains to be elucidated.MethodsFor cerebrospinal fluid (CSF) and extracellular space of the brain exchange instantly, we performed a cohort study, applying CSF of SAH patients utilizing different sedatives or no sedation to metabolomics. Baseline CSF metabolome was corrected by selecting patients of the same SAH and agitation severity. CSF components were analyzed to identify the most affected metabolic pathways and sensitive biomarkers of each sedative. Markers might represent the outcome of the patients were also investigated.ResultsPentose phosphate pathway was the most significantly interfered (upregulated) pathway in midazolam (p = 0.0000107, impact = 0.35348) and propofol (p = 0.00000000000746, impact = 0.41604) groups. On the contrary, dexmedetomidine decreased levels of sedoheptulose 7-phosphate (p = 0.002) and NADP (p = 0.024), and NADP is the key metabolite and regulator in pentose phosphate pathway. Midazolam additionally augmented purine synthesis (p = 0.00175, impact = 0.13481) and propofol enhanced pyrimidine synthesis (p = 0.000203, impact = 0.20046), whereas dexmedetomidine weakened pyrimidine synthesis (p = 0.000000000594, impact = 0.24922). Reduced guanosine diphosphate (AUC of ROC 0.857, 95%CI 0.617–1, p = 0.00506) was the significant CSF biomarker for midazolam, and uridine diphosphate glucose (AUC of ROC 0.877, 95%CI 0.631–1, p = 0.00980) for propofol, and succinyl-CoA (AUC of ROC 0.923, 95%CI 0.785–1, p = 0.000810) plus adenosine triphosphate (AUC of ROC 0.908, 95%CI 0.6921, p = 0.00315) for dexmedetomidine. Down-regulated CSF succinyl-CoA was also associated with favorable outcome (AUC of ROC 0.708, 95% CI: 0.524–0.865, p = 0.029333).ConclusionPentose phosphate pathway was a crucial target for sedatives which alter brain metabolism. Midazolam and propofol enhanced the pentose phosphate pathway and nucleotide synthesis in poor-grade SAH patients, as presented in the CSF. The situation of dexmedetomidine was the opposite. The divergent modulation of cerebral metabolism might further explain sedative pharmacology and how sedatives affect the outcome of SAH patients.

The blood-CSF-brain route of neurological disease: The indirect pathway into the brain.

The brain is protected by the endothelial blood-brain barrier (BBB) that limits the access of micro-organisms, tumour cells, immune cells and autoantibodies to the parenchyma. However, the classic model of disease spread across a disrupted BBB does not explain the focal distribution of lesions seen in a variety of neurological diseases and why lesions are frequently adjacent to the cerebrospinal fluid (CSF) spaces. We have critically reviewed the possible role of a blood-CSF-brain route as a disease entry pathway into the brain parenchyma. The initial step of this pathway is the transfer of pathogens or immune components from the blood into the CSF at the choroid plexuses, where the blood-CSF barrier (BCSFB) is located. The flow of CSF results in disease dissemination throughout the CSF spaces. Access to the brain parenchyma from the CSF can then occur across the ependymal layer at the ventricular surface or across the pial-glial barrier of the subarachnoid space and the Virchow-Robin spaces. We have reviewed the anatomy and physiology of the blood-CSF-brain pathway and the brain barriers controlling this process. We then summarised the evidence supporting this brain entry route in a cross-section of neurological diseases including neuromyelitis optica, multiple sclerosis, neurosarcoidosis, neuropsychiatric lupus, cryptococcal infection and both solid and haematological tumours. This summary highlights the conditions that share the blood-CSF-brain pathway as a pathogenetic mechanism. These include the characteristic proximity of lesions to CSF, evidence of disruption of the brain barriers and the identification of significant pathology within the CSF. An improved understanding of pathological transfer through the CSF and across all brain barriers will inform on more effective and targeted treatments of primary and secondary diseases of the central nervous system.

Intraventricular immune checkpoint inhibition with nivolumab in relapsed primary central nervous system lymphoma.

SUMMARY Intrathecal nivolumab combined with its systemic administration was recently found safe and effective in melanoma with leptomeningeal dissemination, prompting us to evaluate intraventricular nivolumab for recurrent primary CNS lymphoma (PCNSL) in an elderly patient unable to tolerate aggressive systemic polychemotherapy. Intraventricular nivolumab achieved a lasting (&amp;gt;12 months) complete remission including parenchymal lesions distant from cerebrospinal fluid spaces. No toxicities or adverse events related to the mode of administration were noted. Our case suggests intraventricular nivolumab is active in recurrent parenchymal PCNSL. Together with detected 9p24.1 gains this argues for further prospective evaluation, for which our treatment protocol provides a framework.

Evaluation of single-dose cefuroxime concentrations in the spinal cord, cerebrospinal fluid, and epidural space in relation to lumbar spine surgery: An experimental porcine study

Evaluation of single-dose cefuroxime concentrations in the spinal cord, cerebrospinal fluid, and epidural space in relation to lumbar spine surgery: An experimental porcine study