Cisterna Magna Research Articles

Fetal and neonatal outcomes of posterior fossa anomalies: a retrospective cohort study

The primary aim of this study was to estimate the incidence of posterior fossa anomalies (PFA) and assess the associated outcomes in King Abdulaziz Medical City (KAMC), Riyadh. All fetuses diagnosed by prenatal ultrasound with PFA from 2017 to 2021 in KAMC were analyzed retrospectively. PFA included Dandy–Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC), and isolated vermian hypoplasia (VH). The 65 cases of PFA were 41.5% DWM, 46.2% MCM, 10.8% VH, and 1.5% BPC. The annual incidence rates were 2.48, 2.64, 4.41, 8.75, and 1.71 per 1000 anatomy scans for 2017, 2018, 2019, 2020, and 2021, respectively. Infants with DWM appeared to have a higher proportion of associated central nervous system (CNS) abnormalities (70.4% vs. 39.5%; p-value = 0.014) and seizures than others (45% vs. 17.9%; p-value = 0.041). Ten patients with abnormal genetic testing showed a single gene mutation causing CNS abnormalities, including a pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1, and a variant of uncertain significance in the PNPLA8 gene. Our result showed that the most common PFA is DWM and MCM. The autosomal recessive pathogenic mutation is the major cause of genetic disease in Saudi patients diagnosed with PFA.

Prognostic and morphological factors in pediatric cerebellar contusions

Background: Although uncommon, cerebellar contusions are associated with significant morbidity and mortality. Literature is lacking in the prognostic and morphological factors relating to their clinical picture and outcomes, especially within children. The objective of this study is to evaluate prognostic and anatomic factors in the clinical picture of cerebellar contusions, including effacement of the 4th ventricle and cisterna magna. Methods: This is a retrospective chart review over 11 years across two medical centers. Patients included were under 18 years who presented with a cerebellar contusion. Patients were stratified within the study group based on discharge Glasgow outcome scale (GOS) and reviewed for prognostic factors contributing to outcome. Mid sagittal area of the 4th ventricle and cisterna magna were measured using magnetic resonance imaging and compared within the groups. Results: A total of 21 patients met the study criteria, of which 16 (76.2%) were male, with an average patient age of 8.65 years. Poor outcome at discharge (GOS <4) was associated with decreased admission Glasgow coma scale (P = 0.003), admission motor response (P = 0.006), pupil reactivity (P = 0.014), presence of concomitant subarachnoid hemorrhage (P = 0.010), contusion volume (P < 0.001), and decreased area of the cisterna magna (P = 0.012). Patients with poor outcomes were also more likely to require surgical intervention (P = 0.042). Conclusion: There are multiple prognostic factors associated with the overall outcome following cerebellar contusions. The rate of good outcomes in this study was superior to that in previous studies in adults.

185 Deuterium MRI for CSF Studies in Normal and Hydrocephalic Rats

INTRODUCTION: The recent characterization of the glymphatic system has revived interest in the interaction of cerebrospinal fluid (CSF) with brain tissue via perivascular spaces. Traditional CSF tracers, such as gadolinium and iohexal, are large molecules that do not cross the blood brain barrier (BBB). The primary component of CSF, however, is water, which is BBB permeable. METHODS: Eight adult male rats underwent cisterna magna catheterization for intrathecal infusion. Brain MR images were obtained in a 7 tesla small-animal MRI system. Temporal T1-weighted images (T1WI) were obtained before, during, and after intrathecal infusion of D2O. Five rats then underwent ventricular kaolin injection for induction of hydrocephalus, after which repeat imaging with intrathecal D2O infusion was performed. RESULTS: Intrathecal deuterium infusion produced consistent changes on MRI imaging. Because conventional MRI does not sense deuterium, the T1WI showed a loss in proton signal with D2O infusion. Rapid D2O uptake of <2.5 minutes was noted in CSF spaces, brain tissue, and saggital and straight venous sinuses. CONCLUSIONS: Use of deuterium as an intrathecal contrast agent provides a physiologically realistic model of CSF behavior. Efforts are ongoing to quantify the relationship between MRI signal loss and deuterium tissue concentration for comparative analysis between healthy and hydrocephalic rats. The loss of MRI signal in the straight sinus after intrathecal infusion implicates the deep venous system in the clearance of CSF, suggesting that CSF is reabsorbed into the venous system via the brain tissue itself. Because traditional CSF tracers do not cross the BBB, the role of the brain tissue in the reabsorption of CSF has been overlooked.

'Choroid bar': easy-to-seek marker of normal posterior fossa at 12-14 weeks' gestation.

Our objectives were: (1) to assess the visualization rate of the choroid bar in a consecutive series of 306 first-trimester scans; (2) to verify, in this cohort of fetuses, the normality of the posterior fossa later in pregnancy; and (3) to confirm the non-visualization of the choroid bar in a retrospective series of fetuses with posterior fossa malformations. This study included a prospective and a retrospective series. The former comprised 306 fetuses undergoing routine obstetric ultrasound at our unit in both the first and second trimesters over a 6-month period, while the latter comprised 12 cases of posterior fossa malformations. In the prospective study, the presence of the choroid bar, which is defined as a visually continuous, homogeneously hyperechogenic, thick structure bridging the cisterna magna from side to side, was evaluated at the end of the first-trimester nuchal translucency scan. In the retrospective study, previously acquired three-dimensional volume datasets were processed in order to assess whether the choroid bar could be visualized in cases of open spinal dysraphisms and vermian cystic anomalies. In the prospective study, confirmation of a normal posterior fossa was based on the sonographic features of this anatomical region at the time of the second-trimester anomaly scan at 19-21 weeks' gestation, while, in the retrospective study, it was based on autopsy results, when available, or further direct imaging of the defect later in pregnancy. In the prospective study, the choroid bar could be visualized in all 306 fetuses, on transabdominal ultrasound in 287 (93.8%) cases and on transvaginal ultrasound in 19 (6.2%) cases. The choroid bar was displayed with a ventral/dorsal approach in 67 (21.9%) cases, with a lateral approach in 56 (18.3%) cases and with both in 183 (59.8%) cases. All 306 cases were confirmed to have a sonographically normal posterior fossa at 19-21 weeks. On the other hand, in the retrospective study, it was not possible to visualize the choroid bar in any of the fetuses with posterior fossa malformations. We have described a new sign, the choroid bar, consistent with a normal posterior fossa at 12-14 weeks' gestation. The choroid bar provides the option of screening for major abnormalities of the posterior fossa, since its absence raises suspicion of both open spinal dysraphisms and posterior fossa cystic malformations. At the same time, it is easy to visualize, as it can be seen with all lines of insonation. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Pneumococcal Meningitis Induces Hearing Loss and Cochlear Ossification Modulated by Chemokine Receptors CX3CR1 and CCR2.

Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobial therapies to control infection. Methods to improve hearing outcomes for those who survive bacterial meningitis remains elusive. We used a mouse model of pneumococcal meningitis to evaluate the impact of mononuclear phagocytes on hearing outcomes and cochlear ossification by altering the expression of CX3CR1 and CCR2 in these infected mice. We induced pneumococcal meningitis in approximately 500 C57Bl6 adult mice using live Streptococcus pneumoniae (serotype 3, 1 × 105 colony forming units (cfu) in 10µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recovery. We used microcomputed tomography (microCT) scans to quantify cochlear volume loss caused by neo-ossification. We also performed perilymph sampling in live mice to assess the integrity of the blood-perilymph barrier during various time intervals after meningitis. We then evaluated the effect of CX3CR1 or CCR2 deletion in meningitis symptoms, hearing loss, macrophage/monocyte recruitment, neo-ossification, and blood labyrinth barrier function. Sixty percent of mice with pneumococcal meningitis developed hearing loss. Cochlear fibrosis could be detected within 4days of infection, and neo-ossification by 14days. Loss of spiral ganglion neurons was common, and inner ear anatomy was distorted by scarring caused by new soft tissue and bone deposited within the scalae. The blood-perilymph barrier was disrupted at 3days post infection (DPI) and was restored by seven DPI. Both CCR2 and CX3CR1 monocytes and macrophages were present in the cochlea in large numbers after infection. Neither chemokine receptor was necessary for the induction of hearing loss, cochlear fibrosis, ossification, or disruption of the blood-perilymph barrier. CCR2 knockout (KO) mice suffered the most severe hearing loss. CX3CR1 KO mice demonstrated an intermediate phenotype with greater susceptibility to hearing loss compared to control mice. Elimination of CX3CR1 mononuclear phagocytes during the first 2weeks after meningitis in CX3CR1-DTR transgenic mice did not protect mice from any of the systemic or hearing sequelae of pneumococcal meningitis. Pneumococcal meningitis can have devastating effects on cochlear structure and function, although not all mice experienced hearing loss or cochlear damage. Meningitis can result in rapid progression of hearing loss with fibrosis starting at four DPI and ossification within 2weeks of infection detectable by light microscopy. The inflammatory response to bacterial meningitis is robust and can affect all three scalae. Our results suggest that CCR2 may assist in controlling infection and maintaining cochlear patency, as CCR2 knockout mice experienced more severe disease, more rapid hearing loss, and more advanced cochlear ossification after pneumococcal meningitis. CX3CR1 also may play an important role in the maintenance of cochlear patency.

Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children

BackgroundPallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern. Moreover, a literature review differentiating the different types of neuroimaging data was conducted for comparison with our population.ResultsThirty-one individuals were enrolled (17 females/14 males; age range 0.1–17.5 years old at first MRI). An experienced pediatric neuroradiologist reviewed brain MRIs, blindly to clinical data. Brain abnormalities were observed in all but one individual (compared to the 34% frequency found in the literature review). Corpus callosum abnormalities were found in 20/30 (67%) patients: 6 had callosal hypoplasia; 8 had global hypoplasia with hypoplastic splenium; 4 had only hypoplastic splenium; and 2 had a thin corpus callosum. Cerebral hypoplasia/atrophy was found in 23/31 (74%) and ventriculomegaly in 20/31 (65%). Other frequent features were the enlargement of the cisterna magna in 15/30 (50%) and polymicrogyria in 14/29 (48%). Conversely, the frequency of the latter was found to be 4% from the literature review. Notably, in our population, polymicrogyria was in the perisylvian area in all 14 cases, and it was bilateral in 10/14.ConclusionsBrain abnormalities are very common in PKS and occur much more frequently than previously reported. Bilateral perisylvian polymicrogyria was a main aspect of our population. Our findings provide an additional tool for early diagnosis.Further studies to investigate the possible correlations with both genotype and phenotype may help to define the etiopathogenesis of the neurologic phenotype of this syndrome.

Investigation of Antibody Pharmacokinetics in the Brain Following Intra-CNS Administration and Development of PBPK Model to Characterize the Data.

Despite the promising potential of direct central nervous system (CNS) antibody administration to enhance brain exposure, there remains a significant gap in understanding the disposition of antibodies following different intra-CNS injection routes. To bridge this knowledge gap, this study quantitatively investigated the brain pharmacokinetics (PK) of antibodies following intra-CNS administration. The microdialysis samples from the striatum (ST), cerebrospinal fluid (CSF) samples through cisterna magna (CM) puncture, plasma, and brain homogenate samples were collected to characterize the pharmacokinetics (PK) profiles of a non-targeting antibody, trastuzumab, following intracerebroventricular (ICV), intracisternal (ICM), and intrastriatal (IST) administration. For a comprehensive analysis, these intra-CNS injection datasets were juxtaposed against our previously acquired intravenous (IV) injection data obtained under analogous experimental conditions. Our findings highlighted that direct CSF injections, either through ICV or ICM, resulted in ~ 5-6-fold higher interstitial fluid (ISF) drug exposure than IV administration. Additionally, the low bioavailability observed following IST administration indicates the existence of a local degradation process for antibody elimination in the brain ISF along with the ISF bulk flow. The study further refined a physiologically based pharmacokinetic (PBPK) model based on new observations by adding the perivascular compartments, oscillated CSF flow, and the nonspecific uptake and degradation of antibodies by brain parenchymal cells. The updated model can well characterize the antibody PK following systemic and intra-CNS administration. Thus, our research offers quantitative insight into antibody brain disposition pathways and paves the way for determining optimal dosing and administration strategies for antibodies targeting CNS disorders.

Abstract B003: The OTX2 gene induces tumor growth and triggers leptomeningeal metastasis by regulating the mTOR signaling pathway in medulloblastomas

Abstract B003: The OTX2 gene induces tumor growth and triggers leptomeningeal metastasis by regulating the mTOR signaling pathway in medulloblastomas

A technique for repeated blood and cerebrospinal fluid sampling from individual rats over time without the need for repeated anesthesia

Ethical animal use follows the 3R’s: Replacement, Reduction and Refinement. Here, we present the use of simultaneous jugular vein and cisterna magna catheterization via a port system in rats for repeated fluid sampling for 14 consecutive days without loss of catheter patency. This technique allows repeated intra-animal sampling without anesthesia and, if used with pooling samples from a cohort of animals, replaces the need for terminal collections for sufficient sample volumes.

Cerebrospinal Fluid Diversion from the Cisterna Magna in Patients with Idiopathic Intracranial Hypertension and Slit Ventricles: Long-Term Effectiveness, Revision Rates, and Clinical Outcomes

ObjectiveIdiopathic intracranial hypertension (IIH) is a cerebrospinal fluid (CSF) disorder defect that is frequently treated with CSF shunts. Shunts utilizing the cisterna magna as a proximal reservoir have been described in literature, however, long-term outcomes are unknown. The present study aims to describe the long-term effectiveness, revision rates, and clinical outcomes of this shunt in 14 patients with IIH and slit ventricles. MethodsA single-center retrospective review of 14 IIH patients treated by cisterna magna shunts was performed. Shunt histories, including revision rate and time until first shunt failure for ventricular, lumbar, and cisterna magna shunts were recorded. “Revision rate” was calculated as the total number of shunt revisions over years of total shunt placement. The average follow-up time was 12.08 years. ResultsThe mean age at first cisterna magna shunt placement was 18.1 years (6.6 – 43.3 years) and all patients had radiological evidence of slit ventricles. Cisterna magna shunts improved or resolved clinical symptoms for all 14 patients and had a lower rate of revisions (0.42 revision/year) compared to ventricular (0.72 revision/year) and lumbar (1.30 revision/year) shunts. Of the 11 patients still requiring CSF diversion at the end of the study, eight had functioning shunts that utilized the cisterna magna. ConclusionsThe cisterna magna shunt may be a suitable option for patients with IIH and slit ventricles. Further study is needed to understand the clinical utility of this shunt for the population in which it is indicated.

MRI-based vertebral bone quality score in cervical ossification of the posterior longitudinal ligament: a comparison with cervical spondylotic myelopathy using propensity score matching

BACKGROUNDBone mineral density plays a key role in the assessment of operative instrumentation complications and clinical outcomes. The MRI-based vertebral bone quality (VBQ) score has been introduced as a novel marker of bone quality. However, few studies have investigated the relationship between VBQ score and patients associated with cervical ossification of the posterior longitudinal ligament (OPLL). PURPOSEThe aims of the study were (1) to reveal bone mineral density between cervical OPLL and cervical spondylotic myelopathy (CSM) group by VBQ score, (2) to compare the VBQ score of cervical OPLL between male and female group, (3) to explore the relationship between segmental VBQ scores associated with OPLL. STUDY DESIGNRetrospective cohort study. PATIENT SAMPLEConsecutive series of 425 patients at a single academic institution. OUTCOME MEASURESMRI based measurements of C2–C7 VBQ scores. METHODSPreoperative non-contrast T1-weighted MRIs of the cervical spine was used to measure the VBQ score. The VBQ score was defined as the mean value of the signal intensity of the vertebrae divided by that of the cerebrospinal fluid (CSF) space at the cisterna magna. Patients with cervical OPLL and CSM were matched based on age, sex, body mass index (BMI), comorbidity, medication history, diet habit, smoking, alcohol consumption via propensity score matching (PSM). Normality of each VBQ score was tested by the Shapiro-Wilk test. Wilcoxon's rank-sum test was used to compare matched cohorts. Kruskal-Wallis test was performed to compare the VBQ scores between segments. Multivariate logistic regression analysis was used to evaluate factors associated with the development of cervical OPLL. RESULTSA total of 425 patients were assessed. For final analysis, 135 paired patients were compared between the cervical OPLL and CSM groups, and 22 paired patients were compared between male and female group associated with cervical OPLL. There were no statistically significant differences in age, sex, BMI, comorbidity, medication history, diet habit, smoking, alcohol between the matched cohorts. OPLL group was associated with lower VBQ score compared with CSM group at C3, while there were no differences in VBQ score for the other levels between the two groups. There were no differences between male and female group associated with OPLL in C2–C7 VBQ scores. VBQ scores of cervical OPLL are variable between segments, with significantly lower scores at C6, C7 compared with C1–C5. Multivariate logistic regression analysis showed that BMI was correlated with the development of OPLL (regression coefficient, 0.162; 95% confidence interval, 0.010–0.037). Additional risk factors included hypertension, calcium supple history and smoking. CONCLUSIONSThis study demonstrates that cervical OPLL is associated with lower VBQ score at C3, with no differences for the other levels when compared with CSM derived from measurements on MRI. No differences were found between male and female group associated with OPLL in C2–C7 VBQ scores. Cervical OPLL were found to have smaller VBQ score at C6, C7 compared with C1–C5. Our findings provide new insight for bone density assessment in cervical OPLL patient.

Changes in arterial myocyte excitability induced by subarachnoid hemorrhage in a rat model

Aneurismal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by the rupture of the cerebral arteries and the extravasation of blood to the subarachnoid space and is accompanied by severe comorbidities. Secondarily associated vasospasm is one of the main side effects after hydrocephalus and possible rebleeding. Here, we analyze the alterations in function in the arteries of a rat model of SAH.For this, autologous blood was injected into the cisterna magna. We performed electrophysiological, microfluorimetric, and molecular biology experiments at different times after SAH to determine the functional and molecular changes induced by the hemorrhage. Our results confirmed that in SAH animals, arterial myocytes were depolarized on days 5 and 7, had higher [Ca2+]i on baseline, peaks and plateaus, and were more excitable at low levels of depolarization on day 7, than in the control and sham animals. Microarray analysis showed that, on day 7, the sets of genes related to voltage-dependent Ca2+ channels and K+ dynamics in SAH animals decreased, while the voltage-independent Ca2+ dynamics genes were over-represented. In conclusion, after SAH, several mechanisms involved in arterial reactivity were altered in our animal model, suggesting that there is no unique cause of vasospasm and alterations in several signaling pathways are involved in its development.

Glymphatic fluid transport is suppressed by the aquaporin-4 inhibitor AER-271.

The glymphatic system transports cerebrospinal fluid (CSF) into the brain via arterial perivascular spaces and removes interstitial fluid from the brain along perivenous spaces and white matter tracts. This directional fluid flow supports the clearance of metabolic wastes produced by the brain. Glymphatic fluid transport is facilitated by aquaporin-4 (AQP4) water channels, which are enriched in the astrocytic vascular endfeet comprising the outer boundary of the perivascular space. Yet, prior studies of AQP4 function have relied on genetic models, or correlated altered AQP4 expression with glymphatic flow in disease states. Herein, we sought to pharmacologically manipulate AQP4 function with the inhibitor AER-271 to assess the contribution of AQP4 to glymphatic fluid transport in mouse brain. Administration of AER-271 inhibited glymphatic influx as measured by CSF tracer infused into the cisterna magna and inhibited increases in the interstitial fluid volume as measured by diffusion-weighted MRI. Furthermore, AER-271 inhibited glymphatic efflux as assessed by an in vivo clearance assay. Importantly, AER-271 did not affect AQP4 localization to the astrocytic endfeet, nor have any effect in AQP4 deficient mice. Since acute pharmacological inhibition of AQP4 directly decreased glymphatic flow in wild-type but not in AQP4 deficient mice, we foresee AER-271 as a new tool for manipulation of the glymphatic system in rodent brain.

The "Brain Milking" Method for the Isolation of Neural Stem Cells and Oligodendrocyte Progenitor Cells from Live Rats.

Tissue-specific neural stem cells (NSCs) remain active in the mammalian postnatal brain. They reside in specialized niches, where they generate new neurons and glia. One such niche is the subependymal zone (SEZ; also called the ventricular-subventricular zone), which is located across the lateral walls of the lateral ventricles, adjacent to the ependymal cell layer. Oligodendrocyte progenitor cells (OPCs) are abundantly distributed throughout the central nervous system, constituting a pool of proliferative progenitor cells that can generate oligodendrocytes. Both NSCs and OPCs exhibit self-renewal potential and quiescence/activation cycles. Due to their location, the isolation and experimental investigation of these cells is performed postmortem. Here, we describe in detail "brain milking", a method for the isolation of NSCs and OPCs, amongst other cells, from live animals. This is a two-step protocol designed for use in rodents and tested in rats. First, cells are "released" from the tissue via stereotaxic intracerebroventricular (i.c.v.) injection of a "release cocktail". The main components are neuraminidase, which targets ependymal cells and induces ventricular wall denudation, an integrin-β1-blocking antibody, and fibroblast growth factor-2. At a second "collection" step, liquid biopsies of cerebrospinal fluid are performed from the cisterna magna, in anesthetized rats without the need of an incision. Results presented here show that isolated cells retain their endogenous profile and that NSCs of the SEZ preserve their quiescence. The denudation of the ependymal layer is restricted to the anatomical level of injection and the protocol (release and collection) is tolerated well by the animals. This novel approach paves the way for performing longitudinal studies of endogenous neurogenesis and gliogenesis in experimental animals.

Navigating Uncharted Waters: Comparative Analysis of Clinical Progression and Outcomes in Vestibular Schwannoma Patients with Papilledema and without Hydrocephalus, Versus Those without Papilledema and Hydrocephalus: A Comprehensive Institutional Insight

Papilledema's association with hydrocephalus (HCP)-linked larger vestibular schwannoma (VS) is established but cases lacking concurrent HCP require further investigation. This retrospective comparative observational study, conducted from July 2018 to July 2023, examined 120 VS patients undergoing surgery. Patients were categorized into Group 1 (papilledema without HCP) and Group 2 (no papilledema or HCP), with comprehensive data analyzed. In this study, Group 1 (14 patients with papilledema) and Group 2 (106 patients without papilledema or HCP) were compared. Group 1 was younger (mean age 27.21±11.73years) than Group 2 (mean age 54.66±11.44years). Both groups had similar symptom durations and tumor detection times. Group 1 had increased vascularity (P= 0.001), elevated cisterna magna protein levels (P= 0.001), and a higher incidence of neurofibromatosis 2 (P= 0.003). They also experienced longer surgeries (P= 0.001) and more blood loss (P= 0.001), leading to extended postoperative complications. Group 2 showed improved postsurgery visual outcomes (P= 0.001), better Glasgow Outcome Scores (P= 0.001), enhanced facial nerve preservation (P= 0.002), and improved hearing on follow-up (P= 0.003). Logistic regression analysis highlighted prolonged surgery duration (P= 0.057) and papilledema (P= 0.0001) as significant factors influencing visual improvement. Patients with VS require preoperative fundoscopy evaluation due to potential visual loss and papilledema, even without HCP. Early treatment initiation enhances visual and hearing outcomes. Meticulous surgery is vital given the lesion's hypervascular nature and adherence to surrounding structures. Preoperative embolization may aid in preserving neurovascular structures. In developing countries with higher blindness rates, judicious noncontrast computed tomography brain evaluation is crucial for timely detection and treatment initiation of lesions like VS.

Comparative analysis of linezolid, vancomycin, and hyperbaric oxygen therapies in a rat model of ventriculoperitoneal shunt infection.

Staphylococcus epidermidis is the most common causative microorganism of ventriculoperitoneal shunt infections. This study aimed to compare linezolid and vancomycin treatments and to examine the effect of these antibiotics alone and combined with hyperbaric oxygen therapy on the amount of bacterial colonies in the experimental S. epidermidis shunt infection model. A shunt catheter was placed in the cisterna magna of 49 adult male Wistar albino rats. The rats were randomly divided into seven groups, as follows: sterile control, infected control, vancomycin, linezolid, hyperbaric oxygen, vancomycin + hyperbaric oxygen, linezolid + hyperbaric oxygen. In all groups except the sterile control group, 0.2ml 107CFU/mL S. epidermidis was inoculated to the cisterna magna. Parenteral vancomycin was administered 40mg/kg/day to the vancomycin groups, and 50mg/kg/day of enteral linezolid to the linezolid groups. Hyperbaric oxygen groups were given 100% oxygen at a pressure of 2.4 ATA for 50min a day. One day after the last treatment, colony quantities in the shunt catheters and CSF were analyzed. The number of CSF colonies in the linezolid group was significantly lower than in the vancomycin group (p < 0.05). The number of CSF colonies in the linezolid + HBO group was significantly lower than in the vancomycin + HBO group (p < 0.05). Linezolid treatment was found to be more effective than vancomycin in ventriculoperitoneal shunt infection caused by S. epidermidis. There was no statistical difference among other treatment groups. Hyperbaric oxygen therapy is shown to contribute to the sterilization of cultures.

MRI-based lesion quality score assessing ossification of the posterior longitudinal ligament of the cervical spine

BACKGROUND CONTEXTNo method currently exists for MRI-based determination of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine using objective criteria. PURPOSEThe purpose of this study was to develop an MRI-based score to determine whether a lesion represents a cervical OPLL lesion and to establish the objective diagnostic value. STUDY DESIGNRetrospective cohort in a single medical institution. PATIENT SAMPLEThirty-five patients undergoing surgery for OPLL (Group A) and 99 patients undergoing cervical disc arthroplasty for soft disc herniation (Group B) between 2011 and 2020 were retrospectively included. All OPLL lesions on unenhanced MRI scan were correlated with a corresponding CT scan. Demographics were comparable between the two groups. OUTCOME MEASURES (PHYSIOLOGIC MEASURES)Using unenhanced magnetic resonance imaging (MRI), the T1- and T2- lesion quality (LQ) scores were calculated. Receiver operating characteristic (ROC) analysis was performed to calculate the area-under-the-curve (AUC) of both LQ scores as a predictor of the presence of OPLL. Computed tomography- (CT-) based Hounsfield unit (HU) values of OPLL lesions were obtained and compared with both LQ scores. The LQ scores for MRI scanners from different manufacturers were compared using Student's t test to confirm the validity of the LQ score by scanner type. METHODSThe regions of interest for signal intensity (SI) were defined as the darkest site of the lesion and the cerebrospinal fluid (CSF) at the cerebellomedullary cistern. The T1 and T2 LQ scores were measured as the ratio of the SI at the darkest site of the lesion divided by the SI of the CSF. RESULTSThe T1 and T2 LQ scores in Group A were significantly lower than those in Group B (p < 0.001). ROC analysis determined that T1 and T2 LQ scores of 0.46 and 0.07, respectively, could distinguish the presence of OPLL with an accuracy of 0.93 and 0.89, respectively (p<.001). When the T1 LQ score of the lesion is <0.46, a diagnosis of OPLL may be suspected with 100% sensitivity and 92.3% specificity. The HU of the lesion had a moderate negative correlation with the T1 LQ score (r=−0.665, p<.0001). Both LQ scores were unaffected by manufacturer type. CONCLUSIONSThis study found a correlation between the MRI-based T1 LQ scores and CT-based HU value for identifying OPLL lesions. Additional studies will be needed to validate that the T1 LQ score from the unenhanced MRI scan can identify cervical OPLL.

Enhanced meningeal lymphatic drainage ameliorates lipopolysaccharide-induced brain injury in aged mice

BackgroundSepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction caused by sepsis. Neuroinflammation induced by sepsis is considered a potential mechanism of SAE; however, very little is known about the role of the meningeal lymphatic system in SAE.MethodsSepsis was established in male C57BL/6J mice by intraperitoneal injection of 5 mg/kg lipopolysaccharide, and the function of meningeal lymphatic drainage was assessed. Adeno-associated virus 1-vascular endothelial growth factor C (AAV1-VEGF-C) was injected into the cisterna magna to induce meningeal lymphangiogenesis. Ligation of deep cervical lymph nodes (dCLNs) was performed to induce pre-existing meningeal lymphatic dysfunction. Cognitive function was evaluated by a fear conditioning test, and inflammatory factors were detected by enzyme-linked immunosorbent assay.ResultsThe aged mice with SAE showed a significant decrease in the drainage of OVA-647 into the dCLNs and the coverage of the Lyve-1 in the meningeal lymphatic, indicating that sepsis impaired meningeal lymphatic drainage and morphology. The meningeal lymphatic function of aged mice was more vulnerable to sepsis in comparison to young mice. Sepsis also decreased the protein levels of caspase-3 and PSD95, which was accompanied by reductions in the activity of hippocampal neurons. Microglia were significantly activated in the hippocampus of SAE mice, which was accompanied by an increase in neuroinflammation, as indicated by increases in interleukin-1 beta, interleukin-6 and Iba1 expression. Cognitive function was impaired in aged mice with SAE. However, the injection of AAV1-VEGF-C significantly increased coverage in the lymphatic system and tracer dye uptake in dCLNs, suggesting that AAV1-VEGF-C promotes meningeal lymphangiogenesis and drainage. Furthermore, AAV1-VEGF-C reduced microglial activation and neuroinflammation and improved cognitive dysfunction. Improvement of meningeal lymphatics also reduced sepsis-induced expression of disease-associated genes in aged mice. Pre-existing lymphatic dysfunction by ligating bilateral dCLNs aggravated sepsis-induced neuroinflammation and cognitive impairment.ConclusionThe meningeal lymphatic drainage is damaged in sepsis, and pre-existing defects in this drainage system exacerbate SAE-induced neuroinflammation and cognitive dysfunction. Promoting meningeal lymphatic drainage improves SAE. Manipulation of meningeal lymphangiogenesis could be a new strategy for the treatment of SAE.

Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury.

The treatment of spinal cord injury (SCI) with uncultivated human bone marrow-derived stromal cells (bmSCs) prepared by negative selection has been proposed to be therapeutically superior to treatment with stem cells that were expanded in vitro. To explore their use in clinical trials, we studied the functional effects of delayed application at 7 days after SCI by testing different doses of bmSCs. Spinal cord contusion injury was induced in adult male Wistar rats at the thoracic level T9. Human bmSCs were prepared by negative selection without expansion in vitro (NeuroCellsTM). Treatment consisted of one 150 µL injection into the cisterna magna containing 0.5 or 2.5 million fresh bmSCs or 2.5 million bmSCs. The recovery of motor functions was evaluated during a surveillance period of six weeks (6 W), during which spinal cords were assessed histologically. Treatment resulted in a significant, dose-dependent therapeutic effect on the recovery of motor performance. The histological analysis revealed a lower degree of axonal degeneration and better survival of neurons and oligodendrocytes in bmSCs treated rats. Our results support delayed intrathecal application of bmSCs prepared by negative selection without expansion in vitro as a treatment of SCI.

The Cell Permeant Phosphopetpidemimetic of VASP Alleviates Motor Function Deficits After Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) due to the rupture of an intracranial aneurysm leads to delayed vasospasm and neuroischemia, which can result in profound neurologic deficit and death. Therapeutic options after SAH are currently limited to hemodynamic optimization and nimodipine, which have limited clinical efficacy. Experimental SAH results in cerebral vasospasm have demonstrated the downregulation of nitric oxide (NO)-protein kinase G (PKG) signaling elements. VP3 is a novel cell permeant phosphopeptide mimetic of VASP, a substrate of PKG and an actin-associated protein that modulates vasorelaxation in vascular smooth muscle cells. In this study, we determined that intravenous administration of high doses of VP3 did not induce systemic hypotension in rats except at the maximal soluble dose, implying that VP3 is well-tolerated and has a wide therapeutic window. Using a single cisterna magna injection rat model of SAH, we demonstrated that intravenous administration of low-dose VP3 after SAH improved neurologic deficits for up to 14days as determined by the rotarod test. These findings suggest that strategies aimed at targeting the cerebral vasculature with VP3 may improve neurologic deficits associated with SAH.