Cerebrospinal Fluid Characteristics Research Articles

Evaluation of the Bio-Speedy Meningitis/Encephalitis Panel in the Diagnosis of Central Nervous System Infections

Infections of the central nervous system (CNS) can lead to severe outcomes if not accurately diagnosed and treated. The broad spectrum of pathogens involved in CNS infections can make diagnosis challenging. Polymerase chain reaction (PCR) -based multiplex molecular diagnostic panels can rapidly and simultaneously detect multiple neuropathogens in cerebrospinal fluid (CSF). This study was aimed to assess the Bio-Speedy Meningitis/Encephalitis RT-PCR MX-17 panel (Bioeksen, İstanbul, Türkiye), a novel multiplex PCR test, in diagnosing CNS infections. The panel can detect a range of pathogens, including Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, enterovirus (EV), herpes simplex virus (HSV) 1 and 2, HHV-6, HHV-7, HHV-8, human parechovirus (HPeV), varicella zoster virus (VZV), cytomegalovirus (CMV) and Cryptococcus gatti/neoformans in CSF samples. This retrospective study included 128 CSF samples from 128 patients sent to Bursa Uludağ University Health Application and Research Center Microbiology Laboratory between June 2022 and July 2023 to search for CNS infectious agents. Patient clinical, radiological and laboratory data were collected from the Hospital Information Record System (HIRS). Bacterial pathogens were identified through culture, while viral pathogens were detected in CSF samples using the Fast Track Diagnostics (FTD) multiplex RT-PCR panel (Fast Track Diagnostics Ltd., Luxembourg) for HSV-1, HSV-2, VZV, EV, mumps virus and HPeV. The stored CSF samples were then tested using the BioSpeedy panel and the results were compared with those of the culture and the FTD panel. Pathogens that were detected were considered positive if they were consistent with the patient's symptoms and CSF characteristics according to infectious disease and pediatric infectious disease specialists. Pathogens detected but not supported by the patient's symptoms and CSF characteristics were classified as uncertain clinical relevance (UCR). Out of the 128 patients tested for CNS infectious agents, 44 (34.4%) were diagnosed with a CNS infection. The overall pathogen detection rate with all methods was 43.2% (19/44). The Bio-Speedy panel identified pathogens in 29.5% (13/44) of the patients, followed by the FTD panel (20.5%, 9/44) and culture (9.1%, 4/44). Four bacteria were identified with culture, three of which were also detected by the Bio-Speedy panel. Additionally, six bacteria were identified with Bio-Speedy panel, that were not identified by culture. The FTD panel identified nine viruses, four of which were also identified by Bio-Speedy. In total, the Bio-Speedy panel detected 13 of the 19 positive pathogens (nine bacteria and four viruses: [S.pneumoniae (n= 3), VZV (n= 3), N.meningitidis (n= 2), H.influenzae (n= 2), L.monocytogenes (n= 1), E.coli (n= 1) ve EV (n= 1)]. However, the Bio-Speedy panel identified 15 pathogens [S.pneumoniae (n= 1), E.coli (n= 1), C.gatti/neoformans (n= 1), CMV (n= 8), HHV-6 (n= 3) ve HHV-7 (n= 1)] considered as UCR. The Bio-Speedy identified the causative pathogens in the highest percentage (29.5%) of patients with confirmed CNS infections. Nevertheless, test results should be interpreted based on patient characteristics to ensure appropriate patient management. Using multiple methods and multiplex tests may improve diagnostic accuracy for CNS infections.

Intrathecal methotrexate, central nervous system toxicity, and response to N-methyl-D-aspartate antagonism: An adult case series

Abstract Background Methotrexate (MTX) is administered for the treatment of central nervous system (CNS) hematologic cancers, prophylaxis of CNS dissemination of certain hematological cancers, and in solid tumor leptomeningeal disease. MTX treatment can be limited by CNS toxicity. Dextromethorphan is used to treat MTX neurotoxicity, with most data derived from pediatric case series. In this report, we profile 4 adult patients who developed intrathecal (IT) MTX neurotoxicity to better characterize their response to dextromethorphan treatment. Methods A case series of 4 patients who developed neurologic symptoms attributed to IT MTX neurotoxicity subsequently treated with dextromethorphan was devised. Demographic data, clinical characteristics, electroencephalography results, magnetic resonance imaging, cerebrospinal fluid (CSF) characteristics, and dextromethorphan treatment outcomes were described. Results Of the 4 patients developing MTX neurotoxicity, neurologic symptoms developed over a timeframe of 2 to 14 days from the precedent MTX exposure. Radiologic phenotypes included subcortical white matter diffusion-restricting lesions, bi-hemispheric subcortical white matter T2-FLAIR hyperintensities, as well as other findings described in the report. Time elapsed from initiation of dextromethorphan to neurologic symptom resolution ranged from 1 to 2 days. Conclusions The profiles of 4 adult patients developing suspected IT MTX neurotoxicity syndromes with subsequent response to Dextromethorphan add further data to guide the management of such patients.

Clinical features, cerebrospinal fluid changes, and prognosis in Chinese patients with autoimmune encephalitis.

Autoimmune encephalitis (AE) is a rare, treatable disease of the central nervous system (CNS) caused by an antibody-related immune response. This study is to investigate the correlation of clinical features, cerebrospinal fluid (CSF) characteristics, and prognosis in patients with AE. A total of 71 patients diagnosed with antibody-positive AE were retrospectively analyzed. The patients were divided into three groups: anti-NMDAR group, anti-LGI1 group, and other types. Clinical data were collected to analyze clinical features and CSF results, and prognosis was determined by modified Rankin Scale (mRS). There was statistical difference in the incidences of decreased consciousness level (P < 0.001), memory loss (P = 0.017), speech disorders (P = 0.035), and dyskinesia (P = 0.001) in different antibodies groups. Younger age (P = 0.018), elevated CSF chloride content (P = 0.006), and white blood cells > 50/mm3 (P = 0.026) were highly correlated with ICU admission. Anti-LGI1 encephalitis had a relatively small risk for ICU admission (P = 0.034), and a lower risk of poor functional recovery (P = 0.048) and recurrence (P = 0.041). Patients with first-line treatment failure (P = 0.021) had an increased risk of poor functional recovery. Delayed treatment (P = 0.011) would increase the risk of recurrence. There are differences in age, gender, clinical characteristics, and CSF results in different subtypes of AE. First-line therapy failure would have poor functional recovery, and delayed therapy would increase the risk of relapse. Chloride ion content and white blood cell count in cerebrospinal fluid are positively correlated with the patient's exacerbation and admission to ICU. These indicators have certain clinical value for the prognosis of AE patients.

Nomogram to Predict the Outcome of Ventriculoperitoneal Shunt Among Patients with Non-HIV Cryptococcal Meningitis

BackgroundThe ventriculoperitoneal (VP) shunt is widely acknowledged as a treatment option for managing intracranial hypertension resulting from non-HIV cryptococcal meningitis (CM). Nonetheless, there is currently no consensus on the appropriate surgical indications for this procedure. Therefore, it is crucial to conduct a preoperative evaluation of patient characteristics and predict the outcome of the VP shunt to guide clinical treatment effectively. MethodsA retrospective analysis was conducted on data from 85 non-HIV CM patients who underwent VP shunt surgery at our hospital. The analysis involved studying demographic data, preoperative clinical manifestations, cerebrospinal fluid (CSF) characteristics, and surgical outcomes and comparisons between before and after surgery. A nomogram was developed and evaluated. ResultsThe therapy outcomes of 71 patients improved, whereas 14 cases had worse outcomes. Age, preoperative cryptococcus count, and preoperative CSF protein levels were found to influence the surgical outcome. The nomogram exhibited exceptional predictive performance (AUC = 0.896, 95% CI: 0.8292–0.9635). Internal validation confirmed the nomogram's excellent predictive capabilities. Moreover, decision curve analysis demonstrated the nomogram's practical clinical utility. ConclusionThe surgical outcome of VP shunt procedures in non-HIV CM patients was associated with age, preoperative cryptococcal count, and preoperative CSF protein levels. We developed a nomogram that can be used to predict surgical outcomes in non-HIV CM patients.

Cerebrospinal Fluid Biomarkers of Symptomatic Neurosyphilis in People With HIV Compared with Uninfected Individuals.

We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n = 42), presumptive NS (n = 74), systemic syphilis (SS) (n = 38), serological diagnosis of syphilis (n = 18), PWH without SS and NS (n = 10), and negative control (n = 72). In PWoH, for presumptive NS, the combination of CSF TP > 45mg/dL and/or WBC > 5.0 cells/mm3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS, however the DCPC were better in the suppressed group. In PWoH, the value of CSF TP > 45mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count > 20 cell/mm3, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of > 10 or > 20 cells/mm3, was moderately applicable for screening.As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, better in the former. These biomarkers could be included for presumptive NS diagnosis. DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection.

Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined usingreal-time quantitative polymerase chain reaction,while EV species were identified by5'UTR region sequencing.Median viral load was 5.72 log10 copies/mL and did not differ by subjects'age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Characteristics of cerebrospinal fluid biomarkers/imaging findings in ptaients with amyloid PET‐negative dementia

AbstractBackgroundIn daily clinical practice, we often encounter cases with atypical clinical symptoms and imaging findings, even amoung those diagnosed with Alzheimer’s disease.MethodForty‐nine cases of undiagnosed patients with atypical clinical symptoms or imaging findings underwent both amyloid PET and cerebrospinal fluid(CSF) examinations.They were divided into amyloid‐positive group(n = 25) and amyloid‐negative group(n = 24).The cerebrospinal fluid findings,neuropsychological examination findings,MRI findings,and SPECT findings were compared between the two groups.ResultCSF findings showed significant differences in amyloid‐β42,amyloid‐β42/40, and P‐tau between the two groups.There was no significant difference in MRI findings.SPECT findings showed a significant difference in decreased blood flow in the right parietal lobe and bilateral precuneus.ConclusionIn dementia patients with atypical clinical symptoms and imaging findings, CSF findings and decreased blood flow in the right parietal lobe and bilateral precuneus are suggested to be useful indicators to distinguish whether amyloid is involved in the back ground pathology.

Cerebrospinal fluid cytochemical analysis from COVID-19 patients with neurological disorders

Background: The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people around the world. Most cytochemical studies of cerebrospinal fluid (CSF) in patients infected with SARS-CoV-2 have shown abnormal results. The objective of the present investigation was to determine the physical, cytological, and chemical alterations of the CSF cytochemical examination of COVID-19 patients with neurological disorders in Peru. Methods: An observational and cross-sectional study was carried out at the Edgardo Rebagliati Martins Hospital. The study population consisted of 94 CSF samples obtained by lumbar puncture from inpatient patients. Likewise, the paired T-test and one-way ANOVA with the Bonferroni post-hoc test was used to determine the differences in the values of CSF biochemical markers. Results: The most frequent neurological disorders were encephalopathy (43%) and brain tumor (23%). The most relevant physical characteristics were cloudy and reddish fluids in the brain tumor and intracerebral hemorrhage; however, in encephalopathies, transparent-looking liquids were observed. CSF glucose from patients with encephalopathy (30%) and intracerebral hemorrhage (13%) had concentrations &gt;70 mg/dL. Proteins &gt;45mg/dl corresponded to 20% of patients with encephalopathy and 17% of patients with intracerebral hemorrhage and brain tumor. Likewise, no differences were found in glucose concentration between neurological disorders (p&gt;0.05); however, differences in protein concentration were observed (p=0.001). Finally, among the cytological characteristics, it was found that patients with encephalopathy (33%) and brain tumor (20%) presented a leukocyte count &lt;5 cells/ul. Conclusion: These findings suggest that the characteristics of CSF may differ depending on the type of neurological complication experienced by patients with COVID-19.

Cerebrospinal fluid proteomics in meningitis patients with reactivated varicella zoster virus.

This study investigated the proteomic characteristics of cerebrospinal fluid (CSF) in patients with varicella zoster virus (VZV) meningitis to understanding the pathogenesis of central nervous system (CNS) infection by reactivated VZV. We used data-independent acquisition model to analyze the CSF proteomic differences of 28 patients with VZV meningitis and 11 herpes zoster (HZ) patients. According to the clinical manifestations at discharge, 28 VZV meningitis patients were divided into favorable outcome group and unfavorable outcome (UO) group and their differences in CSF proteome were also analyzed. Compared with the HZ group, the proteins (CXCL10, ELANE, IL-1RN, MPO, PRTN3, etc.) related to inflammation and immune cell activation were significantly upregulated in the VZV meningitis group (p < .01). The protein related to the nerve function and energy metabolism (CKMT1B, SLITRK3, Synaptotagmin-3, KIF5B, etc.) were significantly downregulated (p < .05). The levels of a pro-inflammatory factor, IL-18, in CSF were significantly higher in patients in the UO group as compared to patients with favorable prognosis (p < .05). Inflammatory immune response is an important pathophysiological mechanism of CNS infection by VZV, and the CSF IL-18 levels might be a potential prognostic indicator of the outcomes of VZV meningitis.

A hospital-based retrospective study: early recognition of neuronal surface antibodies by clinical manifestations and CSF inflammation indicators in patients with unexplained epilepsy

Background There is a lack of actual and comprehensive data on the detection rate of neuronal surface antibodies in patients with unexplained epilepsy in China. Thus, we attempted to analyze the differences in clinical manifestations, cerebrospinal fluid (CSF) characteristics, seizure types and other aspects of antibody-positive and negative patients, to identify suspected antibody-positive epilepsy patients. Methods In total, 137 inpatients with unexplained epilepsy were consecutively included, and neuronal surface antibodies (NSAbs) were detected by serological and/or CSF evaluations. The clinical features and seizure characteristics were analyzed between the NSAb-positive and negative patients. In addition, patients were divided into four groups based on CSF and blood antibody titers. CSF cell count and protein content were analyzed in relation to antibody titers. Results There were 45 (32.8%) patients tested positive for antibodies. Multivariate analyses revealed that age, mental status changes or memory deterioration, CSF protein, CSF cell count, treatment, days of hospitalization, outcome, duration of symptoms before hospitalization, status epilepticus, and number of antiepileptic drugs were significantly associated with the NSAb-positive group and changes in inflammatory indicators in routine CSF analysis were associated with antibody titers. Conclusions A relatively high proportion of patients with unexplained epilepsy have positive NSAbs. Patients with the above clinical characteristics need to be highly suspected of NSAbs positivity and should be tested for antibodies in time to assist treatment. The decrease of CSF cell count and protein content has suggestive value for the decrease of antibody titer, which should be evaluated in the follow-up.

Characterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis

PurposeThere is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital.MethodsA retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis.ResultsThe most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p < 0.001). The CHANCE score was developed to differentiate BM from other causes of CSF pleocytosis: Multivariate regression revealed that CSF cell count > 100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956).ConclusionOverall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making.

Multiplex real-time PCR FilmArray performance in the diagnosis of meningoencephalitis: lights and shadows.

We aimed to evaluate the performance of the FilmArray (FA) meningitis/encephalitis (ME) panel. Secondarily, we analyzed the false positive (FP) and false negative (FN) results, as well as the predictive values of the technique, regarding the cerebrospinal fluid (CSF) characteristics. FA is a multiplex real-time PCR detecting 14 of the most common ME pathogens in CSF. All FA performed at our hospital (2018-2022) were retrospectively reviewed. FA was compared to conventional techniques and its performance was assessed based on the final diagnosis of the episode. FA was performed in 313 patients with suspicion of ME. Most patients had altered mental status (65.2%) and fever (61%). Regarding CSF characteristics, 49.8% and 53.7% presented high CSF proteins and pleocytosis, respectively. There were 84 (26.8%) positive FA results, mainly for HSV-1 (10.9%), VZV (5.1%), Enterovirus (2.6%), and S. pneumoniae (1.9%). In the 136 cases where both FA and routine methods were performed, there was a 25.7% lack of agreement. We identified 6.6% FN results, but 28.6% FP, mainly due to HSV-1. This resulted in a high negative predictive value (NPV) of 93.4%, but a positive predictive value (PPV) of 73%. Remarkably, PPV as low as 36.9%, and 70.2%, were found in cases without pleocytosis, or lack of high CSF protein levels, respectively. FA was associated with high NPV, but frequent FP results and low PPV, particularly for HSV-1, and especially in patients without high CSF protein levels or pleocytosis.

Transverse myelitis in myelin oligodendrocyte glycoprotein antibody-associated disease.

Transverse myelitis (TM) is the second most common presentation of myelin oligodendrocyte antibody-associated disease (MOGAD), occurring in approximately 26% of affected patients. The diagnosis may be complicated by the lack of diagnostic specificity of low titers of MOG antibody in serum, fluctuation in seropositivity overtime, including initially normal MRI in up to 10% of patients, and in many instances complete resolution of radiological abnormalities when MRI is done in a significantly delayed fashion. The use of preventive disease modifying treatments is limited by the uncertainty whether the disease process will remain monophasic or become relapsing, as well as by the lack FDA approved treatments. In this review, we discuss clinical, radiological and cerebrospinal fluid (CSF) characteristics, including the significance of MOG titers and changes in the seropositivity status for the diagnosis of MOGAD-associated TM, its radiological features and management options, highlighting the data on the risk of relapses associated with TM at presentation and the need for further randomized clinical trials to empower effective treatment algorithms.

Neuronal autoantibodies in a sample of Egyptian patients with drug-resistant epilepsy

BackgroundEpilepsy is one of the most common and chronic neurological diseases. About one-third of epilepsy patients do not achieve seizure freedom despite adequate therapy with antiseizure medications (ASMs) and develop drug-resistant epilepsy (DRE). Autoimmunity is increasingly being recognized as a cause of epilepsy in those patients. Some cases are associated with antibodies against several target antigens, including neuronal extracellular proteins as well as intracellular structures. In such patients, immunotherapy may be highly effective. This study aimed to investigate the presence of NMDA-R, AMPA1-R, AMPA2-R, CASPR2, LGI1, GABAB-R, and GAD65 autoantibodies in a sample of Egyptian patients with new-onset DRE; also, to assess the clinical, cerebrospinal fluid (CSF), electroencephalogram (EEG), and radiological characteristics of those patients. Twenty-five patients with recent onset DRE were recruited from the department of Neurology at Ain Shams University (ASU) hospitals. All patients underwent serum and CSF antibody testing using cell-based assay (CBA) at the Immunology unit of the Clinical pathology laboratory at ASU hospitals. This is beside routine CSF analysis, EEG and MRI brain with contrast.ResultsOut of 25 patients with recent onset DRE, one (4%) patient tested positive to anti-NMDA-R antibodies and another one (4%) tested positive to anti-GAD 65 in both serum and CSF. Although the remaining 23 patients tested negative for the 7 autoantibodies, yet 92% of them achieved either seizure freedom or more than 50% reduction in the frequency of seizure and 84% had marked improvement in seizure-associated symptoms after receiving immunotherapy trial. Also, evidence of neuroinflammation was detected in the CSF and MRI brain of the majority of those patients.ConclusionsAutoimmunity should be considered as a possible etiology of new-onset DRE. It is essential to provide insight into the clinical phenotypes and other associated features of those patients, as there are probably numerous patients who are not positive for one of the available antibodies via clinical laboratory testing. In addition to early diagnosis, early treatment and empirical immunotherapy trial based on the clinical judgment is crucial and is likely to improve outcomes with near-complete seizure freedom.

Lumbar Puncture and Meningitis in Infants with Proven Early- or Late-Onset Sepsis: An Italian Prospective Multicenter Observational Study.

Background: To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design: We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli, diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results: LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions: Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

0765 Enlarged perivascular spaces in infancy: associations with autism diagnosis, cerebrospinal fluid volume, and later sleep problems

Abstract Introduction Since the re-discovery of the glymphatic system, there has been an increased interest in perivascular spaces (PVS) and cerebrospinal fluid (CSF) characteristics in relation to sleep. Enlarged PVS (ePVS) are associated with neurological disorders and sleep problems, and excessive extra-axial CSF (EA-CSF) volume is associated with autism spectrum disorder (ASD). However, ePVS has not been studied in infancy in relation to autism, EA-CSF volume, or sleep problems. The objectives of this study, therefore, are to examine whether ePVS is 1) more prevalent in infants who later develop ASD, 2) related to EA-CSF volume, and 3) associated with later sleep problems. Methods The study was conducted on a prospective, longitudinal cohort from the Infant Brain Imaging Study (IBIS). Participants underwent neuroimaging at 6-, 12-, and 24-months of age, and parent-reported Children’s Sleep Habits Questionnaires (CSHQ) were collected at a follow-up visit at school age (age range = 7-12 years, M = 10.0). A total of 311 participants were included: 47 infants at high familial likelihood for ASD who were later diagnosed with ASD (HL+), 180 high likelihood infants not diagnosed with ASD (HL-), and 84 low likelihood control infants (LL-). The CSHQ was available on a subset of 109 participants. Results Significant group differences in ePVS rates were found at 24 months of age (p=0.041), with 44.7% of the HL+ group having ePVS, compared to 26.7% in the HL- group (p=0.017) and 26.2% in the LL- group (p=0.031). ePVS at 24 months was associated with greater EA-CSF volume from 6-24 months (p=0.002) and greater sleep disturbances at school-age (p=0.006), regardless of ASD diagnosis. Conclusion The presence of ePVS during infancy was associated with ASD diagnosis, elevated EA-CSF volume, and more frequent sleep disturbances. Results suggest that infants with ePVS should be monitored for early signs of ASD and potential long-term sleep problems, particularly sleep disturbances. Further examination is needed to establish whether early ePVS is ASD-specific or an indication of early glymphatic system dysfunction that can put infants and children at risk for atypical brain development and later sleep problems. Support (if any)

Multiple ultrafast shunt failure in oncological COVID-19 pediatric patient

Introduction: Ventriculoperitoneal shunts (VPS) are one the most frequents interventions performed in Pediatric Neurosurgery, but their failure rate continues to be high. A relation between early and repeated VPS failure and the characteristics of cerebrospinal fluid (CSF) has been previously described, and there have also been reports of alterations in CSF due to coronavirus infectious disease (COVID-19).&#x0D; Case presentation: A ten-year-old girl with a low grade thalamic glioma previously treated with two partial resections, chemotherapy and proton beam radiotherapy, developed hydrocephalus with intracranial hypertension. After emergent management with external ventricular drain, a VPS shunt with a programmable valve was implanted. The patient was diagnosed of COVID-19 in between these two procedures. Afterwards, she suffered from multiple shunt complications, with several events of obstruction. Her CSF had always very high protein concentration and COVID-19 tests were persistently positive.&#x0D; Discussion: Obstruction is the main cause of VPS malfunction in children, and many studies have tried to elucidate risk factors for failure, as younger age or type of shunt. High protein concentration and cells count in CSF could influence shunt failure, but evidence is controversial. Moreover, COVID19 could also be related to such CSF alterations.&#x0D; Conclusion: Early and repeated shunt failures are a clinical problem with no clear treatment stablished. Many factors can be associated to such complications, including CSF alterations, which may also be related to COVID19. Evidence is scarce and contradictory in many aspects, and pediatric neurosurgeons have to face this problem frequently, so more studies with management recommendations are needed.

Discrepancy in clinical and laboratory profiles of NMOSD patients between AQP4 antibody positive and negative: can NMOSD be diagnosed without AQP4 antibody?

AQP4-IgG has been considered as the pathogenic factor leading to NMOSD. However, about 20-30% of patients lack AQP4-IgG. So far, all therapeutic medicines are ineffective for NMOSD patients without AQP4 IgG. Thus AQP4-IgG is the pathogenic factor of NMOSD has been suspected and challenged. In addition, lack of efficacy of immunotherapy in NMOSD without AQP4 IgG has been a serious problem in the neurology. Identifying the clinical and laboratory characteristics and diversities between NMOSD patients with and without AQP4-IgG can be helpful to further explore the pathogenesis of NMOSD and guide clinical treatment. This is a single-centre retrospective study in The First Hospital of Jilin University, China including 92 patients diagnosed as NMOSD from January 2013 to January 2015. The characteristics of clinic, blood, cerebrospinal fluid (CSF), and image between AQP4-IgG negative (AQP4-IgG-) and AQP4-IgG positive (AQP4-IgG+) NMOSDs were compared. Our results showed that in the AQP4-IgG+ group, the ratio of women to men was 5.55, while in AQP4-IgG- group was 1.54 (P = 0.0092). In the AQP4-IgG+ patients, the expanded disability status scale (EDSS) was from 0 to 8.5, with an average of 5.550 ± 0.25, and the AQP4-IgG- patients had the EDSS score from 0 to 9, with an average of 4.032 ± 0.36 (P = 0.0006), which mainly affected movement system (P < 0.05) and superficial sensory impairment (P < 0.05). In the AQP4-IgG+ group, the blood brain barrier (BBB) permeability (P = 0.0210) and myelin basic protein (MBP) were increased (P = 0.0310) when compared to AQP4-IgG- group. Higher level IL-17 was seen in AQP4-IgG+ group than AQP4-IgG- group (P= 0.0066). Our results demonstrated that the NMOSD with AQP4-IgG more likely occurred in women and presented more severe clinical symptoms as well as significant BBB damage and increased MBP and IL-17 in CSF and blood, respectively compared with NMOSD without AQP4-IgG group. The differences in clinical and laboratory profiles between NMOSD with and without AQP4-IgG indicate the heterogeneity of NMOSD, in which AQP4-IgG may not be the only pathogenic molecule. It is necessary to find more pathogenic factors and to explore the new pathogenesis of NMOSD and therapeutic methods in the future.

Flow cytometry increases the proportion of valuable samples in cerebrospinal fluid with normal cell count in malignant blood diseases

The alteration of cerebrospinal fluid (CSF) in hematologic neoplasms is a poor prognostic marker. The characteristics of CSF are usually analyzed by flow cytometry or cytology. However, paucicellular CSF samples (≤5 cells/dL) can sometimes be considered unsuitable for analysis due to the low number of events. To evaluate the proportion of samples reported as suitable for analysis obtained by cytometry (FCM) and cytology in paucicellular CSF samples. 169 samples ofpaucicellular CSF corresponding to 115 patients with hematologic neoplasms were selected. The samples were obtained by lumbar puncture in tubes conditioned with EDTA and Transfix®. We characterized the immunophenotype ofCSF samples with an 8-color panel, and 55 samples (32%) were in a small sample tube (SST). In all cases, monocytes were identified by CD14 labeling and T lymphocytes by CD3 labeling. The acquisition was carried out in a FACSCantoII® cytometer, and the analysis was performed using Infinicyt® software. The proportion of samples suitable for analysis was higher in FCM compared to cytology (98% vs 61%, p < 0.000). We identified the presence of T lymphocytes and/or monocytes in most samples (98% and 90%, respectively). In the SST samples, the number of events recorded in low-volume samples (< 1 mL) was lower than in samples with higher volume (140 vs 556, p < 0.001), with a median of identification of 3 cell populations. FCM allows the analysis of a higher proportion ofpaucicellular CSF samples than cytology in hematologic neoplasms study.

A Case of Acute Motor Sensory Axonal Neuropathy, a Rare Form of Guillain-Barre Syndrome, Developing After Multiple COVID-19 Infections (P13-8.009)

<h3>Objective:</h3> Guillain-Barre syndrome (GBS), an autoimmune polyneuropathy characterized by ascending weakness and characteristic cerebrospinal fluid (CSF) findings, has been identified in patients previously diagnosed with COVID-19, treated for COVID-19 infection, or vaccinated against the same. GBS is divided into axonal and demyelinating subtypes, and confirmatory testing such as electromyography and nerve conduction studies can help differentiate between subtypes. Here we present a case with recurrent COVID-19 infections, most recently treated with bebtelovimab, who developed acute motor sensory axonal neuropathy (AMSAN), a rare variant of axonal GBS. <h3>Background:</h3> A 33-year-old female presented with progressive ascending weakness and sensory loss that started two weeks after COVID-19 infection. She was fully vaccinated, however, had four episodes of COVID-19 infection within the past year and a half. Two weeks after the most recent infection, which was treated with bebtelovimab, she developed rapidly progressive weakness and sensory impairment in bilateral lower extremities quickly involving upper extremities. She received two rounds of intravenous immunoglobulin (IVIG) three and five weeks after symptoms onset. Her symptoms continued to progress requiring hospitalization. Exam showed severe weakness in all limbs with distal muscle atrophy in upper extremities. Imaging was negative. CSF demostrated albuminocytological dissociation. Nerve conduction studies concluded severe motor and sensory axonal neuropathy with active denervation which led to the suspicion of Acute Motor and Sensory Axonal Neuropathy (AMSAN), a rare variant of GBS. She underwent plasmapheresis with only minimal improvement. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> Many cases of GBS have been reported after COVID-19 infection but only a few of them are about AMSAN. This case presents unique features including multiple COVID-19 infections despite prior vaccination, and the development of this rare variant of GBS. It raises the concern of multiple COVID-19 infections having a cumulative impact on peripheral nervous system leading to more severe forms of GBS with poor response to treatment. <b>Disclosure:</b> Dr. Narvaez Caicedo has nothing to disclose. Mr. Rao has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Wu has nothing to disclose.