Comparative evaluation of the diagnostic and prognostic performance of CNSide™ versus standard cytology for leptomeningeal disease.

Background: This retrospective study compares the real-world performance of cerebrospinal fluid (CSF) CNSide™ versus cytology in leptomeningeal disease (LMD). Methods: Consecutive patients with suspected LMD who underwent lumbar punctures for CSF cytology and CNSide™ from January 2020 to December 2022 were reviewed. LMD was classified by EANO criteria. Descriptive statistics, confusion matrix, Kaplan-Meier curves, and Cox proportional regression were used. Results: Median age for 87 evaluable patients was 63 years (range: 23-93); 82 (94%) met EANO criteria for possible/probable/confirmed LMD (EANO/LMD). The commonest primary cancers were breast (36,44.0%) and lung (34,41.5%). Primary lung harbored actionable mutations in 18 (53.0%); primary breast expressed hormone receptors in 27 (75%), and HER2 amplification in 8 (22%). Uncontrolled systemic disease was detected in 35 (40%), while 25 (46%) received systemic therapy with medium/high CNS penetrance at LMD diagnosis. The median time from initial cancer to LMD diagnosis was 31 months (range: 13-73). LMD was confirmed by CSF cytology in 23/82 (28%), all identified by CNSide™. CNSide™ identified 13 additional cases (36/82, 43.9%), increasing diagnostic yield by 56.5%. Median overall survival (mOS) was 31 weeks (95%CI: 21-43), significantly worse for CNSide™ positive versus negative: 4.0 versus 16.0 weeks, respectively (HR = 0.50, P = .010). While survival since LMD diagnosis did not differ by histology, time to LMD diagnosis from initial cancer diagnosis was longer for breast (48.5 months, IQR: 30.0-87.5) versus lung (8 months, IQR:0.5-16.0) cohorts. mOS was longer for patients eligible for intrathecal chemotherapy (HR: 0.189, 95%CI: 0.053-0.672, P = .010). Conclusions: This retrospective, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant molecular CSF analyses.

Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.

Adeno-associated virus (AAV) vectors have emerged as a promising tool in the development of gene therapies for various neurological diseases, including Alzheimer's disease and Parkinson's disease. However, the blood-brain barrier (BBB) poses a significant challenge to successfully delivering AAV vectors to the brain. Strategies that can overcome the BBB to improve the AAV delivery efficiency to the brain are essential to successful brain-targeted gene therapy. This review provides an overview of existing strategies employed for AAV delivery to the brain, including direct intraparenchymal injection, intra-cerebral spinal fluid injection, intranasal delivery, and intravenous injection of BBB-permeable AAVs. Focused ultrasound has emerged as a promising technology for the noninvasive and spatially targeted delivery of AAV administered by intravenous injection. This review also summarizes each strategy's current preclinical and clinical applications in treating neurological diseases. Moreover, this review includes a detailed discussion of the recent advances in the emerging focused ultrasound-mediated AAV delivery. Understanding the state-of-the-art of these gene delivery approaches is critical for future technology development to fulfill the great promise of AAV in neurological disease treatment.

Impact of introducing a new biological matrix into a validated bioanalytical method: Focus on matrix protein content.

International guidance on bioanalytical method validation recommends the practice of partial validation when introducing a new matrix from the same species into a previously fully validated assay. Planning the partial validation protocol should include an evaluation of analyte chemistry, consideration of sample container materials, and a comparison of properties between the relevant biological matrices. Transition of a serum/plasma-validated bioanalytical method to analysis from a low-protein matrix, such as urine, cerebral spinal fluid, or oral fluid can result in inconsistent analyte recovery. The low recovery can potentially be mistaken for signal suppression or lack of drug stability and may be more pronounced in low-concentration or low-volume samples. In addition, adsorption and absorption interactions with containers may be exacerbated in low-protein matrices. Several possibilities exist for mitigating the impact of non-specific binding and low-protein matrices, including surfactants, bovine serum albumin, and ß-cyclodextrin. Finally, higher matrix protein can facilitate analyte stability. Given all this, matrix protein content should not be overlooked when anticipating a partial bioanalytical method validation.

Arterial pulsation dependence of perivascular cerebrospinal fluid flow measured by dynamic diffusion tensor imaging in the human brain.

Perivascular cerebrospinal fluid (pCSF) flow is a key component of the glymphatic system. Arterial pulsation has been proposed as the main driving force of pCSF influx along the superficial and penetrating arteries; however, evidence of this mechanism in humans is limited. We proposed an experimental framework of dynamic diffusion tensor imaging with low b-values and ultra-long echo time (dynDTIlow-b) to capture pCSF flow properties during the cardiac cycle in human brains. Healthy adult volunteers (aged 17-28 years; seven men, one woman) underwent dynDTIlow-b using a clinical 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with simultaneously recorded cardiac output. The results showed that diffusion tensors reconstructed from pCSF were mainly oriented in the direction of the neighboring arterial flow. When switching from vasoconstriction to vasodilation, the axial and radial diffusivities of the pCSF increased by 5.7% and 4.94%, respectively, suggesting that arterial pulsation alters the pCSF flow both parallel and perpendicular to the arterial wall. DynDTIlow-b signal intensity at b=0 s/mm2 (i.e., T2-weighted, [S(b=0 s/mm2)]) decreased in systole, but this change was ∼7.5% of a cardiac cycle slower than the changes in apparent diffusivity, suggesting that changes in S(b=0 s/mm2) and apparent diffusivity arise from distinct physiological processes and potential biomarkers associated with perivascular space volume and pCSF flow, respectively. Additionally, the mean diffusivities of white matter showed cardiac-cycle dependencies similar to pCSF, although a delay relative to the peak time of S(b=0 s/mm2) was present, suggesting that dynDTIlow-b could potentially reveal the dynamics of magnetic resonance imaging-invisible pCSF surrounding small arteries and arterioles in white matter; this delay may result from pulse wave propagation along penetrating arteries. In conclusion, the vasodilation-induced increases in axial and radial diffusivities of pCSF and mean diffusivities of white matter are consistent with the notion that arterial pulsation can accelerate pCSF flow in human brain. Furthermore, the proposed dynDTIlow-b technique can capture various pCSF dynamics in artery pulsation.

Cerebrospinal fluid viral escape in HIV patients on antiretroviral therapy: A systematic review of reported cases.

Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28-73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one-third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape.

Does hyperphenylalaninemia induce brain glucose hypometabolism? Cerebral spinal fluid findings in treated adult phenylketonuric patients.

Despite numerous studies in human patients and animal models for phenylketonuria (PKU; OMIM#261600), the pathophysiology of PKU and the underlying causes of brain dysfunction and cognitive problems in PKU patients are not well understood. In this study, lumbar cerebral spinal fluid (CSF) was obtained immediately after blood sampling from early-treated adult PKU patients who had fasted overnight. Metabolite and amino acid concentrations in the CSF of PKU patients were compared with those of non-PKU controls. The CSF concentrations and CSF/plasma ratios for glucose and lactate were found to be below normal, similar to what has been reported for glucose transporter1 (GLUT1) deficiency patients who exhibit many of the same clinical symptoms as untreated PKU patients. CSF glucose and lactate levels were negatively correlated with CSF phenylalanine (Phe), while CSF glutamine and glutamate levels were positively correlated with CSF Phe levels. Plasma glucose levels were negatively correlated with plasma Phe concentrations in PKU subjects, which partly explains the reduced CSF glucose concentrations. Although brain glucose concentrations are unlikely to be low enough to impair brain glucose utilization, it is possible that the metabolism of Phe in the brain to produce phenyllactate, which can be transported across the blood-brain barrier to the blood, may consume glucose and/or lactate to generate the carbon backbone for glutamate. This glutamate is then converted to glutamine and carries the Phe-derived ammonia from the brain to the blood. While this mechanism remains to be tested, it may explain the correlations of CSF glutamine, glucose, and lactate concentrations with CSF Phe.

Is cranioplasty the optimal treatment for contralateral subdural effusion after decompressive craniectomy?: a case report.

Introduction and importance: Contralateral subdural effusion (CSDE) is a rare complication secondary to decompressive craniectomy (DC), which can lead to encephalocele and neurologic deterioration. The authors report a case that confirm the existence of unidirectional membrane valve, and cranioplasty is an effective treatment for CSDE. Case presentation: The authors reported a case of 43-year-old female was diagnosed with ruptured intracranial aneurysm and treated with interventional embolization. She underwent DC because of postoperative cerebral infarction subsequently. Her conscious state deteriorated accompanied by encephalocele in postoperative 2 week. A craniocerebral computed tomography (CT) confirmed the diagnosis of CSDE with cerebral hernia. A compression bandaging of the skull defect was applicated, whereas, her conscious state progressive deteriorated. She was transferred to the author's hospital where she underwent burr-hole drainage and clinical symptom has been improved. However, a relapse of CSDE was observed after the removal of drainage tube. Continuous lumbar drainage was employed, and which was ineffective for CSDE in this case. Finally, she underwent cranioplasty, with the help of drainage of subdural effusion, CSDE was completely resolved. Clinical discussion: CSDE is occasionally observed in patients after DC. Intracranial pressure (ICP) gradient and unidirectional membrane valve are the possible mechanisms of CSDE. At present, there is no optimal therapy for CSDE. For symptomatic CSDE patients, one or more treatment measures should be applicated. Conclusion: Cranioplasty is one of the curative and optimal method to treat symptomatic CSDE patients, early cranioplasty combined with burr-hole drainage should be performed for conservative treatment failed and intractable cases.

Characteristic profiling of soluble factors in the cerebrospinal fluid of patients with neurosyphilis.

BACKGROUND: Soluble inflammatory factors have been investigated in the cerebrospinal fluid (CSF) of neurosyphilis patients with low-throughput technology. This study aimed to illustrate the characteristics of soluble factors profiles in CSF of neurosyphilis patients. METHODS: We measured the concentrations of 45 cytokines/chemokines/growth factors in CSF from 112 untreated syphilis cases, including latent syphilis (LS), asymptomatic neurosyphilis (ANS), meningeal neurosyphilis (MNS), meningovascular neurosyphilis (MVNS), paralytic dementia (PD) and ocular syphilis (OS). RESULTS: Thirty-three differentially expressed soluble factors (DeSFs) were categorized into three clusters. DeSFs scores of cluster 1 and 2 (DeSFS1 and DeSFS2) were positively correlated with elevated neopterin and neurofilament light subunit (NF-L) concentration, respectively. DeSFs scores of cluster 3 were positively correlated with WBC, protein, NF-L and neopterin. Patients with LS, ANS, and OS exhibited an overall lower abundance of DeSFs. PD patients exhibited significantly increased levels of cluster 1 and 3, and the highest total DeSFs score, while patients with MNS and MVNS showed enhanced levels of cluster 2. ROC analysis revealed that DeSFS1 effectively discriminated PD, and DeSFS2 discriminated MNS/MVNS with high accuracy. CONCLUSIONS: Patients with neurosyphilis at different stages have distinctive patterns of soluble factors in CSF, which are correlated with immune status and neuronal damage.

Management of Tarlov cysts: an uncommon but potentially serious spinal column disease-review of the literature and experience with over 1000 referrals.

Tarlov cysts were thought to be anatomic variants of uncertain etiology and clinical significance when initially described over 80 years ago. They are often detected in routine lumbosacral imaging and generally not reported in a differential diagnosis. There is increasing evidence that at least some Tarlov cysts are symptomatic and can have a significant adverse impact on patients' health and well-being. Women are disproportionately affected with this condition, often presenting with long-standing pain and neurological dysfunctions. Significant gender bias has been a concern in the management of these patients. Unfortunately, there is no consensus on patient selection or management approaches for symptomatic Tarlov cysts. This review article updates information on the prevalence, diagnosis, clinical significance, and treatments of these cysts. Based on these findings and experience with over 1000 patient referrals, a treatment decision algorithm for symptomatic Tarlov cysts was constructed to provide guidance for appropriate management of patients with these complex cysts.

Post-translational modifications linked to preclinical Alzheimer's disease-related pathological and cognitive changes.

INTRODUCTION: In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults. METHODS: We constructed a protein co-expression network using 3869 cerebrospinal fluid (CSF) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically-relevant outcomes. RESULTS: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p-tau181 (M4: ß = 2.44, p < 0.001, M7: ß = 2.57, p < 0.001) and executive function performance (M4: ß = -2.00, p = 0.005, M7: ß = -2.39, p < 0.001). DISCUSSION: In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post-translational modifications for early cognitive and pathological changes.

Sex modifies effects of imaging and CSF biomarkers on cognitive and functional outcomes: a study of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. Two of 3 patients with AD are biologically female; therefore, the biological underpinnings of this diagnosis disparity may inform interventions slowing the AD progression. To bridge this gap, we conducted analyses of 1078 male and female participants from the Alzheimer's Disease Neuroimaging Initiative to examine associations between levels of cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes. The Chow test was used to quantify sex differences by determining if biological sex affects relationships between the studied biomarkers and outcomes. Multiple magnetic resonance imaging (whole brain, entorhinal cortex, middle temporal gyrus, fusiform gyrus, hippocampus), position emission tomography (AV45), and CSF (P-TAU, TAU) biomarkers were differentially associated with cognitive and functional outcomes. Post-hoc bootstrapped and association analyses confirmed these differential effects and emphasized the necessity of using separate, sex-stratified models. The studied imaging/CSF biomarkers may account for some of the sex-based variation in AD pathophysiology. The identified sex-varying relationships between CSF/imaging biomarkers and cognitive/functional outcomes warrant future biological investigation in independent cohorts.

A rare case of tumefactive demyelination of brain: A case report and literature review.

This case report highlights the diagnostic challenges encountered in a 30-year-old female presenting with fever followed by Wernicke's aphasia without right-sided weakness, ultimately diagnosed as tumefactive demyelination (TD). TD is a rare neurological condition often misidentified as brain tumors or inflammatory disorders. The case emphasizes the importance of precise differentiation through advanced magnetic resonance imaging, showing restricted diffusion at lesion edges and the absence of gadolinium enhancement. Accurate diagnosis is crucial for tailored treatment and prognostic assessment. This case contributes to our understanding of TD and underscores the need for continued research and collaboration in the field of rare neurological disorders.

A rare case of Sphingomonas paucimobilis ventriculitis.

Introduction: Nosocomial ventriculitis is a severe infection that habitually plagues neurological intensive care units. It is usually associated with external ventricular drains. Unfortunately, classic cerebral spinal fluid parameters are less specific and sensitive compared to community acquired meningitis. This is in part secondary to indolent bacteria commonly infecting external ventricular drains leading to ventriculitis. Case report: Herein, a rare case of Sphingomonas paucimobilis ventriculitis in an immunocompetent host is reported. The patient had classic symptoms of ventriculitis, but her cerebral spinal fluid parameters were benign and initial cultures were negative. Consequently, treatment was tailored to an assumed respiratory infection only to have recurrence of her symptoms. Repeat analysis of her cerebral spinal fluid was again benign, but her cerebral spinal fluid culture grew S. paucimobilis. Subsequently, the patient was treated with cefepime, which resolved her symptoms. She completed a two-week course and has had no recurrence of her infection. Conclusions: This case reinforces the need for clinicians to have heightened awareness of this emerging pathogen, its antibiotic resistance patterns, and the unique composition of this bacterium's cell wall which has ramifications on disease presentation.

The low ratio of ghrelin in plasma and cerebrospinal fluid might be beneficial to sleep.

OBJECTIVE: Ghrelin is physiologically important for maintaining sleep rhythm. Cigarette smoking has been demonstrated to significantly increase the risk of insufficient sleep by regulating ghrelin at the central and peripheral levels. No research has been published to study the relationship between active smoking and sleep via ghrelin level in cerebrospinal fluid (CSF). METHODS: A total of 139 Chinese males were recruited and divided into active smokers (n = 77) and non-smokers (n = 62). The levels of CSF and plasma ghrelin were measured. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep. RESULTS: Non-smokers had lower PSQI scores (1.71 ± 1.93) than active smokers (3.70 ± 1.78). Non-smokers have significantly lower plasma ghrelin levels and lower plasma/CSF ghrelin ratio but higher CSF ghrelin than active smokers. Among non-smokers, plasma ghrelin levels were not correlated with PSQI scores (all p > 0.05), CSF ghrelin levels were positively correlated with PSQI scores (r = 0.309, p = 0.019), and the plasma/CSF ghrelin ratio was negatively correlated with PSQI scores (r = -0.346, p = 0.008). CONCLUSIONS: This study is the first to reveal the relationship between cigarette smoking, high CSF ghrelin levels and insufficient sleep, suggesting that maintaining a normal plasma/CSF ghrelin ratio may be the physiological mechanism of healthy sleep, and the insufficient sleep population must quit smoking.

A comparison between neurological clinical signs, cerebrospinal fluid analysis, cross-sectional CNS imaging, and infectious disease testing in 168 dogs with infectious or immune-mediated meningoencephalomyelitis from Brazil.

This retrospective study evaluated canine patients with presumptively diagnosed meningoencephalomyelitis (ME) based on neurological clinical signs, cerebrospinal fluid (CSF) analysis, cross-sectional imaging, and infectious disease testing with a limited neurological-focused polymerase chain reaction (PCR) panel performed on blood and CSF. The first goal was to determine the proportion of dogs where the condition was caused by an infectious agent versus a probable immune-mediated etiology (i.e., meningoencephalomyelitis of unknown origin; MUO) in our geographic region. The secondary goals of this study were to examine and define associations between abnormal CSF test results and cross-sectional neuroimaging findings, in addition to defining the age and most common neurological clinical signs in each group of ME. A total of 168 dogs matched the inclusion criteria with magnetic resonance imaging (MRI) performed in 130 dogs and computed tomography (CT) performed in 38 dogs. Presumptive MUO was observed in 152/168 (90.5%) of dogs and infectious ME was identified in 16/168 (9.5%) of dogs (p < 0.0001). Canine distemper virus (CDV) was the most common cause of infectious ME in 10/16 dogs (62.5%). Of the total cases with a positive infectious disease result, 3/16 (18.7%) had normal CSF results and 13/16 (81.3%) had abnormal CSF results (p = 0.0078). MRI and CT abnormalities in the brain were detected in 74 and 39% of dogs with inflammatory CSF, respectively. MRI and CT abnormalities in the spinal cord were detected in 90 and 57% of dogs with inflammatory CSF results, respectively. Age was not significantly different between infectious ME and presumptive MUO groups (p = 0.15). Seizures were the most common clinical sign reported for both MUO (36.8% of cases) and infectious ME (31.2% of cases). In conclusion, presumptive MUO is significantly more common than infectious ME in this population of dogs. Furthermore, although normal CSF results were uncommon in dogs with infectious ME, this finding occurred in several patients (3/16), suggesting that infectious disease testing should be considered even in the face of normal CSF results. Finally, MRI was more sensitive than CT in the detection of abnormalities when dogs with ME had inflammatory CSF results but was not 100% sensitive, suggesting CSF analysis should be performed to rule out inflammation even when no abnormalities are detected on MRI or CT.

A novel strategy to increase the therapeutic potency of GBM chemotherapy via altering parenchymal/cerebral spinal fluid clearance rate.

Patients with glioblastoma (GBM) face a poor prognosis with a median survival of less than two years. Escalating the dose of chemotherapy is often impossible due to patient comorbidities; thus, we focused on modulating brain clearance as a mechanism to enhance drug accumulation. Given the recently identified interconnectivity between brain parenchymal fluid and cerebral spinal fluid (CSF), we reasoned enhancing drug concentration in the CSF also increases drug concentration in the parenchyma where a GBM resides. To improve drug accumulation in the CSF, we impair the motility of ependymal cell cilia. We identified FDA-approved therapeutics that interact with cilia as a "side effect." Therapeutics that inhibit airway cilia also inhibit ependymal cilia. Multiple cilia-inhibiting drugs, when administered in combination with GBM chemotherapy temozolomide (TMZ), significantly improved the overall survival of mice bearing orthotopic GBM. Combining TMZ with lidocaine results in 100% of animals surviving tumor-free to the study endpoint. This treatment results in a ~ 40-fold increase in brain TMZ levels and is well-tolerated. Mice bearing MGMT methylated, human PDX orthotopic GBM also responded with 100% of animals surviving tumor-free to the study endpoint. Finally, even mice bearing TMZ-resistant, orthotopic GBM responded to the combination treatment with 40% of animals surviving tumor-free to the study endpoint, implying this strategy can sensitize TMZ-resistant GBM. These studies offer a new concept for treating malignant brain tumors by improving the accumulation of TMZ in the CNS. In the future, this regimen may also improve the treatment of additional encephalopathies treated by brain-penetrating therapeutics. SIGNIFICANCE: We exploit the interconnectivity of parenchymal and cerebral spinal fluid to enhance the amount of temozolomide that accumulates in the central nervous system to improve the survival of mice bearing brain tumors.

Advances and applications of fluids biomarkers in diagnosis and therapeutic targets of Alzheimer's disease.

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease with challenging early diagnosis and effective treatments due to its complex pathogenesis. AD patients are often diagnosed after the appearance of the typical symptoms, thereby delaying the best opportunity for effective measures. Biomarkers could be the key to resolving the challenge. This review aims to provide an overview of application and potential value of AD biomarkers in fluids, including cerebrospinal fluid, blood, and saliva, in diagnosis and treatment. METHODS: A comprehensive search of the relevant literature was conducted to summarize potential biomarkers for AD in fluids. The paper further explored the biomarkers' utility in disease diagnosis and drug target development. RESULTS: Research on biomarkers mainly focused on amyloid-ß (Aß) plaques, Tau protein abnormal phosphorylation, axon damage, synaptic dysfunction, inflammation, and related hypotheses associated with AD mechanisms. Aß42 , total Tau (t-Tau), and phosphorylated Tau (p-Tau), have been endorsed for their diagnostic and predictive capability. However, other biomarkers remain controversial. Drugs targeting Aß have shown some efficacy and those that target BACE1 and Tau are still undergoing development. CONCLUSION: Fluid biomarkers hold considerable potential in the diagnosis and drug development of AD. However, improvements in sensitivity and specificity, and approaches for managing sample impurities, need to be addressed for better diagnosis.

A pilot study for evaluating the feasibility of using alpha-defensin to support the diagnosis of ventriculitis.

OBJECTIVES: Nosocomial ventriculitis is a difficult infectious condition to diagnose given that typical cerebral spinal fluid (CSF) parameters, commonly used in the diagnosis of meningitis, lack sensitivity and specificity in nosocomial ventriculitis. Consequently, novel diagnostics are needed to aid in diagnosing this condition. Herein a pilot study using alpha-defensins (α-defensins) to diagnose ventriculitis is discussed. METHODS: From May 01, 2022, to December 30, 2022, ten patients with culture-proven external ventricular drain (EVD)-associated ventriculitis and ten patients without EVD-associated ventriculitis had CSF preserved. Levels of α-defensins were compared between the two cohorts with enzyme-linked immunosorbent assay. RESULTS: There was a statistically significant (P ˂0.0001) higher level of CSF α-defensins in the ventriculitis cohort compared to the non-ventriculitis cohort. The levels of α-defensins were not affected by blood in CSF or bacterial virulence. Patients with other infectious conditions had increased levels of α-defensins but these levels were still statistically significantly (P ˂0.001) less than those seen in the ventriculitis cohort. CONCLUSION: This pilot study shows that α-defensins have promise as a biomarker to aid in the diagnosis of ventriculitis. If larger studies support the findings here, this biomarker can help improve diagnostic accuracy and decrease unwarranted empirical broad-spectrum antibiotic use in suspected EVD-associated ventriculitis.

Case report: Varicella associated neuropsychiatric syndrome (VANS) in two pediatric cases.

Background: Viral or bacterial infections can trigger auto-immune inflammatory reactions and conditions in children. Self-reactivity arises due to similarities in molecular structures between pathogenic microorganisms and regular body structures with consequent immune-cross reactions. Reactivation of latent Varicella Zoster Virus (VZV) infections can cause neurological sequalae, including cerebellitis, post-herpetic neuralgias, meningo/encephalitis, vasculopathy and myelopathy. We propose a syndrome caused by auto-immune reactivity triggered by molecular mimicry between VZV and the brain, culminating in a post-infectious psychiatric syndrome with childhood VZV infections. Case presentation: Two individuals, a 6-year-old male and 10-year-old female developed a neuro-psychiatric syndrome 3-6 weeks following a confirmed VZV infection with intrathecal oligoclonal bands. The 6-year-old male presented with a myasthenic syndrome, behavior deterioration and regression in school, he was poorly responsive to IVIG and risperidone, however had a pronounced response to steroid treatment. The 10-year-old female presented with marked insomnia, agitation, and behavioral regression as well as mild bradykinesia. A trial of neuroleptics and sedatives resulted in a mild unsustained reduction in psychomotor agitation and IVIG was also unsuccessful, however the patient was very responsive to steroid therapy. Conclusion: Psychiatric syndromes with evidence of intrathecal inflammation temporally related to VZV infections that are responsive to immune modulation have not been described before. Here we report two cases demonstrating neuro-psychiatric symptoms following VZV infection, with evidence of persistent CNS inflammation following the resolution of infection, and response to immune modulation.

To intervene or not to intervene: A case of symptomatic neurocysticercosis complicated by ventriculitis.

Although well described in the current literature, Neurocysticercosis [NCC] remains an enigma when confronted by practitioners. This is in part due to the haphazard nature of the parasitic infection on the central nervous system [CNS]. These include single or multiple anatomic sites of infection, stage of parasitosis, and the resultant inflammatory response. As a result, NCC can present with a complex constellation of symptomatic presentations, making therapeutic regiments highly individualized. Despite intervention, other impediments may arise post-therapy due to the nature of the infection. We present a case of rapidly progressive symptomatic NCC that initially was successfully treated, however would eventually succumb to complications of ventriculitis.