Role and Relevance of Cerebrospinal Fluid Cells in Diagnostics and Research: State-of-the-Art and Underutilized Opportunities

Otto, Ferdinand; Harrer, Christine; Pilz, Georg; Wipfler, Peter; Harrer, Andrea

doi:10.3390/diagnostics12010079

Cited by 6 publications

(8 citation statements)

References 85 publications

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“…With this information, it is possible that the elevation in the presented patient's monocytes arose from the central nervous system involvement of her disease. We attributed her neurological symptoms to NPSLE after correlating her symptoms with her elevation in anti-dsDNA antibody levels and CSF findings, as well as by observing her response to steroids [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

The Diagnostic Dilemma of “The Great Imitator”: Heart and Cerebral Involvement of Lupus Manifesting as Bilateral Upper and Lower Extremity Weakness

Santos,

Kure,

Sanchez

et al. 2023

Case Reports in Rheumatology

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Background. Systemic lupus erythematous (SLE) is an autoimmune condition which can cause complex, multiorgan dysfunction. This autoimmune disease is caused by the production of antinuclear antibodies which allows this disease to target virtually any organ in the human body. When a patient experiences an unpredictable worsening of disease activity, it is generally considered a lupus flare. Organ dysfunction due to a lupus flare tends to manifest as separate events in the literature and rarely do we witness multiple compounding organ failures during a lupus flare. If we do witness organ dysfunction and failure, rarely do we see cardiac and cerebral involvement. Typically, patients take immunosuppressants for a long term to avoid the patient’s disease process from worsening and to provide prophylaxis from a flare to occur. Despite the availability in preventive strategies, some patients will have increased disease activity multiple times throughout their lifetime and will need increases in their medication doses or changes to their regimen. Some flares can be managed in the clinic, but more severe ones may be life-threatening that they require intravenous medications and hospitalization to achieve remission. In the following case, we see a patient with a past medical history of SLE on multiple immunosuppressants who arrived at the hospital with acute, bilateral weakness of the upper and lower extremities. It was later determined via various imaging and laboratory testing that she was having an SLE flare that was directly causing myocarditis which progressed to global ischemia of the brain via myocardial hypoperfusion. She experienced substantial recovery from her flare with treatment with high-dose, intravenous corticosteroids. Case Report. A 27-year-old female with a 2-year history of lupus and a 1-week history of paroxysmal atrial fibrillation presented with three days of bilateral focal neurological deficits in the arms and legs. She was found to have ischemic cardiac and neurologic manifestations during her hospital stay. Conclusion. Our patient presented with reversible focal neurological deficits, elevated high-sensitive troponin levels, and high lupus serum antibodies who showed significant improvement after the introduction of high-dose steroids. This case recommends keeping a large differential and to not discount patients’ past comorbidities for causing atypical symptomatology.

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Section: Discussionmentioning

confidence: 99%

The Diagnostic Dilemma of “The Great Imitator”: Heart and Cerebral Involvement of Lupus Manifesting as Bilateral Upper and Lower Extremity Weakness

Santos,

Kure,

Sanchez

et al. 2023

Case Reports in Rheumatology

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“…The CSF sample must be analysed within one to two hours after LP. This to avoid toxic reactions within the CSF that can severely alter the inflammatory phenotype and limit the life span of the CSF cells with misleading results [28]. The different cell subpopulations are prone to decay at varying rate; the granulocytes are affected first, followed by monocytes, and finally, lymphocytes [28].…”

Section: Csf Cell Countmentioning

confidence: 99%

Tick-borne diseases and the central nervous system : clinical and immunological aspects

Gyllemark

2023

Linköping University Medical Dissertations

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Lyme neuroborreliosis (LNB) is the dominating form of disseminated infection by the tick-borne bacteria Borrelia (B.) burgdorferi in Sweden as well as in Europe. The diagnosis of the manifestation is based on typical symptoms, together with elevated mononuclear cell count in the cerebrospinal fluid (CSF) and elevated levels of Borrelia-specific antibodies in the CSF. The diagnostic arsenal has, in recent years, been complemented by analysis of the chemokine CXCL13 in the CSF, with increasing levels in the early phase of the disease, even before antibodies can be detected in the CSF. Most patients recover within a couple of months after antibiotic treatment, but a few can suffer from residual symptoms. The mechanisms behind this are still puzzling, but there are indications that the host´s immune response may play a role. Prognostic markers would be desirable and increased understanding of pathogenetic mechanisms may provide a basis for development of new treatment strategies. Other agents besides B. burgdorferi have, however, also been detected in ticks collected in Sweden, but the knowledge of their impact on human health and their ability to invade the central nervous system (CNS) is limited.The aims of this thesis were to investigate a set of cytokines and chemokines associated with Th1 (CXCL10), Th2 (CCL22), Th17 (IL-17A, CXCL1, CCL20) and B cell (APRIL, BAFF, CXCL13) -related immunity and its association with recovery in patients with LNB included both retrospectively and prospectively. The chemokine CXCL13 was further analysed, comparing the performance of two different diagnostic methods. In a large cohort of patients investigated for LNB we investigated signs of other tick-borne diseases by analysing serum and CSF using both molecular and serological techniques.In the retrospective cytokine/chemokine study, all investigated cytokines and chemokines; namely, APRIL, BAFF, CXCL13, IL-17A, CXCL1, and CCL20 could be detected at elevated levels in patients with LNB compared to controls. Patients with recovery > 3 months had higher levels of APRIL, BAFF, and IL-17A. In the prospective study, patients with short recovery (< 1 month) had lower levels of CCL20 and patients with prolonged recovery (> 6 months) had higher levels of IL-17A. The analysis of the chemokine CXCL13 with both an enzyme-linked immunosorbent assay (ELISA) with a best-performanced cut-off of 56 pg/mL and bead-based (Luminex) method with a best-performance cut-off of 158 pg/mL (both assays with 100% sensitivity and specificity) displayed the importance of different cut-offs depending on which method that is used.In 600 patients, we analysed serum and CSF with PCR for the different tick-borne agents Anaplasma phagocytophilum, B. burgdorfer spp. (including B. miyamotoi), Neoehrlichia (N.) mikurensis, Rickettsia spp., Babesia spp. and tick-borne encephalitis virus. N. mikurensis and B. burgdorferi could be detected by PCR in sera from two patients. Neither PCR, nor serological analysis could detect any potential co-infections.In conclusion, we ca...

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“…CSF pleocytosis is a hallmark of neuroinflammation commonly seen in meningitis, autoimmune diseases, and leptomeningeal disease [ 10 ]. For instance, the detection of neoplastic cells within CSF indicates the leptomeningeal spread of cancer.…”

Section: Csf As a Repertoire Of Biomarkers In Diseases Of The Cnsmentioning

confidence: 99%

“…Massive granulocytosis (>1000 cells/μL) is seen in bacterial meningitis, and mononuclear pleocytosis with activated lymphocytes and monocytes is seen in viral meningitis. Aseptic bacterial meningitis secondary to less common pathogens such as Mycobacterium tuberculosis , Listeria monocytogenes , Treponema Pallidum , or Borrelia burgdorferi also results in mononuclear pleocytosis [ 10 ]. Autoimmune diseases of the CNS such as Multiple Sclerosis and Autoimmune Encephalitis have lymphocyte-predominant pleocytosis [ 10 ].…”

Section: Csf As a Repertoire Of Biomarkers In Diseases Of The Cnsmentioning

confidence: 99%

“…Aseptic bacterial meningitis secondary to less common pathogens such as Mycobacterium tuberculosis , Listeria monocytogenes , Treponema Pallidum , or Borrelia burgdorferi also results in mononuclear pleocytosis [ 10 ]. Autoimmune diseases of the CNS such as Multiple Sclerosis and Autoimmune Encephalitis have lymphocyte-predominant pleocytosis [ 10 ].…”

Section: Csf As a Repertoire Of Biomarkers In Diseases Of The Cnsmentioning

confidence: 99%

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Single-Cell RNA Sequencing of Cerebrospinal Fluid as an Advanced Form of Liquid Biopsy for Neurological Disorders

et al. 2022

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Diagnosis and longitudinal monitoring of neurological diseases are limited by the poor specificity and limited resolution of currently available techniques. Analysis of circulating cells in cerebrospinal fluid (CSF) has emerged as a promising strategy for the diagnosis, molecular characterization, and monitoring of neurological disease. In comparison to bulk sequencing analysis, single-cell sequencing studies can provide novel insights into rare cell populations and uncover heterogeneity in gene expression at a single-cell resolution, which has several implications for understanding disease pathology and treatment. Parallel development of standardized biofluid collection protocols, pre-processing strategies, reliable single-cell isolation strategies, downstream genomic analysis, and robust computational analysis is paramount for comprehensive single-cell sequencing analysis. Here we perform a comprehensive review of studies focusing on single-cell sequencing of cells in the CSF of patients with oncological or non-oncological diseases of the central nervous system.

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Role and Relevance of Cerebrospinal Fluid Cells in Diagnostics and Research: State-of-the-Art and Underutilized Opportunities

Cited by 6 publications

References 85 publications

The Diagnostic Dilemma of “The Great Imitator”: Heart and Cerebral Involvement of Lupus Manifesting as Bilateral Upper and Lower Extremity Weakness

The Diagnostic Dilemma of “The Great Imitator”: Heart and Cerebral Involvement of Lupus Manifesting as Bilateral Upper and Lower Extremity Weakness

Tick-borne diseases and the central nervous system : clinical and immunological aspects

Single-Cell RNA Sequencing of Cerebrospinal Fluid as an Advanced Form of Liquid Biopsy for Neurological Disorders

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