Cerebrospinal Fluid Cell Count Research Articles

Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets.

To investigate the clinical efficacy of dexamethasone (Dex) combined with isoniazid in tuberculous meningitis (TBM) and its effect on peripheral blood T cell subsets. A total of 235 patients with TBM were divided into the control group (117 cases) and the observation group (118 cases). Both groups were given conventional treatment, the control group was further given isoniazid, and the observation group was further given Dex combined with isoniazid. The therapeutic effect and improvement of clinical symptoms were evaluated, peripheral blood T lymphocyte subsets and neurological function were observed, and patients' prognosis was evaluated. The total effective rate of the observation group was higher. The recovery time of cerebrospinal fluid (CSF) pressure, CSF protein content, CSF cell count, and hospital stays in the observation group were shorter. The duration of cervicogenic headache, fever, vomiting, and coma in the observation group was shorter. CD3+ and CD4+/CD8+ proportions in the observation group were higher, and CD8+ proportion was lower. The NIHSS score and MRS score of the observation group were lower, as well as the incidence of adverse reactions. Dex combined with isoniazid alleviates clinical symptoms and neurological abnormalities and regulates peripheral blood T cell subsets in TBM.

A case of autoimmune glial fibrillary acidic protein astrocytopathy with various symptoms such as optic disc edema and cerebellar ataxia

A 59-year-old man had developed visual abnormality, nausea, headache, and weight loss since three months before. The ophthalmologist found severe optic disc edema in both eyes, and referred him to our hospital. The patient had mild cerebellar ataxia. Increased cerebrospinal fluid pressure, increased protein and cell counts, positive oligoclonal band, and contrast-enhanced head MRI showed multiple linear perivascular radial gadolinium enhancement around bilateral lateral ventricles. His subjective and objective findings significantly improved with steroid treatment. The cerebrospinal fluid was found to be positive for glial fibrillary acidic protein (GFAP) antibodies, and a diagnosis of GFAP astrocytopathy was obtained. When optic edema or radial contrast effects was observed on contrast-enhanced MRI, GFAP astrocytopathy should be considerd. Prompt immunotherapy is required to circumvent the development of permanent visual impairment.

Clinical characteristics and genetic analysis of children with Omicron BF.7.14 type novel coronavirus-related acute necrotizing encephalopathy.

To explore the clinical characteristics, etiological factors, and clinical-related genetic variant of children with acute necrotizing encephalopathy (ANE) related to the Omicron BF.7.14 novel coronavirus. Genomic variations were detected through whole exome sequencing. Additionally, we summarized the clinical data to explore the inheritance patterns associated with novel coronavirus-related ANE. This study included four patients (2 males and 2 females) with an average age of 2.78 ± 1.93 years. All the patients had prodromal symptoms of Omicron BF.7.14 virus infection, and exhibited symptoms such as altered consciousness, seizures and cognitive/language disturbances. Cranial MRI scans revealed damage to the thalamus, basal ganglia and brainstem. The cerebrospinal fluid (CSF) cell counts were nearly normal, but protein level in CSF increased significantly. Genetic analysis revealed a novel truncated variant of CRMP2 gene in one patient who suffered more severe coma score and prognosis and dead in the later stages. All children exhibited a decrease in the absolute count of T lymphocytes, helper T cells, suppressor T cells, and NK cells to varying degrees. Furthermore, levels of cytokines, including IL-1 β, IL-5, IL-6 and IL-8 were significantly elevated in the CSF, especially in patient with truncated variant of CRMP2 gene. The Omicron BF.7.14 type novel coronavirus can lead to ANE, characterized by T cell immunosuppression and a significant increase in cytokine levels in the CSF. The truncated variation of CRMP2 gene may affect the prognosis of ANE by affecting the migration of cerebral T cells.

Clinical features of five Japanese cases with leucine-rich glioma inactivated-1 (LGI1) antibody-positive encephalitis

We studied the clinical features of five Japanese cases with leucine-rich glioma inactivated-1 (LGI1) antibody-positive encephalitis. Their symptoms included seizures, hallucinations, memory impairment, apathy, anxiety, agitation, faciobrachial dystonic seizure (FBDS), and ictal piloerection. All five patients showed hippocampal fluid attenuated inversion recovery (FLAIR) hyperintensity on brain MRI even though their cell counts of cerebrospinal fluid (CSF) were normal range. Four patients had syndrome of inappropriate secretion of antidiuretic hormone. One patient with FBDS also showed basal ganglia lesion on her brain MRI. Sodium channel blockers apparently lowered the frequency of FBDS. One patient had a thyroid cancer and underwent thyroidectomy. Substantial response to immunotherapy was seen in four out of five cases. At follow-up ≥2 years, all five patients had never relapsed. In cases of limbic encephalitis with normal CSF cell counts and hyponatremia, we should consider LGI1 antibody-positive encephalitis and conduct immunotherapy immediately.

Enhancing the cytological features and diagnostic significance of cerebrospinal fluid in bacterial meningitis.

The objective of this study was to investigate the cytological features and diagnostic significance of cerebrospinal fluid (CSF) in bacterial meningitis (BM). Patients diagnosed with BM at the First Affiliated Hospital of Nanchang University Hospital between August 2021 and April 2022 were enrolled. Clinical, cranial imaging, CSF-next-generation sequencing, CSF examination, and CSF cytology data were retrospectively analyzed. CSF cytology samples were prepared using a CSF cell pelletizer (precipitation method) and stained using the May-Grunwald-Glemsa (MGG) method. The χ2 test was employed to compare the positive rate of routine CSF count and CSF cytology. Eight patients (four males and four females), aged 41-67 years, were included. Among them, two patients had undergone brain surgery within the past 4 months, one patient had an 8-year history of otitis media, and two patients had a history of sudden toothache. Clinical manifestations included fever, headache, sudden disturbance of consciousness, and neck stiffness. CSF cytology revealed abnormal inflammatory changes dominated by neutrophils in seven patients. Routine CSF cell counts exceeded 100/uL in only four cases, indicating a higher positive rate of CSF cytology for detecting CSF inflammatory reactions compared to routine cell count. Comparative detection of bacteria through the observation of CSF cytology inflammatory status in BM patients are more useful for diagnosing BM than routine CSF counts.

Where to Draw Cerebrospinal Fluid from an External Ventricular Drain? Comparison of Cerebrospinal Fluid Parameters between Two Different Collection Sites

Background: High cerebrospinal fluid (CSF) sampling frequency is considered a risk factor for external ventricular drain (EVD)-associated infections. To reduce manipulation at the proximal port and potentially minimize the risk of an infection, we aimed to analyze whether CSF parameters sampled from the far distal collection bag could provide reliable results compared to the proximal port. Methods: We included patients who were treated with an EVD at our neurosurgical intensive care unit (ICU) between June 2021 and September 2022. CSF sampling, including microbiological analysis, was performed simultaneously from the proximal port and the collection bag. Spearman’s correlation coefficients were calculated to assess the correlation of CSF cell count, protein, lactate and glucose between the two sample sites. Results: We analyzed 290 pairs of CSF samples in 77 patients. Ventriculitis was identified in 4/77 (5%) patients. In 3/4 patients, microbiological analysis showed the same bacterial species at both sample sites at the same time. Spearman’s correlation coefficient showed that CSF cell count (r = 0.762), lactate (r = 0.836) and protein (r = 0.724) had a high positive correlation between the two collection sites, while CSF glucose (r = 0.663) showed a moderate positive correlation. Conclusion: This study shows that biochemical CSF parameters can be reliably assessed from the EVD collection bag.

Clinical Course of Adult T-Cell Leukemia-Lymphoma with Central Nervous System Involvement

Background: Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell lymphoma with a highly diverse clinical presentation. Although central nervous system (CNS) involvement is common, the detailed clinical presentation of CNS-ATL needs to be clarified. Objective: This study aims to clarify the clinical course of ATL with CNS involvement. CNS involvement was classified according to the criteria of JALSG202 for acute lymphocytic leukemia as follows: Grade I: no symptoms and cerebrospinal fluid (CSF)cell count less than 5/μl and presence of abnormal lymphocytes; Grade II: asymptomatic and CSF cell count 5-50/μl and presence of abnormal lymphocytes; Grade III: symptomatic or CSF cell counts > 50 cells/μl and presence of abnormal lymphocytes. Results: The analysis included 213 cases of ATL treated at Kagoshima University Hospital from 2002 to 2021. Of these aggressive ATL cases, the clinical subtypes at initial presentation were as follows: acute type 109, lymphoma type 54, chronic type 30, smoldering type 18, and 2 cases were unclassifiable. The median age of the patients was 63 years, and 96 cases (45.1%) were women. Sixty patients had received allogeneic hematopoietic stem cell transplants. During the clinical course, 28 patients (13.1%) with a median age of 61 years and 13 women（46.4%）had CNS involvement. Two cases were classified as Grade I, six as Grade II, and 20 as Grade III. Among them, nine patients (4.2%) showed neurological symptoms at the initial ATL diagnosis, and 1 patient presented with neurological findings at the time of chronic to acute transformation. Of the remaining 203 patients, prophylactic intrathecal chemotherapy was administered in 101 cases, at which time CNS involvement was diagnosed in 9 cases (8.9%). Three patients developed symptomatic involvement while responding to chemotherapy. One patient developed symptomatic involvement when refractory to chemotherapy. Four cases were CNS recurrence with systemic disease progression after remission. Two cases were identified as primary CNS-ATL. The simplified ATL-PI (Prognostic Index) at initial ATL diagnosis for the 28 patients with CNS involvement revealed four cases with high-risk, thirteen with intermediate-risk, two with low-risk, six not eligible due to indolent ATL subtypes, and three cases with unknown risk. The incidence of CNS involvement by ATL subtype was 17.8% (19/107) for acute type, 1.8% (1/54) for lymphoma type, 16.7% (5/30) for chronic type, and 0% for smoldering type (excluding 1 case of unknown subtype and 2 cases of primary CNS-ATL) at ATL diagnosis. At the diagnosis of CNS involvement, 15 (53.6％) patients showed at least 5% of ATL cells in the peripheral blood. During a median observation period of 429 days, the 1-year cumulative incidence of CNS involvement was 12.3% (95% CI 8.3-17.1%). High-dose methotrexate-based therapy was administered to 5 patients with CNS involvement, which had a certain effect on CNS lesions but had limited efficacy for other lesions. All of these cases were treated with concomitant intrathecal chemotherapy. The 2-year overall survival rate after diagnosis of CNS involvement was 16.9% (95% CI 4.9-35.2%). The CNS-IPI (International Prognostic Index) did not predict CNS involvement in ATL. Conclusions: This is the largest study to examine the clinical course of CNS involvement of ATL. The 1-year cumulative incidence of CNS involvement was 12.3%, indicating that CNS involvement is an early complication after diagnosis of aggressive ATL, especially in leukemic subtypes. The prognosis after the diagnosis of CNS involvement was also clarified. The high frequency of CNS involvement during prophylactic intrathecal chemotherapy in patients with ATL without neurological symptoms suggests that it is an important clinical question that needs to be addressed.

Elevated phospholipids and acylcarnitines C4 and C5 in cerebrospinal fluid distinguish viral CNS infections from autoimmune neuroinflammation

BackgroundViral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and understanding of pathogenesis. We hypothesized that virus-host cell interactions lead to different changes in central nervous system (CNS) metabolism than autoimmune processes and searched for metabolite biomarkers in cerebrospinal fluid (CSF) to distinguish between the two conditions.MethodsWe applied a targeted metabolomic/lipidomic analysis to CSF samples from patients with viral CNS infections (n = 34; due to herpes simplex virus [n = 9], varicella zoster virus [n = 15], enteroviruses [n = 10]), autoimmune neuroinflammation (n = 25; autoimmune anti-NMDA-receptor encephalitis [n = 8], multiple sclerosis [n = 17), and non-inflamed controls (n = 31; Gilles de la Tourette syndrome [n = 20], Bell’s palsy with normal CSF cell count [n = 11]). 85 metabolites passed quality screening and were evaluated as biomarkers. Standard diagnostic CSF parameters were assessed for comparison.ResultsOf the standard CSF parameters, the best biomarkers were: CSF cell count for viral infections vs. controls (area under the ROC curve, AUC = 0.93), Q-albumin for viral infections vs. autoimmune neuroinflammation (AUC = 0.86), and IgG index for autoimmune neuroinflammation vs. controls (AUC = 0.90). Concentrations of 2 metabolites differed significantly (p < 0.05) between autoimmune neuroinflammation and controls, with proline being the best biomarker (AUC = 0.77). In contrast, concentrations of 67 metabolites were significantly higher in viral infections than controls, with SM.C16.0 being the best biomarker (AUC = 0.94). Concentrations of 68 metabolites were significantly higher in viral infections than in autoimmune neuroinflammation, and the 10 most accurate metabolite biomarkers (AUC = 0.89–0.93) were substantially better than Q-albumin (AUC = 0.86). These biomarkers comprised six phosphatidylcholines (AUC = 0.89–0.92), two sphingomyelins (AUC = 0.89, 0.91), and acylcarnitines isobutyrylcarnitine (C4, AUC = 0.92) and isovalerylcarnitine (C5, AUC = 0.93). Elevated C4 and C5 concentrations suggested dysfunctional mitochondrial β-oxidation and correlated only moderately with CSF cell count (Spearman ρ = 0.41 and 0.44), indicating that their increase is not primarily driven by inflammation.ConclusionsChanges in CNS metabolism differ substantially between viral CNS infections and autoimmune neuroinflammation and reveal CSF metabolites as pathophysiologically relevant diagnostic biomarkers for the differentiation between the two conditions. In viral CNS infections, the observed higher concentrations of free phospholipids are consistent with disruption of host cell membranes, whereas the elevated short-chain acylcarnitines likely reflect compromised mitochondrial homeostasis and energy generation.

Retrospective Review of Patients Treated with Intrathecal Rituximab for Primary and Secondary CNS Lymphoma and Leukemia

Background: Rituximab has been studied and incorporated into the treatment of primary and secondary CNS lymphoma (Grommes 2017; Bobillo 2023). Systemic rituximab, a CD20-targeting monoclonal antibody, is widely used in the treatment of various B-cell malignancies (Klein 2021); however penetration into the central nervous system (CNS) is limited (Petereit 2009; Harjunpää 2001). Although there are conflicting data regarding the efficacy of IV rituximab in primary CNS lymphoma (Schmitt 2019; Ferrari 2022; Bromberg 2019), its role in other B-cell malignancies with CNS involvement has not been adequately described. In particular, its role in treating the cerebrospinal fluid (CSF) space is unclear. The rationale for direct administration of rituximab into the CSF via lumbar puncture or Ommaya reservoir is to allow for consistent treatment of this compartment in order to effectively clear the CSF of lymphoma cells (Kadoch 2014). Limited data exist regarding the efficacy and safety of intrathecal rituximab (Bonney 2011 Aslan 2022; van de Fling 2008; Santiago 2021; Soares 2019). Current intrathecal armamentarium for leptomeningeal lymphoma is very limited and more data on the efficacy and safety of intrathecal rituximab is needed in these patients. Methods: This is a retrospective, single center study of adult patients with a diagnosis of leukemia or lymphoma who received intrathecal (IT) rituximab between 1/1/2016 and 12/31/2022 at Hackensack Meridian Health. Rituximab 25 mg IT was administered weekly either via lumbar puncture or into an Ommaya reservoir. The primary objective of this study was to evaluate the efficacy and safety of IT rituximab. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan Meier method. Descriptive statistics were used to summarize data for categorical and continuous variables. Results: Twelve patients were identified to have received IT rituximab at our institution between 1/1/2016 and 12/31/2022. Median age was 60 years (range 45-81), 54% were male, and 69% white. Disease types included primary CNS lymphoma (67%), diffuse large B-cell lymphoma (17%), PTLD of the CNS (8%), and chronic lymphocytic leukemia (8%). In regards to CNS disease involvement, 58% of patients presented with parenchymal and leptomeningeal disease, 33% with leptomeningeal disease only, and 8% with parenchymal disease only. There were 12 patients who received IT rituximab for the treatment of malignant CNS disease with characteristics and outcomes as shown in Table 1. The median number of IT rituximab treatments administered were 8 (range 2-9). Of the 10 patients evaluable for response, 92% of patients achieved complete response in the CSF following treatment with IT rituximab as evaluated by flow cytometry, cytology, cell count and protein levels in CSF. One patient that did not achieve CSF remission has an unusual case of relapsing/remitting CLL and leukemic meningitis. There were 2 patients unevaluable for response to IT rituximab: one patient received only 2 treatments prior to switching to hospice care; and the other patient had a severe adverse reaction (tightening of throat, flushing, toe numbness) after IT rituximab and was not continued on treatment. At a median follow-up of 19.7 months, median PFS was not reached (NR) (95% CI, 0.5-NR) ( Figure 1). Median OS was 70.1 months (95% CI, 1.2-NR). Six (50%) patients experienced adverse reactions from IT rituximab treatment, including perioral numbness, headache, nausea, and flushing ( Table 1). No treatment-related deaths occurred. One (8%) patient experienced a severe adverse reaction following administration of IT rituximab. This patient developed tightening of the throat, flushing, and toe numbness after the first IT rituximab and symptoms resolved with administration of hydrocortisone and diphenhydramine. No further IT rituximab doses were administered. Another patient experienced a mild reaction consisting of headache, fatigue, nausea, diaphoresis, hypotension, and bradycardia following the fourth dose of IT rituximab in combination with IV rituximab, but was able to complete his treatment course. Conclusions: The use of IT rituximab appears safe and showed promising activity in B cell malignancies, specifically as part of induction in patients with leptomeningeal disease and PCNSL as those patients achieved cytologic response.

The role of intrathecal free light chains kappa for the detection of autoimmune encephalitis in subacute onset neuropsychiatric syndromes

Intrathecal synthesis of free light chains kappa (FLCK) is increasingly recognized as a marker of inflammatory CNS pathologies. Here, we tested the performance of FLCK in differentiating autoimmune encephalitis (AIE) from non-inflammatory etiologies in subacute onset neuropsychiatric syndromes. Patients undergoing diagnostic work-up for suspected autoimmune encephalitis at our department between 2015 and 2020 were retrospectively assessed for definitive diagnosis, available CSF and blood samples, as well as complete clinical records. Intrathecal FLCK was measured along with established CSF markers of CNS inflammation. The study cohort consisted of 19 patients with antibody-mediated AIE (AIE+), 18 patients with suspected AIE but without detectable autoantibodies (AIE–), 10 patients with infectious (viral) encephalitis (INE), and 15 patients with degenerative encephalopathies (DGE). 25 age- and sex-matched patients with non-inflammatory neurological diseases (NIND) were used as a control group. All AIE+ patients exhibited intrathecal synthesis of FLCK compared to only 39% of AIE– patients and 81% of patients in the INE group. No intrathecal synthesis of FLCK was found in DGE and NIND patients. While intrathecal FLCK was equally specific for an inflammatory etiology as oligoclonal bands (OCB) in the cerebrospinal fluid (CSF), the sensitivity of intrathecal FLCK for any inflammatory intrathecal process was higher than that of OCB (83% vs. 38%). Intrathecal FLCK synthesis was found to discriminate AIE+ from non-inflammatory encephalopathies and AIE– when the CSF cell count was normal [receiver operating characteristic (ROC) analysis area under the curve (AUC): 0.867, p = 0.002], while it failed to differentiate between AIE+ and INE in the presence of CSF pleocytosis (AUC: 0.561, p = 0.607). In conclusion, in the absence of CSF pleocytosis, intrathecal FLCK discriminated AIE+ from competing diagnoses in our cohort of subacute onset neuropsychiatric syndromes. In addition to established markers of CSF inflammation, intrathecal FLCK might support clinical decision-making and contribute to selecting patients for (repeated) antibody testing.

A-135 Improving Cell Count Turnaround Times With the GloCyte® Automated Cell Counter for CSF: A Retrospective Study at MercyOne Des Moines Medical Center

Abstract Background Accurate, STAT cerebrospinal fluid (CSF) cell counts are critical in the diagnosis of meningitis, malignancy, demyelinating disease, and hemorrhage. Due to historical limitations with the linearity of automated analyzers, CSF cell counts have traditionally been performed manually with a hemocytometer and the aid of a brightfield optical microscope. Manual cell counting is time-consuming, subjective due to reliance on human interpretation, and requires a high degree of skill. This poses significant challenges for clinical laboratories of all sizes facing unprecedented med tech shortages. The purpose of this study was to evaluate the impact of implementing the GloCyte Automated Cell Counter for CSF, an FDA-cleared device with linearity down to 0 cells/µL, on result turnaround times. Methods Result turnaround time data for CSF specimens processed in the hematology lab at MercyOne Des Moines Medical Center, a 600-bed hospital in Des Moines, Iowa, was analyzed in a retrospective study of two cell counting methods- (1) manual cell counting using a Neubauer-Improved hemocytometer and (2) GloCyte, a benchtop cell counting device that uses fluorescence technology and highly specific reagents to automate RBC and TNC cell counts in less than 5 min. Turnaround times for 227 CSF specimens counted manually during an approximately six-month period prior to the implementation of GloCyte (January 2, 2017 to June 29, 2017) were compared to those for 133 specimens analyzed on GloCyte over a similar duration (January 4, 2021 to June 30, 2021). In this study, turnaround times were defined as the time between specimen arrival in the lab and result verification. Correlation between the methods was previously established in the MercyOne Des Moines Medical Center laboratory. Results The data demonstrated a significant, 16–30-minute improvement in turnaround times with GloCyte compared to the manual hemocytometer method. Median turnaround times, analyzed to adjust for add-ons that resulted in longer turnaround times pre- and post-GloCyte implementation, were 1:38h for specimens counted manually vs 1:08 h for specimens analyzed on GloCyte. The average turnaround time for the 227 CSF specimens counted manually was 2:03 h compared to 1:46 h for the 133 samples analyzed on GloCyte. The MercyOne Des Moines Medical Center laboratory processed 456 CSF cell counts in 2022, equating to a reduction in turnaround time of 122–228 h annually with the implementation of GloCyte. Conclusion This study demonstrates that GloCyte can be implemented to significantly improve turnaround times for CSF cell counts. The MercyOne Des Moines Medical Center laboratory realized several benefits from the reduction in turnaround times- GloCyte has (1) freed up significant tech time for other tasks, (2) standardized CSF cell counting to mitigate tech to tech variability, (3) increased lab staff satisfaction and decreased stress levels, and (3) increased physician satisfaction. For MercyOne Des Moines Medical Center’s sister site, MercyOne West Des Moines Medical Center, a 146-bed hospital that infrequently performs CSF cell counts, GloCyte has provided peace of mind in performing cell counts accurately with techs of all skill levels.

A Journey from Schizophrenia to Paraneoplastic Limbic Encephalitis

A 58-year female presented with behavioral changes, dementia, and hallucinations for which she was initially treated as a case of schizophrenia. Later she developed hypersomnolence, speech difficulty and urinary incontinence. She also developed seizures later. On investigations cerebrospinal fluid (CSF) cell count was high and chest x-ray revealed homogeneous opacity over the left upper and midzone. Contrast-enhanced computerized tomography (CECT) Thorax revealed apical segment collapse consolidation with air bronchogram and bilateral pleural effusion. Multiple hepatic and bony metastasis s/o primary bronchoalveolar carcinoma. Osteolytic lesions were also found on skull x-ray and on pelvis x-ray. Tissue diagnosis couldn’t be done as the patient’s general condition deteriorated and the patient left against medical advice. From the above clinical picture and investigation findings, it was diagnosed as a case of paraneoplastic limbic encephalitis.

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.

The spectrum of cerebrospinal fluid findings in tuberculous meningitis and their relation to severity, radiological features, and outcome.

The aim of the study was to evaluate cerebrospinal fluid (CSF) findings in tuberculous meningitis (TBM) and correlate it with severity, radiological features, and outcome of TBM. In a retrospective study, data from admitted TBM patients were analyzed, and findings of CSF examinations were recorded. The CSF was categorized as typical (protein 50-500 mg/dL, cells 50-500/mm3, and glucose 50% or lower of blood sugar); those above and below these values were categorized as increased or decreased, respectively. The CSF findings were correlated with stage of TBM, and 3-month outcome and radiological features. Paradoxical response was also noted. There were 111 patients with TBM (definite 34, highly probable 77). On admission, 20 patients were in Stage I, 63 in Stage II, and 28 in Stage III TBM. CSF cells were in typical range in 73, low in 27 and increased in 11 patients. Protein was in typical range in 92 patients decreased in 11 patients and increased in eight patients. Sugar was normal in 41 and reduced in 70 patients. CSF cells, glucose, and protein did not correlate with the severity of meningitis. Fifteen patients had normal initial magnetic resonance imaging (MRI). Tuberculomas were present in 53 patients, hydrocephalus in 43 patients, basal exudates in 43 patients, and infarction in 44 patients. Mixed findings were present in 65 patients. The MRI features did not correlate with CSF. Second CSF was available after a median duration of 26 (13-276) days in 50 patients. The CSF cells were decreased in 20 and increased in 30 patients, protein increased in 30 and sugars decreased in 16 patients. Paradoxical worsening occurred in 27 patients. Fifty-one patients recovered completely, 41 partially, 15 had poor, three patients were lost to follow-up, and one died. CSF parameters did not correlate with 3-month outcome or paradoxical worsening. CSF parameters do not differ significantly between baseline and 1 month CSF, but cells and lymphocytes changed significantly between 1st month and 3rd month CSF. Typical CSF findings were present in 66% and did not correlate severity of TBM, radiological features paradoxical worsening or 3-month outcome. CSF cell count decreased within 3 months of treatment.

What is autoimmune encephalitis-associated epilepsy? Proposal of a practical definition.

Seizures resulting from cerebral autoimmunity are either acutely symptomatic in the context of autoimmune encephalitis (AIE) with neural surface antibodies, or they are indicative of an enduring predisposition to seizures, that is, epilepsy. Here, we propose a practical definition for autoimmune encephalitis-associated epilepsy (AEAE): Seizures associated with antibodies against glutamic acid decarboxylase, paraneoplastic syndromes, or Rasmussen encephalitis are classified as AEAE. AEAE secondary to AIE with antibodies against the N-methyl-D-aspartate receptor, leucine-rich glioma inactivated protein 1, contactin-associated protein-2, or γ-aminobutyric acid-B receptor can be diagnosed if the following criteria are met: seizures persist for at least 2 years after immunotherapy initiation; no signs of encephalitis on magnetic resonance imaging and no fluorodeoxyglucose positron emission tomography hypermetabolism; normal cerebrospinal fluid cell count; and a substantial decrease in antibody titers. This classification corresponds to different disease mechanisms. While AIE results from the pathogenic effects of neural antibodies, AEAE is probably the consequence of encephalitis-related tissue damage and thereby mainly structurally mediated. The distinction between AIE and AEAE also has practical consequences: In AIE, immunotherapy is usually highly beneficial, whereas anti-seizure medication has little effect. In AEAE, immunotherapy is less promising and the usual anti-seizure interventions are preferable. In addition, the diagnosis of AEAE has social consequences in terms of driving and professional limitations.

Meta-analysis of Cerebrospinal Fluid Cell Count and Biochemistry to Diagnose Meningitis in Infants Aged < 90 Days.

Cerebrospinal fluid (CSF) white blood cell (WBC) count, protein, and glucose (cytochemistry) are performed to aid in the diagnosis of meningitis in young infants. However, studies have reported varying diagnostic accuracies. We assessed the diagnostic accuracy of CSF cytochemistry in infants below 90 days and determined the certainty of evidence. We searched PubMed, Embase, Cochrane Library, Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases in August 2021. We included studies that evaluated the diagnostic accuracy of CSF cytochemistry compared with CSF culture, Gram stain, or polymerase chain reaction in neonates and young infants <90 days with suspected meningitis. We pooled data using the hierarchical summary receiver operator characteristic (ROC) model. Of the 10,720 unique records, 16 studies were eligible for meta-analysis, with a cumulative sample size of 31,695 (15 studies) for WBC, 12,936 (11 studies) for protein, and 1,120 (4 studies) for glucose. The median (Q1, Q3) specificities of WBC, protein, and glucose were 87 (82, 91), 89 (81, 94), and 91% (76, 99), respectively. The pooled sensitivities (95% confidence interval [CI]) at median specificity of WBC count, protein, and glucose were 90 (88, 92), 92 (89, 94), and 71% (54, 85), respectively. The area (95% CI) under ROC curves were 0.89 (0.87, 0.90), 0.87 (0.85, 0.88), and 0.81 (0.74, 0.88) for WBC, protein, and glucose, respectively. There was an unclear/high risk of bias and applicability concern in most studies. Overall certainty of the evidence was moderate. A bivariate model-based analysis to estimate the diagnostic accuracy at specific thresholds could not be conducted due to a paucity of data. CSF WBC and protein have good diagnostic accuracy for the diagnosis of meningitis in infants below 90 days of age. CSF glucose has good specificity but poor sensitivity. However, we could not identify enough studies to define an optimal threshold for the positivity of these tests. · Median specificity of CSF leucocyte count, protein and glucose are similar in young infants.. · At median specificity, CSF leukocyte count and protein are more sensitive than glucose.. · Owing to inadequate data, bivariate modelling to suggest optimal diagnostic thresholds is not possible..

Clinical spectrum and laboratory profile of scrub typhus in children: A study from tertiary care hospital in Uttarakhand, Northern India

Background: Scrub typhus is a mite-born disease scrub. It commonly manifests as an acute febrile illness with multi-system involvement. It is regarded as a life-threatening disease in children, with serious complications usually occurring in the 2nd week of illness. Aims and Objectives: The aims of this study were to explore the clinical and laboratory profile of children with scrub typhus. Materials and Methods: All children admitted with scrub typhus over 1-year duration were enrolled in the study. The clinical, laboratory profile, and outcome were observed and analyzed. Results: A total of 47 children were diagnosed with scrub typhus, 17 (36.1%) children had clinical and laboratory evidence of meningitis. The most frequent presenting features were fever (100%), headache (82.4%), vomiting (82.4%), seizures (41.2%), and altered sensorium (70.6%). The mean duration of fever was 6.57 days, eight children (7%) had persistent fever for &gt;14 days duration. Other complications reported were hepatitis 2 (4.3%), hepatosplenomegaly in 18 (38.3%) acute respiratory distress syndrome 2 (4.3%), and shock 31 (66%). The mean cerebrospinal fluid (CSF) protein, glucose, and cell count was 65.75±9.27 mg/dL, 45.00±7.23 mg/dL, and 65.94±52.72 cells/mm3 of CSF, respectively, with lymphocyte count of more than 96% in all cases. Most patients had lymphocytic pleocytosis and the mean lymphocyte percentage was 96.2%±4.5%. Out of all 47 patients, 45 (84.61%) patients recovered with appropriate antibiotics in both groups, while two (15.38%) patients expired in the group without meningitis. Conclusion: A high degree of suspicion and knowledge of the geographical distribution of Rickettsial diseases is crucial for its early diagnosis and favorable outcome. Scrub typhus should be considered in the differential diagnosis of aseptic meningitis.

Lower initial red blood cell count in cerebrospinal fluid predicts good functional outcome in patients with spontaneous subarachnoid haemorrhage.

Red blood cell (RBC) degradation after subarachnoid haemorrhage (SAH) negatively affects functional outcome. Although the detection of RBCs in the cerebrospinal fluid (CSF) is a widely available part of neurological routine diagnostics, the prognostic value as a biomarker remains unclear. This study was undertaken to investigate whether CSF RBC count correlates with established radiological markers of SAH volume and whether the CSF RBC count can predict functional outcome in SAH patients. A total of 121 consecutive spontaneous SAH patients were retrospectively analyzed. CSF was collected from external ventricular drain as part of routine diagnostic procedures. We used multivariable binary logistic regression to investigate associations between CSF RBC counts and functional outcome 3 months after SAH or hospital survival. Good functional outcome was defined as modified Rankin Scale ≤ 2. Patients' age was 60 ± 14 years, and the median admission Hunt & Hess grade (H&H) was 4. CSF samples were collected 2 days after intensive care unit admission. High CSF RBC counts positively correlated with radiological measurements for SAH volume, for example, modified Fisher score (p = 0.002) and Hijdra ventricle score (p = 0.016). Multivariable regression analysis adjusted for age, H&H grade, modified Fisher and Hijdra scores showed that low CSF RBC counts predicted hospital survival (per 100,000 CSF RBCs: adjusted odds ratio [adjOR] = 0.74, 95% confidence interval [CI] = 0.61-0.89, p = 0.001) and good functional outcome after 3 months (per 100,000 CSF RBC: adjOR = 0.76, 95% CI = 0.60-0.96, p = 0.020). CSF RBC counts correlate with radiographic scores quantifying SAH volume and may serve as an early independent biomarker for hospital survival and good functional 3-month outcome in patients requiring ventriculostomy after SAH.

A Summer of Fevers and Fussiness: Eighteen Infants Admitted With Parechovirus Meningitis.

To define the presentation, spectrum of illness, and outcomes in infants with parechovirus (PeV) meningitis admitted to our inpatient general pediatrics service during a spike in incidence of admissions in summer 2022. This study is a retrospective case series of all patients aged 3 months and younger discharged from our institution with a CSF BioFire (BioFire Diagnostics, Salt Lake City, UT) FilmArray Polymerase Chain Reaction Meningitis/Encephalitis Panel result positive for PeV between January 1 and September 19, 2022. We collected and analyzed clinical and demographic data. Eighteen infants with PeV meningitis were admitted within our time frame, with 8 (44%) of the admissions occurring in July. Patients' mean age was 28.7 days and mean length of stay was 50.5 hours. Although all had a history of fever, only 72% were febrile on presentation. Laboratory findings showed a procalcitonin of less than 0.5 ng/mL in 86% of the 14 patients who had it drawn and no cerebrospinal fluid (CSF) pleocytosis in 83% of the patients who had CSF cell counts sent. Neutropenia was present in 17%. Although 89% of infants were given initial antibiotics, antibiotics were discontinued in 63% once their CSF panel returned positive for PeV, and in all by 48 hours. Infants hospitalized with PeV meningitis were febrile and fussy, but experienced uncomplicated hospital stays without neurological deficits. Parechovirus meningitis must be considered as a common cause of acute viral meningitis in young infants even without CSF pleocytosis. This study, although limited in scope and follow-up, can potentially assist in the diagnosis and treatment of PeV meningitis at other institutions.