Pleocytosis Research Articles

Matched oligoclonal bands: Diagnostic utility and clinical characteristics.

To describe patient clinical characteristics associated with matched oligoclonal bands (OCB). A retrospective review at the University of Utah examined patients with matched OCB from 2015 to 2020. Clinical data, diagnosis, and outcomes were collected. Patients were classified with either multiple sclerosis (MS), other inflammatory neurologic disorder (other-IND), or noninflammatory neurologic disorder (NIND). Of 539 identified patients, 436 (53.4% female) were matched-only, while 103 (43.7% female) were matched + unique. Patients with matched-only bands were older (57.4 ± 16 vs. 52 ± 14.2, p < 0.001) and more likely to have a history of autoimmune disease (40.1% vs. 28.2%, p = 0.024) and/or cancer (28.7% vs. 16.5%, p = 0.012). Patients with matched + unique bands were more likely to have CSF pleocytosis (52.4% vs. 25.9%, p < 0.001), high IgG index (52.2% vs. 7.6%, p < 0.001), and an abnormal MRI (86.9% vs. 63.1%, p < 0.001). More than two-thirds of matched-only patients had NIND, while 33% and 41.7% of matched + unique patients had MS and other-IND, respectively. Patients exhibiting matched-only bands and a high IgG index demonstrated a significantly higher incidence of other-IND compared to those with matched-only bands and a normal IgG index (55.6% vs. 30.4%, p = 0.013). While Kaplan-Meier survival curves demonstrated higher mortality in the matched-only cohort compared to the matched + unique cohort (p = 0.02), multivariable Cox regression analysis showed this difference was not statistically significant when adjusting for various factors. A history of cancer was the significant predictor of increased mortality risk (Hazard ratio = 3.147, 95% CI [2.196, 4.51]). Patients with matched only versus matched + unique OCB have distinct clinical profiles.

Significant CSF Pleocytosis Associated with Immune-Checkpoint Inhibitor Meningoencephalitis in Metastatic Squamous Cell Thymic Cancer

Significant CSF Pleocytosis Associated with Immune-Checkpoint Inhibitor Meningoencephalitis in Metastatic Squamous Cell Thymic Cancer

Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy.

Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences. A cohort study spanning 10years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits. Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304days, IQR 1433-3274) indicated favorable outcomes in both groups. This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.

The characterization and the impact of CSF pleocytosis during blinatumomab therapy for adult acute lymphoblastic leukemia

Reactive pleocytosis in the CSF has been observed with blinatumomab but has not been well-described. We performed a retrospective study of 88 patients who received intrathecal chemotherapy (IT) while on blinatumomab with CSF analyzed to determine if pleocytosis had an impact efficacy and safety. Blinatumomab was used for relapsed/refractory 62.5%, MRD-positive 31.8%, and consolidation in MRD-negative 5.7%. The incidence of pleocytosis in CSF was 51% and was more frequent after day 15 (55.8% vs. 18.2%, p = 0.025). Pleocytosis did not impact CR, clearance of MRD positivity, PFS and OS rates. Lower incidence of non-CNS extramedullary relapse was seen (3.7% vs. 30.8%, p = 0.011) with pleocytosis in CSF. Analysis of CSF by flow cytometry showed median CD4:CD8 ratio of 1.34. In conclusion, CSF pleocytosis is prevalent with blinatumomab but only demonstrated lower rates of non-CNS extramedullary relapse but no impact on CNS relapse or neurotoxicity.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients

BackgroundRecognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses.MethodsA prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome.ResultsThis study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384–73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045–28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48–49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25–25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48–12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09–27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798–0.934) with a sensitivity of 0.761 and specificity of 0.869.ConclusionWe established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis

BackgroundIsolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE. MethodsThis multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data was performed. ResultsOf 249 children included, 12 (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11 of 12 = 92%) had at least one abnormal finding on initial ancillary testing: eight of 12 (67%) had an abnormal EEG, six of 12 (50%) had an abnormal MRI, and five of 12 (42%) demonstrated CSF pleocytosis. The single patient with a normal MRI, EEG, and CSF profile had low positive CSF NMDA antibody (titer of 1:1), and symptoms improved without immunotherapy. ConclusionsIsolated first-episode psychiatric symptoms in pNMDARE are uncommon, and the majority of children will exhibit additional neurodiagnostic abnormalities. Delaying immunotherapy in a child with isolated psychiatric symptoms and normal neurodiagnostic testing may be warranted while awaiting confirmatory antibody testing.

Ocular Flutter, Ataxia, and Myoclonus Associated With CSF Pleocytosis and GAD65 Antibodies Years After Curative Treatment of Follicular Thyroid Carcinoma: A Case Report and Literature Review.

Ocular Flutter, Ataxia, and Myoclonus Associated With CSF Pleocytosis and GAD65 Antibodies Years After Curative Treatment of Follicular Thyroid Carcinoma: A Case Report and Literature Review.

Frequency, characteristics, predictors and treatment of relapsing myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD)

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may have a monophasic or relapsing disease course. To date, factors that may predict a relapsing disease course remain largely unknown and only limited data exist regarding the efficacy of different utilized immunotherapy regimens at preventing or reducing relapses. ObjectivesTo assess the characteristics, predictors, and immunotherapy of relapsing MOGAD. MethodsThis multicenter retrospective analysis included all MOGAD cases at the University of Florida, Baylor College of Medicine and the University of California San Diego with minimum follow-up time of 6 months. Cox proportional hazards regression analyses, corrected for age and sex, were performed to evaluate hazard ratios (HR) of predictors of a relapsing disease course and to compare relapse hazards for utilized immunotherapies. ResultsThe majority of included participants (51/79 [64.6 %]) had a relapsing course, and of these individuals, 68.6 % (35/51) experienced their first relapse within the first year. However, 10/51 (19.6 %) participants experienced their first relapse ≥5 years (5–15 years) after the initial presentation. Predictors of a relapsing course were CSF pleocytosis (>150 cells/mm3; HR 3.3 [1.18 – 9.24]; p = 0.023), a pediatric disease onset at age < 9 years (HR 2.69 [1.07–6.75]; p = 0.035), and an initial presentation with the clinical syndrome of meningoencephalitis (HR 3.42 [1.28 – 9.17]; p = 0.015),. In participants with a relapsing course, 13/24 (54.2 %) patients remained relapse-free on rituximab, 4/8 (50 %) on mycophenolate mofetil, and 11/14 (78.6 %) on scheduled immunoglobulins. Patients treated with immunoglobulins had significantly fewer relapses compared to patients treated with other immunotherapies (HR: 0.1 [0.2 – 0.63]; p = 0.014). ConclusionsIn our cohort, the majority of MOGAD patients relapsed. The initial relapse occurred most frequently within the first year, but first relapses also took place over a decade after the initial presentation. Prepubertal onset, severe CSF pleocytosis, and the clinical syndrome of meningoencephalitis may be predictors of a relapsing course. Of the currently available off-label steroid-sparing treatments, scheduled immunoglobulins may be the most effective in relapse prevention.

Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease.

Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients. Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed. Fifteen patients (60% women), with a median age of 53 years (48.5 - 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 - 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites. This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

Seroprevalence of neuronal antibodies in diseases mimicking autoimmune encephalitis

Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays and lineblots. However, lineblots may reveal the presence of neuronal antibodies in patients with various non-autoimmune etiologies. Herein we describe patients with non-autoimmune etiologies (cohort B) and detectable neuronal antibodies and compare them to definite cases of autoimmune encephalitis (cohort A) for differences in clinical data. All patients positive for at least one neuronal antibody were retrospectively evaluated for autoimmune encephalitis and/or paraneoplastic neurological syndrome between 2016 and 2022. 39 cases in cohort B and 23 in cohort A were identified. In cohort B, most common diagnoses were neurodegenerative disorders in 9/39 (23.1%), brain tumors in 6/39 (15.4%) while most common detected antibodies were anti–titin (N10), anti-recoverin (N11), anti-Yo (N8) and all were detected in serum only. Differential aspects between cohort A and B were CSF pleocytosis (14/23 (60.8%) vs 11/35 (31.4%), p = 0.042, respectively), MRI features suggestive of encephalitis (6/23 (26.1%) vs 0 (0%), p = 0.002, respectively) and epilepsy restricted to temporal lobes (14/23 (60.9%) vs 2/30 (6.7%), p = 0.0003, respectively). A large proportion of lineblot results were non-specific when only serum was tested and were frequently found in non-autoimmune neurological conditions.

Autoimmune-associated epilepsy in an outpatient epilepsy clinic: A retrospective study

PurposeTo analyse cases with suspected autoimmune-associated epilepsy (AAEp) and to compare them to patients with acute symptomatic seizures secondary to autoimmune encephalitis (ASS-AEn). MethodsSingle-centre retrospective analysis of patients with suspected AAEp seen in an outpatient epilepsy clinic between 2014 and 2021. Differences according to autoimmune testing results and their responsiveness to immunotherapy were assessed and compared with our cohort of patients with ASS-AEn. ResultsA total of 30 patients were included: 18 women (60%); mean age 28.2 years at seizure-onset. AAEp was diagnosed in 14 (46.6%), on the basis of antineuronal antibodies, CSF pleocytosis/OCB (oligoclonal bands), MRI with neuroinflammation, and/or PET hypermetabolism. Thirteen patients (43.3%) received immunotherapy, of whom 5 responded (38.4%). Delay between epilepsy-onset and autoimmune testing was longer in patients with negative autoimmune-testing and in non-responders. Viral prodrome (P < .035), associated neurological signs/symptoms and MRI showing neuroinflammation were more common in responders. ASS-AEn patients were older (P < .019), and more frequently presented coexisting neurological signs/symptoms (P < .0001), antineuronal cell-surface antibodies (P < .009), neuroinflammation on MRI, PET hypermetabolism (P < .01), CSF pleocytosis (P < .047), and higher APE (antibody prevalence in epilepsy)/RITE (response to immunotherapy in epilepsy)-scores (P < .022/P < .004). Drug-refractoriness (P < .033) was more common in AAEp. ASS-AEn received immunotherapy more frequently, with better outcomes. Diagnosis and treatment delay were longer in AAEp (P < .0001). ConclusionIsolated/chronic AAEp is a rare, drug-resistant epileptic-disorder. Early diagnosis is essential for immunotherapy. However, diagnostic and therapeutic delay is longer in AAEp than in ASS-AEn. This may indicate that currently there is less capacity to detect AAEp than ASS-AEn.

2713. Risk factors and clinical presentation of Herpes Simplex Virus Encephalitis in cancer patients

Abstract Background Herpes Simplex Virus Encephalitis (HSVE) can have lifelong sequelae. Presentation can be nonspecific in cancer patients. Cerebrospinal fluid testing may be falsely negative early in illness [1]. New immune-based or targeted radiation (RT) modalities may change risk, incidence of HSVE in cancer patients. Methods Retrospective study at Memorial Sloan Kettering Cancer Center (MSK). Review of records of patients with CSF meningitis/encephalitis (ME) PCR panels from 8/1/2016 to 7/31/2022. All unique patients who received brain RT at MSK during those dates were used to calculate incidence rates. Results 2749 patients had 5497 CSF analyses with ME panel. Of these, 12 tests from 10 patients showed HSV-1 or -2; 1 patient had relapsing HSVE and 3 positive HSV2 tests each done at least 6 months apart. Table 1 shows 10 patients with HSVE. 8 had solid tumors, 6 with receipt of chemo- or immunotherapy within 30 days. All solid tumor patients with HSVE had brain RT; 6 received steroids. 1 patient with relapsing HSVE was on immune checkpoint inhibitor (ICI). 4/8 patients with MRIs (Table 2) lacked typical findings; 4/8 patients with EEGs had focal temporal seizure activity. CSF pleocytosis was absent in 4/10 cases. 5 patients had residual deficits. 4 died due to progression of disease. Incidence of HSVE with brain radiation was 2.6/10,000 patient-years. Conclusion General population incidence of HSVE ranges from 1-4 per million population per year [2]. Those receiving cancer treatment and brain RT have elevated HSVE risk. We found the risk after brain RT is much higher: 2.6/10,000 person-years. Only 1 of 10 patients in our series made a full recovery. Other key findings include: Limitations: Disclosures Mini Kamboj, MD , ASCO: speaker fee|Medscape: speaker fee|MJH life sciences: speaker fee|Regeneron: Advisor/Consultant|Web md: speaker fee

1670. It Is Likely Not HSV: Decreasing Empiric Acyclovir Use In Low-Risk Infants

Abstract Background Neonatal HSV infection is a rare but potentially devastating disease. Institutional practices regarding which neonates must be treated empirically with acyclovir varies. While some centers elect to treat all neonates presenting with fever or hypothermia, some treat only those considered at risk. Our goal was to decrease empiric acyclovir use in low-risk neonates admitted to the Infectious Disease (ID) ward. Methods Quality improvement initiative aimed to decrease acyclovir exposure in neonates 15 to 28 days old hospitalized on the ID ward for fever/hypothermia without a focus, risk factors, or clinical signs for HSV (Figure 1). Interventions included development of a risk stratification algorithm (Figure 2), consensus building among Emergency Medicine and ID providers, and order set implementation. We reviewed all neonates with HSV infections for delayed acyclovir initiation as a balancing measure. The pre-study baseline period was 2019 to 2020, and the study period was 2020, to March 31, 2023. Control charts were used to assess the interventions.Figure 1Key Driver Diagram.Figure 2Risk stratification algorithm for HSV empiric treatment in low-risk infants. Results The mean acyclovir use per quarter in neonates who met low risk criteria decreased from 79% during the baseline period (7/2019-6/2020) to 30% in the post-intervention period (7/2020-3/2023) (p = &amp;lt; 0.0001) (Figure 3). Most common reasons why patients failed low risk criteria were: CSF pleocytosis in the setting of a traumatic LP, minimally abnormal lab values (slightly increased ALT, slightly decreased platelets), no LP in well-appearing patient and alternative fever etiology (URI symptoms with positive respiratory infection array). There were no cases of delayed acyclovir initiation in patients with HSV disease. Only one patient with HSV disease fell within the age range but was admitted to the ICU following cardiac arrest and appropriately started on acyclovir therapy.Figure 3Control chart of empiric acyclovir use in low-risk infants. Conclusion Our algorithm, targeted to limit empiric acyclovir therapy in neonates with fever/hypothermia without a focus at low risk for HSV, led to a significant decrease in acyclovir exposure sustained for &amp;gt; 2 years after implementation. Interestingly, it also led to decreased in acyclovir use in patients who failed low risk criteria, but this did not result in missed diagnosis of HSV disease, likely because our algorithm was conservative and HSV infection is rare. Disclosures All Authors: No reported disclosures

Autoantibody status, neuroradiological and clinical findings in children with acute cerebellitis

BackgroundAcute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes. ObjectiveTo investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC. Material and methodsChildren presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI. Children fulfilling the above-mentioned criteria and a complete data set including clinical presentation, CSF studies, testing for neuronal/cerebellar and MOG antibodies as well as MRI scans performed at disease onset were eligible for this retrospective multicenter study. Results36 patients fulfilled the inclusion criteria for AC (f:m = 14:22, median age 5.5 years). Ataxia was the most common cerebellar symptom present in 30/36 (83 %) in addition to dysmetria (15/36) or dysarthria (13/36). A substantial number of children (21/36) also had signs of encephalitis such as somnolence or seizures. In 10/36 (28 %) children the following autoantibodies (abs) were found: MOG-abs (n = 5) in serum, GFAPα-abs (n = 1) in CSF, GlyR-abs (n = 1) in CSF, mGluR1-abs (n = 1) in CSF and serum. In two further children, antibodies were detected only in serum (GlyR-abs, n = 1; GFAPα-abs, n = 1). MRI signal alterations in cerebellum were found in 30/36 children (83 %). Additional supra- and/or infratentorial lesions were present in 12/36 children, including all five children with MOG-abs. Outcome after a median follow-up of 3 months (range: 1 a 75) was favorable with an mRS ≤2 in 24/36 (67 %) after therapy. Antibody (ab)-positive children were significantly more likely to have a better outcome than ab-negative children (p = .022). ConclusionIn nearly 30 % of children in our study with AC, a range of abs was found, underscoring that autoantibody testing in serum and CSF should be included in the work-up of a child with suspected AC. The detection of MOG-abs in AC does expand the MOGAD spectrum.

Ocular syphilis on the rise: a 10-year analysis from 2010 to 2020.

The purpose of the study was to evaluate the incidence of ocular syphilis as well as diagnostic parameters, comorbidities, and visual outcomes over a 10-year time period in West Virginia. A retrospective chart review included 25 eyes of 17 patients with ocular syphilis between 2010 and 2020. The incidence of systemic syphilis at a large tertiary referral center has increased from 27 cases in 2010 to 105 cases in 2020. Seventeen patients were identified with ocular syphilis. Bilaterality was present in 47.1% of cases. In this study, 70.6% of patients were male and 29.4% were female. The median age of presentation was 40.2years (range 21-63). Panuveitis was the most common (60.0%) followed by isolated anterior uveitis (16.0%), chorioretinitis (12.0%), inner retinitis (4.0%), and papillitis (8.0%). Forty percent of patients had visual acuity worse than 20/400 on presentation. Post-treatment visual acuity improved in all patients. Rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TP-PA) tests were positive in 84.6% and 100% of cases, respectively. CSF venereal disease research laboratory (VDRL) was positive in 36.4%, CSF pleocytosis was present in 72.7%, and elevated CSF protein was observed in 81.8%. Human immunodeficiency virus (HIV) co-infection was present in 31.3%. A majority of patients experienced maculopapular rash and/or history of genital chancre. The anatomic classification of presenting uveitis (anterior, intermediate, posterior, and panuveitis) did not correlate with clinical variables including age, gender, HIV status, serologic test, presence of rash, or year of diagnosis (p > 0.05). Ocular syphilis is becoming increasingly prevalent and can present with a variety of ocular findings; therefore, it should be considered in the differential diagnosis for patients with ocular inflammation. Visual prognosis is excellent with timely diagnosis and treatment.

Severe Neuroinvasive West Nile Virus in Association With Anti-CD20 Monotherapy for Multiple Sclerosis.

The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS). This is a case series study. In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ2 p < 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies. Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.

Letter to editors: - Multiple sclerosis and related disorders - Netravathi etal., 2022.

We first reported the association of Myelin oligodendrocyte glycoprotein (MOG) antibodies with COVID-19 vaccines. 29 (17 female; mean age of 38 years) cases of CNS demyelination in patients who received a SARS-CoV-2 vaccine, either first or second dose, within the past 42 days. Twenty-seven occurred in temporal association with ChAdOx1-S vaccine; two in association with BBV152 vaccine. MOG antibodies were positive in 10 (34.5%) patients. One patient with ADEM and tumefactive demyelinating lesions did not respond to immunotherapy and died after a prolonged intensive care unit stay and sepsis. As compared to the control group; the postvaccinial cases were found to have a significantly higher mean age, presence of encephalopathy (p value= 0.0007), CSF pleocytosis (p value=0.0094) and raised CSF protein (p value=0.0062).

CSF neopterin and quinolinic acid are biomarkers of neuroinflammation and neurotoxicity in FIRES and other infection-triggered encephalopathy syndromes.

Infection-triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES syndromes have recognisable MRI neuroimaging phenotypes, there are otherwise few biomarkers of disease. Early detection to enable immune modulatory treatments could improve outcomes. We measured CSF neopterin, quinolinic acid, kynurenine and kynurenine/tryptophan ratio using a liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) system. The CSF of 18 children with ITES were compared with acute encephalitis (n = 20), and three control groups, namely epilepsy (n = 20), status epilepticus (n = 18) and neurogenetic controls (n = 20). The main ITES phenotypes in 18 patients were acute encephalopathy with biphasic seizures and late restricted diffusion (AESD, n = 4), febrile infection-related epilepsy syndrome (FIRES n = 4) and other ITES phenotypes. Influenza A was the most common infectious trigger (n = 5), and 50% of patients had a preceding notable neurodevelopmental or family history. CSF neopterin, quinolinic acid and kynurenine were elevated in ITES group compared to the three control groups (all p < 0.0002). The ROC (area under curve) for CSF neopterin (99.3%, CI 98.1-100) was significantly better than CSF pleocytosis (87.3% CI 76.4-98.2) (p = 0.028). Elevated CSF neopterin could discriminate ITES from other causes of seizures, status epilepticus and febrile status epilepticus (all p < 0.0002). The elevated CSF metabolites normalised during longitudinal testing in two patients with FIRES. CSF neopterin and quinolinic acid are neuroinflammatory and excitotoxic metabolites. This CSF metabolomic inflammatory panel can discriminate ITES from other causes of new onset seizures or status epilepticus, and rapid results (4 h) may facilitate early immune modulatory therapy.

Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia.

Autoimmune encephalitis (AIE) may present with prominent cognitive disturbances without overt inflammatory changes in MRI and CSF. Identification of these neurodegenerative dementia diagnosis mimics is important because patients generally respond to immunotherapy. The objective of this study was to determine the frequency of neuronal antibodies in patients with presumed neurodegenerative dementia and describe the clinical characteristics of the patients with neuronal antibodies. In this retrospective cohort study, 920 patients were included with neurodegenerative dementia diagnosis from established cohorts at 2 large Dutch academic memory clinics. In total, 1,398 samples were tested (both CSF and serum in 478 patients) using immunohistochemistry (IHC), cell-based assays (CBA), and live hippocampal cell cultures (LN). To ascertain specificity and prevent false positive results, samples had to test positive by at least 2 different research techniques. Clinical data were retrieved from patient files. Neuronal antibodies were detected in 7 patients (0.8%), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX, and anti-NMDAR. Clinical symptoms atypical for neurodegenerative diseases were identified in all 7 and included subacute deterioration (n = 3), myoclonus (n = 2), a history of autoimmune disease (n = 2), a fluctuating disease course (n = 1), and epileptic seizures (n = 1). In this cohort, no patients with antibodies fulfilled the criteria for rapidly progressive dementia (RPD), yet a subacute deterioration was reported in 3 patients later in the disease course. Brain MRI of none of the patients demonstrated abnormalities suggestive for AIE. CSF pleocytosis was found in 1 patient, considered as an atypical sign for neurodegenerative diseases. Compared with patients without neuronal antibodies (4 per antibody-positive patient), atypical clinical signs for neurodegenerative diseases were seen more frequently among the patients with antibodies (100% vs 21%, p = 0.0003), especially a subacute deterioration or fluctuating course (57% vs 7%, p = 0.009). A small, but clinically relevant proportion of patients suspected to have neurodegenerative dementias have neuronal antibodies indicative of AIE and might benefit from immunotherapy. In patients with atypical signs for neurodegenerative diseases, clinicians should consider neuronal antibody testing. Physicians should keep in mind the clinical phenotype and confirmation of positive test results to avoid false positive results and administration of potential harmful therapy for the wrong indication.