Initial Cerebrospinal Fluid Research Articles

‘When nature breaks the rules’: Guillain-barré syndrome presenting with descending paralysis

Guillain-Barré Syndrome (GBS) typically presents with ascending paralysis, but we report an atypical case involving descending paralysis in a 36-year-old male. The patient experienced upper limb weakness and respiratory muscle involvement, progressing to respiratory distress. Initial cerebrospinal fluid (CSF) analysis and nerve conduction studies (NCS) were normal, delaying the diagnosis. Treatment with intravenous immunoglobulin (IVIG) led to partial recovery. This case highlights the diagnostic challenges of atypical GBS presentations and the importance of early intervention.

Absence of Cerebrospinal Fluid Pleocytosis in Encephalitis.

Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis. This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis. Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p<0.001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization. CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis.

Antibody-positive autoimmune encephalitis and paraneoplastic neurological syndrome: A Swedish case series.

This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p=.0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.

A comparison of clinical features between neurobrucellosis and tuberculous meningitis

BackgroudThis study aims to compare the clinical manifestations, imaging findings, routine tests, biochemistry indicators and cerebrospinal fluid cytology between neurobrucellosis and tuberculous meningitis. The objective is to evaluate the similarities and differences of these two diseases and improve early diagnosis.MethodsA comprehensive evaluation was conducted by comparing clinical data, imaging results, routine tests findings, biochemistry indicators and cerebrospinal fluid cytology of patients admitted to the Department of Neurology, the Second Hospital of Hebei Medical University from 2019 to 2021. Statistical analysis was applied to identify significant differences and similarities between the two diseases.ResultsPreliminary analysis demonstrated both diseases commonly present with symptoms such as fever, headache. However, there were no statistical differences between neurobrucellosis and tuberculous meningitis in early clinical data, imaging results, routine tests findings, biochemistry indicators. Further analysis indicates there is a statistically significantly difference in the lymphocyte ratio and neutrophil ratio in the cerebrospinal fluid between the two groups.ConclusionsNeurobrucellosis and tuberculous meningitis share similarities in early clinical manifestations, imaging findings and initial cerebrospinal fluid parametes, making early-stage differentiation challenging. The ratio of lymphocytes and neutrophil in the cerebrospinal fluid and a detailed medical history investigation can provide clues for early clinical diagnosis. So the examination of CSF cytology might be a potential to distinguish these two diseases and become a powerful tool in the future.

Endoscopic Ventricular Lavage in Pediatric Pyogenic Cerebral Ventriculitis Associated with Shunt: Outcomes and Technical Notes

Pyogenic cerebral ventriculitis (PCV) is a rare infectious entity characterized by a potent inflammatory reaction of the ventricular ependyma, which in most cases leads to death. We aim to present the technical note and protocol, based on our center's 10-year experience of the use of endoscopic ventricular lavage in pediatric patients with PCV and ventriculoperitoneal shunt (VPS). For this study, all pediatric patients (<16 years) with VP shunts and PCV who were treated with endoscopic ventricular lavage between January 2012 and January 2022 were included. 34 pediatric patients with ventriculitis were analyzed. The median age was 6 years, with 61.7% being male. Most consultations occurred on Day 2 of symptoms. Fever (38.2%) and altered consciousness (26.5%) were the most common initial symptoms. Early ventriculitis was observed in 67.7% of patients. Pathogen identification in the initial cerebrospinal fluid (CSF) sample was 70.6%, while samples from ventricular peritoneal shunt (VPS) yielded 23.53% and catheter culture 79.4%. Gram-positive bacteria, mainly S.epidermidis (44.1%), was the most commonly isolated agent. Endoscopic ventricular lavage was performed in 73.5% on the second or third day. Reinfection occurred in 23.5%, and 26.5% of patients died. Concordance analysis showed 85.3% agreement between LP and catheter tip samples. Functionality improved, with 55.88% achieving a Lansky score of 90. Early ventriculitis was associated with better Lansky scores. Endoscopic ventricular lavage can be a useful tool in the management of PCV in cases with VP shunts. Our study suggests a higher chance of isolating an infection-causing germ in the catheter tip culture specimen compared to the cerebrospinal fluid (CSF) culture. However, future studies with a larger number of patients, or multicentric studies are required for further analysis.

Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model

BackgroundSyringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand local fluid osmoregulation in post-traumatic SM (PTSM) to highlight important pathways for future molecular interventions.MethodsA rat PTSM model consisting of a laminectomy at the C7 to T1 level followed by a parenchymal injection of 2 μL quisqualic acid (QA) and an injection of 5 μL kaolin in the subarachnoid space was utilized 6 weeks after initial surgery, parenchymal fluid and cerebrospinal fluid (CSF) were collected, and the osmolality of fluids were analyzed. Immunohistochemistry (IHC), metabolomics analysis using LC–MS, and mass spectrometry-based imaging (MSI) were performed on injured and laminectomy-only control spinal cords.ResultsWe demonstrated that the osmolality of the local parenchymal fluid encompassing syrinxes was higher compared to control spinal cords after laminectomy, indicating a local osmotic imbalance due to SM injury. Moreover, we also found that parenchymal fluid is more hypertonic than CSF, indicating establishment of a local osmotic gradient in the PTSM injured spinal cord (syrinx site) forcing fluid into the spinal cord parenchyma to form and/or expand syrinxes. IHC results demonstrated upregulation of betaine, ions, water channels/transporters, and enzymes (BGT1, AQP1, AQP4, CHDH) at the syrinx site as compared to caudal and rostral sites to the injury, implying extensive local osmoregulation activities at the syrinx site. Further, metabolomics analysis corroborated alterations in osmolality at the syrinx site by upregulation of small molecule osmolytes including betaine, carnitine, glycerophosphocholine, arginine, creatine, guanidinoacetate, and spermidine.ConclusionsIn summary, PTSM results in local osmotic disturbance that propagates at 6 weeks following initial injury. This coincides with and may contribute to syrinx formation/expansion.

Analysis of the relationship between drug susceptibility of Cryptococcus neoformans isolates and mortality in HIV-negative cryptococcal meningitis

ObjectivesThe relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood. MethodsWe conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year. ResultsAll of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality. ConclusionMost Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.

Long-Term Outcomes of T-Cell Acute Lymphoblastic Leukemia and Risk Factors for Survival in a Multicenter Registry Study from Brazil

Introduction T-cell acute lymphoblastic leukemia (T-ALL) constitutes around 25% of all newly diagnosed cases of acute lymphoblastic leukemia (ALL) in adults. While most pediatric treatment protocols categorize patients (pts) based on their phenotype, this approach is seldom applied to adults. Nevertheless, there is a scarcity of reported cohorts specifically focusing on adult T-ALL. Often, these cases are studied alongside B-cell cases, despite their notable biological differences, or grouped with T-cell lymphoblastic lymphoma, which exhibits a more favorable prognosis compared to T-ALL. The objective of this study is to present outcomes and identify prognostic factors for survival of adults newly diagnosed with T-ALL, utilizing data from a real-world multicenter registry study conducted in Latin America. Methods This registry encompassed four different academic centers in Brazil. The study included pts aged 15 years and above newly diagnosed with T-ALL between January 2009 and June 2022. Clinical data were collected from medical records after ethical approval. Overall (OS) and event-free (EFS) survivals were calculated by Kaplan-Meier method, with Cox regression multivariate analysis (MVA) for finding risk factors and competing risk analysis for relapse. Results A total of 97 pts were included, with a median age of 27 years (range, 15 - 82). Thymic T-ALL accounted for 51% of the cases. Mediastinal bulky was found in 48% and positivity of initial cerebrospinal fluid (CSF) evaluation was 12.5% (by morphology or flow cytometry). Baseline features of this cohort are summarized in table 1. Most pts (88%) were treated with pediatric-inspired regimens (asparaginase [ASP]-based), mostly adapted GMALL (43%) and adapted BFM (22%). Native E. coli ASP was used in 76% and pegylated ASP (PEG-ASP) was used in remaining cases. During presentation or treatment, 15% of the subjects experienced thrombosis of any site, with most cases being associated with the use of ASP (64%) and diagnosed during induction (64%). Following the frontline regimen, 77.3% of pts achieved complete response (CR). Overall, 11.3% of pts died during the induction phase, while 8% were primary refractory. Univariate analysis for CR showed correlation with age (p=0.002), bulky size (p=0.016), and use of ASP (p=0.009). Median follow-up period was 6 years. Overall, allogeneic stem cell transplant (alloHSCT) was performed in 18 pts, being 11/18 in first CR. Five-year OS and 5y EFS were 43.7% (95% confidence interval [CI]: 34.4-55.5) and 36.4% (95% CI 27.9-47.5), respectively. Over the follow-up, 5-year relapse rate and non-relapse mortality (NRM) were 35.6% and 27.9%, respectively. Among pts who underwent alloHSCT, 5y OS was 64%. In the univariate analysis, older age (HR 1.02 [1.01-1.04], p&amp;lt;0.01) was associated with lower OS. Conversely, thymic T-ALL (HR 0.54 [0.3-0.96], p=0.03) and use of ASP (HR 0.35 [0.17-0.716], p&amp;lt;0.01) were associated with higher OS. Initial white blood cell count was not statistically associated with OS. Subsequently, we performed a subgroup analysis focusing on the adult and young adult population (AYA, age between 15-45 years). In this subgroup (n=85), 89% were treated with pediatric-inspired regimens and 5y OS was 46.5%. In the univariate analysis, thrombosis (HR 2.21 [1.09-4.48], p=0.02) was associated with lower OS, while thymic T-ALL (HR 0.48 [0.24-0.93], p=0.03) and the use of ASP (HR 0.317 [0.13-0.75], p&amp;lt;0.01) were associated with higher OS. In the MVA for AYA, thymic T-ALL (HR 0.50 [0.25-0.98], p=0.04) and thrombosis (HR 2.23 [0.97-5.13], p=0.054) remained associated with OS, while older age was not (HR 1.004 [0.96 - 1.04], p=0.81) (Figure 1). Conclusions Reported outcomes of T-ALL in this registry from Latin America are comparable to older reports from large groups worldwide. Currently, European groups have reported OS rates surpassing 70% for adults with T-ALL.However, in our setting, even in the AYA population, OS was disappointing. This could be attributed to increased NRM due to treatment toxicity and limited access to HSCT, which may have contributed to these findings. As previously reported, thymic T-ALL remains a lower-risk subtype. Additionally, thrombosis has emerged as an independent risk factor for OS in the AYA population, which is a novel finding that warrants further research. To the best of our knowledge, this is the first study specifically focusing on adult T-ALL from Latin America.

Cerebrospinal fluid and plasma ascorbate concentrations following subarachnoid haemorrhage

BackgroundAscorbate, the biologically active form of vitamin C, is the primary neural anti-oxidant. Ascorbate concentrations have never been quantified following aneurysmal subarachnoid haemorrhage (aSAH). ObjectiveTo quantify plasma and cerebrospinal fluid (CSF) ascorbate concentrations in patients following SAH. Design, Setting, Participants, Main Outcome MeasuresCohort study in which plasma and CSF ascorbate concentrations were measured longitudinally in 12 aSAH patients admitted to a quaternary referral intensive care unit and compared to one-off samples obtained from 20 pregnant women prior to delivery in a co-located obstetric hospital. Data are median [interquartile range] or median (95 % confidence intervals). ResultsForty-eight plasma samples were obtained from the 12 aSAH patients (eight females, age 62 [53–68] years). Eight participants with extra-ventricular drains provided 31 paired CSF-plasma samples. Single plasma and CSF samples were obtained from 20 pregnant women (age 35 [31–37] years). Initial plasma and CSF ascorbate concentrations post aSAH were less than half those in pregnant controls (plasma: aSAH: 31 [25–39] μmol/L vs. comparator: 64 [59–77] μmol/L; P < 0.001 and CSF: 116 [80–142] μmol/L vs. 252 [240–288] μmol/L; P < 0.001). Post aSAH there was a gradual reduction in the CSF:plasma ascorbate ratio from ∼4:1 to ∼1:1. Six (50 %) patients developed vasospasm and CSF ascorbate concentrations were lower in these patients (vasospasm: 61 (25, 97) vs. no vasospasm: 110 (96, 125) μmol/L; P = 0.01). ConclusionPost aSAH there is a marked reduction in CSF ascorbate concentration that is most prominent in those who develop vasospasm.

Association between cerebrospinal fluid clusterin and biomarkers of Alzheimer's disease pathology in mild cognitive impairment: a longitudinal cohort study.

Clusterin, a glycoprotein implicated in Alzheimer's disease (AD), remains unclear. The objective of this study was to analyze the effect of cerebrospinal fluid (CSF) clusterin in relation to AD biomarkers using a longitudinal cohort of non-demented individuals. We gathered a sample comprising 86 individuals under cognition normal (CN) and 134 patients diagnosed with MCI via the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. To investigate the correlation of CSF clusterin with cognitive function and markers of key physiological changes, we employed multiple linear regression and mixed-effect models. We undertook a causal mediation analysis to inspect the mediating influence of CSF clusterin on cognitive abilities. Pathological characteristics associated with baseline Aβ42, Tau, brain volume, exhibited a correlation with initial CSF clusterin in the general population, Specifically, these correlations were especially prominent in the MCI population; CSF Aβ42 (PCN = 0.001; PMCI = 0.007), T-tau (PCN < 0.001; PMCI < 0.001), and Mid temporal (PCN = 0.033; PMCI = 0.005). Baseline CSF clusterin level was predictive of measurable cognitive shifts in the MCI population, as indicated by MMSE (β = 0.202, p = 0.029), MEM (β = 0.186, p = 0.036), RAVLT immediate recall (β = 0.182, p = 0.038), and EF scores (β = 0.221, p = 0.013). In MCI population, the alterations in brain regions (17.87% of the total effect) mediated the effect of clusterin on cognition. It was found that variables such as age, gender, and presence of APOE ε4 carrier status, influenced some of these connections. Our investigation underscored a correlation between CSF clusterin concentrations and pivotal AD indicators, while also highlighting clusterin's potential role as a protective factor for cognitive abilities in MCI patients.

Lower levels of Th1 and Th2 cytokines in cerebrospinal fluid (CSF) at the time of initial CSF shunt placement in children are associated with subsequent shunt revision surgeries

ObjectiveWe compare cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. We also describe the cytokine profiles across surgical episodes for children who undergo multiple subsequent revision surgeries. MethodsThis pilot study was nested within an ongoing prospective multicenter study collecting CSF samples and clinical data at the time of CSF shunt surgeries since August 2014. We selected cases where CSF was available for children who underwent an initial CSF shunt placement and had no subsequent shunt revision surgeries during >=24 months of follow-up (n = 7); as well as children who underwent an initial CSF shunt placement and then required repeated CSF shunt revision surgeries (n = 3). Levels of 92 human cytokines were measured using the Olink immunoassay and 41 human cytokines were measured using Luminex based bead array on CSF obtained at the time of each child’s initial CSF shunt placement and were displayed in heat maps. ResultsQualitatively similar profiles for the majority of cytokines were observed among the patients in each group in both Olink and Luminex assays. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Pro- and anti-inflammatory cytokines were selected a priori and shown across subsequent revision surgeries for the 3 patients. Cytokine patterns differed between patients, but within a given patient pro-inflammatory and anti-inflammatory cytokines acted in a parallel fashion, with the exception of IL-4. ConclusionsHeat maps of cytokine levels at the time of initial CSF shunt placement for each child undergoing only a single initial CSF shunt placement and for each child undergoing repeat CSF shunt revision surgeries demonstrated qualitatively similar profiles for the majority of cytokines. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Better stratification by patient age, etiology, and mechanism of failure is needed to develop a deeper understanding of the mechanism of inflammation in the development of hydrocephalus and response to shunting in children.

Prospective outcome analysis of multiple sclerosis cases reveals candidate prognostic cerebrospinal fluid markers.

Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging. We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.2 years of follow-up. Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed. CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group. The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases.

Initial and follow-up evaluations on cerebrospinal fluid involvement by hematologic malignancy.

Central nervous system (CNS) involvement is a serious complication in hematologic malignancy, and early detection and management of CNS involvement in these cases significantly impact the prognosis. Currently, there is no consensus on the use of multiparametric flow cytometry (MFC) and conventional cytology (CC) testing for initial and follow-up cerebrospinal fluid (CSF) specimens to diagnose CNS involvement by hematologic malignancy. In our institution, after initial MFC and CC, two subsequent negative MFCs are required before discontinuing MFC. The aim of this study is to evaluate the outcome of this approach. CSF cytology and MFC reports were retrieved from Laboratory Information System, and data was reviewed. Between January 2020 and December 2021, 1789 CSF samples from 280 patients were submitted for CSF analysis. For those 517 CSF samples tested by both MFC and CC, 97 cases tested positive by both MFC and CC with 95% concordance. Eighteen cases were MFC + /CC - and 7 were MFC - /CC + . Thirty-six cases had initially positive MFCs followed by more than one MFC evaluation. Among those 36 cases, 22 cases (61.1%) converted to negative after the second follow-up sample, 9 cases (25%) were continuously positive for at least three samples, and 5 cases (13.9%) exhibited negative to positive conversion. Compared to negative CSF cases, positive CSFs had higher total nucleated cell count and higher total protein levels while red blood cells, glucose, and lactate dehydrogenase levels remained at comparable levels. The concordance between MFC and CC was excellent. The high incidence of positive MFCs on two or more follow-up samples and the high frequency of negative MFC to positive conversion indicate the necessity of repeated negative MFCs before discontinuing MFC. The fact that more than half of the positive cases converted to negative after the second CSF specimen and most follow-up positive cases can be detected by CC alone suggests it is adequate to use CC alone for follow-up CSF study after two consecutive negative MFCs.

Evaluation of retinal vascular and structural alterations in pediatric idiopathic intracranial hypertension patients without papilledema

PurposeThe aim of this study was to evaluate retinal structural and microvascular alterations using optical coherence tomography-angiography (OCTA) in pediatric idiopathic intracranial hypertension (IIH) patients with regressed papilledema. MethodsThis study included 40 eyes of 21 IIH patients and 69 eyes of 36 healthy controls. Radial peripapillary capillary (RPC) vessel density and peripapillary retinal nerve fiber layer (RNFL) thickness were evaluated by XR Avanti AngioVue OCTA (Optovue, Fremont, CA, USA). The data were obtained from measurement zones that are automatically divided into two equal hemispheres (superior and inferior) and eight quadrants (superior-temporal, superior-nasal, inferior-temporal, inferior-nasal, nasal-superior, nasal-inferior, temporal-superior, temporal-inferior). Initial cerebrospinal fluid (CSF) pressure, grade of papilledema, and duration of follow-up were recorded. ResultsThere were significant differences in RPC vessel densities and RNFL thicknesses between the study groups (p ˃ 0.05). Significantly higher RPC vessel density measurements were observed in the patient group for the whole image, peripapillary, inferior-hemi, and whole nasal quadrants (p < 0.05). Except for the temporal-superior, temporal-inferior, inferior-temporal, and superior-temporal quadrants, the RNFL in all regions was significantly thicker in the IIH group than in the control group (p ˂ 0.001). ConclusionsRNFL thickness and RPC vessel density were significantly different between the IIH patient and control groups, suggesting that retinal microvascular and subclinical structural changes that were potentially secondary to CSF pressure can persist after the resolution of papilledema. However, our results should be confirmed by further longitudinal studies investigating the progress of these alterations to determine their effects on peripapillary tissues.

A Perplexing Case of Borrelia Burgdorferi (P9-10.003)

<h3>Objective:</h3> To expose a potential Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) mimicker and understand the significance of diagnostic tests in a case of Bannwarth syndrome. <h3>Background:</h3> Lyme borreliosis is an infectious disease affecting the skin, nervous system, and joints transmitted by the bite of Ixodes Ricinus. Neurological manifestations occur in 3–15% of the cases. Bannwarth syndrome is reported in 3% of the CDC-verified cases of Lyme disease. It presents early within weeks to a few months of initial infection, mainly characterized by painful polyradiculoneuritis. <h3>Design/Methods:</h3> <h3>Case:</h3> A 67-year-old male presented with progressive bilateral upper extremity weakness, sparing the lower extremities with diffuse areflexia, facial diplegia, dysarthria, dysphagia, and diplopia. <h3>Results:</h3> Initial exam was remarkable for bilateral arm weakness with left-sided lower motor neuron facial palsy and dysarthria. Symptoms quickly worsened to facial diplegia and dysphagia with inability to manage secretions. Magnetic resonance imaging (MRI) brain showed hyperintensity with enhancement of the left cerebellum and cauda equina enhancement on MRI lumbar spine. Cerebrospinal fluid (CSF) analysis was remarkable for elevated protein (448 mg/dl), mild pleocytosis (8/mm³), and albumin cytological dissociation. Monoclonal protein IgG kappa was present in the gamma globulin region. History, exam and initial work-up led to a tentative diagnosis of pharyngeal-cervical-brachial variant of AIDP. He was treated with plasmapheresis with mild improvement. Initial Lyme serum and CSF serology were positive with a positive confirmatory CSF western blot. His inpatient electromyography exposed asymmetric, subacute cervical polyradiculopathy with signs of active axonal denervation and reinnervation changes with no acquired demyelination. The patient was started on intravenous Ceftriaxone and physical therapy with significant improvement. <h3>Conclusions:</h3> Lyme disease is a magnificent chameleon; hence it is crucial to keep it among the differential diagnosis. This case emphasizes the importance of EMG amongst diagnostic tools given it ultimately, in combination with Lyme testing, changed the diagnosis and management for the patient. <b>Disclosure:</b> Dr. Sahni has nothing to disclose. Dr. Samaniego has nothing to disclose. Dr. Gates has nothing to disclose.

An Atypical Presentation of Immune-mediated, Demyelinating Polyneuropathy with Multiple Antibodies to Nerve and Myelin Proteins Following SARS-CoV2 mRNA Vaccination (P10-5.009)

<h3>Objective:</h3> This case describes an atypical demyelinating polyneuropathy temporally associated with SARS-CoV2 mRNA vaccination and characterized by the presence of multiple co-existing autoantibodies. <h3>Background:</h3> A 62-year-old woman developed distal, symmetric upper and lower extremity sensorimotor impairments and areflexia three weeks after SARS-CoV2 booster vaccination (Pfizer-BioNTech). Initial cerebrospinal fluid analysis demonstrated cytoalbuminologic dissociation (protein 76mg/dL). Intravenous immunoglobulin (IVIg) (2 gm/kg total) was prescribed. The patient’s symptoms and signs resolved. Asymmetric, proximal appendicular weakness, distal appendicular sensory loss, gait impairment, and areflexia reoccurred approximately one week later. Plasma exchange (PLEX) was completed, resulting in marked clinical improvement. Clinical worsening again reoccurred in the weeks following PLEX completion. Electrodiagnostic and serologic studies were obtained. Immunomodulatory therapies were escalated with IVIg (repeat 2 gm/kg), corticosteroid, and rituximab therapies prescribed. Sustained symptom improvement was evidenced. <h3>Design/Methods:</h3> Case report with literature review. <h3>Results:</h3> Nerve conduction and electromyography studies demonstrated absent F-waves, prolonged distal motor latencies, and reduced recruitment of normal motor units consistent with a demyelinating polyneuropathy. Ga1NAc-GD1a IgG, beta-tubulin IgG, and neurofascin-155 IgG antibodies were detected in serum samples obtained prior to IVIg therapy (Washington University Neuromuscular Laboratory Demyelinating Neuropathy Panel). <h3>Conclusions:</h3> The patient’s clinical syndrome was ultimately consistent with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The asymmetric pattern of weakness, robust initial treatment response(s), and severe fluctuations were atypical for classical CIDP, but consistent with demyelinating disease marked by specific autoantibodies. Uniquely, Ga1NAc-GD1a IgG, beta-tubulin IgG, and neurofascin-155 IgG antibodies were identified. Antibodies against axons and myelin proteins have been recently reported in patients with acute and chronic demyelinating polyneuropathies. Antibodies to neurofascin isoforms, anti-tubulin and Ga1NAc-GD1a can result in severe phenotypes with variable treatment responses, including robust treatment response to B-cell targeted therapies. To our knowledge, this is a novel case due to multiple co-existing, potentially pathogenic, autoantibodies. A possible immune-mediated mechanism precipitated by SARS-CoV2 vaccination requires further investigation. <b>Disclosure:</b> Dr. Saban has nothing to disclose. Dr. Leech has nothing to disclose. Dr. Carlson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Carlson has received research support from Horizon Therapeutics. Dr. Carlson has a non-compensated relationship as a Health Service Subcommittee Member with American Academy of Neurology that is relevant to AAN interests or activities. Dr. Sauer has nothing to disclose. The institution of Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. The institution of Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Ragole has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. The institution of Dr. Ragole has received research support from Alexion Pharmaceuticals.

Effect of two additional doses of intrathecal methotrexate during induction therapy on serious infectious toxicity in pediatric patients with acute lymphoblastic leukemia.

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses. The impact of additional intrathecal (IT) MTX on systemic toxicity in induction therapy is unknown. Between June 1st 2010 and February 28th 2017, a total of 6,136 ALL patients aged 1-17 years were enrolled onto the AIEOP-BFM ALL 2009 trial. The effect of three versus five doses of IT MTX during induction therapy on the incidence of severe infectious complications was analyzed. Among 4,706 patients treated with three IT MTX doses, 77 (1.6%) had a life-threatening infection during induction as compared to 59 of 1,350 (4.4%) patients treated with five doses (P<0.001; Odds Ratio 2.86 [95% Confidence Interval 1.99-4.13]). In a multivariate regression model, treatment with additional IT MTX proved to be the strongest risk factor for life-threatening infections (Odds Ratio 2.85 [1.96-4.14]). Fatal infections occurred in 16 (0.3%) and 38 (1.6%) patients treated with three or five IT MTX doses, respectively (P<0.001). As the relevance of additional intrathecal MTX in induction for relapse prevention in CNS2 patients is unclear, doses of intrathecal therapy have been reduced for these patients. (Clinicaltrials.gov identifiers: NCT01117441 and NCT00613457).

Failure of Early Mycological Clearance in HIV-Negative Cryptococcal Meningitis.

Negative cerebrospinal fluid (CSF) cultures at 2 weeks after antifungal treatment (early mycological clearance [EMC]) should be a treatment goal of cryptococcal meningitis (CM). However, EMC in human immunodeficiency virus (HIV)-negative patients with CM is poorly understood. We conducted a retrospective review of medical records and 1-year follow-up of 141 HIV-negative patients with CM with an initial positive CSF culture for Cryptococcus neoformans. Multivariate logistic regression was performed to analyze clinical features and laboratory and CSF findings of patients with CM with different EMC statuses. Random forest models were used to predict failure of EMC. All-cause mortality and clinical functional status were analyzed. Of 141 patients, 28 (19.9%) had EMC failure. The 1-year mortality rate was 5.7% (8/141). Multivariate analysis showed that non-amphotericin B (AmB)-based regimens, baseline log10 Cryptococcus count/mL, baseline CSF opening pressure (CSF-OP) >30 cm H2O, and baseline serum creatinine were significantly associated with EMC failure. A parsimonious predictive rule given by the decision tree identified patients with CM with non-AmB-based therapy and baseline CSF-OP >30 cm H2O as being at high risk of EMC failure. Incidence of all-cause mortality, the follow-up modified Rankin Scale, and Karnofsky performance status scores were not significantly related to EMC. EMC failure in HIV-negative CM is attributed to non-AmB-based therapy and is associated with log10 Cryptococcus count/mL and CSF-OP >30 cm H2O at baseline. Because of the small number of deaths, we are not able to comment on whether or not EMC is associated with mortality.

Neuroinvasive West Nile Virus Infection in Solid Organ Transplant Recipients.

Literature on the natural course of neuroinvasive West Nile virus (WNV) infection in solid organ transplant (SOT) recipients is sparse. In the setting of a 2021 WNV outbreak in Arizona, we reviewed our institution's experience with neuroinvasive WNV infection in patients with SOT. We retrospectively identified SOT recipients treated for neuroinvasive WNV at Mayo Clinic in Arizona from 2007 through 2021. Clinical manifestations, disease course, and outcomes were analyzed. Among 24 SOT recipients with WNV infection identified during the study period, 13 infections occurred in 2021. Most patients had gastrointestinal tract symptoms and fever at disease presentation. Five patients had cognitive impairment, and 14 initially or eventually had acute flaccid paralysis. Clinically significant deterioration occurred at a median of 4 (range, 1-11) days after hospital admission. Seventeen patients (71%) were transferred to the intensive care unit, with 15 requiring mechanical ventilation. Initial cerebrospinal fluid analysis mainly demonstrated a neutrophil-predominant pleocytosis. Almost all patients (n = 23) were treated with intravenous immunoglobulin alone or in combination with interferon alfa-2b. Sixteen patients had clinical improvement, 4 of whom recovered completely. Six patients died during hospitalization due to complications of neuroinvasive WNV infection. Two patients were discharged to hospice without clinical recovery. The overall 30-day mortality rate was 36%. Despite advances in supportive care, neuroinvasive WNV infection is associated with substantial morbidity and mortality in SOT recipients. Flaccid paralysis is an indicator of poor prognosis. This article is protected by copyright. All rights reserved.

Autoimmune complications and clinical outcomes of herpes simplex encephalitis in children: A case series

Objective: To report the neurologic prognosis and autoimmune complications of 16 cases of childhood herpes simplex virus encephalitis. Methods: The study was conducted at Şanlıurfa Training and Research Hospital, Turkey from June 2017 to August 2019. The study included 16 pediatric patients aged between 6 months and 17 years (median age 77.7 months) who were diagnosed with herpes simplex virus type 1 encephalitis by pediatric infectious disease and pediatric neurology clinics. Patients were followed using patient records, and interviews at the pediatric neurology clinic or via the telephone. Clinical and demographic data, received therapies, neurologic prognosis and complications were evaluated. Results: Patients with and without autoimmune encephalitis were compared in terms of age, sex, symptom duration before treatment, initial cerebrospinal fluid protein, glucose, red blood count and white blood count but no significant difference was found. Autoimmune complications were seen in four patients. N-methyl-D-aspartate encephalitis was observed in three patients and choreoathetosis was seen in one patient. The average follow-up period was 48.3 months. Twenty-five percent of the patients were receiving multiple antiepileptic drug (AED) treatment, 43.8% were receiving single AED treatment and 31.3% were not receiving AED treatment at the end of the follow-up. Motor disability was observed in 12.5% and drug-resistant epilepsy was observed in 6.3% who had autoimmune complications. Conclusions: Seizures and movement disorders were controlled with immunotherapy and autoantibodies should be studied routinely. Treatment should be started early upon recognition of autoimmune complications through follow-up by measuring autoantibody levels and clinical examination results. Effective prevention and curative treatment modalities are needed to avoid herpes simplex virus encephalitis complications.