CSF Protein Concentration Research Articles

Accuracy of urinary dipstick for glucose and protein determination in canine cerebrospinal fluid.

To evaluate the precision of urinary dipstick (UD) to assess protein and glucose concentrations in canine CSF samples compared to the standard methods. Cerebrospinal fluid protein and glucose were measured in 22 samples from dogs with neurological diseases affecting the CNS using UD and biochemistry (pyrogallol red and glucose oxidase reaction, respectively). Results were converted into scores to allow comparison between methods. The proportion of divergence between methods and its CI were calculated. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and accuracy (Ac) of UD were determined for 2 cutoff levels of CSF protein (15 and 30 mg/dL) and glucose (40 and 100 mg/dL). The proportion of divergence between methods was 64% (95% CI, 44% to 84%) for CSF protein (representing 14 of 22 erroneous samples), of which 92.9% (13 of 14) had a UD score lower than biochemistry. For CSF glucose, 73% (16 of 22 erroneous samples; 95% CI, 54% to 91%) had divergence between methods, of which 87.5% (14 of 16) had a UD score higher than biochemistry. Urinary dipstick had better results when the cutoff level was 15 mg/dL for protein (Se, 78.9%; Sp, 66.7%; PPV, 93.7%; NPV, 33.3%; Ac, 77.3%) and 40 mg/dL for glucose (Se, 89.5%; Sp, 33.3%; PPV, 89.5%; NPV, 33.3%; Ac, 81.8%) concentrations. Urinary dipstick was unreliable in estimating canine CSF protein and glucose concentrations. The UD underestimated protein and overestimated glucose levels in the canine CSF, which could have a significant diagnostic impact and should discourage its use as a bedside test.

CSF Findings in Chinese Patients with NMDAR, LGI1 and GABABR Antibody-Associated Encephalitis.

CSF inflammation in subtypes of antibody-defined autoimmune encephalitis (AE) ranges in intensity from moderate to severe. In a retrospective, cross-sectional study, we characterized CSF findings in Chinese patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E), anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1-E), and anti-gamma aminobutyric acid-B receptor encephalitis (GABABR-E). The AE cases, including 102 NMDAR-E, 68 LGI1-E and 15 GABABR-E, were included. CSF inflammatory parameters consisted primarily of CSF leukocytes, oligoclonal bands (OCBs), and CSF/serum albumin ratios (QAlb). Ten serum cytokines were evaluated in order to classify AE subtypes. 88% of NMDAR-E, 80% of GABABR-E, and 51% of LGI1-E patients had aberrant CSF features. In NMDAR-E, the CSF leukocyte count, CSF protein concentration, and age-adjusted QAlb were significantly higher than in LGI1-E, but did not differ from GABABR-E. Blood-CSF barrier dysfunction was less common in NMDAR-E patients with >40 years old. On admission, inflammatory CSF response was more prevalent in NMDAR-E patients with a higher CASE score. With age <60 years, CSF inflammatory changes were less frequent in LGI1-E patients, but more common in GABABR-E patients. MCP-1, IL-10, IL-1β, and IL-4 were potential classifiers for NMDAR-E, LGI1-E, and GABABR-E, and correlated substantially with CSF leukocyte count and QAlb. Subtype-specific patterns are formed by the various inflammatory CSF parameters in NMDAR-E, LGI1-E, and GABABR-E, and their correlation with disease severity, age, and disease duration. CSF inflammatory characteristics associated with MCP-1, IL-10, IL-1β, and IL-4 may be potential immunopathogeneses targeting markers for these AE subtypes.

Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel - a retrospective study to develop a diagnostic decision rule.

The Biofire® FilmArray® Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule. Adult patients, who underwent CSF analysis with the ME panel between August 2016 and June 2021 at the University Hospital Basel, were included. Demographic, clinical, microbiological, and laboratory data were extracted from the electronic health record. Factors associated with a positive ME panel result were identified, and a decision rule was developed to potentially optimize the diagnostic yield and reduce the number of unnecessary tests. 1,236 adult patients received at least one panel in the observed period, of whom 106 panels tested positive (8.6%). The most frequently observed pathogens were Varicella Zoster Virus (VZV, 27%), Streptococcus pneumoniae (19%), Enterovirus (16%), Herpes simplex Virus 1/2 (16%), and Human Herpesvirus 6 (HHV-6, 13%). Fever, vomiting, headache, and photophobia were more frequently present in test positive patients as were significantly higher CSF leukocytes and protein concentrations. When simulating a decision rule based on CSF leukocytes and protein concentration, only 35% of all patients would have qualified for a ME panel tests, thereby increasing the positivity rate to 22.7%. 10 of 106 positive ME panels would have been missed, only involving HHV-6 and VZV (6 and 4 cases, respectively). As these subjects were either severely immunocompromised or had clinical features of shingles we propose extending the testing algorithm by including those criteria. The ME panel positivity rate at our institution was similar as previously published. Our results highlight the need for diagnostic-stewardship interventions when utilizing this assay by implementing a stepwise approach based on a limited number of clinical and laboratory features. This decision rule may improve the pretest probability of a positive test result, increase the quality of test utilization, and reduce costs.

Genetics to MRI‐DTI: HFE mutation delays AD white matter degeneration in ApoE4 carriers

AbstractBackgroundThe HFE gene involves iron metabolism that directly participates in white matter (WM) myelination process. ApoE4 are known to affect normal myelination through disruptions of iron and lipid metabolism in AD. Thus, we investigated the effect of HFE SNP concurred with the ApoE4 gene mutation in AD WM degeneration. Associations of a neuronal inflammation marker, CSF sTREM2, with DTI measures and cognitive decline were explored for a mechanism under the context of iron metabolism in AD WM degeneration.MethodWhite matter degeneration of ApoE4 carriers with and without HFEH63D polymorphism was investigated using DTI from ADNI database.1 Soluble TREM2 (sTREM2) and pathological protein concentrations in CSF were measured for each CN and AD patients with and without HFE SNP concurred with the ApoE4 gene mutation.ResultMean diffusivity and radial diffusivity of DTI demonstrated an extensive and precipitous age‐related WM degeneration in ADWT/ApoE4+ carriers (as shown in Figure1). This WM degeneration was significantly attenuated in the ADH63D/ApoE4+ subjects with lessened cognitive decline (as shown in Table1, Figure1). The decreased CDR‐cognitive impairment in AD subjects was negatively associated with sTREM2 and positively associated with RD of bilateral inferior longitudinal fasciculus and PTAU (as shown in Table2).ConclusionThe attenuation of WM degeneration and cognitive decline by HFEH63D in AD ApoE4 carriers during aging may involve an effect of reducing neuroinflammation during aging, consistent with reports that HFEH63D establishes a neuroprotective milieu2 and attenuates AD WM neurodegeneration.3 Our in‐vivo data establish a link between interactions of genetic mutation of ApoE with HFE and AD WM degeneration during aging.Reference1. Meadowcroft MD, Wang J, Purnell CJ, et al. Reduced Cerebral White Matter Integrity Assessed by DTI in Cognitively Normal H63D‐HFE Polymorphism Carriers. J Neuroimaging. 2018;28:126‐133.2. Wang L, Johnson EE, Shi HN, Walker WA, Wessling‐Resnick M, Cherayil BJ. Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. J Immunol. 2008;181:2723‐2731.3. Urrutia PJ, Hirsch EC, González‐Billault C, Núñez MT. Hepcidin attenuates amyloid beta‐induced inflammatory and pro‐oxidant responses in astrocytes and microglia. J Neurochem. 2017; 142:140‐152.

African American patients with Multiple Sclerosis (MS) have higher proportions of CD19+ and CD20+ B-cell lineage cells in their cerebrospinal fluid than White MS patients

ObjectivesTo compare proportions of B-cell lineage CD19+ and CD20+ cells in CSF of African-American (AA) and White (W) patients with MS. BackgroundAA MS patients are more likely to have oligoclonal bands in CSF, higher IgG index in CSF, and higher circulating plasmablasts in blood than W MS patients. It is unknown whether the proportion of B-cells in CSF differs between AA and W patients in MS. MethodsDemographics, disease-related information, treatment history were retrospectively collected on patients with MS who self-identified as AA or W and underwent flow cytometry of CSF during diagnostic work-up. Proportion of B-lymphocytes, T-lymphocytes, NK cells, monocytes, and plasma cells were analyzed with flow cytometry. Results20 AA and 56 W MS patients fulfilled our inclusion criteria. The groups had similar demographics, CSF cell counts, protein and glucose CSF concentrations, and oligoclonal band number. IgG index was higher in AA compared to W (1.08 vs. 0.85, p = 0.031). AA had higher proportions of CD19+ (5.46 % AA vs. 2.26 % W, p = 0.006) and CD20+ (4.64 % AA vs. 1.91 % W, p = 0.004) cells but did not significantly differ in proportion of CD4+, CD8+, CD38+ bright B-cells, NK cells and monocytes. ConclusionsB-cells are overrepresented in the CSF of African American patients with MS relative to Whites.

Revealing Individual Neuroanatomical Heterogeneity in Alzheimer Disease Using Neuroanatomical Normative Modeling.

Alzheimer disease (AD) is highly heterogeneous, with marked individual differences in clinical presentation and neurobiology. To explore this, we used neuroanatomical normative modeling to index regional patterns of variability in cortical thickness. We aimed to characterize individual differences and outliers in cortical thickness in patients with AD, people with mild cognitive impairment (MCI), and controls. Furthermore, we assessed the relationships between cortical thickness heterogeneity and cognitive function, β-amyloid, phosphorylated-tau, and ApoE genotype. Finally, we examined whether cortical thickness heterogeneity was predictive of conversion from MCI to AD. Cortical thickness measurements across 148 brain regions were obtained from T1-weighted MRI scans from 62 sites of the Alzheimer's Disease Neuroimaging Initiative. AD was determined by clinical and neuropsychological examination with no comorbidities present. Participants with MCI had reported memory complaints, and controls were cognitively normal. A neuroanatomical normative model indexed cortical thickness distributions using a separate healthy reference data set (n = 33,072), which used hierarchical Bayesian regression to predict cortical thickness per region using age and sex, while adjusting for site noise. Z-scores per region were calculated, resulting in a Z-score brain map per participant. Regions with Z-scores <-1.96 were classified as outliers. Patients with AD (n = 206) had a median of 12 outlier regions (out of a possible 148), with the highest proportion of outliers (47%) in the parahippocampal gyrus. For 62 regions, over 90% of these patients had cortical thicknesses within the normal range. Patients with AD had more outlier regions than people with MCI (n = 662) or controls (n = 159) (F(2, 1,022) = 95.39, p = 2.0 × 10-16). They were also more dissimilar to each other than people with MCI or controls (F(2, 1,024) = 209.42, p = 2.2 × 10-16). A greater number of outlier regions were associated with worse cognitive function, CSF protein concentrations, and an increased risk of converting from MCI to AD within 3 years (hazard ratio 1.028, 95% CI 1.016-1.039, p = 1.8 × 10-16). Individualized normative maps of cortical thickness highlight the heterogeneous effect of AD on the brain. Regional outlier estimates have the potential to be a marker of disease and could be used to track an individual's disease progression or treatment response in clinical trials.

CSF Proteome Changes Depend on APOE Genotype in Prodromal AD

AbstractBackground APOE Ɛ4, the major genetic risk factor for sporadic Alzheimer’s disease (AD), has a dose‐dependent effect on the risk of development of AD. It remains unclear how APOE Ɛ4 dose affects different pathophysiological processes in AD, and therefore we studied APOE genotype effects on the CSF proteome of prodromal AD individuals.MethodCSF proteomics was performed using TMT‐MS in 77 prodromal AD individuals (mean age 70±7 years, 42 (55%) female, n=25 Ɛ3Ɛ3, n=38 Ɛ3Ɛ4, n=14 Ɛ4Ɛ4) and 41 cognitively normal individuals used as a reference group (mean age 64±7 years, 21 (51%) female, biomarker A‐T‐, all Ɛ3Ɛ3) from the EMIF cohort. APOE Ɛ2‐carriers were excluded due to the low number. In total, 2535 proteins were detected, of which we selected 1143 observed in at least 70% of the individuals. APOE genotype effects on CSF protein concentrations were tested with linear regressions adjusting for age and sex in comparison to our reference group.ResultIn total, 134 (12%) proteins showed APOE genotype dependent differences in prodromal AD individuals compared with the reference group (P &lt; 0.05, Fig. 1). Of these, 6 proteins, including SMOC1 and YWHAB, showed differences in all prodromal AD individuals, reflecting general disease processes. Comparing each genotype to the reference group, 23 proteins differed in Ɛ3Ɛ3 prodromal AD, of which 21 showed higher concentrations, without enrichment for any specific biological pathways; 54 proteins differed in Ɛ3Ɛ4 prodromal AD, of which 51 proteins, enriched for glucose metabolism, showed higher concentrations; and 110 proteins differed in Ɛ4Ɛ4 prodromal AD, of which 98 proteins, enriched for glucose metabolism, (oxidative stress‐induced) apoptosis and interleukin‐12 signaling, showed higher concentrations and 12 proteins, enriched for complement activation, showed lower concentrations. Comparing APOE Ɛ4 dose within prodromal AD, 21 proteins showed differences between Ɛ3Ɛ4 and Ɛ4Ɛ4, of which 7 proteins, enriched for complement activation, showed downregulation in Ɛ4Ɛ4.ConclusionThe CSF proteome of prodromal AD individuals showed APOE genotype dependent alterations, which were associated with distinct biological processes, including glucose metabolism, apoptosis and complement activation. Most of these alterations were Ɛ4 dose‐dependent. These differences should be considered in selection of future therapy targets.

P-124: High protein concentration in CSF is a hallmark in multiple myeloma with CNS involvement

P-124: High protein concentration in CSF is a hallmark in multiple myeloma with CNS involvement

LGI1 antibody-associated encephalitis without evidence of inflammation in CSF and brain MRI.

This study aimed to explore the frequency and distinct characteristics of adult patients with LGI1 antibody-associated encephalitis in the absence of inflammatory abnormalities in both routine CSF analysis and brain MRI. We conducted a retrospective study of adult patients with antibodies targeting LGI1 and then screened patients with no evidence of inflammation in brain MRI and normal results in routine CSF analysis, including white blood cell count, protein concentration, IgG, and oligoclonal bands. Among 80 patients with LGI1 antibody-associated encephalitis in our center, 31 (38.8%) fulfilled the screening criteria. For these patients, the onset age was 57.0 ± 14.7years, and 19 (61.3%) were female. Viral prodrome occurred in 5 patients (16.1%). Faciobrachial dystonic seizures (FBDS) were the most predominant symptom (38.7%), followed by seizure onset (22.6%) and memory deficits (19.4%). The sensitivity of antibody detection in serum was higher than CSF (96.8% vs. 48.4%, p < 0.001). Most patients (30/31, 96.8%) benefited from the first-line immunotherapy, and 23 patients (74.2%) achieved complete recovery, yet 3 patients (9.7%) had clinical relapses in 2-year follow-up after discharge. The patients had a higher prevalence of females (61.9% vs. 26.7%, p = 0.003) and were more frequently associated with FBDS during the disease course (38.7% vs. 10.2%, p = 0.004). However, there was no difference in treatment outcomes and recurrence ratio between the two groups (p = 0.144 and p = 0.515). Moreover, we divided all 80 patients into four groups according to antibody titer levels in serum and CSF at the time of diagnosis, respectively. WBC and protein concentrations in CSF showed no difference among the four groups. The absence of evidence of inflammation in routine CSF analysis and brain MRI did not rule out anti-LGI1 associated encephalitis. FBDS and the subacute onset of cognitive dysfunction should push forward with autoantibody testing for patients even without inflammatory abnormalities. The routine inflammatory indicators in CSF seemed to be unrelated to antibody titer levels.

Neuronal intermediate filament paraneoplastic autoimmunity complicating avelumab therapy of Merkel cell carcinoma

A 67-years-old woman developed subacute oculomotor nerve palsy and cerebellar gait instability while receiving avelumab as immunotherapy for Merkel cell carcinoma. Brain MRI revealed oculomotor nerve T2/FLAIR hyperintensity and contrast enhancement, CSF cell number and protein concentration were slightly increased. Antibodies against intracellular and surface antigens were excluded through commercial assays, but home-made immunohistochemistry on rat brain sections showed a “neurofilament-like” pattern. Antibodies against neuronal intermediate filament (NIF-IgG) were thus tested and resulted positive in both serum and CSF, confirming the diagnosis of NIF-IgG autoimmunity. Avelumab was discontinued and treatment with steroids and intravenous immunoglobulins led to partial improvement.

803 Extracorporeal Filtration of Blood and Blood Breakdown Products from CSF via Spinal Catheter (PILLAR-XT) Following Aneurysmal Subarachnoid Hemorrhage

INTRODUCTION: Delayed cerebral ischemia (DCI) is a secondary injury of aneurysmal subarachnoid hemorrhage (aSAH), and is considered to be related to blood and blood breakdown products (BBPs) in the CSF. Previously, bulk drainage of CSF post-aSAH via lumbar drain appeared to result in decreased DCI. If inflammation related to BBPs plays a role in DCI, accelerating removal of BBPs following aSAH could be of significant therapeutic benefit. This study evaluated a system designed to accelerate removal by rapidly filtering BBPs from CSF while returning filtered CSF to the patient via a dual lumen catheter and extracorporeal filtration system (Neurapheresis™ System). METHODS: Patients with aSAH had a dual lumen lumbar, intrathecal catheter placed after aneurysm securement and received up to 72±4 hours Neurapheresis therapy. The catheter aspirated blood-contaminated CSF from the lumbar cistern and returned filtered CSF to the thoracic subarachnoid space, routing BBPs to a waste bag. RESULTS: Of 7 males (24.1%) and 22 females (75.9%), a catheter was successfully placed in 27 subjects out of 29 attempts (93.1% success rate. The mean duration of treatment was 34:18 hrs [3:39 – 62:17] (n=27), and the system maintained its expected, controlled, safe drainage rate, mean 6.5 ml/hr [2.1 – 12.5] (n=27). Mean paired RBC values in CSF (106/mm3) declined by 84.5±22.3% (n=21) by the end of treatment. Mean paired total protein (mg/dL) declined by 85.3±8.3% (n=21) to within normal range. Paired Hijdra Sum Scores (sum of ten cistern blood fullness scores - maximum score: 30) declined by 60.1±24.1% (n=25); the largest decline was noted between catheter placement and catheter removal. CONCLUSIONS: In this feasibility study, Neurapheresis was associated with a decline in RBC and protein concentration in CSF, and improvement in blood clearance as measured by Hijdra Sum Scores. The procedure was safe and well tolerated in this study.

Determination of Postmortem Interval by Estimating CSF Proteins Concentration after Death, by Dye Binding Method at a Tertiary Care Hospital in Lahore, Pakistan

Introduction: Postmortem interval (PMI) is the time lapse between death of a person and its postmortem examination i.e. autopsy. Estimating the postmortem interval (PMI) is an imperative perspective of forensic medicine.&#x0D; Aims &amp; Objectives: This study was conducted to see the impact of CSF protein estimation on determination of PMI.&#x0D; Place and duration of study: It was an observational correlational study, conducted for one year at Department of Forensic Medicine, King Edward Medical University Lahore.&#x0D; Material &amp; Methods: A total of 119 cadavers were included in this study. Chemicals used were disodium molybdate, pyrogallol, succinic acid. The minimum detectable concentration of total proteins in CSF with dye binding method using pyrogallol red was determined as 0.022g/l. Two ml of CSF was taken from each cadaver. Clear, colorless samples were taken in test tubes. Turbid and blood contained samples were not included in study. Protein concentration was determined using photospectrometry. Statistical analysis was done by SPSS-23. Quantitative variables like age were presented as mean ± SD. Qualitative variables like gender were presented as frequency and percentages. For comparison between PMI and CSF proteins concentration correlation was applied.&#x0D; Results: Males accounted for majority of our subjects. The mean value of proteins in CSF was 219.91± 113.121 mg/dl. The most common PMI was 11 to 20 hours. CSF proteins increased gradually over 72 hours after death. The results of present study showed a significant positive correlation between time of death and CSF proteins concentration after death.&#x0D; Conclusion: It is observed that as a whole protein concentration increased with increasing time of death. Hence, CSF protein concentration can be used in estimating time since death.

A.1 CSF Findings in Early Active Autoimmune Encephalitis

Background: Treatment decisions for patients with autoimmune encephalitis (AE) frequently need to be made before results from autoantibody testing are available, as early treatment is associated with better outcomes. Cerebrospinal fluids (CSF) white blood cell (WBC) count and protein concentration measured early on in the disease process is often used, in combination with other clinical factors, to evaluate the likelihood that a patient has AE. Methods: CSF characteristics (WBC count, protein concentration, and oligoclonal banding) measured in a first AE presentation, prior to results of autoantibodies being available, were retrospectively analyzed at two tertiary care centers. Results: Ninety-five patients were included in the study. CSF WBC counts and protein levels were within normal limits for 27% (CI95%: 19–37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6–16) of patients had “normal” CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0–544) and the median CSF protein concentration was 0.42 g/L (range: 0.15–3.92). Conclusions: A substantial proportion of patients with early active AE had a CSF WBC count or protein concentration within the normal. Inclusion of CSF oligoclonal banding may help identify a higher proportion of patients with an inflammatory CSF profile early in the disease process.

BACTERIAL MENINGITIS: A SERIOUS COMPLICATION OF ACUTE OTITIS MEDIA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Otitis media can be complicated by bacterial meningitis that can have high mortality and morbidity. With the advent of antibiotics this complication is significantly rare but delay in getting treatment for Otitis media increases the risk of meningitis exceptionally. (1) We present a case of otitis media complicated by bacterial meningitis in a young adult patient. CASE PRESENTATION: A 36 years old male presented with complaints of right ear pain and discharge. On presentation he was febrile to 102 F. On examination he was sick in appearance with a tender right ear and purulent discharge. He was intubated for airway protection and altered mental status. Initial lab investigations showed a WBC count of 24.3 k/ul. Lactic acid and Procalcitonin were raised. CT Scan of head showed right mastoid effusion. Blood cultures were sent and a Lumbar puncture with an opening pressure of 55 cmH2O was done. Patient was started on vancomycin and ceftriaxone along with intravenous steroids. CSF analysis showed a WBC count of 11400 k/ul, predominantly neutrophils. CSF protein content was >750 mg/dl with no glucose in it. A tympanostomy tube was placed in the right middle ear for drainage and purulent discharge was sent for culture and sensitivity. MRI Scan of head showed restricted diffusion in subarachnoid spaces consistent with pus and ventriculitis in the setting of meningitis without any evidence of abscess. Right sided mastoid effusion was also present. Magnetic resonance venography was negative for venous thrombosis. Blood, middle ear fluid and CSF cultures grew streptococcus pneumoniae and staphylococcus epidermidis. Patient improved clinically after 72 hours on antibiotics and was extubated after that with normalization of inflammatory markers. Antibiotics were tailored as per sensitivity data and will require mastoidectomy as outpatient after completion of intravenous antibiotics. DISCUSSION: Most common organisms causing otitis media and its complications include streptococcus pneumoniae, group A streptococci, staphylococcus aureus, H. Influenzae and pseudomonas aeruginosa. (2) In some cases no bacterial organism is isolated. Due to the development of antibiotic therapies the complications of otitis media can be controlled. Delay in receiving antibiotic therapy can complicate the middle ear infection. If otitis media is complicated by middle ear effusion then tympanostomy tube can help in drainage of the purulent material preventing the seeding of other surrounding structures. It can extend to mastoid and further to brain tissue if not treated in a timely fashion resulting in meningitis and abscess formation as happened in our patient it resulted in meningitis. Appropriate antibiotics with surgical intervention for drainage if needed is the course of treatment. CONCLUSIONS: Acute otitis media should be treated in a timely fashion to avoid the complication of bacterial meningitis. REFERENCE #1: 1. Harmes KM, Blackwood RA, Burrows HL, Cooke JM, Harrison RV, Passamani PP. Otitis media: diagnosis and treatment. Am Fam Physician. 2013 Oct 1;88(7):435-40. Erratum in: Am Fam Physician. 2014 Mar 1;89(5):318. Dosage error in article text. PMID: 24134083. REFERENCE #2: 2. Leichtle A, Hoffmann TK, Wigand MC. Otitis media – Definition, Pathogenese, Klinik, Diagnose und Therapie [Otitis media: definition, pathogenesis, clinical presentation, diagnosis and therapy]. Laryngorhinootologie. 2018 Jul;97(7):497-508. German. doi: 10.1055/s-0044-101327. Epub 2018 Jul 9. Erratum in: Laryngorhinootologie. 2018 Jul;97(7):E2. PMID: 29986368 DISCLOSURES: No relevant relationships by Muhammad Ibrar Islam, source=Web Response No relevant relationships by Namra Mahmood, source=Web Response No relevant relationships by Junaid mir, source=Web Response

Clinical, laboratory and brain Magnetic Resonance Imaging (MRI) characteristics of asymptomatic and symptomatic HIV-negative neurosyphilis patients

IntroductionThere are few studies concerning the differences between asymptomatic neurosyphilis (ANS) and symptomatic neurosyphilis (SNS). This study aimed to summarize clinical, laboratory and brain Magnetic Resonance Imaging (MRI) characteristics of HIV-negative patients with ANS and SNS. MethodsData from 43 HIV-negative patients with ANS and 59 HIV-negative patients with SNS were retrospectively collected from our hospital between December 2012 and December 2018. ResultsCompared with the ANS group, SNS group had more patients that were male, age≥45 years, had brain MRI abnormalities, and exhibited higher serum/cerebrospinal fluid (CSF) TRUST titer, CSF WBC count, CSF protein concentration (P < 0.05). Multivariate regression analysis revealed that male sex, age ≥45 years and CSF TRUST titer were risk factors for SNS [odds ratio (OR) = 7.946,P = 0.001;OR = 3.757, P = 0.041; OR = 2.713, P = 0.002; respectively]. The brain MRI findings of 78 patients without comorbidities showed that ischemic infarct lesions presented in 17/37 (45.95%) of patients with ANS; infarct ischemic stroke (73.17%) especially multiple cerebral infractions (46.34%), cerebral atrophy (48.78%) were also common presentations in the SNS group. ConclusionsPatients with HIV-negative ANS and SNS presented different clinical, laboratory and brain MRI features. Male sex, age ≥45 years and elevated CSF TRUST titer may have an increased risk of developing neurological symptoms. Brain MRI abnormalities may present prior to clinical symptoms. Multiple cerebral infarctions without explained reasons or cerebral atrophy should alert clinicians the possibility of SNS.

Leukoencephalopathy and conduction blocks in PLEKHG5-associated intermediate CMT disease

Biallelic variants in PLEKHG5 have been reported so far associated with different clinical phenotypes including Lower motor neuron disease (LMND) [also known as distal hereditary motor neuropathies (dHMN or HMN) or distal spinal muscular atrophy (DSMA4)] and intermediate Charcot-Marie-Tooth disease (CMT). We report four patients from two families presenting with intermediate CMT and atypical clinical and para-clinical findings. Patients presented with predominant distal weakness with none or mild sensory involvement and remain ambulant at last examination (22–36 years). Nerve conduction studies revealed, in all patients, intermediate motor nerve conduction velocities, reduced sensory amplitudes and multiple conduction blocks in upper limbs, outside of typical nerve compression sites. CK levels were strikingly elevated (1611–3867 U/L). CSF protein content was mildly elevated in two patients. Diffuse bilateral white matter lesions were detected in one patient. Genetic analysis revealed three novel frameshift variants c.1835_1860del and c.2308del (family 1) and c.104del (family 2). PLEKHG5-associated disease ranges from pure motor phenotypes with predominantly proximal involvement to intermediate CMT with predominant distal motor involvement and mild sensory symptoms. Leukoencephalopathy, elevated CK levels and the presence of conduction blocks associated with intermediate velocities in NCS are part of the phenotype and may arise suspicion of the disease, thus avoiding misdiagnosis and unnecessary therapeutics in these patients.

Non-linear ventriculo – Lumbar protein gradients validate the diffusion-flow model for the blood-CSF barrier

BackgroundConcentrations of blood-derived proteins increase non-linearly between ventricular and lumbar CSF, which could not be satisfactorily explained by known barrier models. MethodsProtein data analysis with OriginLab. Interpretations with Quotient diagrams by CSF/ Statistics software. Results1. Nonlinearly increasing protein concentrations between ventricular and lumbar CSF are fitting to a Gaussian error function, the differential of the nonlinear concentration distribution function between blood and CSF. Increasing CSF protein concentrations (changing steady state), either due to barrier dysfunctions with reduced CSF flow rate or due to normal steady influx along the rostro-caudal flow path, increase the local gradient at the diffusion flow interface and thus the molecular current through the barrier.2. With a time- and space-related derivation, the hyperbolic relation between two molecules in CSF (e.g., QIgG: QAlb in quotient diagrams) is independent of the position in subarachnoid space: The reference line, Qlim, in quotient diagrams allows detection of intrathecal synthesis in ventricular, cisternal and lumbar CSF. Detection of intrathecal synthesis is not influenced by CSF extraction volume, only the barrier function, QAlb, is volume sensitive. ConclusionsCommon biophysics for barrier dysfunction and normal protein gradients provide additional evidence for the diffusion-flow interface model for barrier functions.

CSF Surfactant Protein Changes in Preterm Infants After Intraventricular Hemorrhage.

Introduction: Surfactant proteins (SP) have been shown to be inherent proteins of the human CNS and are altered during acute and chronic disturbances of CSF circulation. Aim of the study was to examine the changes of surfactant protein concentrations in CSF of preterm babies suffering from intraventricular hemorrhage.Patients and Methods: Consecutive CSF samples of 21 preterm infants with intraventricular hemorrhages (IVH) and posthemorrhagic hydrocephalus (PHHC) were collected at primary intervention, after 5–10 days and at time of shunt insertion ~50 days after hemorrhage. Samples were analyzed for surfactant proteins A, B, C, and G by ELISA assays and the results were compared to 35 hydrocephalus patients (HC) without hemorrhage and 6 newborn control patients.Results and Discussion: Premature patients with IVH showed a significant elevation of surfactant proteins SP-A, C, and G compared to HC and control groups: mean values for the respective groups were SP-A 4.19 vs. 1.08 vs. 0.38 ng/ml. Mean SP-C 3.63 vs. 1.47 vs. 0.48 ng/ml. Mean SP-G 3.86 vs. 0.17 vs. 0.2 ng/ml. SP-A and G concentrations were slowly falling over time without reaching normal values. SP-C levels declined faster following neurosurgical interventions and reached levels comparable to those of hydrocephalus patients without hemorrhage.Conclusion: Intraventricular hemorrhages of premature infants cause posthemorrhagic CSF flow disturbance and are associated with highly significant elevations of surfactant proteins A, C, and G independent of total CSF protein concentrations.

Comparison of tick-borne encephalitis between children and adults\u2014analysis of 669 patients

The aim of our study was to compare the course of TBE in children and adults. A retrospective analysis of the medical records of 669 patients was performed. The patients were categorized into 2 groups: Group I with 68 children and group II with 601 adults. TBE symptoms in children were milder compared with adults, with meningitis in 97% of cases. In adults, meningoencephalitis and meningoencephalomyelitis made up 49.26% of cases. Nausea and vomiting are more frequent in children, while neurological manifestations are more frequent in adults. There were no differences in CSF pleocytosis at the onset of disease in both groups, while CSF protein concentration was higher in adults. Children treated with corticosteroids over 7 days had higher checkup pleocytosis than pleocytosis at the onset of disease compared with adults. Corticosteroid use prolongs the disease duration but does not influence the development of TBE sequelae. Children had more favourable outcomes than adult patients.

Evaluation of cell-free DNA as a diagnostic marker in cerebrospinal fluid of dogs.

To determine whether cell-free DNA (cfDNA) was detectable in CSF samples from dogs, whether CSF sample volume impacted CSF cfDNA concentration measurement, and whether CSF cfDNA concentration was associated with CNS disease category or CSF RBC count (RBCC), nucleated cell count (NCC), or protein concentration, which could aid in the diagnosis of neurologic diseases in dogs. 80 CSF samples collected from dogs with (n = 60) and without (20) clinical neurologic disease between February 2017 and May 2018. Results for CSF RBCC, NCC, protein concentration, and cfDNA concentration were compared across CSF groups established on the basis of whether they were obtained from dogs with (case groups) or without (control group) clinical signs of neurologic disease In addition, 5 paired CSF samples representing large (3.0-mL) and small (0.5-mL) volumes, were used to evaluate whether sample volume impacted measurement of CSF cfDNA concentration. cfDNA was detected in 76 of the 80 (95%) CSF samples used to evaluate parameters across disease categories and in all 5 of the paired samples used to evaluate whether sample volume impacted cfDNA quantification. There were no substantial differences in cfDNA concentrations identified between groups (on the basis of disease category or sample volume), and the CSF cfDNA concentration did not meaningfully correlate with CSF RBCC, NCC, or protein concentration. Although results indicated that the CSF cfDNA concentration could not be used to differentiate between categories of neurologic disease in dogs of the the present study, further investigation is warranted regarding the use of CSF analysis, including sequencing specific cfDNA mutations, for diagnosing and monitoring neurologic disease in dogs.