Increased Intrathecal B and Plasma Cells in Patients With Anti-IgLON5 Disease

Background and ObjectivesDespite detection of autoantibodies, anti-IgLON5 disease was historically considered a tau-associated neurodegenerative disease, with limited treatment options and detrimental consequences for the patients. Observations in increasing case numbers hint toward underlying inflammatory mechanisms that, early detection provided, open a valuable window of opportunity for therapeutic intervention. We aimed to further substantiate this view by studying the CSF of patients with anti-IgLON5.MethodsWe identified 11 patients with anti-IgLON5 from our database and compared clinical, MRI, and CSF findings with a cohort of 20 patients with progressive supranuclear palsy (PSP) (as a noninflammatory tauopathy) and 22 patients with functional neurologic disorder.ResultsPatients with anti-IgLON5 show inflammatory changes in routine CSF analysis, an increase in B-lymphocyte frequency, and the presence of plasma cells in comparison to the PSP-control group and functional neurologic disease controls. Patients with intrathecal plasma cells showed a clinical response to rituximab.DiscussionOur findings indicate the importance of inflammatory mechanisms, in particular in early and acute anti-IgLON5 cases, which may support the use of immune-suppressive treatments in these cases. The main limitation of the study is the small number of cases due to the rarity of the disease.

Bilateral Optic Neuritis Caused by Meningococcal Meningoencephalitis

In this article, we described a case of pathogen-induced bilateral optic neuritis accompanying meningococcal meningoencephalitis in an adolescent male. A 15-year-old boy presented to our emergency room due to progressive severe headache, stiff neck, diffuse extremity pain, fever, and nausea concerning meningoencephalitis. Intravenous ceftriaxone, metamizole, and ondansetron were started immediately. Due to acute autonomic dysregulation and development of petechiae, he was transferred to the pediatric intensive care unit. Next morning, the patient developed severe visual impairment. Investigations revealed elevated C-reactive protein, procalcitonin and leucocyte count, decreased platelet count, and clotting activation. Cerebrospinal fluid (CSF) analysis revealed increased leucocyte count, protein, and decreased glucose concentration with pathological CSF cytology. Brain magnetic resonance imaging revealed an increased contrast enhancement in the optic nerve sheath, consistent with acute bilateral optic neuritis. He was started on high-dose intravenous pulse methylprednisolone therapy. After treatment with ceftriaxone und pulse steroids, the patient was discharged in good condition without any visual sequel.

Case Report: Semantic Variant of Primary Progressive Aphasia Associated With Anti-Glial Fibrillary Acid Protein Autoantibodies

BackgroundFrontotemporal lobar degeneration is a heterogeneous disorder entailing a semantic variant of primary progressive aphasia (svPPA). A subtype of frontotemporal dementia associated with glutamate receptor subunit 3 (GluA3) antibody of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was recently identified. Here, we describe the novelty of a svPPA associated with anti-glial fibrillary acid protein (GFAP) antibodies.MethodsTo diagnose this 68-year-old woman we conducted a clinical examination, neuropsychological testing, CSF analysis, MRI and 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET)/computed tomography (CT) imaging.ResultsThe clinical phenotype corresponds to a svPPA based on impaired confrontation naming and single-word comprehension. In addition, we observed spared speech production, impaired object knowledge, and surface dyslexia - further supporting the diagnosis of svPPA. Additional characteristic imaging features such as anterior temporal hypometabolism in 18F-FDG PET/CT confirmed patient’s svPPA diagnosis. CSF analysis revealed signs of axonal degeneration, as both tau and phosphorylated tau proteins exceeded normal levels. Her serum showed anti-GFAP autoantibodies.ConclusionWe diagnosed a svPPA in this patient and report an association between serum anti-GFAP antibodies and svPPA never reported in the literature so far, thereby expanding the clinical spectrum of svPPA and anti-GFAP-antibody related disease. Further research is needed to elucidate the underlying immunopathology of this disease entity to ultimately improve treatment.

The utility of Coccidioides antigen and antibody detection in cerebrospinal fluid in the diagnosis of canine central nervous system coccidioidomycosis

OBJECTIVE To evaluate the utility of enzyme immunoassays (EIAs) for the detection of Coccidioides antigen and antibody in CSF in the diagnosis of CNS coccidioidomycosis in dogs. ANIMALS 51 dogs evaluated for CNS disease in a single specialty center in Tucson in 2016. PROCEDURES Excess CSF after routine analysis was banked after collection from dogs presented to the neurology service. Samples were tested by EIA for presence of Coccidioides antigen and antibody. Clinical data were collected from medical records retrospectively. RESULTS 22 dogs were diagnosed with CNS coccidioidomycosis (CCM) or another neurologic disease (non-CCM). These groups of dogs overlapped in the presenting complaints, MRI results, and routine CSF analysis results. Four dogs, all with CCM, had positive antigen EIA results. With clinical diagnosis used as the reference standard, CSF antigen testing had low sensitivity (20%) but high specificity (100%) for diagnosis of CCM. Ten dogs with CCM and 4 dogs with other diagnoses had antibody detected in CSF by EIA. Sensitivity of CSF antibody testing was 46%, specificity was 86%, and positive and negative predictive values for the study population were 71% and 68%, respectively. Clinical Relevance Diagnosis of CNS coccidioidomycosis in dogs in an endemic region was hampered by overlap of clinical signs with other neurologic disorders and the low sensitivity of confirmatory diagnostics. The evaluated Coccidioides-specific EIAs performed on CSF can aid in the diagnosis. A prospective study is warranted to corroborate and refine these preliminary findings

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

Cerebrospinal fluid (CSF) has recently experienced a revival in diagnostics and research. However, little progress has been made regarding CSF cell analysis. For almost a century, CSF cell count and cytomorphological examination have been central diagnostic parameters, with CSF pleocytosis as a hallmark finding of neuroinflammation and cytology offering valuable clues regarding infectious, autoimmune, and malignant aetiologies. A great deal of information, however, remains unattended as modern immune phenotyping technologies have not yet been broadly incorporated into routine CSF analysis. This is a serious deficit considering the central role of CSF cells as effectors in central nervous system (CNS) immune defence and autoimmune CNS processes, and the diagnostic challenges posed by clinically overlapping infectious and immune-mediated CNS diseases. Here, we summarize historical, specimen-intrinsic, methodological, and technical issues determining the state-of-the-art diagnostics of CSF cells and outline future perspectives for this underutilized window into meningeal and CNS immunity.

Laboratory finding of CSF analysis in patients with meningitis at Elamin Hamid Pediatrics Hospital in Khartoum, Sudan

Bacterial meningitis in infants and children is a serious clinical entity with signs and symptoms that commonly do not allow distinguishing the diagnosis and the causative agents. The only method to determine if meningitis is the cause of these symptoms is a lumbar puncture. Lumbar puncture is the gold standard for the diagnosis and should be done in all suspected cases of meningitis unless contraindicated. Objectives: The purpose of this study is to identify the importance of the microbiological study of cerebrospinal fluid (CSF) in patients suspected to have acute meningitis. Despite the availability of all other investigations and Imaging for diagnosis of meningitis but CSF analysis remains the most available, accurate, and cheaper for diagnosis of meningitis in children. Methodology and result: This is a prospective study. 71 patients were included. All patients were clinically suspected to have acute meningitis. A lumbar puncture for CSF analysis was done for all patients. The data was collected and analysed. CSF culture was done. The culture was negative In 58 patients (81.7%) and positive in 13 patients (18.3%). Streptococcus was found in 3 patients (4.2 %), staphylococcus epidermidis in 2 patients (2.8%), E Coli in 2 patients (2.8%), klebsiella in 2 patients (2.8%), pneumococci in 2 patient (2.8%), salmonella in 1 patient (1,4%) and Bacilli in 1 patient (1.4 %). Recommendation: Lumbar Puncture (LP) remains the easiest, cheapest and accurate investigation for diagnosis of meningitis in children mainly in rural areas in Sudan and other developing countries. It’s mandatory to offer training for doctors and medical staff for doing lumber punctures safely and accurately and to offer well-equipped laboratories for such essential investigations. It’s not only the role of doctors and medical staff but is a governmental obligation as well. This can save a lot of sick children and prevent mortality and morbidity of acute meningitis in children.

Clinical characteristics and outcome of neonates with neonatal mastitis: a hospital based study

Background: Neonatal mastitis is not an uncommon condition, mostly occurs due to Staphylococcus aureus (S. aureus), sometimes leading to breast abscess with detrimental effects.Methods: Our study was retrospective, hospital based observational study carried out at Government Medical College, Baramulla from August 2017 to August 2019, all cases with features of neonatal mastitis were included in the study and also admitted in hospital. Clinical and laboratory data along with demographic data was recorded and analysed.Results: 23 cases were included with age of presentation 8 to 28 days. Babies particularly male babies received breast massage (N=10), besides this pain (15) and redness (N=23) was most common clinical characteristics purulent discharge seen in 2 cases and 7 cases were febrile. Laboratory findings include decreased total leucocyte count (TLC) and positive C-reactive protein (CRP), pus culture from samples revealed S. aureus in 11 cases, coagulase-negative staphylococci (CONS) in 3 cases, E. coli in 2 cases and sterile in 7 cases. Most of cases were sensitive to penicillin (N=14) and in two cases were methicillin resistant S. aureus (MRSA) strains resistant to methicillin. All patients responded well to intravenous (IV) antibiotics while as 8 cases required (I and D), blood cultured showed growth in 19 cases while cerebrospinal fluid (CSF) analysis was sterile in all patients. Above all babies were discharged successfully without any complications.Conclusions: We concluded from our study that neonatal mastitis if treated early has better outcome rather than practicing misbeliefs like breast massage to express so called witch’s milk, in addition we conclude that neonatal mastitis is not an uncommon problem.

Unravelling the Association Between Amyloid-PET and Cerebrospinal Fluid Biomarkers in the Alzheimer’s Disease Spectrum: Who Really Deserves an A+?

Background: Association between cerebrospinal fluid (CSF)-amyloid-β (Aβ)42 and amyloid-PET measures is inconstant across the Alzheimer’s disease (AD) spectrum. However, they are considered interchangeable, along with Aβ 42/40 ratio, for defining ‘Alzheimer’s Disease pathologic change’ (A+). Objective: Herein, we further characterized the association between amyloid-PET and CSF biomarkers and tested their agreement in a cohort of AD spectrum patients. Methods: We include ed 23 patients who underwent amyloid-PET, MRI, and CSF analysis showing reduced levels of Aβ 42 within a 365-days interval. Thresholds used for dichotomization were: Aβ 42 < 640 pg/mL (Aβ 42+); pTau > 61 pg/mL (pTau+); and Aβ 42/40 < 0.069 (ADratio+). Amyloid-PET scans were visually assessed and processed by four pipelines (SPMCL, SPMAAL, FSGM, FSWC). Results: Different pipelines gave highly inter-correlated standardized uptake value ratios (SUVRs) (rho = 0.93–0.99). The most significant findings were: pTau positive correlation with SPMCL SUVR (rho = 0.56, p = 0.0063) and Aβ 42/40 negative correlation with SPMCL and SPMAAL SUVRs (rho = –0.56, p = 0.0058; rho = –0.52, p = 0.0117 respectively). No correlations between CSF-Aβ 42 and global SUVRs were observed. In subregion analysis, both pTau and Aβ 42/40 values significantly correlated with cingulate SUVRs from any pipeline (R2 = 0.55–0.59, p < 0.0083), with the strongest associations observed for the posterior/isthmus cingulate areas. However, only associations observed for Aβ 42/40 ratio were still significant in linear regression models. Moreover, combining pTau with Aβ 42 or using Aβ 42/40, instead of Aβ 42 alone, increased concordance with amyloid-PET status from 74% to 91% based on visual reads and from 78% to 96% based on Centiloids. Conclusion: We confirmed that, in the AD spectrum, amyloid-PET measures show a stronger association and a better agreement with CSF-Aβ 42/40 and secondarily pTau rather than Aβ 42 levels.

A Perplexing Case of Pituitary Apoplexy Masquerading as Meningoencephalitis

Pituitary apoplexy (PA) is extremely rare in children and adolescents. It is a life-threatening condition usually results from sudden hemorrhage or infarction induced swelling in a pituitary adenoma. The clinical manifestations of PA include severe headaches, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Therefore, the presence of meningeal irritation may lead to misdiagnosis as a case of meningoencephalitis or spontaneous subarachnoid hemorrhage, and delay in the proper management of the disease. We report a case of 17-year-old pubertal boy who developed sudden severe headache, vomiting, slurring of speech and abnormal behaviour followed by impaired sensorium with fever. The patient who was initially diagnosed with meningoencephalitis (ME) based on clinical presentation and cerebrospinal fluid (CSF) analysis, which was consistent with bacterial meningitis. MRI of brain was performed, confirming a pituitary macroadenoma with hemorrhage and ischemic changes in both basal ganglia and pons. A complete analysis of the pituitary hormones revealed decreased cortisol and thyroid hormone level and hyperprolactinemia and he was subsequently started on placement corticosteroid and L-thyroxine therapy and cabergoline. After 14/ days of antimicrobial therapy with ceftriaxone and ampicillin, the patient improved and was discharged on hormone replacement therapy and surgical advised. Hereby, we report our case with a review of literatures. Bangladesh J Medicine July 2022; 33(1) : 85-88

Bilateral facial colliculus syndrome caused by pontine tegmentum infarction: a case report

Background Bilateral facial colliculus syndrome is a rare clinical presentation in patient with pontine infarction. We herein described a case of bilateral facial paralysis and complete horizontal gaze palsy possibly caused by paradoxical embolization from patent foramen ovale related stroke. Case presentation A 55-year-old male presented with sudden onset of complete peripheral facial palsy and horizontal gaze palsy after Valsava maneuver. MRI revealed symmetric involvement of bilateral pontine tegmentum in accordance with the location of facial colliculus. CSF analysis and follow-up MRI showed no evidence of central demyelinating disease. Subsequent echocardiography revealed patent foramen ovale and closure surgery was performed. Conclusions Facial colliculus syndrome with symmetric dorsal pontine tegmentum involvement may a rare manifestation in posterior circulation stroke.