Infectious Meningoencephalitis Research Articles

Cerebral Cortical Encephalitis and Other Meningocortical Manifestations of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease in Children: Case Series and Review of the Literature.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a neuroinflammatory disorder (MOGAD) with heterogeneous phenotype including paroxysms of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, brainstem demyelination, and encephalitis. Fluid-attenuated inversion recovery hyperintense cortical lesions in MOG-associated encephalitis with seizures, or FLAMES, is a manifestation of cerebral cortical encephalitis seen less frequently than other typical MOG antibody-associated disease presentations. Cases of FLAMES are rarer in children, and frequently initially misdiagnosed with infectious meningoencephalitis. Other meningocortical manifestations of MOG antibody-associated disease have been described and likely exist along a continuum. In this retrospective single-center case series, we describe the demographic, clinical, radiographic, laboratory, and electroencephalographic features of 5 children with clinicoradiographic features consistent with the spectrum of MOG-IgG-positive meningocortical syndromes.

Changes in the Distribution of Pathogens Causing Meningoencephalitis Before and During the COVID-19 Pandemic.

Infectious meningoencephalitis (ME) is a major global health concern. Viruses are the most frequently implicated etiologies, whereas bacterial causes, although life-threatening, constitute a lesser proportion of ME cases, together with other pathogens. The strict implementation of COVID-19 mitigation measures led to the decreased viral and non-viral infectious diseases. Therefore, this study aimed to investigate the effect of these mea-sures on ME-causing pathogens by age groups. This retrospective study aimed to determine and compare the rates of pathogen-positive ME cases during the pre-pandemic (P-1) and pandemic (P-2) periods. Molecular diagnostic methods using the cerebrospinal fluid of patients from all age groups were included. The positivity rate difference of the ME-causing pathogens between the two study periods was compared and the distribution pattern of the pathogens among the age groups was determined. The overall positivity rate for at least one ME-causing pathogen during P-1 was 22.0% (503/2,284), which significantly declined to 7.3% (83/1,141) during P-2 (p < 0.001). Particularly, a statistically significant decline in the pathogen positivity was observed in the groups 4 - 6 (≥ 3 years) (p < 0.001, p < 0.001, and p = 0.041, respectively). Specifically, the enterovirus cases decreased significantly, whereas the varicella zoster virus and herpes simplex virus-2 cases increased. Among bacterial causes, the S. agalactiae, S. pneumoniae, and E. coli K1 ME cases significantly increased. Men and women had no significant differences in the positivity rate during either study period. COVID-19 mitigation measures significantly impacted the positivity rates and the distribution of ME-causing agents, especially in the age groups ≥ 3 years, although not uniformly.

A comparison of infectious and autoimmune meningoencephalitis: Clinical presentation, biochemical markers and MRI findings

Objective: This study investigates distinguishing patterns in lesion distribution, relevant clinical presentation and biochemical markers in MRI to differentiate infective encephalitis (IE) and autoimmune encephalitis (AE). Methods: Retrospective study of adult patients with a confirmed diagnosis of IE and AE admitted to the Neurology unit from January 2012 to December 2020 with MRI Brain. Selected cases with confirmed IE (according to the 2013 Infective Encephalitis Consortium diagnostic criteria) or antibody-positive AE (detection of Neuronal auto-antibody from blood or CSF), coupled by clinical presentation. MRI brain lesion distribution, lobar involvement, enhancement, haemorrhage, vasculopathy and atrophy were analysed. Results: Forty-seven patients (21 IE and 26 AE, respectively) were selected. IE group are older (48.0 ± 16.81) compared to AE (28.4 ± 14.10). Fever and vomiting were significant in IE (p&lt;0.001), whereas psychosis, seizure, movement disorder, and tumour (ovarian teratoma) were significant in the AE cohort. Cerebrospinal fluid (CSF) analysis showed elevated leucocytes with polymorphism and high protein levels in IE (2.081 g/L ± 2.93 vs AE (0.352g/L ± 0.18). MR imaging detected abnormal findings in 61.9% of cases with infectious encephalitis (IE), while 76.9% of cases with autoimmune encephalitis (AE) exhibited normal MRI results. Asymmetrical lesions and inferior frontal lobe distribution (57.1%) were significantly prevalent in IE (p&lt;0.05). Enhancement patterns and haemorrhage were rarely observed in AE patients. Conclusion: IE presented at an older age, with the majority having MRI findings such as asymmetrical lesions, leptomeningeal enhancement, and involvement of medial temporal, hippocampus and inferior frontal cortex. IE clinically presents with fever, vomiting, and elevated CSF leucocytes and protein levels. AE presents at a younger age with seizure, psychosis, movement disorder, tumour (ovarian teratoma). Fewer AE have MRI findings, and if present, tend to be symmetrical in distribution. Lobar involvement in the inferior frontal was the MRI feature that significantly favoured the diagnosis of IE compared to AE. IE and AE have distinct clinical, biochemical, and MRI abnormalities that can be discriminated between the 2 entities.

Epidemio-clinical aspects and neuro-meningeal tuberculosis prognosis in Batna

Neuromeningeal tuberculosis is rare, affecting around 1-2% of all tuberculosis cases and 5% of extra pulmonary tuberculosis cases. Our aim is to describe the epidemio-clinical, prognostic and evolutionary aspects of neuromeningeal tuberculosis. Materials and methods: To determine the spectrum of etiological agents of HIV-negative encephalitis and meningoencephalitis in Batna, we conducted a prospective study using an expanded testing approach. Patients were recruited from three departments (intensive care unit, infectious diseases department, pediatrics) during the period from April 1, 2012, to August 31, 2015. Data were collected according to the FLIPS case definition with a standardized form. We sought to identify etiological pathogens following a standardized procedure and to describe the epidemiological, clinical and biological features and outcomes associated with different causes. Results: A total of 141 patients with infectious encephalitis and meningoencephalitis were included in the study. Bacterial etiology was determined in 65/141 (46.1%) of whom 30 cases (21.3%) were of tuberculous origin; 21 confirmed and/or probable cases 9 possible cases with high clinical, epidemiological and radiological probability. The median age was 30.5 (0-83), predominantly female 12/18, 23.3% comorbidity with a frequency of motor deficits (86.7%) and psychiatric disorders (26.8%), respiratory involvement was present in 60% of cases, pleocytosis was present in 22/25 (73.4%). hyperalbuminorachy in 66. 7%, and hypoglycorachia in (46.7%). Anti-tuberculosis treatment was instituted in 90% of cases,17.6% were initially admitted to an intensive care unit, and the median length of hospital stay was 38.5 (1-146). death was identified in 46.6%, with 10% having sequelae. Conclusion: In our study, in addition to viruses, bacteria (especially intracellular) can be responsible for encephalitis and meningoencephalitis, in varying proportions. The most frequent and leading form of bacterial meningoencephalitis in adults is tuberculosis, the prognosis of which depends on early treatment.

Stroke without cerebral arteriopathy in sickle cell disease children: causes and treatment.

Cerebral arteriopathy (CA) in children with sickle cell disease (SCD) is classically described as chronic stenosis of arteries in the anterior brain circulation, leading to ischemic stroke. Some studies have, however, reported strokes in children with SCD but without CA. In order to better understand the etiology and risk factors of these strokes, we retrospectively analyzed ischemic strokes occurring in a large cohort of children over a 13-year period. Between 2007 and 2020, 25 of 1,500 children with SCD had an ischemic stroke in our center. Among them, 13 (52%) had CA, described as anatomical arterial stenosis, while 12 (48%) did not. Patients with stroke without CA were older than patients with stroke attributed to SCD-CA (9.0 years old vs. 3.6 years old; P=0.008), and more frequently had SC genotype (25% vs. 0%, respectively). Their strokes more frequently involved the posterior circulation, with cerebellar involvement in 42%. Retained stroke etiologies in patients without typical SCD-related CA were reversible cerebral vasoconstriction syndrome, cerebral fat embolism, arterial thrombosis or thromboembolism, hyperviscosity, vasculitis in a context of infectious meningo-encephalitis, and severe hemodynamic failure. No recurrence was observed in the 24 months following stroke, even though 67% of the patients in this group were no longer receiving exchange transfusions. In conclusion, in a cohort of pediatric SCD patients with an efficient stroke screening strategy, half of the ischemic strokes that occurred were related to causes other than CA. They affected a different population of SCD children and systematic long-term transfusion programs may not be necessary in these cases.

Evaluation of pathogen from the FilmArray meningitis/encephalitis panel and recommendations on atypical findings.

Infectious meningoencephalitis is a potentially fatal clinical condition that causes inflammation of the central nervous system secondary to the installation of different microorganisms. The FilmArray meningitis/encephalitis panel allows the simultaneous detection of 14 pathogens with results in about one hour. This study is based on retrospectively evaluating the implementation of the FilmArray meningitis/encephalitis panel in a hospital environment, highlighting the general results and, especially, analyzing the consistency of the test results against the clinical and laboratory conditions of the patients. Data were collected through the results reported by the BioFire FilmArray system software from the meningitis/encephalitis panel. The correlated laboratory tests used in our analysis, when available, included biochemical, cytological, direct and indirect microbiological tests. In the analyzed period, there were 496 samples with released results. Of the total of 496 samples analyzed, 88 (17.75%) were considered positive, and 90 pathogens were detected, and in 2 of these (2.27%) there was co-detection of pathogens. Viruses were the agents most frequently found within the total number of pathogens detected. Of the 496 proven samples, 20 (4.03%) were repeated, 5 of which were repeated due to invalid results, 6 due to the detection of multiple pathogens and 9 due to disagreement between the panel results and the other laboratory tests and/or divergence of the clinical-epidemiological picture. Of these 20 repeated samples, only 4 of them (20%) maintained the original result after repeating the test, with 16 (80%) being non-reproducible. The main factor related to the disagreement of these 16 samples during retesting was the detection of bacterial agents without any relationship with other laboratory tests or with the patients' clinical condition. In our study, simply reproducing tests with atypical results from the FilmArray meningitis/encephalitis panel proved, in most cases, effective and sufficient for interpreting these results.

Pneumocephalus and meningoencephalitis as a complication of otitis media in a dog

AbstractA 3‐year‐old Maltese dog presented with vestibular signs that worsened after a grass seed was removed from the right external ear canal. Neurological examination was suggestive of a brainstem lesion. Magnetic resonance imaging of the head was performed, and findings were consistent with infectious meningoencephalitis and otogenic pneumocephalus secondary to intracranial extension of right otitis media. A culture of the right middle ear effusion yielded Staphylococcus epidermidis. The dog was euthanased under general anaesthesia due to worsening of the cardiovascular and respiratory parameters. Pneumocephalus in dogs has been described secondary to surgery, trauma, meningocele and meningoencephalocele. To the authors' knowledge, this is the first case report describing otogenic pneumocephalus in a dog.

Elevated Interleukin-31 Levels in Serum, but Not CSF of Dogs with Steroid-Responsive Meningitis-Arteritis Suggest an Involvement in Its Pathogenesis.

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated disease, but the exact pathomechanism remains unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize that IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, and atopic dermatitis, and of healthy control dogs using a competitive canine IL-31 ELISA. The mean serum IL-31 level in dogs with SRMA (n = 18) was mildly higher compared to dogs with atopic dermatitis (n = 3, p = 0.8135) and MUO (n = 15, p = 0.7618) and markedly higher than in healthy controls (n = 10, p = 0.1327) and dogs with infectious meningoencephalitis (n = 3, no statistics). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value for dogs with SRMA (n = 23) was quite similar to that for healthy controls (n = 8, p = 0.4454) and did not differ markedly from dogs with MUO (n = 19, p = 0.8724) and infectious meningoencephalitis. Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 immune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

Humoral Immune Response of Mice against a Vaccine Candidate Composed of a Chimera of gB of Bovine Alphaherpesviruses 1 and 5.

Infectious bovine rhinotracheitis (IBR) and bovine meningoencephalitis are caused by Bovine alphaherpesvirus (BoHV) types 1 and 5, which seriously threaten the global cattle industry. Vaccination to improve immunity is the most direct and effective means to prevent these conditions. Glycoprotein B (gB) is essential for the attachment of both viruses to permissive cells, and is a major target of the host immune system, inducing a strong humoral response. The aim of this study was to evaluate, in a murine model, the immune response of a candidate vaccine formulation composed of a chimeric BoHV-1 and BoHV-5 gB (DgB), expressed in Komagataella phaffii. The chimeric DgB vaccine adjuvanted with Montanide 50 ISA V2 or aluminum hydroxide was administered intramuscularly or subcutaneously. A control group and a group that received a commercial vaccine were inoculated subcutaneously. Higher titers of neutralizing antibodies against BoHV-1, BoHV-5, and a natural BoHV-1/5 recombinant strain were obtained with the oil-based candidate vaccine formulation administered intramuscularly. The results demonstrated that the chimeric DgB conserved important epitopes that were able to stimulate a humoral immune response capable of neutralizing BoHV-1, BoHV-5, and the recombinant strain, suggesting that the vaccine antigen is a promising candidate to be further evaluated in cattle.

Pediatric opsoclonus myoclonus ataxia syndrome in the setting of COVID-19 (P5-9.010)

<h3>Objective:</h3> To describe peri-infectious opsoclonus myoclonus ataxia syndrome (OMAS) in the setting of COVID-19 infection in children. <h3>Background:</h3> OMAS is well described in pediatric patients with peripheral neuroblastic tumors and less defined in the setting of peri-infectious etiologies such as SARS-CoV-19 which is better appreciated in adults. <h3>Design/Methods:</h3> We describe two separate cases of peri-infectious COVID-19 OMAS in pediatric patients at a tertiary Children’s Hospital in 2022, both previously healthy female patients, 2 years and 18 months of age. <h3>Results:</h3> Patient A is a two year-old female who initially presented with ataxia in context of acute COVID-19 infection at 16 months of age and later developed abnormal eye movements, myoclonus and irritability with multiple relapses over a nine month period. Patient B is a 18 month-old female presenting with acute onset abnormal eye movements and ataxia at age 14 months and later developed myoclonic jerks and irritability with sleep disturbance, subsequently found to have COVID-19 antibodies, now with remission of symptoms. Both patients had comprehensive work up for malignancy, toxic-metabolic encephalopathy, structural central nervous system disease, infectious meningoencephalitis and genetic ataxia syndromes. Both were treated with IVIG and high dose steroids. Patient A had subsequent relapses and required escalation of treatment to ACTH. Patient A had a more complicated course which included treatment with acetazolamide and levetiracetam for myoclonus. Her myoclonic jerks demonstrated intermittent electrographic correlates on EEG. <h3>Conclusions:</h3> While OMAS associated with neuroblastic tumors is well described in the pediatric literature, it is less well known in relation to peri-infectious phenomena, particularly SARS-CoV-2 infection in children. Prior published reports of OMAS related to COVID-19 infection in adults indicated a favorable prognosis after initial treatment. However, we present a case with repeated relapses and the need for more aggressive treatment. The present report broadens the phenotypic spectrum for OMAS outside of paraneoplastic etiologies. <b>Disclosure:</b> Dr. Yakir has nothing to disclose. Dr. Most has nothing to disclose. Dr. Hermel has nothing to disclose. Dr. Zimbric has received personal compensation in the range of $0-$499 for serving as a Survey volunteer with Opinionsite. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as a Consultant for Sinopia Biosciences. An immediate family member of Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Pet Dx. Dr. Friedman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology. Dr. Friedman has stock in Friedman Bioventure . Dr. Rho has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nutricia. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerecin. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Rho has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. Dr. Rho has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. The institution of Dr. Rho has received research support from National Institutes of Health. Dr. Rho has received publishing royalties from a publication relating to health care.

Clinical Manifestation, Auxiliary Examination Features and Prognosis of GFAP Autoimmunity: a Chinese Cohort Study (P5-5.029)

<h3>Objective:</h3> To report the clinical manifestation and auxiliary examination features of 15 Chinese patients with glial fibrillary acidic protein (GFAP) autoimmunity. <h3>Background:</h3> GFAP astrocytopathy is a corticosteroid responsive inflammatory central nervous system (CNS) disorder spectrum predominantly affecting meninges, brain, spinal cord, and optic nerve mimics infectious meningoencephalitis. IgG antibodies binding to GFAP are specific biomarkers with diagnostic significance. <h3>Design/Methods:</h3> From June 2016 to December 2019, patients with suspected neurological autoimmune disease were scanned for autoantibodies by immunohistochemistry. Samples showed a characteristic immunoreactive pattern reminiscent of GFAP of astrocytes were selected and confirmed by cell-based assay. <h3>Results:</h3> Fifteen patients (8 male, 7 female) with a median age at onset of 53 years were identified as GFAP-IgG positive. Eleven of 15 patients presented with an acute monophasic course, of which 10 had antecedent flu-like symptoms. The predominant phenotype was meningoencephalitis (46.7%), followed by meningoencephalomyelitis in 40% of cases. Magnetic resonance imaging revealed enhancement in 10 of 13 patients. Inflammatory CSF showed mild lymphocyte-predominant pleocytosis with a median of 51/μl, elevated protein with a median of 87.5mg/dl. Five of six patients tested for CSF specific oligoclonal bands were positive. Five patients had coexisting antibodies, including NMDAR-IgG in 3 patients, Yo and MOG-IgG in one each patient. One patient underwent stereotactic brain biopsy and neuropathology diagnosis was diffuse large B-cell lymphoma with normal reactive fibrillary astrocytes. One patient had ovarian teratoma. Eleven of 15 patients received both intravenous immunoglobulin and steroids. Among them, 3 patients also received immunosuppressive agents later. During 2-year follow-up, nine of 15 patients achieved complete clinical remission. <h3>Conclusions:</h3> The clinical presentation of GFAP astrocytopathy is heterogeneous, including acute monophasic course or chronic relapsing courses. Patients with an acute monophasic course with antecedent infection symptoms responded well to immunotherapy. In case of primary central nervous system lymphoma, GFAP autoimmunity doesn’t equal to autoimmune GFAP astrocytopathy. <b>Disclosure:</b> Dr. Liu has nothing to disclose. Dr. Zhang has nothing to disclose.

Diagnostic Relevance of the Medullary Vein Sign in Neurosarcoidosis (P9-5.003)

<h3>Objective:</h3> To evaluate the diagnostic potential of the medullary vein sign as an imaging marker in neurosarcoidosis. <h3>Background:</h3> Neurosarcoidosis is a rare manifestation of sarcoidosis that can be inferred through the clinical presentation, cerebral spinal fluid (CSF) analysis, and magnetic resonance imaging (MRI) scans. However, its accurate diagnosis remains a significant challenge due to the variability in its diagnostic criteria and the overlapping clinical and imaging features with other conditions. One under-researched finding in these patients is the engorgement of the medullary vein on susceptibility-weighted imaging (SWI), termed as the ‘medullary vein sign’; postulated to be a specific sign for neurosarcoidosis, its reliability has not yet been fully elucidated. <h3>Design/Methods:</h3> A single-center retrospective study was performed between March 31st, 2022, and August 1st, 2022. Two neuroradiologists independently examined MRI images using SWI/gradient echo sequences for medullary vein engorgement. A total of 32 patients were reviewed, and the diagnosis was based on imaging, biopsy, and CSF analysis. Finally, the sensitivity and specificity of the medullary vein sign were calculated. <h3>Results:</h3> Out of 32 patients, seven were diagnosed with definitive neurosarcoidosis; the remaining were classified as possible (n=16), probable (n=5), and other (n=4) causes of infectious meningoencephalitis, including two cases of autoimmune encephalitis. Among these, the medullary vein sign was detected in seven patients: five with confirmed, and two with possible neurosarcoidosis. Overall, the sensitivity was 71.4%, and the specificity was 92.3%. CSF was largely inconclusive, and MRI was not the major diagnostic factor in most cases. <h3>Conclusions:</h3> Our findings confirm the high specificity of the medullary vein sign for neurosarcoidosis and suggest that SWI is an effective tool for early detection, especially compared to conventional MRI and CSF analysis. Incorporating this in the current diagnostic criteria may result in timely intervention, and we encourage radiologists to look for this marker in patients with suspected neurosarcoidosis. <b>Disclosure:</b> Dr. Srivastava has nothing to disclose. Dr. Sharma has nothing to disclose. Dr. Joseph has nothing to disclose. Dr. Feizi has nothing to disclose. Dr. Sriwastava has nothing to disclose.

Evaluation of the Novel CE-IVD-Marked Multiplex PCR QIAstat-Dx Meningitis/Encephalitis Panel.

Central nervous system (CNS) infections such as meningitis and encephalitis are life-threatening conditions that demand hospital care and prompt identification of the causative agent. Since 2015, there has been only one CE-IVD-marked rapid multiplexed diagnostic assay in cassette format for bacterial and viral detection from cerebrospinal fluid (CSF): the BioFire FilmArray meningitis/encephalitis (ME) panel. In the beginning of 2022, Qiagen introduced the QIAstat-Dx meningitis/encephalitis panel. It is a CE-IVD-marked multiplex PCR cassette test intended for the identification of suspected infectious meningitis, encephalitis, or meningoencephalitis caused by bacterial, viral, or fungal pathogens. In this study, we evaluated patient and quality control samples using the QIAstat-Dx meningitis/encephalitis panel and compared the results to those of the BioFire FilmArray meningitis/encephalitis panel and reference methods (current routine analysis methods in our laboratory, PCR, or cultivation). The combined positive percent agreement between the two panel assays was 100%, and the negative percent agreement was 94%. We further compared specifically herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) dilution series using six commercial herpesvirus assays, including the two cassette tests. The results suggested that real-time PCR methods (with separate extraction) were the most sensitive methods. When comparing the cassette tests, the BioFire FilmArray meningitis/encephalitis panel produced more positive results than the QIAstat-Dx meningitis/encephalitis panel in the herpesvirus analyses. IMPORTANCE The diagnosis of infectious meningitis and encephalitis relies mostly on specific PCR and culturing methods, but commercial syndromic panel assays are bringing a change in diagnostics. With multiplexed analysis, the identification of the pathogen is potentially faster, and less sample material is needed. The novel QIAstat-Dx meningitis/encephalitis panel assay is intended for the rapid identification of pathogens from cerebrospinal fluid for suspected central nervous system (CNS) infection, which is a life-threatening condition and difficult to diagnose. We studied the performance of this panel assay using patient samples and dilution series of selected viruses. The evaluation data for this novel meningitis/encephalitis panel assay are useful for other clinical laboratories and organizations using or considering using this test.

The Contribution of Multiplex Polymerase Chain Reaction in the Diagnosis of Central Nervous System Infections in Intensive Care Units.

Introduction The aim of this study was to evaluate the contribution and limits of BioFire® FilmArray® meningitis/encephalitis panel (FA MEP) polymerase chain reaction (PCR) (bioMérieux, Marcy-l'Étoile, France) (product references: LLC RFIT-ASY-0118) coupled with bacterial and fungal culture in the diagnosis of central nervous system infections (CNSIs). Methods This was a retrospective observational study including all patients (adults and children) hospitalized in the intensive care units (ICUs) of a Moroccan university hospital, who benefited from multiplex PCR on a cerebrospinal fluid (CSF) sample. Results A total of 112 PCRs were performed, with a positivity rate of 18%. Bacterial etiology was the most frequent (70%), represented mainly by Streptococcus pneumoniae (45%), followed by viruses (25%), with four isolates of Herpes simplex virus (HSV) 1. On 94 samples, there was an agreement between the culture and PCR results. Their discordance was found in 18 cases, including 16 suspected CNSIs recovered only by PCR and two diagnoses confirmed only by bacterial culture. Conclusion This study revealed the significant impact of multiplex PCR on the early and targeted diagnostic and therapeutic management of infectious meningitis and meningoencephalitis in intensive care unit patients.

Viral meningoencephalitis with damage to the right temporal lobe with a favorable outcome

Herpes simplex virus (HSV) is the most commonly identified cause of infectious meningoencephalitis in Western countries. Previous studies showed that neurological defects can form during HSV meningoencephalitis, ranging from symptomatic epilepsy to mental and movement disorders. The recovery of Cognitive Mental Functions (CMF) in a patient who survived HSV meningoencephalitis was evaluated. The results were compared with MRI and EEG data. A follow-up observation of the patient was carried out for more than 1 year. During the observation period, the patient showed improvement of CMF, while MRI scans showed no observable improvement. Current neuropsychological methods give enough information for the assessment of CMF in patients after neurological infections and are essential for evaluating new treatment methods and monitoring of possible deterioration or relapse.

Overlapping syndrome mimicking infectious meningoencephalitis in a patient with MOG and GFAP IgG

BackgroundCentral nervous system overlapping autoimmune syndromes are uncommon, especially with the coexistence of MOG-IgG and GFAP-IgG.Case presentationA 23-year-old woman presented with transient convulsions, a loss of consciousness, persistent fever, headache, and vomiting. Cerebrospinal fluid (CSF) analysis revealed elevated cellularity, and magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement. She had fever and headache with antiviral and antibiotic treatment for 2 weeks, and she had empirical anti-tuberculosis treatment and oral prednisolone therapy. She was followed for 3 months after presentation with improved symptoms and normal CSF analysis. A 3-month follow-up MRI showed asymmetric lesions in the cerebellum, corona radiata, and white matter with enhancement. The anti-tuberculosis treatment was continued, and steroid therapy was discontinued. After she stopped taking prednisolone, an interrupted headache gradually appeared. MRI at 4 months after presentation revealed a partial reduction in lesions but enlarged areas in the left cerebellum and right parietal white matter and a new lesion in the region of the right ependyma with linear enhancement. Her CSF was positive for anti-myelin oligodendrocyte glycoprotein (MOG) and anti-glial fibrillary acidic protein (GFAP) antibodies using a transfected cell-based assay. She was diagnosed with overlapping syndrome of MOG‑IgG‑associated disease and GFAP astrocytopathy. She received steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone and the addition of an immunosuppressant (tacrolimus, 3 mg per day). Six months after the initial presentation, she had no symptoms. An MRI showed that the lesions had diminished, and no enhancement was found.ConclusionsWe report a case that was positive for double antibodies, which was initially misdiagnosed as infectious meningoencephalitis. This case broadens the clinical and phenotypic presentation of the overlapping syndrome spectrum.

Perplexing Infectious Etiology of a Case of Hypopituitarism and Central Diabetes Insipidus

Injury to the hypothalamus and both the anterior and posterior components of the pituitary gland is rare, but can result from infiltrative processes such as sarcoidosis, Langerhans cell histiocytosis, granulomatous with polyangiitis, and lymphocytic hypophysitis. Meningitis, pituitary infection, traumatic brain injury, and surgical instrumentation are other etiologies.A 40 year old man with mild cognitive impairment due to remote meningitis was evaluated for progressive somnolence. He was obtunded and cerebrospinal fluid (CSF) analysis revealed 11 WBC with lymphocytic pleocytosis (90% lymphocytes), highly elevated protein of 588 mg/dL (ref range 12-60 mg/dL), and low glucose of 17 mg/dL (ref range 40-70 mg/dL). MRI Brain revealed basilar meningitis/rhombencephalitis and suspected infectious vasculitis induced right middle cerebral artery territory stroke. Of note, there was substantial T2 hyperintense signaling in the hypothalamus and pituitary areas, which has been reported with tuberculosis (TB), Coccidioidomycosis (Cocci), and the aforementioned etiologies. He received broad antimicrobials, including TB treatment and fluconazole. He developed sinus bradycardia, hypotension, hypoglycemia, and hypothermia. Labs demonstrated inappropriately normal TSH of 1.4 mclU/mL (ref range 0.35-4.94 mclU/mL), low free T4 (fT4) of 0.50 ng/dL (ref range 0.7-1.48 ng/dL) with repeat fT4 undetectably low the following day, and AM cortisol less than 0.5mcg/dL (ref range 4-22 mcg/dL). Levothyroxine and steroids were initiated. He then developed central diabetes insipidus (DI) for which DDAVP was initiated. Comprehensive infectious and autoimmune meningoencephalitis workup was unrevealing. Serum and CSF tests for Listeria PCR, Cocci antibody and antigen, and TB were negative upon multiple, serial checks spanning weeks. CSF analysis one month later showed improvement in protein level (106 mg/dL), but still with elevated WBC (10 WBCs, 98% lymphocytes). MRI one month later demonstrated improvement in edema and the areas of ischemia and vasculitis were less. His adrenal insufficiency and central DI were transient and improved, no longer requiring steroids or DDAVP. He remains on levothyroxine for central hypothyroidism.The MRI and CSF findings point to an infectious etiology for hypopituitarism and central DI. We suspect an indolent bacteria such as Listeria or a fungus, likely Cocci, or TB meningitis. Cocci seemed to provide a unifying explanation as it classically creates infarcts and causes vasculitis. However, serial CSF tests were negative for Cocci, as well as for TB and Listeria. Marked improvement on follow up MRI also makes TB meningitis less likely as imaging would not resolve so quickly. This is a mysterious case; he improved on broad antimicrobial therapy and is being monitored closely in the outpatient setting.

Atypical Presentation of Anti-NMDAR encephalitis in a Male Patient – an Unfortunate Mimic

Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuroinflammatory disorder with a predilection for females. Males present differently, with seizures rather than the better-recognized constellation of psychiatric and behavioral symptoms dominating the initial stages of the disease, providing a potential substrate for delayed recognition and treatment. Case Presentation An 18-year-old man presented with fever and “seizures. When examined, he was febrile but alert and coherent. His neurologic, respiratory, cardiovascular, and abdominal examinations were unremarkable. Diagnosed with infective meningoencephalitis, he was started on intravenous ceftriaxone and acyclovir concurrently with anti-epileptic medications. However, he deteriorated into refractory status epilepticus. Electroencephalograms showed left temporo-parietal seizures. Cerebrospinal fluid analysis revealed inflammatory features, but the virologic assays and bacterial cultures returned negative. Magnetic resonance imaging scans performed in the first and second week from symptom-onset demonstrated the interval development of widespread sulcal T2 hyperintensity, with florid and diffuse leptomeningeal enhancement. Anti-NMDAR antibodies were subsequently detected in his cerebrospinal fluid by indirect immunofluorescence. Diagnosed with anti-NMDAR encephalitis, he received plasmapheresis, methylprednisolone and immunoglobulin infusions. Conclusion Anti-NMDAR encephalitis should be considered in patients, especially males, who are treated for suspected infectious meningoencephalitis, but continue to deteriorate, even in the absence of prominent psychiatric or behavioral symptoms, considering how the initial symptoms differ between the genders. The interval development of diffuse and florid leptomeningeal enhancement on sequential magnetic resonance imaging scans of our patient has not been described in prior reports, and may be reflective of the underlying inflammatory processes.

A blank slate – apropos a clinical case

IntroductionDissociative Amnesia remains an enigmatic and controversial entity. It is classically described as responsible for autobiographic amnesia associated with a traumatic event.ObjectivesTo report a clinical case and review the literature.MethodsWe collected data from the patient’s clinical file with his informed consent. We conducted a non-systematic review of the literature.ResultsA 46-years-old patient presents to the emergency department for sudden global retrograde amnesia, with multiple domain amnestic syndrome (impairing verbal and visual memory, processing speed, mental flexibility, calculus, executive functions and language). He was initially admitted for a suspected infectious meningoencephalitis, which was not confirmed. Later an autoimmune encephalitis was pursued. Brain MRI showed a nonspecific left temporal and hipocampal hyperintensity and the EEG a mild left temporal dysfunction. The autoimmune encephalitis panel was negative and the formal diagnostic criteria were not met. The neurologic examination at discharge presented only with autobiographical and semantic amnesia. On the mental state examination, he presented with depressive symptoms reactive to the situation. There was no evident traumatic event apart from a promotion received the day before the amnesia started. He was prescribed escitalopram 10 mg/day. The amnesia was maintained at 9 months follow-up.ConclusionsOur case report illustrates a case of amnesia without evident organic or psychogenic cause, assumed as a dissociative amnesia. Further studies are necessary to clarify the pathophysiology of this condition and develop specific treatments.DisclosureNo significant relationships.

Causes of Mortality of Northern Sea Otters (Enhydra lutris kenyoni) in Alaska From 2002 to 2012

Most of the world’s sea otters reside in Alaska, but there has never been an assessment of long-term mortality patterns for this keystone predator. We examined data collected from 780 northern sea otter (Enhydra lutris kenyoni)carcasses recovered in Alaska from 2002 to 2012 to evaluate the causes of mortality and risk factors associated with death. A smaller group (n= 144, 18%) of fresh non-frozen carcasses were included in a more detailed mortality analysis. Forty-four% of the fresh dead otters were determined to have died from infectious endocarditis, meningoencephalitis, and/or septicemia due to systemic streptococcosis (“Strepsyndrome”).Streptococcus lutetiensis, a member of theStreptococcus bovis/equinus(SB/E) group was most commonly isolated, although other members of the SB/E group were identified. There were fewer cases whereS. phocaeand other streptococci were isolated. A regression analysis revealed age and location risk factors forStrepsyndrome. Subadults were the highest risk age group, and otters recovered from the Kachemak Bay region were 3.6 times (95% CI: 2.2–5.9) more likely to die fromStrepsyndrome than otters recovered elsewhere. Diagnosis of thisStrepsyndrome had not been reported in other marine mammals in Alaska. Sporadic cases of septicemia and infectious endocarditis due toS. lutetiensishave been seen in the southern sea otter population in California. Other causes of death for the fresh otters included neurologic diseases (10%), trauma (8%), nutritional diseases (7%), cardiovascular diseases (7%), gastrointestinal diseases /parasites (6%), undetermined (5%), septicemia (3%), and neoplasia (3%). All other causes of death (oiling, hepatobiliary, fungal, marine biotoxins, pulmonary) were at or below 1%. Twenty percent of fresh animals were positive for phocine distemper virus (PDV) by polymerase chain reaction (PCR, 11/55), 18% seropositive for PDV (7/38), and paramyxovirus-like particles were demonstrated by electron microscopy within inclusion bodies from one animal. Low concentrations of the harmful algal bloom toxins domoic acid and saxitoxin were also detected in 26% and 22% of fresh animals, respectively. Protozoal disease was rare. These patterns of disease differ from sea otters in other regions and possible reasons are discussed.