Encephalitis associated with anti-mGluR5 antibodies.

A 30-year-old woman had 5 days of visual hallucinations, nystagmus, memory impairment and mutism. On examination, she was disorientated with reduced attention span, gaze-evoked nystagmus, paratonia and abnormal frontal reflexes. Cerebrospinal fluid (CSF) showed 80 cells, protein 0.41 g/L and glucose 3.2 mmol/L (plasma glucose 5.0 mmol/L). MR scan of the brain showed involvement of limbic and extra-limbic regions and brainstem. Commercial cell-based assays were negative, but tissue-based assays showed neuropil staining, and cell-based assays for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies were positive in serum and CSF. Six months later, she was diagnosed with Hodgkin's lymphoma. This case emphasises the broader clinical spectrum of anti-mGluR5 encephalitis, challenging its initial characterisation as Ophelia syndrome. It underscores the significance of interpreting commercial cell-based assays and advocates for tissue-based assay testing followed by cell-based assay testing in serum and CSF for diagnosing rare autoimmune encephalitis.

Quality of podcasts recorded by nursing lecturers as pre-class learning material for students: An observational study.

AIM: To evaluate the quality of podcasts produced by lecturers as pre-class learning material; to verify lecturers' buy-in, after a specific workshop, regarding the practice of producing and using podcasts. BACKGROUND: The teaching-learning process has undergone significant changes in recent years with the proposal of the flipped classroom strategy, which places the student at the center of the learning process and uses technology that requires adaptation of lecturers, both inside and outside the classroom. Pre-class learning material is one of the features of the flipped classroom model. It provides basic concepts for problem solving in small group discussion in classroom. Podcasts for this educational purpose are a recent technology and their innovative characteristics require deeper understanding in terms of their influence and usability. DESIGN: Prospective, descriptive and quantitative study. SETTING AND POPULATION: A workshop on the production of educational podcasts was offered to 23 lecturers on the Nursing course. METHODS: Data were collected in the second semester of 2021 and the quality analysis was based on criteria available in the literature. RESULTS: Eighteen professors (78 %) participated in the study and 46 podcasts were produced. Most professors being nurses (61 %), followed by biologists (28 %). Most have a doctorate degree (72 %). These podcasts were available for a mean of five days before the classes and their mean access rate by students was 58 %. There was no correlation between the access rate and the period of availability before the relative class. Most podcasts were informative (100 %) and monologues (98 %). The average duration was 6.2 min, which is within the ideal duration recommended in the literature. All of the podcasts included a description of the learning objectives at the beginning and most of them also included a closing message at the end. CONCLUSION: The nursing lecturers were able to produce their podcasts, which met quality criteria and reached the standards suggested by experts in the field.

Personal protective equipment simulation training is associated with lower COVID-19 infection among healthcare workers.

OBJECTIVE: To describe the personal protective equipment training strategies during the beginning of the pandemic and to investigate the association between training and COVID-19 infection among healthcare workers. METHODS: This cross-sectional study conducted between March and May 2020 included 7,142 healthcare professionals who were eligible for both online and face-to-face simulation-based training on personal protective equipment use. Simulation training attendance was assessed by reviewing the attendance list, and the COVID-19 sick leave records recovered from the institutional RT-PCR database used to grant sick leave. The association between personal protective equipment training and COVID-19 was investigated using logistic regression, adjusted for sociodemographic and occupational characteristics. RESULTS: The mean age was 36.9 years (± 8.3), and 72.6% of participants were female. A total of 5,502 (77.0%) professionals were trained: 3,012 (54.7%) through online training, 691 (12.6%) through face-to-face training, and 1,799 (32.7%) through both strategies. During the study period, 584 (8.2%) COVID-19 cases were diagnosed among these professionals. The number of positive RT-PCR tests was 180 (11.0%) for untrained professionals, 245 (8.1%) for those trained only online, 35 (5.1%) for those trained face-to-face, and 124 (6.9%) for those trained with both strategies (p<0.001). Participants who received face-to-face training had a 0.43 lower risk of contracting COVID-19. CONCLUSION: Personal protective equipment training decreased the odds of COVID-19 among healthcare professionals, with face-to-face simulation-based training being most effective.

Neurobrucellosis Mimicking Primary CNS Vasculitis-Should We Perform CSF Metagenomics Before Brain Biopsy?: A Case Report.

Objective: To report a patient with neurobrucellosis mimicking primary CNS vasculitis (PCNSV) diagnosed by CSF metagenomic next-generation sequencing (mNGS). Methods: A 32-year-old male patient with a prior stroke developed headache, dizziness, fever, and memory complaints in the past 30 days. Physical examination was unremarkable except for slight apathy. He was investigated with brain MRI, cerebral digital angiography, CSF analysis with mNGS, and brain biopsy. Results: An examination of the brain MRI showed a left nucleocapsular gliosis compatible with prior stroke; MR angiogram showed circular enhancement of distal branches of the middle cerebral arteries. Digital angiogram revealed stenosis of intracranial carotid arteries and the left middle cerebral artery. The CSF disclosed 42 cells/mm3, 46 mg/dL of glucose, and 82 mg/dL of protein. Brain biopsy showed a chronic leptomeningeal inflammatory process, not fulfilling criteria for PCNSV. mNGS revealed the presence of Brucella sp. genetic material. He was treated with antibiotics with full remission of systemic and neurologic symptoms. Discussion: Brucellosis is an endemic disease in developing countries and may mimic PCNSV. Our patient fulfilled the criteria for possible PCNSV; however, brain biopsy was inconsistent with PCNSV, and CSF mNGS disclosed neurobrucellosis. This case illustrates the importance of CSF mNGS in the differential diagnosis of CNS vasculitis.

Personal protective equipment simulation training is associated with lower COVID-19 infection among healthcare workers

ABSTRACT Objective To describe the personal protective equipment training strategies during the beginning of the pandemic and to investigate the association between training and COVID-19 infection among healthcare workers. Methods This cross-sectional study conducted between March and May 2020 included 7,142 healthcare professionals who were eligible for both online and face-to-face simulation-based training on personal protective equipment use. Simulation training attendance was assessed by reviewing the attendance list, and the COVID-19 sick leave records recovered from the institutional RT-PCR database used to grant sick leave. The association between personal protective equipment training and COVID-19 was investigated using logistic regression, adjusted for sociodemographic and occupational characteristics. Results The mean age was 36.9 years (± 8.3), and 72.6% of participants were female. A total of 5,502 (77.0%) professionals were trained: 3,012 (54.7%) through online training, 691 (12.6%) through face-to-face training, and 1,799 (32.7%) through both strategies. During the study period, 584 (8.2%) COVID-19 cases were diagnosed among these professionals. The number of positive RT-PCR tests was 180 (11.0%) for untrained professionals, 245 (8.1%) for those trained only online, 35 (5.1%) for those trained face-to-face, and 124 (6.9%) for those trained with both strategies (p<0.001). Participants who received face-to-face training had a 0.43 lower risk of contracting COVID-19. Conclusion Personal protective equipment training decreased the odds of COVID-19 among healthcare professionals, with face-to-face simulation-based training being most effective.

The Role of Autoantibody Testing in Modern Personalized Medicine.

Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters. The accelerated identification of numerous biological variables associated with diverse health conditions contributes to the fulfillment of one of the pre-requisites for PM. The advent of multiplex analytical platforms contributes to the determination of thousands of biological parameters using minute amounts of serum or other biological matrixes. Finally, big data analysis and machine learning contribute to the processing and integration of the multiplexed data at the individual level, allowing for the personalized definition of susceptibility, diagnosis, prognosis, prevention, and treatment. Autoantibodies are traditional biomarkers for autoimmune diseases and can contribute to PM in many aspects, including identification of individuals at risk, early diagnosis, disease sub-phenotyping, definition of prognosis, and treatment, as well as monitoring disease activity. Herein we address how autoantibodies can promote PM in autoimmune diseases using the examples of systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, idiopathic inflammatory myopathies, autoimmune hepatitis, primary biliary cholangitis, and autoimmune neurologic diseases.

Serum BDNF and cognitive dysfunction in SLE: findings from a cohort of 111 patients.

OBJECTIVE: The association between brain-derived neurotrophic factor (BDNF) and neuropsychiatric systemic lupus erythematosus (NPSLE) is controversial in the literature. Cognitive dysfunction (CD) is a common, underdiagnosed NPSLE manifestation, but its pathophysiology is unknown. Thus, we investigate serum BDNF as a potential biomarker of CD in a cohort of SLE patients. METHODS: We included 63 SLE patients, 48 NPSLE, and 57 age- and gender-matched controls (CON). All participants underwent neuropsychological assessment. Data on cardiovascular comorbidities, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics damage index (SLICC-DI) were compiled. Multiple regression analyses evaluated predictors of serum BDNF levels. RESULTS: Serum BDNF levels were lower in SLE and NPSLE patients than in CON (SLE 800.4 ± 502.7 vs. NPSLE 779.7 ± 426.3 vs. CON 1,345.5 ng/mL ± 438.4; p < 0.001). In addition, hypertension (B: - 192.5, SE: 84.3, 95% CI: - 359.7 to - 25.3, p = 0.024) and SLICC-DI score (B: - 75.9, SE: 27.2, 95% CI: - 129.8 to - 22, p = 0.006) were predictors of serum BDNF levels in SLE. There was no relation between BDNF levels and CD. CONCLUSION: BDNF levels are lower in SLE patients than CON and inversely associated with hypertension and SLICC-DI scores. No association between BDNF levels and CD or NPSLE was observed in this cohort. These findings indicate that BDNF may be associated with overall burden in SLE rather than specific manifestations such as cognition impairment. Key Points • BDNF is associated with an overall burden in SLE rather than specific manifestations such as cognition dysfunction. • BDNF levels are reduced in patients with SLE, and higher SLICC-DI scores and hypertension are independent predictors of lower serum BDNF levels. • The cognitive dysfunction rate is elevated (46%) among Brazilian SLE patients.

Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study.

Background: IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features. Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD. Results: A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD. Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis.

OBJECTIVE: To clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters. METHODS: Clinical information on new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons. RESULTS: Eleven new patients were identified (10 adults, 1 child);4 were female. In these and 19 previously reported cases (n = 30, median age 55 years), the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurologic symptoms. A tumor was found in 3 of 26 (11%). Brain MRI was abnormal in 7 of 19 (37%) at onset and showed cerebellar atrophy in 10 of 12 (83%) at follow-up. Twenty-five of 30 (83%) patients received immunotherapy. Follow-up was available for 25: 13 (52%) had clinical stabilization; 10 (40%) showed significant improvement; and 2 died. At the peak of the disease, patients with bad outcome at 2 years (modified Rankin Scale score > 2, n = 7) were more likely to have higher degree of initial disability, as reflected by a worse Scale for Assessment and Rating of Ataxia score, and more frequent need of assistance to walk. Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in cultured neurons. CONCLUSIONS: Anti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in long-term disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons.

NMDAR Encephalitis Associated With Acute Chikungunya Virus Infection: A New Trigger?

Background: Anti-NMDAR encephalitis is the most frequent cause of autoimmune encephalitis. Chikungunya (CHIK) is an arbovirus responsible for outbreaks of fever, cutaneous rash and arthritis in underdeveloped countries, and a trigger for autoimmunity. Case Presentation: We report a five-year-old male patient with fever, myalgia, headache and conjunctivitis for 5 days. After 1 week he developed tonic-clonic seizures and evolved with dystonia and oromandibular dyskinesia followed by onset of focal motor seizures, decreased level of consciousness, dysautonomia and central apnea. Brain MRI was normal, CSF analysis revealed 15 cells, protein 16.6 mg/dL and glucose 68 mg/dL. Anti-NMDAR antibodies were detected in serum and CSF after 3 weeks of symptom onset. CHIK serology was positive for both IgM and IgG, suggesting a recent infection. Dengue and Zika serologies were negative. CSF PCR for herpes viruses and arboviruses (CHIK, Dengue and Zika) were negative. Conclusion: We report the occurrence of anti-NMDAR encephalitis after acute CHIK infection. The biphasic course, positivity for both CHIK IgM and IgG and negative CHIK CSF PCR results, as well as a dramatic response to immunotherapy suggest an immune-mediated pathogenesis. Because of the global epidemic of CHIK infection and unknown mechanisms involving CHIK and autoimmunity, patients with acute CHIK infections and neurological manifestations should be considered for antineuronal antibody testing.

Cognitive and Psychiatric Evaluation in SYNE1 Ataxia.

SYNE1 gene mutations were identified as a cause of late-onset pure cerebellar syndrome. Non-cerebellar symptoms, including cognitive impairment, were already described in this condition. The aim of this study was to perform a detailed cognitive and psychiatric description of patients with SYNE1 gene mutations. We performed neuropsychological and psychiatric evaluations of six patients with SYNE1 ataxia and compared their performance with 18 normal controls paired for age and education level. SYNE1 ataxia patients present cognitive dysfunction, characterized by impairment in attention and processing speed domains. Otherwise, the psychiatric assessment reported low levels of overall behavioral symptoms with only some minor anxiety-related complaints. Although this is a small sample of patients, these results suggest that SYNE1 ataxia patients may represent a model to investigate effects of cerebellar degeneration in higher hierarchical cognitive functions. For further studies, abstract thinking impairment in schizophrenia may be related to dysfunction in cerebellum pathways.

Acute cerebellar ataxia: differential diagnosis and clinical approach.

Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.

Acute cerebellar ataxia: differential diagnosis and clinical approach / Ataxia cerebelar aguda: diagnóstico diferencial e abordagem clínica

ABSTRACT Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.

RESUMO A ataxia cerebelar é um achado comum na prática neurológica e tem uma grande variedade de causas, desde a degeneração cerebelar crônica e lentamente progressiva à lesão cerebelar aguda devido a infarto, edema ou hemorragia, configurando uma verdadeira emergência neurológica. Ataxia cerebelar aguda é uma síndrome que ocorre em menos de 72 horas em indivíduos previamente saudáveis. A ataxia aguda geralmente resulta em hospitalização e extensa investigação laboratorial. Os clínicos são frequentemente confrontados com a decisão sobre a extensão e o momento dos testes de rastreio iniciais, em particular para detectar as causas tratáveis. O principal grupo de doenças que podem causar ataxias agudas discutidas neste artigo são: acidente vascular cerebral, infecciosas, tóxicas, imunomediadas, paraneoplásicas, deficiência de vitaminas, lesões estruturais e doenças metabólicas. Esta revisão enfoca a etiologia e considerações diagnósticas para a ataxia aguda.

Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases.

BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs.

Autoimmune encephalitis: a review of diagnosis and treatment.

Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. There are a variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures. We reviewed common forms of AIE and discuss their diagnostic approach and treatment.

Autoimmune encephalitis: a review of diagnosis and treatment / Encefalites autoimunes: uma revisão sobre diagnóstico e tratamento

ABSTRACT Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. There are a variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures. We reviewed common forms of AIE and discuss their diagnostic approach and treatment.

RESUMO As encefalites autoimunes (EAI) são a principal causa de encefalite não-infecciosa. As manifestações neurológicas são variadas, incluindo alterações comportamentais ou psiquiátricas, disautonomia, transtornos do movimento e epilepsia. Habitualmente a instalação dos sintomas ocorre em até 6 semanas, de forma aguda ou subaguda. As EAI podem ser desencadeadas por tumores, quadros infecciosos virais ou ainda apresentar etiologia criptogênica. Este artigo revisa as principais EAI, estratégias de diagnóstico e tratamento.

Neurological complications of solid organ transplantation.

Solid organ transplantation is a significant development in the treatment of chronic kidney, liver, heart and lung diseases. This therapeutic approach has increased patient survival and improved quality of life. New surgical techniques and immunosuppressive drugs have been developed to achieve better outcomes. However, the variety of neurological complications following solid organ transplantation is broad and carries prognostic significance. Patients may have involvement of the central or peripheral nervous system due to multiple causes that can vary depending on time of onset after the surgical procedure, the transplanted organ, and the intensity and type of immunosuppressive therapy. Neurological manifestations following solid organ transplantation pose a diagnostic challenge to medical specialists despite extensive investigation. This review aimed to provide a practical approach to help neurologists and clinicians assess and manage solid organ transplant patients presenting with acute or chronic neurological manifestations.