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.

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.

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.

Cerebrovascular disease in patients with antiphospholipid antibody syndrome: a transcranial Doppler and magnetic resonance imaging study.

Objective: Transcranial Doppler (TCD) and brain MRI may be useful in evaluating patients with APS, helping to stratify the risk of cerebrovascular ischaemic events in this population. This study aimed to assess the frequency of brain MRI abnormalities in patients with primary antiphospholipid syndrome, secondary antiphospholipid syndrome and SLE and correlate to TCD findings. Methods: The study, conducted over four years at two autoimmune disease referral centres, included 22 primary antiphospholipid syndrome patients, 24 secondary antiphospholipid syndrome patients, 27 SLE patients without APS and 21 healthy controls. All participants underwent TCD to assess cerebral haemodynamics, detect microembolic signals and evaluate right-to-left shunts, followed by brain MRI and magnetic resonance angiography. MRI scans were reviewed for acute microembolism, localized cortical infarctions, border infarctions, lacunar infarctions, ischaemic lesions, white matter hyperintensity, micro and macro haemorrhages and arterial stenosis ≥50% of the cervical carotid artery, by two neuroradiologists blinded to the clinical data. Results: Brain MRI findings were similar between the groups, except for lacunar infarction, more frequent in patients with secondary antiphospholipid syndrome (P = 0.022). Patients with intracranial stenosis detected by TCD had a higher frequency of territorial infarction (40% vs 7.5%, P = 0.02), lacunar (40% vs 11.3%, P = 0.075) and border zone infarcts (20% vs 1.9%, P = 0.034). Conclusions: Patients with intracranial stenosis presented a higher frequency of territorial, lacunar and border zone infarcts, suggesting that evaluating the intracranial vasculature should not be neglected in patients with APS and stroke.

HLA dependency and possible clinical relevance of intrathecally synthesized anti-IgLON5 IgG4 in anti-IgLON5 disease.

Background: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance. Methods: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method. Results: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab. Conclusion: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.

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.

Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features.

The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado­Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey­Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color­Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color­Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit.

Cognitive deficits in Machado-Joseph disease correlate with hypoperfusion of visual system areas.

Cognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD)-SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. The aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. The neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin' Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR <0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. The visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease.

Sjogren-Larsson syndrome.

Sjogren-Larsson syndrome is a rare disease characterized by the occurrence of mental retardation, spastic diplegia and ichthyosis. The involvement of brain and skin is justified by a mutation in FALDH gene that affects the metabolism of fatty acids and leads to abnormal accumulation of lipids. The normal formation of multilamellar membranes in the stratum corneum and myelin is impaired. The aim of this chapter is to review the classical manifestation of the disease and its differential diagnosis.

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.

Sleep disorders in machado-joseph disease: frequency, discriminative thresholds, predictive values, and correlation with ataxia-related motor and non-motor features.

Sleep disorders are common complaints in patients with neurodegenerative diseases such as spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD)--SCA3/MJD. We evaluated the frequency of sleep disorders in SCA3/MJD patients against controls matched by age and gender, and correlated data with demographic and clinical variables. The main sleep disorders evaluated were rapid eye movement (REM) sleep behavior disorder (RBD), restless leg syndrome (RLS), and excessive daytime sleepiness (EDS). We recruited 40 patients with clinical and molecular-proven SCA3/MJD and 38 controls. We used the following clinical scales to evaluate our primary outcome measures: RBD Screening Questionnaire, International RLS Rating Scale, and Epworth Sleepiness Scale. To evaluate ataxia-related motor and non-motor features, we applied the International Cooperative Ataxia Rating Scale, the Scale for the Assessment and Rating of Ataxia, and the Unified Parkinson's Disease Rating Scale part III. Psychiatric manifestations were tested with the Hamilton Anxiety Scale, and Beck Depression Inventory. The frequency of RBD and RLS were significantly higher in the SCA3/MJD group than in the control group (p < 0.001). There was no difference between both groups with regard to EDS. The accuracy of RDBSQ to discriminate between cases and controls was considered the best area under the ROC curve (0.86). Within-SCA3/MJD group analysis showed that anxiety and depression were significantly correlated with RDB, but not with RLS. Additionally, depression was considered the best predictive clinical feature for RDB and EDS.

Behçet disease: clinical features and management in a Brazilian tertiary hospital.

BACKGROUND: Behçet disease (BD) is prevalent in Central and East Asia and in the Eastern Mediterranean area where most studies have been performed. Few studies have evaluated patients with BD in Brazil. OBJECTIVES: The objective of the study was to describe clinical manifestations of BD and their therapy in a single center in Brazil. METHODS: Sixty patients who met the International Study Group Criteria for BD and were under follow-up at the Vasculitis Unit of the Universidade Federal de São Paulo were evaluated in a retrospective observational study. RESULTS: Mean age at study was 40.0 (SD, 10.7) years, and the female-male ratio was 1.2:1.0. The frequency of disease manifestations was as follows: oral ulcers, 100%; genital ulcers, 93.3%; ocular manifestations, 63.3%; arthritis, 46.7%; cutaneous lesions, 71.7%; positive pathergy test, 22.7%; neurologic involvement, 28.3%; thrombosis, 13.3%; and gastrointestinal involvement, 3.3%. Arthritis and erythema nodosum were more prevalent among women, whereas papulopustular lesions were more common in men. The frequency of each treatment modality was as follows: colchicine, 78.3%; thalidomide, 26.7%; colchicine and penicillin, 21.7%; dapsone, 8.3%; and pentoxyphyline, 8.3%. These treatments were mainly used for mucocutaneous manifestations. Immunosuppressive drugs were prescribed for 70% of the patients, including azathioprine (35.0%), cyclophosphamide (28.3%), cyclosporin A (21.7%), methotrexate (18.3%), and chlorambucil (6.7%). Infliximab was used in 5.0% of refractory patients. No differences were observed between sexes related to severe manifestations of BD. CONCLUSIONS: Although reported elsewhere, Brazilian men with BD did not have a worse prognosis. Women had a higher frequency of arthritis manifestations.

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.

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.

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.