Case Of Autoimmune Encephalitis Research Articles

The therapeutic effect of ofatumumab in autoimmune encephalitis: A case series.

The management of autoimmune encephalitis (AE) with immunotherapy is non-standardized, especially in refractory AE. Ofatumumab (OFA), an anti-CD20 antibody, has not been reported in the treatment of AE. This study presented three AE cases that received the OFA treatment. OFA was administered subcutaneously at a dose of 20mg two or three times within three weeks. There were some mild adverse effects, including low-grade fever and dizziness. They had favorable responses (reduced antibody titer and clinical symptom improvement). Their symptoms were stable and even improved during a three-month follow-up. Thus, OFA injection is demonstrated to be safe and effective in treating AE. This is the first report about OFA treatment in AE, depicting its potential as a therapeutic option.

Viral, Bacterial, Metabolic, and Autoimmune Causes of Severe Acute Encephalopathy in Sub-Saharan Africa: A Multicenter Cohort Study

To assess whether viral, bacterial, metabolic, and autoimmune diseases are missed by conventional diagnostics among children with severe acute encephalopathy in sub-Saharan Africa. One hundred thirty-four children (6 months to 18years) presenting with nontraumatic coma or convulsive status epilepticus to 1 of 4 medical referral centers in Uganda, Malawi, and Rwanda were enrolled between 2015 and 2016. Locally available diagnostic tests could be supplemented in 117 patients by viral, bacterial, and 16s quantitative polymerase chain reaction testing, metagenomics, untargeted metabolomics, and autoimmune immunohistochemistry screening. Fourteen (12%) cases of viral encephalopathies, 8 (7%) cases of bacterial central nervous system (CNS) infections, and 4 (4%) cases of inherited metabolic disorders (IMDs) were newly identified by additional diagnostic testing as the most likely cause of encephalopathy. No confirmed cases of autoimmune encephalitis were found. Patients for whom additional diagnostic testing aided causal evaluation (aOR 3.59, 90% CI 1.57-8.36), patients with a viral CNS infection (aOR 7.91, 90% CI 2.49-30.07), and patients with an IMD (aOR 9.10, 90% CI 1.37-110.45) were at increased risk for poor outcome of disease. Viral and bacterial CNS infections and IMDs are prevalent causes of severe acute encephalopathy in children in Uganda, Malawi, and Rwanda that are missed by conventional diagnostics and are associated with poor outcome of disease. Improved diagnostic capacity may increase diagnostic yield and might improve outcome of disease.

Cerebrospinal fluid YKL‐40 level evolution is associated with autoimmune encephalitis remission

Because of its heterogeneity in clinical presentation and course, predicting autoimmune encephalitis (AIE) evolution remains challenging. Hence, our aim was to explore the correlation of several biomarkers with the clinical course of disease. Thirty-seven cases of AIE were selected retrospectively and divided into active (N= 9), improved (N= 12) and remission (N= 16) AIE according to their disease evolution. Nine proteins were tested in both serum and cerebrospinal fluid (CSF) at diagnosis (T0) and during the follow-up (T1), in particular activated MMP-9 (MMP-9A) and YKL-40 (or chitinase 3-like 1). From diagnosis to revaluation, AIE remission was associated with decreased YKL-40 and MMP-9A levels in the CSF, and with decreased NfL and NfH levels in the serum. The changes in YKL-40 concentrations in the CSF were associated with (1) still active AIE when increasing >10% (P-value=0.0093); (2) partial improvement or remission when the changes were between +9% and -20% (P-value=0.0173); and remission with a reduction > -20% (P-value=0.0072; overall difference between the three groups: P-value=0.0088). At T1, the CSF YKL-40 levels were significantly decreased between active and improved as well as improved and remission AIE groups but with no calculable threshold because of patient heterogeneity. The concentration of YKL-40, a cytokine-like proinflammatory protein produced by glial cells, is correlated in the CSF with the clinical course of AIE. Its introduction as a biomarker may assist in following disease activity and in evaluating therapeutic response.

Clinical characteristics and short-term outcomes of autoimmune encephalitis in adults

To characterize clinical, paraclinical features and short-term outcomes in different types of autoimmune encephalitis (AE) in a one-center cohort of Russian patients, as well as to evaluate the frequency and significance of the joint expression of antineuronal and anti-glial antibodies (Abs) in AE. Forty-one patients were diagnosed with AE at the Research Center of Neurology from November 2020 to December 2022. Demographic, clinical characteristics, results of laboratory tests, MRI of brain, treatment and outcomes of disease were analyzed. The analysis of Abs to glial antigens (myelin-oligodendrocyte glycoprotein - MOG, glial fibrillar acidic protein - GFAP, aquaporin 4 - AQP-4) was performed by indirect immunofluorescence assay (Euroimmun, Germany). In 24 (58.5%) patients was established definite AE, confirmed by specific Abs detection; in 2 (4.9%) - definite limbic encephalitis, in 15 (36.6%) - seronegative probable AE (including 3 cases of Hashimoto's encephalitis). GFAP-Abs in cerebrospinal fluid (CSF) were detected only in two patients - with clinical and MRI-picture of autoimmune GFAP-astrocytopathy (A-GFAP-A). GFAP- and MOG-Abs in the blood were detected in 25.7% and 6%, respectively, AQP-4-Abs were not detected. There were no correlations between co-expression with glial Abs and clinical characteristics. Systemic and antithyroid Abs were present in 15% and 31%, respectively. Paraneoplastic AE accounted for 22%. For the first time in the Russian population, 2 cases of A-GFAP-A, 6 cases of AE associated with COVID-19 were described. The most common first syndrome were epileptic seizure (34%), psychiatric (29%) and cognitive (14%) disorders. Relapses of AE was observed in 22%. Inflammatory changes in CSF were detected in 41%, focal changes on MRI in 68%. First-line immune therapy was performed in all patients, 85% of cases received pulse therapy with methylprednisolone. Second-line immune therapy (rituximab or cyclophosphamide intravenously) was performed in 19.5%, 78% of patients achieved significant improvement during treatment (scores ≤2 on the modified Rankin scale). The results allow us to consider COVID-19 as a trigger of AE. The absence of detection of GFAP-Abs in CSF in patients with other types of AE contributes to the confirmation of the specificity of GFAP-seropositivity of CSF for the diagnosis of A-GFAP-A. The expression of GFAP- and MOG-Abs in AE can serve as confirmation of the immuno-mediated etiology of the disease, which is especially important for the AE diagnosis in the absence of antineuronal Abs.

A Rare Case of Anti-N-Methyl-D-Aspartate Receptor Encephalitis in an Infant Presenting with Regression and Movement Disorder.

A Rare Case of Anti-N-Methyl-D-Aspartate Receptor Encephalitis in an Infant Presenting with Regression and Movement Disorder.

Early predictors of new-onset immune-related seizures: a preliminary study

BackgroundApproximately 60% of patients with autoimmune encephalitis (AE) exhibit secondary acute symptomatic seizures and showed highly sensitive to immunotherapy. However, it is difficult for many patients to receive early immunotherapy since the early identification of the cause in AE is more complex. This study aimed to investigate the early predictors of initial immune-related seizures and to guide the evaluation of treatment and prognosis.MethodsOne hundred and fifty-four patients with new-onset “unknown etiology” seizures with a course of disease less than 6 months were included. Serum and/or cerebrospinal fluid neuron-specific autoantibodies (NSAbs), including N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5- Methyl-4-isoxazole propionic acid receptor 1 (AMPAR1), AMPAR2, anti-leucine rich glioma inactivated 1 antibody (LGI1), anti-gamma-aminobutyric acid type B receptor (GABABR), anti-contact protein-related protein-2 (CASPR2) were used to screen for immune etiology of the seizures. In addition, patients with epilepsy and encephalopathy were also examined via brain MRI, long-term video EEG, antibody prevalence in epilepsy and encephalopathy (APE2) score, and modified Rankin Scale (mRS). A logistic regression model was used to analyze the early predictors of immune etiology.ResultsThirty-four cases (22.1%) were positive for NSAbs. Among all 154 patients, 23 cases of autoimmune encephalitis (AE) (21 cases of NSAbs positive), 1 case of ganglionic glioma (NSAbs positive), 130 cases of epilepsy or seizures (12 cases of NSAbs positive) were recorded. Also, there were 17 patients (11.0%) with APE2 ≥ 4 points, and all of them met the clinical diagnosis of AE. The sensitivity and specificity of APE2 ≥ 4 points for predicting AE were 73.9% and 100%. The results of multivariate analysis showed that the NSAbs and APE2 scores independently influenced the early prediction of initial immune-related seizures (P < 0.05).ConclusionNSAbs and APE2 scores could act as early predictors of initial immune-related seizures.

Neuroimaging characteristics may aid in diagnosis, subtyping, and prognosis in autoimmune encephalitis.

To examine the utility of neuroimaging characteristics as biomarkers of prognosis in seropositive autoimmune encephalitis (AE). In this multi-center study, we retrospectively analyzed 66 cases of seropositive AE. The MRI and PET imaging was assessed by independent visual inspection. Whole brain and regional volumes were imputed by IcoMetrix, an automated volumetric assessment package. The modified Rankin Scale (mRS) was utilized to assess the patients' follow-up disability. Other outcomes were mortality, first line treatment failure, medial temporal lobe (MTL) atrophy, and clinical relapse. Univariate and multivariable regression analysis was performed. Abnormalities on MRI were detected in 35.1% of patients, while PET was abnormal in 46.4%. Initial median whole brain and hippocampal volumes were below the 5th and 20th percentile respectively compared to an age-matched healthy database. After a median follow-up of 715days, 85.2% had good functional outcome (mRS ≤ 2). Nine patients developed MTL atrophy during follow-up. On multivariable analysis, inflammatory MTL changes were associated with development of MTL atrophy (HR 19.6, p = 0.007) and initial hippocampal volume had an inverse relationship with mortality (HR 0.04, p = 0.011). Patients who developed MTL atrophy had a reduced chance of good final mRS (HR 0.16, p = 0.015). Neuroimaging on initial hospital admission may be provide important diagnostic and prognostic information. This study demonstrates that structural and inflammatory changes of the MTL may have importance in clinical and radiological prognosis in seropositive AE.

Autoimmune Encephalitis With Ganglionic a3-AChR Antibodies

Objective To describe a case of autoimmune encephalitis presented as new onset refractory nonconvulsive status epilepticus and autonomic failure caused by alpha-3 ganglionic acetylcholine receptor autoantibodies (a3-AChR Ab). Background Autoimmune autonomic ganglionopathy (AAG) is rare acquired dysautonomia in adults due to a3-AChR Ab. A patient typically presents with subacute autonomic dysfunction, and encephalitis has not been reported yet. Design/Methods NA. Results A 60 years old female presented with progressive worsening of mental status for two weeks. Vital signs were normal. The patient was somnolent, nonverbal, with tonic non-reactive pupils on the exam. CT head showed multiple subcortical hypodensities. MRI brain demonstrated T2-FLAIR hyperintense lesions in bifrontal lobes sparing the U-fibers, with abnormal leptomeningeal/pial perivenular type enhancement. MRI C/T spine, CT chest/Abd/pelvis were negative. Although serum and CSF testing showed inflammatory markers, meningoencephalitis and autoimmune encephalitis panel were negative, except for the serum Paraneoplastic panel was positive with high titer a3-AChR Abs. EEG showed nonconvulsive status epilepticus, which required management with three antiseizure medications. Initially, the patient had little response to empirical pulse methylprednisolone therapy. Later showed good clinical response with plasmapheresis. Later on she presented with nonobstructive small bowel obstruction, resolved with another pulse steroid therapy, discharged on dexamethasone taper. On a three-month follow-up, the patient was in near clinical remission, supported with resolved lesions on a repeat MRI. She never relapsed after two years of follow-up. Conclusions Studies have shown that a3-AChR Abs can result in diverse neurological manifestations, mainly dysautonomia. Our patient presented with encephalitis, dysautonomia, and refractory nonconvulsive status epilepticus. Scans suggested diffuse leukoencephalopathy, patient was found to have high 3-ACHR antibody seropositivity. Initially, the patient was steroid-resistant but showed clinical improvement with plasmapheresis. We have described an interesting case of encephalitis likely associated with a3-AChR Ab that has not been previously described. More studies are required to confirm this association.

Anti-NMDAR encephalitis with seizure-like activity and hemiplegia - a case report and literature review

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis accounts for the vast majority of cases of autoimmune encephalitis. Its common clinical symptoms are psychiatric symptoms, behavioral dysfunction, seizures, speech impairment, cognitive impairment, movement disorders, decreased consciousness, and autonomic instability. This report was aimed to provide evidence for anti-NMDAR encephalitis with seizure-like activity, based on the clinical presentations, brain magnetic resonance imaging (MRI), and electroencephalogram (EEG) recordings.Case presentationWe report a 11-year-old girl who suffered epigastric pain after vigorous physical activity. She felt weakness of the muscles. She had syncope only once and urinary incontinence on the way to the hospital and vomited at the arrival. The entire procedure lasted approximately 15 min. The next night she had recurrent headache attacks along with irritability, like someone “tapping” to the right occipital region. She experienced numbness in the left upper limbs and shallowing of the frontal lines on the left side. Holter monitoring showed normal findings, but brain MRI, EEG recording, and cerebrospinal fluid (CSF) antibody testing showed abnormal results. The patient was finally diagnosed with anti-NMDAR encephalitis. After treatment with glucocorticoids and acyclovir, she fully recovered and was discharged from the hospital.ConclusionsAlthough the patient presented with pain and impaired limb movements, she did not have respiratory or (and) circulatory failure, and the symptoms entirely resolved. Early accurate diagnosis and timely treatment are essential for patients with anti-NMDAR encephalitis.

Validity and prognostic utility of clinical assessment scale for autoimmune encephalitis (CASE) score in children with autoimmune encephalitis

IntroductionThe clinical assessment scale for autoimmune encephalitis (CASE) is a recently developed and validated scale to rate the severity of autoimmune encephalitis (AE) in adults. But it is yet to be validated in pediatric AE cases. MethodsIn a prospective observational study, we determined the validity and prognostic utility of CASE in the pediatric population with a diagnosis of probable or definite AE. We also determined clinical, neuroimaging, or laboratory-based prognostic factors for favorable clinical outcomes at 3 months after presentation. We used weighted kappa statistics and the intra-class correlation coefficient of individual item scores and total scores for determining inter-observer and intra-observer reliability respectively. ResultsWe enrolled a total of 54 patients (28 girls, probable [45%] or definite [55%] AE). Functional status score (FSS), CASE score, and other scores showed significant improvement at the time of discharge and 3-months, as compared to baseline (p < 0.0001). The intra-observer and interobserver reliability of the total scores was excellent (k = 0.94 and 0.95 respectively). CASE was also found to have good internal consistency (Cronbach-α = 0.83). The corrected item-total correlations of all items were >0.40. The correlation between the total CASE score and FSS score at admission, at discharge, and at 3 months was strong (r = 0.90, 0.92, and 0.94, p < 0.001). In multivariate analysis, only seropositivity or definite AE and CASE score at baseline was found to be significant predictive factors for functional status at 3 months (p = 0.03, 0.01). ConclusionCASE score can be used for monitoring the severity of pediatric AE patients. It also has prognostic usefulness for predicting functional independence on follow-up.

Antibody-mediated autoimmune encephalitis evaluated by 18F-DPA714 PET/MRI

SARS-CoV-2 vaccine has considered being the most effective method to prevent SARS-CoV-2 infection. The safety and effectiveness of the SARS-CoV-2 vaccine has been confirmed. However, in very rare cases, autoimmune neurological diseases may occur. In this article, we report three rare cases of autoimmune encephalitis with definite auto-antibody after SARS-CoV-2 vaccination. They all have good prognosis after treatment. In addition, we first use 18F-DPA-714 PET/MRI to evaluate microglia activation in our patients. We found that 18F-DPA-714 PET/MRI may be a powerful tool for quantitative analysis of neuroinflammation in patients of autoimmune encephalitis. Finally, although rare complications may happen after vaccination, we still consider the benefits of vaccination far outweigh the risks. People without contraindications should be vaccinated without delay to prevent infection in current outbreak situation.

Author Response: Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis.

We appreciate the comments of Dr. Vale on our study,1 reminding us that psychosis is a severe ailment and that patients may benefit from CSF studies. As shown by most of our work, we agree that CSF studies should be reincorporated in the evaluation of patients with new onset psychosis.1,2 Dr. Vale also indicates that there are other types of autoimmune encephalitis (AE), and the detection of NMDA receptors (NMDAR) antibodies is not essential for AE diagnosis. We are aware of this concept.3 As indicated in our manuscript, most cases of AE can associate with symptoms of psychosis, but the presence of concurrent neurologic alterations readily excludes a primary psychiatric etiology on clinical grounds. By contrast, the initial symptoms of anti-NMDAR encephalitis can mimic to perfection a first episode of psychosis due to a primary psychiatric disorder.2,4 For this reason, we narrowed our study to this specific AE. Regardless of whether neurofilament light chain (NfL) levels can be found to be elevated in many disorders with neuronal/axonal damage, determination of NfL showed clinical utility in the context of our study.

Development and Validation of a Risk Score to Differentiate Viral and Autoimmune Encephalitis in Adults.

Encephalitis represents a challenging condition to diagnose and treat. To assist physicians in considering autoimmune encephalitis (AE) sooner, we developed and validated a risk score. The study was conducted as a retrospective cohort of patients with a diagnosis of definite viral encephalitis (VE) and AE from​​ February 2005 to December 2019. Clinically relevant and statistically significant features between cases of AE and VE were explored in a bivariate logistic regression model and results were used to identify variables for inclusion in the risk score. A multivariable logistic model was used to generate risk score values and predict risk for AE. Results were externally validated. A total of 1310 patients were screened. Of the 279 enrolled, 36 patients met criteria for definite AE and 88 criteria for definite VE. Patients with AE compared with VE were more likely to have a subacute to chronic presentation (odds ratio [OR] = 22.36; 95% confidence interval [CI], 2.05-243.7), Charlson comorbidity index <2 (OR = 6.62; 95% CI, 1.05-41.4), psychiatric and/or memory complaints (OR = 203.0; 95% CI, 7.57-5445), and absence of robust inflammation in the cerebrospinal fluid defined as <50 white blood cells/µL and protein <50 mg/dL (OR = 0.06; 95% CI, .005-0.50). Using these 4 variables, patients were classified into 3 risk categories for AE: low (0-1), intermediate (2-3), and high (4). Results were externally validated and the performance of the score achieved an area under the curve of 0.918 (95% CI, .871-.966). This risk score allows clinicians to estimate the probability of AE in patients presenting with encephalitis and may assist with earlier diagnosis and treatment.

A-280 Residual Cognitive Weaknesses in a Case of Treated Seronegative Autoimmune Encephalitis

Abstract Objective: Autoimmune encephalitis (AE) refers to a group of syndromes involving brain inflammation due to autoimmune activity and is associated with acute cognitive impairment. While several identified AE-associated antibodies (e.g., NMDAR) can be detected in cerebrospinal fluid and blood serum, many patients who respond well to treatment do not have the AE-associated antibodies. This causes challenges in diagnosis and treatment and has led to limited literature prognosticating cognitive outcomes following treatment in cases of suspected seronegative AE. We describe a case of seronegative AE in a patient with lingering cognitive symptoms after resolution of acute symptoms post-immunotherapy. Method: Patient is a 25-year-old female with a history of ulcerative proctitis who presented with suspected AE in the context of seizure, fever, balance difficulties, and personality changes. While antibodies were not detected, she was diagnosed with AE based on presentation, inflammatory markers, and neuroimaging and was treated with steroids, intravenous immunoglobulin, and plasma exchange. Patient presented for neuropsychological assessment 10 months later with lingering cognitive complaints. Results: Neuropsychological testing posttreatment revealed weaknesses/variability in attention, working memory, processing speed, and aspects of executive functioning including executive aspects of memory. Language, visuospatial functions, and retentive memory were preserved. Conclusion: This case suggested continued frontal-subcortical dysfunction likely related to residual effects of AE. Side effects of medications may have also contributed to her cognitive weaknesses. This case highlights the need for more research examining cognitive prognosis and expected timelines post seronegative AE treatment, given limited existing research. This is an important consideration for interpretations and recommendations from our neuropsychological evaluations.

Alzheimer's disease cerebrospinal fluid biomarkers differentiate patients with Creutzfeldt-Jakob disease and autoimmune encephalitis.

Autoimmune encephalitis (AE) is a potentially treatable cause of rapidly progressive dementia that may mimic Creutzfeldt-Jakob disease (CJD). Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers may discriminate CJD from AD, but utility in discriminating CJD and AE is unclear. This study compared AD CSF biomarkers in CJD and AE. Patients with probable or definite CJD and probable or definite AE who underwent Roche Elecsys AD CSF biomarker testing at Mayo Clinic from March 2020 through April 2021 were included. Total-tau, phosphorylated181 tau and amyloid-β42 levels were compared. Of 11 CJD cases, four were autopsy proven; the rest had positive real-time quaking-induced conversion testing. Disease-associated autoantibodies were detected in 8/15 cases of AE: leucine-rich glioma-inactivated 1 and neuronal intermediate filaments (two cases each), and N-methyl-d-aspartate receptor, contactin-associated protein-like 2, dipeptidyl-peptidase-like protein 6 and immunoglobulin-like cell adhesion molecule IgLON family member 5. Total-tau provided excellent discrimination between CJD and AE in a univariate model (odds ratio 1.46 per 100 pg/ml, 95% confidence interval 1.17-2.11, p < 0.05, c=0.93). Total-tau was elevated in 91% of CJD cases (median > 1300, range 236->1300 pg/ml), of which 55% were above the limit of assay measurement (>1300 pg/ml). Total-tau was elevated in 20% of AE cases (median 158, range 80->1300 pg/ml). Total-tau was greater in CJD than AE. Given that amyloid-β42 and phosphorylated181 tau were comparable, the ratio differences were probably driven by elevated total-tau in CJD. This study supports the role for AD biomarker testing in patients with rapidly progressive dementia.

LINC-06. Prevalence and outcomes of Autoimmune encephalitis in a tertiary hospital in Baguio City, Philippines

INTRODUCTION: Autoimmune Encephalitis is a debilitating neurological disorder that develops as a rapidly progressive encephalopathy, occurring usually less than 6 weeks, caused by brain inflammation. There are limited data on the autoimmune cases in the locality. This study aims to determine the prevalence and outcomes of patients with Autoimmune encephalitis cases admitted in a tertiary hospital in Baguio City, Philippines. METHODOLOGY: This is a descriptive retrospective cross-sectional study that reviewed health records of patients managed as autoimmune encephalitis in a tertiary hospital from January 2015 to December 2020. Descriptive Statistics using frequencies and percentages were employed in the study. RESULTS: A total of 21 patients were included in the study, majority of which were adolescent patients, with male predominance and are residing in rural areas. The most common clinical manifestation presented were fever, behavioral changes, generalized motor seizures, orofacial and limb dyskinesias. EEG revealed abnormal results in 14 patients (66.67%). Majority of patients had normal CSF analysis, while 2 (38.1%) revealed elevated CSF protein levels. Eight patients (38.1%) tested positive for anti-NMDAR titers. Most patients had normal ultrasound and cranial CT Scan (47.62%). The length of stay was more than 2 weeks and majority (80.95%) of patients were discharged improved. CONCLUSION: The prevalence of autoimmune encephalitis is 5/10,000 pediatric population in a span of 6 years which was noted to be increasing over time. The demographic and clinical profile maybe used as predictors of outcome of autoimmune encephalitis, hence, it can help in the management of the said disease.

Autoimmune Encephalitis in COVID-19 Infection: Our Experience and Systematic Review of the Literature.

The neurologic complications of COVID-19 infection are frequent in hospitalized patients; a high percentage of them present neurologic manifestations at some point during the course of their disease. Headache, muscle pain, encephalopathy and dizziness are among the most common complications. Encephalitis is an inflammatory condition with many etiologies. There are several forms of encephalitis associated with antibodies against intracellular neuronal proteins, cell surfaces or synaptic proteins, referred to as autoimmune encephalitis. Several case reports published in the literature document autoimmune encephalitis cases triggered by COVID-19 infection. Our paper first presents our experience in this issue and then systematically reviews the literature on autoimmune encephalitis that developed in the background of SARS-CoV-2 infections and also discusses the possible pathophysiological mechanisms of auto-immune-mediated damage to the nervous system. This review contributes to improve the management and prognosis of COVID-19-related autoimmune encephalitis.

Thyroid Function and Low Free Triiodothyronine in Chinese Patients With Autoimmune Encephalitis.

Background and ObjectivesLow free triiodothyronine (FT3) is usually associated with worse functional outcome in critical illness; however, the information on thyroid dysfunction and autoimmune encephalitis (AE) is limited. This study aims to evaluate the clinical prognostic value of thyroid function and low-T3 syndrome in patients with multiple subtypes of AE. MethodsIn this retrospective study, we identified the hospital records of 319 candidate patients with AE admitted between January 2016 and December 2020. We then extracted the clinical features and outcomes. Modified Rankin scale (mRS) scores were used to evaluate the patients’ neurological function. The serum levels of FT3, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured upon admission. Normal thyroid stimulating hormone level with FT3 below the lower limit of the reference interval (2.63 nmol/L) was defined as low-T3 syndrome.ResultsA total of 237 AE cases remained after screening. Among these, 57.81% (137/237) were men and the average age at onset was 41 y (interquartile range, 12–61 y). We found that 83.54% (198/237) of the patients had a good prognosis, and 16.46% (39/237) had a poor prognosis. Abnormal thyroid function was observed in 30.80% of these patients, with a relatively greater prevalence in the group with a poor prognosis (p < 0.001). The serum FT3 levels in the poor-prognosis group were significantly lower than those in the good-prognosis group (p < 0.001). Low-T3 syndrome occurred in 15.19% of AE cases and was more frequent in patients with poor prognosis (p < 0.001).ConclusionsAbnormal thyroid function in AE is frequent, and serum FT3 levels in patients with poor prognosis are significantly lower than in those with good prognosis. Low-T3 syndrome could be a potential candidate for predicting the prognosis of AE following future research.

Clinical Features and Early Recognition of 242 Cases of Autoimmune Encephalitis.

Objective: To analyze the clinical features of common autoimmune encephalitis and evaluate the sensitivity of antibodies contributing to focal epilepsy signs and symptoms (ACES) score.Methods: Collecting and analyzing the data of 242 patients with autoimmune encephalitis (AE) diagnosed in the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2020 in this retrospective study. The six items of the ACES score (cognitive symptoms, behavioral changes, autonomic symptoms, speech problems, autoimmune diseases, temporal MRI hyperintensities) were screened in patients with complete clinical data.Results: (1) In total, 242 patients were included, with 147 cases of anti-N-methyl-D-aspartate receptor encephalitis, 47 cases of anti-γ-aminobutyric acid type B (GABA-B) receptor encephalitis, and 48 cases of anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis. The most common clinical symptoms are cognitive impairment (77%), behavioral changes (79%), and seizures (71%). In total, 129 cases (54%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, sinus tachycardia, and central hypoventilation. Twelve patients had autoimmune diseases, most of which were of thyroid diseases. (2) One hundred and twenty-seven patients with complete clinical data evaluated ACES score, 126 cases of whom (126/127, 99.2%) were equal to or >2 points, 1 case (1/127, 0.8%) was of <2 points.Interpretation: (1) Cognitive impairment, abnormal behavior, and seizures are the most common manifestations of AE and autonomic symptoms. Thyroid disease is the most autoimmune disease in AE. Clinically, for patients of suspected AE, increasing the knowledge and testing of thyroid function and rheumatism is necessary. (2) ACES score is a simple, effective, and easy-to-operate score, with a certain screening value for most patients suspected of AE.

Olfactory impairment in autoimmune encephalitis: another piece of the puzzle.

BackgroundDespite being long neglected, olfaction has recently become a focus of intense research in neuroscience, as smell impairment has been consistently documented in both neurodegenerative and neuroinflammatory diseases. Considering the close anatomo-functional correlations between the limbic system and the central olfactory structures, we investigated olfaction in a population of patients with autoimmune encephalitis (AE).MethodsNineteen adult subjects (14 males, median age 64 years) diagnosed with definite (14/19) or possible (5/19) AE and followed for ≥ 6 months were enrolled. The Brief Smell Identification Test (B-SIT), a 12-item, forced-choice, scratch-and-sniff measure, was used to assess the patients’ olfactory function in comparison with a group of sex- and age-matched healthy controls (HC). According to the B-SIT score, subjects were classified as anosmic (< 6), hyposmic (6–8) and normal (≥ 9). Electro-clinical, laboratory and neuroimaging findings were reviewed.ResultsSmell impairment was revealed in 15/19 patients (9 hyposmic, 6 anosmic), compared with 5/19 HC (p = 0.0029). Age, gender and smoking habits did not affect the participants’ performance at B-SIT. Olfactory dysfunction appeared more common among patients with definite AE (p = 0.0374), regardless of autoantibody status. Subjects with higher modified Rankin Scale (mRS) scores at AE onset more likely presented hyposmia/anosmia (p = 0.033), and so did those with bilateral ictal/interictal EEG abnormalities (p = 0.006).ConclusionsWe found olfaction to be impaired in a significantly large proportion of AE cases. Smell deficits appeared more common in subjects with severe AE (as indicated by both definite diagnosis and higher mRS score), and might represent an additional feature of immune-mediated encephalitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-022-10959-6.