Acetazolamide as an effective treatment for pilomotor seizures in autoimmune encephalitis.

Pilomotor seizures are strongly associated with autoimmune encephalitis (AE), particularly anti-LGI1 encephalitis. The carbonic anhydrase inhibitor acetazolamide may have special efficacy for treating AE-associated pilomotor seizures. Six patients with AE (five anti-LGI1, one seronegative) and temporal lobe pilomotor seizures (five with seizures inducible by hyperventilation) were treated with acetazolamide, administered in a cycling (2-days-ON, 4-days-OFF) regimen to offset tolerance. Seizures were assessed during epilepsy monitoring unit (EMU) recordings in four inpatients (one of whom also maintained an outpatient seizure diary chronicling 1203 seizures over 1079 days); two outpatients self-reported seizure frequencies. The extended diary revealed an inverse correlation between acetazolamide and proportion of seizures/day: 6%, 2% (days 1, 2 ON); 3%, 13%, 31%, 45% (days 1, 2, 3, 4 OFF). This patient later developed focal status epilepticus upon wean of antiseizure medications during a seropositive AE relapse that was remarkably aborted with acetazolamide monotherapy. The other three EMU patients averaged .56 seizures/day ON, and 3.81 seizures/day OFF (p = .004). The two outpatients reported seizure reductions from 3-5/day to 2/week, and 15-20/day to none, respectively, after initiation of cycling acetazolamide. Likely related to cerebral CO2/pH sensitivity, acetazolamide can be unusually effective in controlling pilomotor seizures in AE, chronically or in acute settings.

Performance of assessment tools in predicting neural autoantibody positivity in patients with seizures.

BACKGROUND: The identification of patients with seizures of unknown etiology who would benefit from neural antibody testing necessitates effective assessment tools. The study aimed to compare the performance of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and the "Obvious" Indications for Neural Antibody Testing in Epilepsy or Seizures (ONES) checklist. We also intended to evaluate whether the performance of the tools varied by types of antibody. METHODS: Patients diagnosed with epilepsy, seizures, or status epilepticus of unknown etiology at West China Hospital from January 2019 to December 2021 were included. Paired serum/cerebrospinal fluid samples were analyzed for antineuronal and antiglial antibodies. The APE2 score and ONES checklist were applied, and their outcomes were compared to laboratory antibody test results. Possible false positive neuronal antibody results were excluded in sensitivity/specificity analysis reasonably. RESULTS: A total of 113 antibody-positive and 159 antibody-negative patients were enrolled in sensitivity/specificity analysis. The ONES checklist showed superior sensitivity than APE2 score (95.6 % vs.79.6 %, P < 0.001). Specificity was not statistically different (60.4 % vs. 57.9 %, P = 0.557). The negative predictive value (NPV) of ONES checklist was higher than that of APE2 score (94.8 % vs 80.7 %, P < 0.001). The positive predictive value of them was not statistically different (61.7 % vs 58.8 %, P = 0.557). APE2 score exhibited lower sensitivity for predicting LGI-Abs (52.9 % vs. 80.3 %, P = 0.022) compared to NMDAR-Abs. Similarly, ONES checklist showed lower sensitivity for LGI1-Abs than NMDAR-Abs (82.4 % vs. 100.0 %, P = 0.009). CONCLUSIONS: The ONES checklist demonstrates superior sensitivity for neural antibody positivity than APE2 score. Specificity of the two assessment tools was similar. ONES checklist performed better NPV than the APE2 score. Both assessment tools performed less well in predicting the presence of LGI1- Abs when compared to NMDAR-Abs.

Mycophenolate mofetil reduces the risk of relapse in anti-leucine-rich glioma-inactivated protein 1 encephalitis: a prospective observational cohort study.

BACKGROUND: Mycophenolate mofetil (MMF) is frequently used in the treatment of neurological autoimmune disorders. However, its effect on the relapse risk in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis is not well studied. METHODS: In this prospective observational cohort study, anti-LGI1 encephalitis patients were grouped according to MMF treatment status (MMF and non-MMF groups). The primary outcome was relapse after disease onset. RESULTS: A total of 83 patients were included, with a median onset age of 60 years. Fifty-four patients were men (65.1%). The MMF group comprised 28 patients and the non-MMF group comprised 55. Median follow-up from symptom onset was 26 months. Relapse occurred in 43 patients (51.8%). Median modified Rankin scale (mRS) score at enrollment was significantly higher in the MMF group than the non-MMF group (3 vs. 2; p = 0.001). Median mRS score at last follow-up was comparable between groups (1 vs. zero; p = 0.184). Both MMF treatment (HR 0.463; 95% CI, 0.231-0.929; p = 0.030) and cognitive impairment at enrollment (HR 3.391; 95% CI, 1.041-11.044; p = 0.043) were independent predictors of relapse. Starting immunotherapy before development of cognitive impairment trended towards reducing relapse risk. Outcome at last follow-up was good (mRS score 0-2) in all patients except for one in the non-MMF group. Adverse events associated with MMF treatment were mild and transient. CONCLUSION: Although the outcome of anti-LGI1 encephalitis patients is generally favorable, relapse is common, especially in those with cognitive impairment. MMF treatment is well-tolerated and can significantly reduce the risk of relapse.

Anti-leucine-rich glioma-inactivated 1 encephalitis revealed by a manic episode: insights from frontal lobe dysfunction in neuropsychiatry through neuropsychology and metabolic imaging. A case report.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a limbic encephalitis that rarely presents as an isolated psychiatric syndrome. Case presentation: A 70-year-old patient first presented with behavioral disorder including hyperactivity, euphoria, with disinhibition and accelerated speech associated with severe insomnia and cognitive disorder. A manic episode was diagnosed and he received various psychotropic medications with no improvement. Invesitgations were negative (MRI showed T2 aspecific hyperintensities with no hyperintensities in limbic regions and EEG was normal). He was transferred to a nursing home, with a diagnosis of neurodegenerative condition. Later, he was referred to our unit for further investigations. A cerebral 18F-FDG-PET revealed an association of frontal hypometabolism and temporal and striatum hypermetabolism and CSF analysis revealed slightly increased white blood cell counts. Plasmatic anti-LGI1 antibodies were detected. The patient was treated with intra-venous immunoglobulin (IvIg) but showed no improvement. Second-line treatment (a combination of rituximab and cyclophosmphamide) was then administered for a year, leading to an improvement of neuropsychiatric symptoms and normalization of metabolic impairment on 18F-FDG-PET. Conclusion: In this report, we describe a novel case of a patient withanti-LGI1 encephalitis with a predominant long-term psychiatric presentation. An atypical presentation (such as atypical psychiatric symptoms, neurocognitive disorder, and hyponatremia) should prompt further investigations such as CSF analysis, considering that MRI and EEG may be normal. FDG-PET might be of interest but few data are available in the literature. Early treatment of anti-LGI1 encephalitis is crucial for overall prognosis and may delay the development of dementia in some cases.

Case Report: Paroxysmal weakness of unilateral limb as an initial symptom in anti-LGI1 encephalitis: a report of five cases.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders, epileptic seizures, faciobrachial dystonic seizures (FBDS), and refractory hyponatremia. Recently, we found an atypical manifestation of anti-LGI1 encephalitis, in which paroxysmal limb weakness was the initial symptom. In this report, we describe five cases of anti-LGI1 encephalitis with paroxysmal limb weakness. Patients had similar presentations, where a sudden weakness involving a unilateral limb was observed, which lasted several seconds and occurred dozens of times each day, with the anti-LGI1 antibody being positive in both serum and cerebrospinal fluid (CSF). FBDS occurred after a mean of 12 days following paroxysmal limb weakness in three of five patients (Cases 1, 4, and 5). All patients were given high-dose steroid therapy, which had a good effect on their condition. Based on this report, we suggest that paroxysmal unilateral weakness may be a kind of epilepsy and be connected to FBDS. As an unusual neurological presentation, paroxysmal weakness can be included in the clinical manifestations of anti-LGI1 encephalitis, helping to raise awareness of the recognition of anti-LGI1 encephalitis in patients with this symptom and leading to early diagnosis and early treatment, which would contribute to improved clinical outcomes.

Anti-LGI1 encephalitis with initiating symptom of seizures in children.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis. Methods: Three anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail. Results: Case 1 showed an adolescent girl with initiating symptom of acute-onset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy. Conclusion: Childhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes.

Psychiatric features in NMDAR and LGI1 antibody-associated autoimmune encephalitis.

Patients with autoimmune encephalitis (AE) often developed psychiatric features during the disease course. Many studies focused on the psychiatric characteristic in anti-NMDAR encephalitis (NMDAR-E), but anti-LGI1 encephalitis (LGI1-E) had received less attention regarding the analysis of psychiatric features, and no study compared psychiatric characteristic between these two groups. The clinical data of AE patients (62 NMDAR-E and 20 LGI1-E) who developed psychiatric symptoms were analyzed in this study. In NMDAR-E, the most common higher-level feature was "behavior changes" (60/62, 96.8%) and the lower-level feature "incoherent speech" was observed in 33 patients (33/62, 53.2%), followed by "agitation" (29/62, 46.8%) and "incongruent laughter/crying" (20/62, 32.3%). Similar to NMDAR-E, "behavior changes" was most common in LGI1-E (17/20, 85.0%), but the features of suicidality, eating, and obsessive-compulsive were not reported. The top three lower-level features were visual hallucinations (9/20, 45.0%), incoherent speech (8/20, 40.0%), and mood instability (7/20, 35.0%). The comparative study found that "incongruent laughter/crying", in lower-level features, was more frequently observed in NMDAR-E (32.3% vs. 0%, p = 0.002). Moreover, the Bush Francis Catatonia Rating Scale (BFCRS) assessing the catatonic symptoms in NMDAR-E were higher than LGI1-E, but the 18 item-Brief Psychiatric Rating Scale (BPRS-18) showed no difference in the two groups. In summary, both NMDAR-E and LGI1-E often developed psychiatric symptoms. In contrast with LGI1-E, the psychiatric feature "incongruent laughter/crying" was more frequently associated with NMDAR-E, and catatonic symptoms were more severe in NMDAR-E.

Use of anti-seizure medications in different types of autoimmune encephalitis: A narrative review.

Seizures are the main manifestation of the acute phase of autoimmune encephalitis (AE). Anti-seizure medications (ASMs) play an important role in controlling seizures in AE patients, but there is currently a lack of consensus regarding the selection, application, and discontinuation of ASMs. This narrative review focuses on the use of ASMs in patients with AE driven by different antibodies. The PubMed, Embase, and MEDLINE databases were searched up until 30 October 2022 using prespecified search terms. We identified 2,580 studies; 23 retrospective studies, 2 prospective studies and 9 case reports were evaluated based on our inclusion criteria. Anti-N-methyl-D-aspartic-acid-receptor (anti-NMDAR) encephalitis is the type of AE that responds best to ASMs, and long-term or combined use of ASMs may be not required in most patients with seizures; these results apply to both adults and children. Sodium channel blockers may be the best option for seizures in anti-leucine-rich-glioma-inactivated-1 (anti-LGI1) encephalitis, but patients with anti-LGI1 encephalitis are prone to side effects when using ASMs. Cell surface antibody-mediated AE patients are more likely to use ASMs for a long period than patients with intracellular antibody-mediated AE. Clinicians can score AE patients' clinical characteristics on a scale to identify those who may require long-or short-term use of ASMs in the early stage. This review provides some recommendations for the rational use of ASMs in encephalitis mediated by different antibodies with the aim of controlling seizures and avoiding overtreatment.

Characterization of neuroinflammation pattern in anti-LGI1 encephalitis based on TSPO PET and symptom clustering analysis.

PURPOSE: TSPO PET with radioligand [18F]DPA-714 is an emerging molecular imaging technique that reflects cerebral inflammation and microglial activation, and it has been recently used in central nervous system diseases. In this study, we aimed to investigate the neuroinflammation pattern of anti-leucine-rich glioma-inactivated 1 (LGI1) protein autoimmune encephalitis (AIE) and to evaluate its possible correlation with clinical phenotypes. METHODS: Twenty patients with anti-LGI1 encephalitis from the autoimmune encephalitis cohort in Huashan Hospital and ten with other AIE and non-inflammatory diseases that underwent TSPO PET imaging were included in the current study. Increased regional [18F]DPA-714 retention in anti-LGI1 encephalitis was detected on a voxel basis using statistic parametric mapping analysis. Multiple correspondence analysis and hierarchical clustering were conducted for discriminate subgroups in anti-LGI1 encephalitis. Standardized uptake value ratios normalized to the cerebellum (SUVRc) were calculated for semiquantitative analysis of TSPO PET features between different LGI1-AIE subgroups. RESULTS: Increased regional retention of [18F]DPA-714 was identified in the bilateral hippocampus, caudate nucleus, and frontal cortex in LGI1-AIE patients. Two subgroups of LGI1-AIE patients were distinguished based on the top seven common symptoms. Patients in cluster 1 had a high frequency of facio-brachial dystonic seizures than those in cluster 2 (p = 0.004), whereas patients in cluster 2 had a higher frequency of general tonic-clonic (GTC) seizures than those in cluster 1 (p < 0.001). Supplementary motor area and superior frontal gyrus showed higher [18F]DPA-714 retention in cluster 2 patients compared with those in cluster 1 (p = 0.024; p = 0.04, respectively). CONCLUSIONS: Anti-LGI1 encephalitis had a distinctive molecular imaging pattern presented by TSPO PET scan. LGI1-AIE patients with higher retention of [18F]DPA-714 in the frontal cortex were more prone to present with GTC seizures. Further studies are required for verifying its value in clinical application.

A case of pediatric anti-leucine-rich glioma inactivated 1 encephalitis with faciobrachial dystonic seizure.

BACKGROUND: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare type of autoimmune encephalitis. A characteristic faciobrachial dystonic seizure (FBDS) is also frequently associated with this disease. Although primarily reported in the adult population, reports of its occurrence in the pediatric population are rare. Here, we describe a case of a 6-year-old girl diagnosed with anti-LGI1 encephalitis that presented with cognitive decline and FBDS. CASE PRESENTATION: The girl was referred to a pediatric neurology department for uncontrolled seizures and dyskinesia. She initially presented with a memory deficit, abnormal movement of the limbs and trunk, and ataxia. Her cerebrospinal fluid exam was unremarkable, but her brain MRI showed focal T2 high signal intensity in the left anterior putamen and right caudate nucleus. In addition, there were refractory episodes of brief tonic or dystonic movement of the face and arms that were suggestive of FBDS. She was initially treated with intravenous methylprednisolone and phenobarbital, then given another pulse of methylprednisolone and intravenous immunoglobulin as her symptoms persisted. Tests for neuronal autoantibodies revealed the presence of anti-LGI1 antibodies. Subsequent human leukocyte antigen (HLA) typing resulted in the identification of HLA-DRB1 DR7(*07:01 g) DR9(*09:01 g). Screening for thymoma and other neoplasms showed no signs of a tumor. She was treated with rituximab, tocilizumab, and antiseizure medications, including oxcarbazepine, valproic acid, and lamotrigine. Her FBDS and cognitive symptoms showed substantial improvements. CONCLUSION: While it is known that anti-LGI1 encephalitis responds well to immunotherapy, our patient showed an incomplete response, requiring further therapy. This is the first report of a pediatric patient with anti-LGI1 encephalitis treated with tocilizumab.

Dataset of a retrospective multicenter cohort study on characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis.

Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited. We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis - two alternative causes of encephalitis - to increase the awareness of ICI-iE and improve its diagnosis and management. To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients' medical records and compared between the groups. The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders - ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis - are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.

Case Report: Paroxysmal hyperhidrosis as an initial symptom in a patient with anti-LGI1 encephalitis.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common cause of autoimmune encephalitis and is characterized by cognitive impairment, psychiatric disorders, and faciobrachial dystonic seizures. In recent decades, literature reports have expanded the phenotypic spectrum associated with the LGI1 autoantibody. The present report describes the case of a 58-year-old man who presented with repetitive unilateral hyperhidrosis of the body and arm as an initial symptom and gradually developed psychiatric symptoms, involuntary movements of the face and arms, and progressive cognitive decline. Anti-LGI1 antibodies were positive in both the serum and cerebrospinal fluid at approximately 2 months after symptom onset, and the patient was, therefore, diagnosed with anti-LGI1 encephalitis. His symptoms, namely hyperhidrosis and involuntary movements, were not relieved by antiepileptic drug treatment, but responded favorably to high-dose steroid therapy and intravenous immunoglobulin. We interpreted the repetitive unilateral hyperhidrosis as possible epilepsy. Based on this case, unilateral hyperhidrosis of the body and arm as a rare neurological presentation can be added to the phenotypic spectrum of anti-LGI1 encephalitis, and early recognition of this manifestation might support timely diagnosis and treatment.

Confusion and Hallucination in a Geriatric Patient. Pitfalls of a Rare Differential: Case Report of an Anti-LGI1-Encephalitis.

Background: Confusion and hallucinations in geriatric patients are frequent symptoms and typically associated with delirium, late-life psychosis or dementia syndromes. A far rarer but well-established differential in patients with rapid cognitive deterioration, acute psychosis, abnormal movements and seizures is autoimmune encephalitis. Exemplified by our case we highlight clinical and economic problems arising in management of geriatric patients with cognitive decline and psychotic symptoms. Case Presentation: A 77-year-old female caucasian patient with an unremarkable medical history was hospitalized after a fall in association with diarrhea and hyponatremia. Upon adequate therapy, disorientation and troubled short-term memory persisted. Within a week the patient developed visual hallucinations. Basic blood and urine samples and imaging (cranial computed tomography and magnetic resonance imaging) were unremarkable. With progressive cognitive decline, amnestic impairment, word finding difficulty and general apathy, psychiatric and neurologic expertise was introduced. Advanced diagnostics did not resolve a final diagnosis; an electroencephalogram showed unspecific generalized slowing. Extended clinical observation revealed visual hallucinations and faciobrachial dystonic seizures. A treatment with anticonvulsants was initiated. Cerebrospinal fluid ultimately tested positive for voltage-gated potassium channel LGl1 (leucine-rich-inactivated-1) antibodies confirming diagnosis of autoimmune anti-LGI1 encephalitis. Immediate immunotherapy (high-dose glucocorticoids and administration of intravenous immunoglobulin G) led to a rapid improvement of the patient's condition. After immunotherapy was tapered, the patient had one relapse and completely recovered with reintroduction of glucocorticoids and initiation of therapy with rituximab. Conclusion: Rapidly progressive dementia in geriatric patients demands a structured and multidisciplinary diagnostic approach. Accurate management and financially supportable care is a major issue in rare diseases such as anti-LGI1-encephalitis. Education and awareness about autoimmune encephalitis of all physicians treating a geriatric population is important in order to involve expertise and establish treatment within reasonable time.

Characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis: A retrospective multicentre cohort study.

AIM: Immune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune checkpoint inhibitor treatment. We aim to identify the characteristics of ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 encephalitis and anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities of encephalitis. METHODS: In this retrospective multicentre cohort study, we collected patients with ICI-iE reported to the Side Effect Registry Immuno-Oncology from January 2015 to September 2021 and compared their clinical features and outcome with 46 consecutive patients with HSV-1 or anti-LGI1 encephalitis who were treated at a German neurological referral centre. RESULTS: Thirty cases of ICI-iE, 25 cases of HSV-1 encephalitis and 21 cases of anti-LGI1 encephalitis were included. Clinical presentation of ICI-iE was highly variable and resembled that of HSV-1 encephalitis, while impairment of consciousness (66% vs. 5%, p = .007), confusion (83% vs. 43%; p = .02), disorientation (83% vs. 29%; p = .007) and aphasia (43% vs. 0%; p = .007) were more common in ICI-iE than in anti-LGI1 encephalitis. Antineuronal antibodies (17/18, 94%) and MRI (18/30, 60%) were mostly negative in ICI-iE, but cerebrospinal fluid (CSF) showed pleocytosis and/or elevated protein levels in almost all patients (28/29, 97%). Three patients (10%) died of ICI-iE. Early immunosuppressive treatment was associated with better outcome (r = 0.43). CONCLUSIONS: ICI-iE is a heterogeneous entity without specific clinical features. CSF analysis has the highest diagnostic value, as it reveals inflammatory changes in most patients and enables the exclusion of infection. Early treatment of ICI-iE is essential to prevent sequelae and death.

Serial assessment of multimodality imaging in anti-leucine-rich glioma-inactivated 1 antibody encephalitis: A case report.

In autoimmune encephalitis, abnormalities of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), arterial spin labeling (ASL) in magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) have been reported. However, there are few studies of long-term follow-up of imaging. We report a case of anti-leucine-rich glioma-inactivated 1 antibody encephalitis whose MRI (DWI, FLAIR and ASL), 99mTcHM-PAO SPECT (PAO-SPECT) and 18F-FDG-PET were evaluated through the clinical course. ASL, PAO-SPECT and 18F-FDG-PET consistently showed abnormalities in almost the same area. Serial assessment of these imaging modalities is useful in evaluating disease activity and efficacy of treatment.

The Detection of Invisible Abnormal Metabolism in the FDG-PET Images of Patients With Anti-LGI1 Encephalitis by Machine Learning.

Objective: This study aims to detect the invisible metabolic abnormality in PET images of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis using a multivariate cross-classification method. Methods: Participants were divided into two groups, namely, the training cohort and the testing cohort. The training cohort included 17 healthy participants and 17 patients with anti-LGI1 encephalitis whose metabolic abnormality was able to be visibly detected in both the medial temporal lobe and the basal ganglia in their PET images [completely detectable (CD) patients]. The testing cohort included another 16 healthy participants and 16 patients with anti-LGI1 encephalitis whose metabolic abnormality was not able to be visibly detected in the medial temporal lobe and the basal ganglia in their PET images [non-completely detectable (non-CD) patients]. Independent component analysis (ICA) was used to extract features and reduce dimensions. A logistic regression model was constructed to identify the non-CD patients. Results: For the testing cohort, the accuracy of classification was 90.63% with 13 out of 16 non-CD patients identified and all healthy participants distinguished from non-CD patients. The patterns of PET signal changes resulting from metabolic abnormalities related to anti-LGI1 encephalitis were similar for CD patients and non-CD patients. Conclusion: This study demonstrated that multivariate cross-classification combined with ICA could improve, to some degree, the detection of invisible abnormal metabolism in the PET images of patients with anti-LGI1 encephalitis. More importantly, the invisible metabolic abnormality in the PET images of non-CD patients showed patterns that were similar to those seen in CD patients.

Relapses of Anti-NMDAR, Anti-GABABR and Anti-LGI1 Encephalitis: A Retrospective Cohort Study.

Objective: To investigate the relapse rate and study the factors that may predict the subsequent relapse in anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis in Northeast China. Methods: In the retrospective cohort study, we consecutively enrolled patients with anti-N1MDAR, anti-GABABR and anti-LGI1 encephalitis between March 2015 and November 2021. The patients were followed up for at least 6 months. The outcome variable was a binary variable of relapse or not. Predictors of relapse were identified. Results: A total of 100 patients were enrolled. Relapse occurred in 26 (26%) patients after a median follow-up of 18 months since the first event. The relapse rates of anti - NMDAR, anti - GABABR and anti - LGI1 encephalitis were 25%, 33.3%, and 28.6%, respectively. The multivariable analysis results suggested that immunotherapy delay at the acute phase was independently associated with an increased risk of relapse in total patients (HR = 2.447, 95% CI = 1.027 - 5.832; P = 0.043). Subgroup analysis results showed that antibody titer was associated with the likelihood of relapse in anti-LGI1 encephalitis. The higher the concentration, the more likely it was for patients to have relapse (p=0.019). Conclusion: The general relapse rate of anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis was 26%. The risk of subsequent relapse was elevated in those with delayed immunotherapy in the first episode. In subgroup of anti-LGI1 encephalitis, higher antibody titer was the risk factors of relapse. Thus, timely and aggressive immunotherapy may be beneficial for patients to prevent subsequent relapse.

Clinical features and outcomes of leucine-rich glioma-inactivated protein 1 and contactin protein-like 2 antibody-associated autoimmune encephalitis in a Chinese cohort.

The present study aimed to investigate the clinical manifestations, epidemiological characteristics, and outcomes of Chinese patients with voltage-gated potassium channel complex (VGKC) antibody-associated encephalitis. Patients diagnosed with VGKC antibody-associated encephalitis at our institution between January 2016 and December 2020 were included in this study. We retrospectively evaluated their clinical features, auxiliary examination results, treatments details, long-term outcomes, and risk factors for poor outcome. Of the 91 included patients, 61 (67.78%) were men and 30 (32.97%) were women. The most common clinical symptoms were seizures (n = 63, 69.23%), memory deficits (n = 62, 68.13%), mental behavioral disorders (n = 29, 31.87%), and hyponatremia (n = 57, 62.64%). Although patients with anti- leucine-rich glioma-inactivated 1 (LGI1) (n = 76) and anti- contactin-associated protein-like 2 (CASPR2) encephalitis (n = 15) had similar clinical manifestations, the former were more diverse. In total, 86 (94.51%) patients were treated with immunotherapy. Over a median follow-up period of 25 months, there were no mortalities and 14 (15.38%) patients experienced a relapse. Univariate analysis indicated differences in sex, modified Rankin Scale scores at onset, movement disorders, central hypoventilation, and intensive care unit occupancy between the good- and poor- outcome groups. Patients with anti-LGI1 and anti-CASPR2 encephalitis showed similar clinical manifestations while presenting delineating characteristics. Those with VGKC antibody-associated diseases generally responded well to immunotherapy and demonstrated favorable clinical outcomes. Several factors affected the prognosis, and a long-term follow-up examination is necessary.

HLA-DRB1*03:01 is associated with female sex and younger age of anti-LGI1 encephalitis.

BACKGROUND AND PURPOSE: This study was undertaken to investigate the association between human leukocyte antigen (HLA) genotype and clinical characteristics of anti-LGI1 encephalitis. METHODS: HLA genotyping was performed in 34 patients with anti-LGI1 encephalitis admitted to West China Hospital between April 2014 and May 2021, as well as in 305 healthy controls. The online tool NetMHCIIpan 4.0 and AutoDock Vina software were used to predict binding between LGI1 peptide and HLA class II molecules. RESULTS: Risk of anti-LGI1 encephalitis was strongly associated with the DRB1*03:01 allele (odds ratio [OR] = 4.31, 95% confidence interval [CI] = 1.96-9.25, corrected p = 2.75 × 10-4 ) and the DRB1*03:01-DQB1*02:01 haplotype (OR = 4.45, 95% CI = 2.02-9.59, corrected p = 2.94 × 10-4 ). Compared to carriers of the DRB1*07:01 allele, those with the DRB1*03:01 allele were more likely to be female (93.3% vs. 33.3%, p = 0.004) and to be younger (median age = 38 vs. 65 years, p < 0.001). DRB1*03:01 carriers showed stronger response to immunotherapy than carriers of the DRB1*07:01 allele, based on median score decrease on the modified Rankin scale (2, interquartile range = 1-2 vs. 1, interquartile range = 0-1; p = 0.03) at 4 weeks after immunotherapy. Prediction and docking algorithms suggested that the LGI1 peptide can bind to the DRB1*03:01 molecule strongly. CONCLUSIONS: The strong association between anti-LGI1 encephalitis and certain HLA class II alleles supports a primary autoimmune origin for the disease. Carriers of the DRB1*03:01 allele in Chinese patients with anti-LGI1 encephalitis are more likely to be female, to suffer earlier disease onset, and to respond better to immunotherapy.

Thymoma-associated anti-LGI1 encephalitis and myasthenia gravis: A unique combination with autoantibodies.

We report a 77-year-old woman with a thymoma, anti-LGI1antibody associated encephalitis (LGI1 encephalitis), and MG accompanied by positive anti-acetylcholine receptor antibodies (AchR Ab) and anti-titin antibodies (titin Ab). She was treated with thymomectomy followed by immunosuppressive therapy, which resulted in immediate amelioration of motor weakness and gradual improvement of cognitive impairment over the next two years. LGI1 Ab were positive at two months after thymomectomy, followed by negative conversion demonstrated on 1 year examination. The AchR Ab level had gradually decreased but titin Ab was positive on re-examination after two years, although the cognition and motor impairment symptoms had been alleviated. In patients with suspected autoimmune encephalitis, the detection of several autoantibodies including LGI1 and thymomas provides useful information for making an accurate diagnosis.