Antibody-associated Autoimmune Encephalitis Research Articles

Autoimmune Encephalitis.

This article focuses on the clinical features and diagnostic evaluations that accurately identify patients with ever-expanding forms of antibody-defined encephalitis. Forms of autoimmune encephalitis are more prevalent than infectious encephalitis and represent treatable neurologic syndromes for which early immunotherapies lead to the best outcomes. A clinically driven approach to identifying many autoimmune encephalitis syndromes is feasible, given the typically distinctive features associated with each antibody. Patient demographics alongside the presence and nature of seizures, cognitive impairment, psychiatric disturbances, movement disorders, and peripheral features provide a valuable set of clinical tools to guide the detection and interpretation of highly specific antibodies. In turn, these clinical features in combination with serologic findings and selective paraclinical testing, direct the rationale for the administration of immunotherapies. Observational studies provide the mainstay of evidence guiding first- and second-line immunotherapy administration in autoimmune encephalitis and, whereas these typically result in some clinical improvements, almost all patients have residual neuropsychiatric deficits, and many experience clinical relapses. An improved pathophysiologic understanding and ongoing clinical trials can help to address these unmet medical needs. Antibodies against central nervous system proteins characterize various autoimmune encephalitis syndromes. The most common targets include leucine-rich glioma inactivated protein 1 (LGI1), N-methyl-d-aspartate (NMDA) receptors, contactin-associated proteinlike 2 (CASPR2), and glutamic acid decarboxylase 65 (GAD65). Each antibody-associated autoimmune encephalitis typically presents with a recognizable blend of clinical and investigation features, which help differentiate each from alternative diagnoses. The rapid expansion of recognized antibodies and some clinical overlaps support panel-based antibody testing. The clinical-serologic picture guides the immunotherapy regime and offers valuable prognostic information. Patient care should be delivered in conjunction with autoimmune encephalitis experts.

Resolution of anti-LGI1-associated autoimmune encephalitis in a patient after treatment with efgartigimod.

Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE. The patient presented with five episodes of generalized tonic-clonic seizures in the past 2weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10mg/kg efgartigimod was administered intravenously once a week for 2weeks. After 2weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3months. This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan.

Anti-Yo antibody-associated Autoimmune Encephalitis due to Breast Adenocarcinoma in a male patient.

Paraneoplastic neurological syndromes occur due to immune-mediated neuronal dysfunction secondary to systemic malignancy, and symptoms can usually be seen before malignancy. There are many subtypes that depend on the antibodies present or the proteins they target. Accurate epidemiological data are lacking as it is difficult to diagnose. We would like to present a case of anti-Yo antibody-associated encephalitis due to breast cancer in a 47-year-old male patient. When we searched the literature, we did not find a case of anti-Yo-associated autoimmune encephalitis due to breast adenocarcinoma in a male patient. For this reason, we find it worth presenting our case.

Anti-CASPR2 antibody-associated autoimmune encephalitis with GFAP Α IGG: A first report

Anti-CASPR2 antibody-associated autoimmune encephalitis with GFAP Α IGG: A first report

Predictive value of persistent antibodies at 6months for relapse in neuronal surface antibody-associated autoimmune encephalitis.

For patients with neuronal surface antibody-associated autoimmune encephalitis (NSAE) whose clinical symptoms gradually improve, the recommended course of immunotherapy in China is about 6months. We aim to explore the relationship between persistent antibody positivity when immunotherapy is discontinued at 6months and subsequent relapse. Prospective inclusion of NSAE patients with clinical remission after 6-month immunotherapy. Their antibody titers and other clinical data were collected at onset and 6months later. Based on the antibody test results at 6months, patients were divided into an antibody-persistent group and an antibody-negative conversion group, and then the rate of relapse between the two groups were compared. The study included 28 NSAE patients who were antibody-positive at diagnosis. After 6-month immunotherapy, there were 16 (57.1%) cases with persistent antibodies and 12 (42.9%) cases with antibody-negative conversion. In the acute phase of onset, seizures were more common in patients with persistent antibodies (87.5% vs. 50.0%, p = 0.044). During a mean follow-up period of 22months, patients with persistent antibodies were more likely to experience relapse than those with antibody-negative conversion (37.5% vs. 0.0%, p = 0.024). There were no significant differences in antibody types, CSF findings, results of MRI and EEG, tumor combination, immunotherapy, and long-term outcome between the two groups (p > 0.05). For patients with persistent antibodies when immunotherapy is discontinued at 6months, persistent antibody positivity was associated with a higher relapse rate.

MOG antibody-associated encephalitis in adult: clinical phenotypes and outcomes (P13-5.020)

<h3>Objective:</h3> We investigated the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis (MOGAE) in adult patients. <h3>Background:</h3> Although MOG antibody-associated disease (MOGAD) can be associated with autoimmune encephalitis, the clinical features and outcomes of MOGAE in adults are largely unknown. <h3>Design/Methods:</h3> From an institutional cohort, we analyzed adult patients with MOGAE followed-up for more than one year. Disease severity was assessed using the modified Rankin scale (mRS) and Clinical Assessment Scales in Autoimmune Encephalitis (CASE) scores. Immunotherapy profiles, outcomes, and disease relapses were evaluated along with serial brain MRI data. <h3>Results:</h3> A total of 40 patients were enrolled and categorized into cortical encephalitis (18 patients), limbic encephalitis (LE, 5 patients), and acute disseminated encephalomyelitis (ADEM, 17 patients). 80.0% of patients achieved good clinical outcomes (mRS 0–2) and 40.0% relapsed. The LE subtype was associated with an older onset age (<i>P</i>=0.004) and poor clinical outcomes (<i>P</i>=0.014) than the other subtypes but with a low rate of relapse (0.0%). 21/25 (84.0%) relapse attacks were associated with an absence or short (≤6 months) immunotherapy maintenance. On MRI, the development of either diffuse cerebral or medial temporal atrophy within the first six-month was correlated with poor outcomes. MOG-antibody was co-present with anti-N-methyl-D-aspartate receptor (NMDAR)-antibody in 13 patients, in whom atypical clinical presentation (cortical encephalitis or ADEM, <i>P&lt;</i>0.001) and disease relapse (46.2% vs. 0.0%, <i>P&lt;</i>0.001) were more frequent compared to conventional NMDAR encephalitis without MOG-Ab. <h3>Conclusions:</h3> Outcomes are different according to the three phenotypes in MOGAE. Short immunotherapy maintenance is associated with relapse, and brain atrophy was associated with poor outcomes. Patients with dual antibodies of NMDAR and MOG have a high relapse rate. <b>Disclosure:</b> Prof. Lee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Advanced Neural Technologies. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biofire Diagnostics. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GC pharma. The institution of Prof. Lee has received research support from GC pharma. Prof. Kim has received intellectual property interests from a discovery or technology relating to health care. Prof. Chu has nothing to disclose. Prof. Lee has nothing to disclose. Woo-jin Lee has nothing to disclose.

Evaluation of CSF albumin quotient in neuronal surface antibody-associated autoimmune encephalitis

Background and ObjectivesDisruption of brain barriers is considered to be involved in the pathogenesis of neuronal surface antibody-associated autoimmune encephalitis (NSAE), but few studies have focused on their relationship. We aimed to explore the association between the integrity of brain barriers and clinical and paraclinical characteristics in patients with NSAE.MethodsThis retrospective study consecutively recruited patients with NSAE. The cerebrospinal fluid (CSF) / serum albumin quotient (Qalb) was used to evaluate the function of brain barriers. The data on demographic information, clinical manifestations, magnetic resonance imaging (MRI), CSF findings and prognosis were collected and analyzed.ResultsOf the 93 patients included, 33 (35.5%) patients were assigned to the elevated Qalb group and 60 (64.5%) patients to the normal Qalb group. Males and prodromal symptoms were more common in elevated Qalb group (both P < 0.05). The CSF white blood cell, protein, immunoglobulin G and albumin were significantly higher in elevated Qalb group (all P < 0.05). Patients with elevated Qalb were more likely to have brain lesions on MRI (60.6% versus 33.3%, P = 0.011). The modified Rankin Scale (mRS) scores at discharge and at last follow-up were significantly higher in patients with elevated Qalb than those with normal Qalb (both P < 0.05). After univariate and multivariate analyses, Qalb elevation (adjusted odds ratio = 3.96, 95% confidence interval = 1.15–13.59, P = 0.029) was demonstrated as the only independent risk factor for a poor prognosis.DiscussionMales, prodromal symptoms, brain lesions on MRI, CSF pleocytosis, and elevated CSF protein were more common in NSAE patients with increased Qalb. Qalb elevation was an independent prognostic indicator for a poor prognosis in NSAE.

MOG antibody-associated encephalitis in adult: clinical phenotypes and outcomes

BackgroundWe investigated the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis (MOGAE) in adult patients.MethodsFrom an institutional cohort, we analysed adult patients with MOGAE followed-up for...

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.

Anti-GAD65 Antibody-Associated Autoimmune Encephalitis With Predominant Cerebellar Involvement Following Toripalimab Treatment: A Case Report of a Novel irAE of Toripalimab

Toripalimab (Junshi Bioscience Co., Ltd) is a new immune checkpoint inhibitor (ICI) that targets programmed cell death protein 1 (PD-1) in various cancers, including metastatic melanoma. No neurological immune-related adverse events (n-irAEs) of toripalimab have been reported, except for neuromuscular involvement. We report a case of a 63-year-old woman who presented with severe vertigo, vomiting, nystagmus, cerebellar ataxia, and cognitive impairment after toripalimab treatment for metastatic melanoma. Compared with the concomitant cognitive dysfunction and a pathological reflex involving the cerebral cortex, the signs and symptoms of cerebellar involvement were much more prominent. Anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody was positive in both serum and cerebrospinal fluid (CSF). After intravenous immunoglobulin (IVIG) and methylprednisolone (IVMP) administration, the symptoms of vertigo and vomiting resolved, with cognitive impairment and cerebellar ataxia remaining. This is the first report of autoimmune encephalitis (AIE) as an n-irAE of toripalimab.

Clinico-radiological characteristics of anti-myelin oligodendrocyte glycoprotein antibody-associated autoimmune encephalitis in children.

To investigate the clinical characteristics and prevalence of paediatric anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis. A total of 94 paediatric patients (46 males, 48 females, median age 9 years 5 months, range: 8 months-17 years 8 months) with autoimmune encephalitis were recruited at Seoul National University Children's Hospital. We evaluated autoantibody status and identified patients with anti-MOG antibody-associated autoimmune encephalitis. Retrospective reviews of medical records were performed to describe clinical presentations, laboratory findings, treatments, and outcomes. Eight patients (five males, three females, median age 11 years 9 months) with anti-MOG antibody-associated encephalitis were identified (8.5% of those with autoimmune encephalitis), one of whom was copositive for anti-N-methyl-d-aspartate receptor (NMDAR) antibodies. Anti-NMDAR antibodies were identified in 23 patients (23 out of 94, 24.5%). Unilateral or bilateral cortical involvement was identified in five patients. Focal contrast enhancement was also identified in three of the five patients with cortical lesions. All patients showed favourable response to immunotherapy with a Modified Rankin Scale ≤2 at the last follow-up. Relapse was found in one patient and clinico-radiological remission was achieved with cyclic intravenous immunoglobulin therapy. Anti-MOG antibody-associated encephalitis accounts for a significant proportion of clinically defined paediatric patients with autoimmune encephalitis. Anti-MOG antibody-associated encephalitis should be included in the clinical spectrum of anti-MOG-associated diseases.

A case of anti-leucine-rich glioma-inactivated 1 antibody-associated autoimmune encephalitis with faciobrachial dystonic seizure

A case of anti-leucine-rich glioma-inactivated 1 antibody-associated autoimmune encephalitis with faciobrachial dystonic seizure

Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.

The role of dendritic cells and their interactions in the pathogenesis of antibody-associated autoimmune encephalitis

Autoimmune encephalitis (AE) is an inflammatory brain disease which is frequently associated with antibodies (Abs) against cell-surface, synaptic or intracellular neuronal proteins. There is increasing evidence that dendritic cells (DCs) are implicated as key modulators in keeping the balance between immune response and tolerance in the CNS. Migratory features of DCs to and from the brain are linked to initiating and maintaining of neuroinflammation. Genetic polymorphisms together with other triggers such as systemic or cerebral viral infection, or systemic malignancies could contribute to the dysbalance of “regulatory” and “encephalitogenic” DCs with subsequent dysregulated T and B cell reactions in AE. Novel in vivo models with implantation of mature DCs containing neuronal antigens could help to study the pathogenesis and perhaps to understand the origin of AE. Investigations of DCs in human blood, lymphoid tissues, CSF, and brain parenchyma of patients with AE are necessary to deepen our knowledge about the complex interactions between DCs, T and B cells during neuroinflammation in AE. This can support developing new therapy strategies.

Clinical Features and Outcomes in Pediatric Autoimmune Encephalitis Associated With CASPR2 Antibody.

Background: Contactin-associated protein-like 2 (CASPR2) neurological autoimmunity has been associated with various clinical syndromes involving central and peripheral nervous system. CASPR2 antibody-associated autoimmune encephalitis is mostly reported in adults. Analysis of the clinical presentation and prognostic data of CASPR2 antibody-associated autoimmune encephalitis in children remains important.Methods: A single-center retrospective review of children diagnosed with CASPR2 antibody-associated autoimmune encephalitis from June 1st, 2018 to October 31st, 2020.Results: Six patients were identified. The median age was 12 years (range 1.8–14), with an overall male predominance of 83% (5/6). Commonest clinical features were psychiatric symptoms (6/6), movement disorders (4/6), altered consciousness (3/6), sleep disorders (3/6), and headache (3/6). Four patients (4/6) received first-line therapy alone (steroids combined with intravenous immunoglobulins), and two patients (2/6) received second-line therapy (rituximab, mycophenolate mofetil, or cyclophosphamide). All patients showed no peripheral nervous system involvement. One patient had comorbidities with systemic lupus erythematosus. No evidence of neoplastic disease was found in the whole cohort. All patients had favorable outcomes (modified Rankin Score 0–2) with recurrence rate at 0%, respectively.Conclusion: CASPR2 antibody-associated autoimmune encephalitis is rare in children. Our findings suggest that this type of encephalitis seems to occur more frequently in older children. Patients respond well to immunotherapy and usually demonstrate a favorable clinical outcome. Associated tumors are extremely rare.

Autoimmune Neurology

Autoimmune neurology is a rapidly developing specialty driven by an increasing recognition of autoimmunity as the cause for a broad set of neurologic disorders and ongoing discovery of new neural autoantibodies associated with recognizable clinical syndromes. The diversity of clinical presentations, unique pathophysiology, and the complexity of available treatments requires a dedicated multidisciplinary team to diagnose and manage patients. In this article, we focus on antibody-associated autoimmune encephalitis (AE) to illustrate broader themes applicable to the specialty. We discuss common diagnostic challenges including the utilization of clinical assessment tools along with the determination of the prognostic significance of certain autoantibodies, with a focus on implications for long-term management. A growing body of literature demonstrates the long-term cognitive, behavioral, and physical sequelae of AE. Dedicated resources are needed to effectively manage these patients. These resources may be best provided by experienced neurology clinics in partnership with other neurologic subspecialists, as well as psychiatrists, neuropsychologists, and physical medicine and rehabilitation providers.

Longitudinal CSF Findings in Autoimmune Encephalitis-A Monocentric Cohort Study.

Autoimmune encephalitis (AIE) poses a diagnostic challenge due to its heterogeneous clinical presentation, which overlaps with various neurological and psychiatric diseases. During the diagnostic work-up, cerebrospinal fluid (CSF) is routinely obtained, allowing for differential diagnostics as well as for the determination of antibody subclasses and specificities. In this monocentric cohort study, we describe initial and serial CSF findings of 33 patients diagnosed with antibody-associated AIE (LGI1 (n=8), NMDA (n=7), CASPR2 (n=3), IgLON5 (n=3), AMPAR (n=1), GAD65/67 (n=4), Yo (n=3), Ma-1/2 (n=2), CV2 (n=2)). Routine CSF parameters of 12.1% of AIE patients were in normal ranges, while 60.6% showed elevated protein levels and 45.4% had intrathecal oligoclonal bands (OCBs). Repeated CSF analyses showed a trend towards normalization of initial pathological CSF findings, while relapses were more likely to be associated with increased cell counts and total protein levels. OCB status conversion in anti-NMDARE patients coincided with clinical improvement. In summary, we show that in routine CSF analysis at diagnosis, a considerable number of patients with AIE did not exhibit alteration in the CSF and therefore, diagnosis may be delayed if antibody testing is not performed. Moreover, OCB status in anti-NMDAR AIE patients could represent a potential prognostic biomarker, however further studies are necessary to validate these exploratory findings.

Clinical efficacy of plasma exchange in patients with autoimmune encephalitis.

ObjectiveTo determine the clinical and antibody response after therapeutic plasma exchange (TPE) in patients with severe refractory antibody‐associated autoimmune encephalitis (AE).MethodsThis single‐center prospective cohort included all patients consecutively admitted to our hospital because of severe refractory AE over the period from July 2014 to June 2019. All patients received immunotherapy (steroids, intravenous immunoglobulin (IVIG), and/or TPE). The primary outcome was evaluated at 1‐ and 2‐month postenrollment, and the long‐term outcome was followed up at 6 and 12 months. AE antibody titers in the cerebrospinal fluid and plasma were evaluated before and after TPE/IVIG.ResultsThis study enrolled 57 patients with severe refractory AE, including anti‐NMDA receptor encephalitis (n = 51), anti‐GABAb receptor encephalitis (n = 3), anti‐LGI 1 encephalitis (n = 2), and anti‐AMPA receptor encephalitis (n = 1). Of all 57 patients, 33 patients received TPE for a total of 193 procedures, and 24 patients with contraindications or refusal of TPE were in the non‐TPE group. Compared with the non‐TPE group, the TPE group exhibited greater clinical improvement: 21 (37%) versus 8 (14%) after 1 month (P = 0.03) and 31 (54%) versus 16 (28%) after 2 months (P = 0.01), respectively. Complications and adverse events associated with TPE occurred in 91 procedures (47%) without serious adverse events associated with the use of TPE.InterpretationTPE might be an effective rescue therapy associated with rapid functional improvement in patients with severe steroid/IVIG refractory antibody‐associated AE from this nonrandomized control trial.

Figural Memory Impairment in Conjunction With Neuropsychiatric Symptoms in IgLON5 Antibody-Associated Autoimmune Encephalitis

BackgroundIgLON5 disease is an autoimmune disorder that shares neuropathological aspects with a tauopathy. Its clinical spectrum is heterogeneous, and figural memory impairment as an initial phenomenon of IgLON5 syndrome has not yet been described. The rationale of this report is to highlight symptoms related to IgLON5 disease that have not been reported to date. This case report will thereby emphasize how important it is to initiate thorough diagnostic methods including cerebrospinal fluid analysis (CSF) before starting early immunotherapy.MethodsWe examined a 65-year-old Caucasian male via neuropsychological tests, magnetic resonance imaging (MRI), electroencephalography (EEG), neurography and polysomnography. He also underwent two lumbar punctures from which we determined specific autoantibodies in cerebrospinal (CSF) and peripheral blood (PB).ResultsThe patient presented initially complaining of memory loss, gradual dysphagia and sleeping dysfunction. Neuropsychological testing at first presentation and follow-up revealed subtle figural and working memory impairment. At onset and at his 6-month follow-up, we detected IgLON5 antibodies in CSF and PB. Furthermore, we identified in the CSF a blood–brain barrier disturbance at disease onset and follow-up, and markers of neuroaxonal damage such as mildly elevated phosphorylated Tau-181 protein with 86 pg/ml (normal range ≤ 61 pg/ml) at onset. Three months after his initial presentation, he was suffering from axonal neuropathy and transient ataxia in the extremities. Assuming a definitive autoimmune encephalitis-associated with anti-IgLON5 antibodies, we applied high-dose steroids monthly (1g methylprednisolone i.v. for five consecutive days) and his memory complaints, ataxia of extremities and peripheral neuropathy as well as sleeping dysfunction decreased.ConclusionsOur findings broaden IgLON5 disease’s clinical spectrum to include predominant and discrete figural memory impairment together with sleeping dysfunction at disease onset. In addition, our report illustrates how important taking an elaborated diagnostic approach is to assuring an accurate diagnosis and the appropriate therapy if a patient presents with a persisting figural memory impairment and sleeping abnormalities so as to avoid overlooking IgLON5 disease and a potentially poor outcome.

Clinical and Electroencephalographic Features of the Seizures in Neuronal Surface Antibody-Associated Autoimmune Encephalitis.

Objectives: To investigate clinical and electroencephalographic features of the seizures in different types of neuronal surface antibody (NSAb)-associated autoimmune encephalitis (AE).Methods: The clinical data of the seizures were analyzed in 18 patients with NSAb-associated AEs diagnosed in the First Affiliated Hospital of Dalian Medical University.Results: From May 2013 to April 2019, a total of 18 cases of NSAb-associated AE were diagnosed, including 9 cases of leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated encephalitis, 7 cases of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, and 2 cases of anti-γ-aminobutyric acid B receptor (GABABR) encephalitis. All nine cases (100%) with LGI1 AE had seizures manifesting in three types: faciobranchial dystonia seizure (FBDS) (44.4%), mesial temporal lobe epilepsy (MTLE)-like seizure (66.7%), and focal to bilateral tonic–clonic seizure (FBTCS) (77.8%). Six of nine (66.7%) showed abnormal signal on hippocampus or basal ganglia in brain MRI. Five of seven cases (71%) with anti-NMDAR encephalitis had seizures manifesting in three types: focal aware seizure (40%), focal-impaired awareness seizure (20%), generalized tonic–clonic seizure (GTCS) (100%), and status epilepticus (SE) (40%). Three of seven (42.8%) showed abnormalities in brain MRI. Both patients with anti-GABABR encephalitis had seizures manifesting in two types: GTCS and MTLE-like seizure, one with SE. One showed abnormal signal on left hippocampus in brain MRI. All patients (100%) with three types of AE had abnormalities in electroencephalogram (EEG), showing diffuse (4/18) or focal slow waves (14/18) in background, interictal (10/18), or ictal (6/18) epileptic discharges in the temporal or other regions; two patients with anti-NMDAR encephalitis showed delta activity or rhythm in frontotemporal region. All patients with seizures showed good response to immunotherapy except one with LGI1 AE.Conclusions: Most patients with NSAb-associated AE had seizures; seizure types varied between different types of AE. In LGI1 AE, the hippocampus and basal ganglia were two main targets; the corresponding seizure type was MTLE-like seizure and FBDS, respectively. Anti-NMDAR encephalitis had more generalized than focal seizures. Delta activity or rhythm in the frontotemporal region in EEG was helpful for diagnosis. Anti-GABABR encephalitis was characterized by refractory seizures as initial symptom, mainly GTCS or MTLE-like seizure. Most seizures in NSAb-associated AE showed good response to immunotherapy, and antiepileptic drugs should be considered as an add-on symptomatic treatment.