Limbic Encephalitis Research Articles

FRI560 A Rare Case Of Hashimoto Encephalopathy

Abstract Disclosure: M. Nokhbehzaeim: None. H.K. Driscoll: None. M. Sanati: None. Background: Hashimoto encephalopathy is a rare syndrome associated with Hashimoto’s thyroiditis. It presents as an encephalopathy without central nervous system infection or tumor. It is also described as steroid-responsive encephalopathy. It is characterized by high titers of antithyroid peroxidase antibodies. Case: 60-year-old female, with known Hashimoto thyroiditis on levothyroxine 200 mcg daily was admitted to the hospital with generalized weakness and lethargy. On admission, her TSH level was 0.085 with a Free T4 of 2.15. Subsequently, the Levothyroxine dose was decreased to 175 mcg and then was held for a few days. During her hospital stay her mental status deteriorated, and she became altered. As a part of the work-up, an MRI of the brain was done. It showed nonspecific left-sided dural thickening with enhancement, consistent with meningitis, but no signs of brain metastasis. She also developed persistent plantar flexion of both ankles and staring forward. MRI of Cervical, Thoracic, and Lumbar spine was done and leptomeningeal carcinomatosis was ruled out. She underwent a lumbar puncture; however, the CSF meningitis panel was negative. She was started on a trial of Dexamethasone 4 mg PO q 12 hours for 5 days. Her repeat thyroid function test revealed TSH: 54.4 and normal Free T4: 1.1. Levothyroxine 150 mcg was restarted, and the dose of Levothyroxine was increased to 175 mcg daily. She underwent a brain biopsy, which was unremarkable. Paraneoplastic panel and GAD 65 antibody were not detected. She was started on a trial of methylprednisolone and IVIG, and she showed significant improvement. Discussion: Hashimoto encephalopathy may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, and myoclonus. Thyroid function is usually clinically and biochemically normal. It is characterized by high titers of antithyroid peroxidase antibodies. The other causes of encephalopathy such as toxic, metabolic, and infectious should be excluded with neuroimaging and CSF examination. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. It is a rare disorder but it is responsive to treatment with corticosteroids. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis. Presentation: Friday, June 16, 2023

A complex case of young child with ADHD, developmental delay who developed seronegative autoimmune encephalitis exacerbated by stimulants

Autoimmune encephalitis (AE) is a group of disorders characterized by a wide clinical spectrum ranging from the typical limbic encephalitis to more complex neuropsychiatric symptoms including abnormal movements, psychosis, deficits in memory and cognition, dysautonomia, seizures, or coma. Psychiatric symptoms can occur early in the disease progress or manifest during its course. These symptoms are challenging and often slow down the diagnosis of AE. This is a crucial aspect considering that early diagnosis and management of AE are critical for a good outcome. However, there is a lack in studies outlining the exact symptomatology and specific appropriate care that would allow clinicians to achieve an early diagnosis and management. Additionally, AE in children mostly presents with neuropsychiatric symptoms and diagnosis is especially challenging in kids because of their limited capacity in describing their symptoms, the normal childhood behavioral changes and the possibility of a comorbid psychiatric diagnosis. We present a complex case of seronegative AE with comorbid ADHD (Attention Deficit Hyperactivity Disorder) and anxiety in a young six-year-old girl.

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes

IntroductionAnti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. ObjectiveTo describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. MethodsRetrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. ResultsNineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3–63.0) years and a median time to diagnosis of 1.0 (0.0–1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie’s Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. ConclusionAnti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

Neurological syndromes and potential triggers associated with antibodies to neuronal surface antigens

BackgroundAutoantibodies against surface neuronal antigens have been associated with specific neurological presentations including autoimmune encephalitis (AE), with variable association with neoplasia and infections. MethodsWe described the phenotype and environmental associations of patients with neurological syndromes associated with antibodies against neuronal surface antigens who were referred to a tertiary center in the South of Brazil. All patients were tested for neuronal autoantibodies using cell-based assays. Clinical, radiological, and laboratory findings were retrospectively reviewed. ResultsWe identified 16 patients, 15 had subacute, and one had a progressive disease course. Among patients with subacute onset, 11 (73 %) were N-Methyl-d-Aspartate receptor (NMDAr-IgG)+, 3 (20 %) were Leucine-rich Glioma-Inactivated-1 (LGI1-IgG)+, and 1 (6 %) was positive for Glycine receptor-IgG. The patient with a progressive disease course had antibodies against IgLON5. Most patients had disease onset in spring and summer suggesting environmental factors for the development of AE. Also, we observed a different pattern of brain lesions when NMDAr-IgG encephalitis followed herpes encephalitis and a previously unreported association with Rosai-Dorfman-Destombe disease. All patients with encephalopathy met criteria for possible AE and all proven NMDAr-IgG+ met criteria for NMDAr-IgG encephalitis. However, only one LGI1-IgG+ patient fulfilled clinical criteria for limbic encephalitis. All but one received high-dose intravenous methylprednisolone, 11 also had intravenous human immunoglobulin, and 4 plasma exchange. Furthermore, all patients received second-line immunotherapy. Importantly, most patients improved with immunotherapy, even when initiated later in the disease course. ConclusionWe identified seasonal variability associated with neuronal surface antibodies suggesting environmental triggers. Also, we described the coexistence of NMDAr-IgG encephalitis with histiocytosis. In our series, most patients received second-line immunotherapy. We observed neurologic improvement after treatment even in cases of delayed diagnosis. Increasing the recognition and availability of tests and treatments for these conditions is of paramount importance in low- and middle-income countries.

A Journey from Schizophrenia to Paraneoplastic Limbic Encephalitis

A 58-year female presented with behavioral changes, dementia, and hallucinations for which she was initially treated as a case of schizophrenia. Later she developed hypersomnolence, speech difficulty and urinary incontinence. She also developed seizures later. On investigations cerebrospinal fluid (CSF) cell count was high and chest x-ray revealed homogeneous opacity over the left upper and midzone. Contrast-enhanced computerized tomography (CECT) Thorax revealed apical segment collapse consolidation with air bronchogram and bilateral pleural effusion. Multiple hepatic and bony metastasis s/o primary bronchoalveolar carcinoma. Osteolytic lesions were also found on skull x-ray and on pelvis x-ray. Tissue diagnosis couldn’t be done as the patient’s general condition deteriorated and the patient left against medical advice. From the above clinical picture and investigation findings, it was diagnosed as a case of paraneoplastic limbic encephalitis.

MRI abnormalities in Creutzfeldt–Jakob disease and other rapidly progressive dementia

ObjectiveTo investigate brain MRI abnormalities in a cohort of patients with rapidly progressive dementia (RPD) with and without a diagnosis of Creutzfeldt–Jakob disease (CJD).MethodsOne hundred and seven patients with diagnosis of prion disease (60 with definite sCJD, 33 with probable sCJD and 14 with genetic prion disease) and 40 non-prion related RPD patients (npRPD) underwent brain MRI including DWI and FLAIR. MRIs were evaluated with a semiquantitative rating score, which separately considered abnormal signal extent and intensity in 22 brain regions. Clinical findings at onset, disease duration, cerebrospinal-fluid 14-3-3 and t-tau protein levels, and EEG data were recorded.ResultsAmong patients with definite/probable diagnosis of CJD or genetic prion disease, 2/107 had normal DWI-MRI: in one patient a 2-months follow-up DWI-MRI showed CJD-related changes while the other had autopsy-proven CJD despite no DWI abnormalities 282 days after clinical onset. CJD-related cortical changes were detected in all lobes and involvement of thalamus was common. In the npRPD groups, 6/40 patients showed DWI alterations that clustered in three different patterns: (1) minimal/doubtful signal alterations (limbic encephalitis, dementia with Lewy bodies); (2) clearly suggestive of alternative diagnoses (status epilepticus, Wernicke or metabolic encephalopathy); (3) highly suggestive of CJD (mitochondrial disease), though cortical swelling let exclude CJD.ConclusionsIn the diagnostic work-up of RPD, negative/doubtful DWI makes CJD diagnosis rather unlikely, while specific DWI patterns help differentiating CJD from alternative diagnoses. The pulvinar sign is not exclusive of the variant form.

Revisiting anti-Hu paraneoplastic autoimmunity: phenotypic characterization and cancer diagnosis.

Anti-Hu are the most frequent antibodies in paraneoplastic neurological syndromes, mainly associated with an often limited stage small cell lung cancer. The clinical presentation is pleomorphic, frequently multifocal. Although the predominant phenotypes are well characterized, how different neurological syndromes associate is unclear. Likewise, no specific study assessed the performance of new-generation CT and PET scanners for cancer screening in these patients. Herein, we aimed to describe the clinical pattern and cancer screening in a retrospective cohort of 466 patients with anti-Hu autoimmunity from the French Reference Centre on Paraneoplastic Neurological Syndromes registry. Clinical presentation, cancer screening and diagnosis were analysed. Among the 466 patients, 220 (54%) had multifocal neurological involvement. A hierarchical cluster analysis grouped the patients into (i) mainly limbic encephalitis, (ii) predominantly peripheral neuropathy and (iii) broad involvement of the nervous system (mixed group). Compared with limbic encephalitis and mixed groups, patients in the neuropathy group more frequently had a chronic onset of symptoms (29 versus 13 and 17%), elevated CSF proteins (83 versus 47 and 67%) and died from cancer progression (67 versus 15 and 28%; all P < 0.05). No significant difference in overall survival was observed between groups. Dysautonomia and brainstem signs were associated with a higher risk of death from the neurological cause; cancer diagnosis was the main predictor of all-cause death, especially when diagnosed within 2 years from clinical onset (all P < 0.05). Three hundred and forty-nine (75%) patients had cancer: in 295 (84%) neurological symptoms preceded tumour diagnosis, being lung cancer in 262 (89%), thereof small cell lung cancer in 227 (87%). First CT scan revealed lung cancer in 205/241 (85%), and PET scan shortened the interval to diagnosis when the initial CT scan was negative [7 months (1-66) in 27 patients versus 14 months (2-45) in 6; P < 0.001]. Although cancer diagnosis mostly occurred within 2 years from clinical onset, 13/295 (4%) patients exceeded that threshold. Conversely, 33 patients (7%) were 'cancer-free' after 2 years of follow-up. However, 13/33 (39%) had initial suspicious imaging findings that spontaneously regressed. In conclusion, although anti-Hu autoimmunity clinical presentation is mostly multifocal, we observed patients with a predominant limbic syndrome or isolated sensory neuropathy. Early implementation of PET scan shortens the interval to cancer diagnosis, which was the strongest predictor of death, especially if diagnosed ≤2 years from clinical onset. As cancer was diagnosed >2 years after clinical onset in few patients, screening should be extended up to 5 years. In addition, tumour regression was suspected in a substantial proportion of 'cancer-free' patients.

NMDA, AMPA and GABA Receptor Antibodies: Relation to Clinical and Electrophysiological Findings in Drug-Resistant Epilepsy

Abstract Background Epilepsy is a neurological disorder characterized by sudden recurrent episodes of convulsions, sensory disturbance, or loss of consciousness, resulting from abnormal electrical brain activity. It can have both genetic and acquired causes, with interaction of these factors in many cases. Auto-antibodies against synaptic receptors have been detected in a number of neurological conditions such as anti-NMDA receptor encephalitis and limbic encephalitis. Recently, three types of synaptic receptors have been the subject of research as regarding their role in the normal physiology of the nervous system, and their involvement in various neurological conditions. These receptors include AMPA receptors, NMDA receptors and GABAB receptors. Antibodies directed against these receptors may be the underlying cause of many cases of drug resistant epilepsy. Objectives To determine the prescence of autoantibodies against AMPA, NMDA and GABAB receptors in drug-resistant epilepsy and their correlation with clinical and electrophysiological findings. Methods The study was conducted on 17 epilepsy patients (12 males and 5 females) who were sampled for both CSF and blood. All CSF and serum samples were examined by the Indirect Immunofluorescence cell based technique for the detection of AntiAMPAR, Anti-NMDAR and Anti-GABAB antibodies. Results Only one case tested positive for Anti-NMDAR antibodies in CSF, while all other serum and CSF samples were negative for other antibodies. These results are still in process since our data will be used in a further study related to auto-immune drug-resistant epilepsy patients involving other auto-antibodies such as Ant-LGI1, Anti-CASPR2 and Anti-DPPX antibodies. Conclusion Testing Anti-NMDAR antibodies can be promising in detecteing drug resistant epilepsy patients even after receiving immunomodulatory treatment protocols.

A case of severe paraneoplastic glutamic acid decarboxylase antibody‐spectrum disorder with improvement through prior immunotherapy before surgical intervention

AbstractBackgroundInitially associated with stiff‐person syndrome, antibodies to glutamic acid decarboxylase (GAD) antibodies are now recognized as indicators of GAD antibody‐spectrum disorders (GAD‐SD), which encompass cerebellar ataxia, autoimmune epilepsy and limbic encephalitis. Paraneoplastic neurological syndromes associated with GAD‐SD are rare, and optimal timing of surgical intervention and impact on neurological symptoms remain poorly understood.Case PresentationWe present the case of a 65‐year‐old woman who developed overlapping symptoms of cerebellar ataxia and stiff‐person syndrome detected through high‐titer GAD antibodies in both serum and cerebrospinal fluid, alongside the presence of a thymoma. Due to severe dysphagia and gait ataxia that rendered her bedridden on admission, surgical intervention was initially deferred. Instead, she received immunotherapies including intravenous methylprednisolone and intravenous immunoglobulin, which remarkably improved neurological symptoms. However, a decline in symptoms occurred on tapering oral prednisolone. Subsequently, a thoracoscopic thymectomy was carried out 27 months after symptom onset, leading to further neurological improvement and successful reduction of prednisolone.ConclusionIn paraneoplastic GAD‐SD cases with severe symptoms at presentation, prioritizing immunotherapy and considering surgical intervention once the symptoms have stabilized might be advantageous.

Mimics of Autoimmune Encephalitis: Validation of the 2016 Clinical Autoimmune Encephalitis Criteria.

The clinical criteria for autoimmune encephalitis (AE) were proposed by Graus et al. in 2016. In this study, the AE criteria were validated in the real world, and common AE mimics were described. In addition, criteria for probable anti-LGI1 encephalitis were proposed and validated. In this retrospective cohort study, patients referred to our national referral center with suspicion of AE and specific neuroinflammatory disorders with similar clinical presentations were included from July 2016 to December 2019. Exclusion criteria were pure cerebellar or peripheral nerve system disorders. All patients were evaluated according to the AE criteria. In total, 239 patients were included (56% female; median age 42 years, range 1-85). AE was diagnosed in 104 patients (44%) and AE mimics in 109 patients (46%). The most common AE mimics and misdiagnoses were neuroinflammatory CNS disorders (26%), psychiatric disorders (19%), epilepsy with a noninflammatory cause (13%), CNS infections (7%), neurodegenerative diseases (7%), and CNS neoplasms (6%). Common confounding factors were mesiotemporal lesions on brain MRI (17%) and false-positive antibodies in serum (12%). Additional mesiotemporal features (involvement extralimbic structures, enhancement, diffusion restriction) were observed more frequently in AE mimics compared with AE (61% vs 24%; p = 0.005). AE criteria showed the following sensitivity and specificity: possible AE, 83% (95% CI 74-89) and 27% (95% CI 20-36); definite autoimmune limbic encephalitis (LE), 10% (95% CI 5-17) and 98% (95% CI 94-100); and probable anti-NMDAR encephalitis, 50% (95% CI 26-74) and 96% (95% CI 92-98), respectively. Specificity of the criteria for probable seronegative AE was 99% (95% CI 96-100). The newly proposed criteria for probable anti-LGI1 encephalitis showed a sensitivity of 66% (95% CI 47-81) and specificity of 96% (95% CI 93-98). AE mimics occur frequently. Common pitfalls in AE misdiagnosis are mesiotemporal lesions (predominantly with atypical features) and false-positive serum antibodies. As expected, the specificity of the criteria for possible AE is low because these criteria represent the minimal requirements for entry in the diagnostic algorithm for AE. Criteria for probable AE (-LGI1, -NMDAR, seronegative) and definite autoimmune LE are applicable for decisions on immunotherapy in early disease stage, as specificity is high.

Autoimmune Limbic Encephalitis in Patients with Hematologic Malignancies after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

Seizure characteristics and outcomes in patients with neurological conditions related to high-risk paraneoplastic antibodies.

Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high-risk paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures. Patients from 2000 to 2020 with seizures and high-risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow-up were evaluated. Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1-IgG (Hu; n = 24, 39%), Ma2-IgG (n = 14, 23%), and CRMP5-IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow-up a median of 25 months after seizure onset. Ongoing seizures at last follow-up were associated with Ma2-IgG or ANNA1-IgG compared to other antibodies (p = .04), highest seizure frequency being at least daily (p = .0002), seizures on electroencephalogram (EEG; p = .03), and imaging evidence of limbic encephalitis (LE; p = .03). Death occurred in 48% throughout the course of follow-up, with a higher mortality in patients with LE than in those without LE (p = .04). Of 31 surviving patients at last follow-up, 55% continued to have intermittent seizures. Seizures in the setting of high-risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1-IgG and Ma2-IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE.

Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis.

Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients presents a clinical challenge, and novel noninvasive imaging biomarkers are urgently needed. Here, we demonstrate that visualization of the translocator protein (TSPO) with [18F]DPA-714-PET-MRI reveals pronounced microglia activation and reactive gliosis in the hippocampus and amygdala of patients suspected with CD8 T cell ALE, which correlates with FLAIR-MRI and EEG alterations. Back-translation into a preclinical mouse model of neuronal antigen-specific CD8 T cell-mediated ALE allowed us to corroborate our preliminary clinical findings. These translational data underline the potential of [18F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell-mediated ALE.

Limbic Encephalitis as a Late Complication of Relapsing Polychondritis: A Case Report and Review of the Literature.

Limbic Encephalitis as a Late Complication of Relapsing Polychondritis: A Case Report and Review of the Literature.

Voltage-Gated Potassium Channels (VGKC) Complex-Associated Disorders: Anti-LGI1 Encephalitis and Anti-Caspr2 Encephalitis

Autoantibodies against LGI1 and Caspr2 complexed with voltage-gated potassium channels (VGKC) cause limbic encephalitis. Anti-LGI1 encephalitis progresses in a subacute course with memory impairment, disorientation, and focal epileptic seizures. Anti-LGI1 encephalitis is preceded by faciobrachial dystonic seizures (FBDS), which are specific involuntary movements and frequently complicated by hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Neutralization of LGI1 by anti-LGI1 antibodies reduces AMPA receptors and induces epileptic seizures and memory impairment. Anti-Caspr2 encephalitis (Morvan's syndrome) is associated with limbic symptoms, severe autonomic disorders, muscle cramps and burning extremity pain due to peripheral nerve hyperexcitability. Thymomas and other malignant tumors may be complicated, and search for them is necessary. Anti-Caspr2 antibodies bind to Caspr2 on the surface of afferent cells in the dorsal root ganglion, and internalization of VGKCs causes a decrease in the K+ current, resulting in neuronal hyperexcitation and severe pain. Early immunotherapeutic intervention may improve the prognosis of these diseases, and measuring these autoantibodies should be performed in the presence of specific clinical signs, even with normal cerebrospinal fluid findings.

Paraneoplastic Neurologic Syndromes

Paraneoplastic neurologic syndromes (PNS) are a group of neurological disorders that are possibly caused by immunological mechanisms triggered by an underlying tumor that involves every part of the nervous system. Autoantibodies were categorized according to the risk of cancer association. Antibodies against intracellular proteins are excellent markers for tumor detection, however, without functional roles in neuronal loss, the direct effector of neuronal damage is thought to be cytotoxic T cells. The frequently associated symptoms include limbic encephalitis, cerebellar ataxia and sensory neuronopathy. The associated tumors are mainly small-cell lung cancer, breast/ovarian/uterine cancers, and thymoma. Timely diagnosis, prompt immunotherapy, and treatment of the underlying tumor are essential for managing PNS. However, we need to be cautious about the high frequency of false-positive/negative results of antibodies using commercial antibody tests. This highlight the importance of the careful evaluation of clinical features. Recently, PNS emerged after immune check point inhibitor administration, and this became a subject of attention exploring its pathogenesis. Other basic studies to understand the immunological background of PNS have been progressing.

Investigation of the presence of specific neural antibodies in dogs with epilepsy or dyskinesia using murine and human assays.

Autoimmune mechanisms represent a novel category for causes of seizures and epilepsies in humans, and LGI1-antibody associated limbic encephalitis occurs in cats. To investigate the presence of neural antibodies in dogs with epilepsy or dyskinesia of unknown cause using human and murine assays modified for use in dogs. Fifty-eight dogs with epilepsy of unknown cause or suspected dyskinesia and 57 control dogs. Serum and CSF samples were collected prospectively as part of the diagnostic work-up. Clinical data including onset and seizure/episode type were retrieved from the medical records. Screening for neural antibodies was done with cell-based assays transfected with human genes for typical autoimmune encephalitis antigens and tissue-based immunofluorescence assays on mouse hippocampus slices in serum and CSF samples from affected dogs and controls. The commercial human und murine assays were modified with canine-specific secondary antibody. Positive controls were from human samples. The commercial assays used in this study did not provide unequivocal evidence for presence of neural antibodies in dogs including one dog with histopathologically proven limbic encephalitis. Low titer IgLON5 antibodies were present in serum from one dog from the epilepsy/dyskinesia group and in one dog from the control group. Specific neural antibodies were not detected using mouse and human target antigens in dogs with epilepsy and dyskinesia of unknown origin. These findings emphasize the need for canine-specific assays and the importance of control groups.

N°303 – Autoimmune limbic encephalitis with anti GAD-65 antibodies sucessfully treated with mycophenolate mofetil

N°303 – Autoimmune limbic encephalitis with anti GAD-65 antibodies sucessfully treated with mycophenolate mofetil

18F-FDG PET and MRI Evaluation of Paraneoplastic Limbic Encephalitis.

Autoimmune limbic encephalitis (paraneoplastic or nonparaneoplastic) is a rare condition involving autoantibodies against intracellular or cell-surface proteins of neurons. Patients typically present with acute and progressive neuropsychiatric symptoms. Although the criterion standard for diagnosis remains detection of autoantibodies in cerebrospinal fluid, there are characteristic imaging features that can aid in diagnosis, notably abnormalities in the bilateral medial temporal lobes on imaging, particularly with nuclear imaging. Here, we present 18F-FDG PET findings of paraneoplastic limbic encephalitis in a 65-year-old man.

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

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. 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. 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. 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.