Limbic Encephalitis Research Articles

Investigation of anti-NMDA receptor antibodies in first episode psychosis patients

IntroductionAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune limbic encephalitis, where psychiatric symptoms are often the initial presentation dominant initially. These patients are mainly admitted to psychiatric wards, due to first episode psychosis (FEP).ObjectivesMultiple studies analysed whether anti-NMDAR antibodies were present in the sera of schizophrenic patients, but results have not verified this hypothesis. It is possible, however, that unknown autoimmune antibodies play a role in FEP, similarly to anti-NMDAR antibodies.Methods40 patients with FEP and 30 healthy controls have been recruited to the study. Patients with affective psychosis, drug-related psychosis and patients with diagnosed encephalitis were excluded. The sera were tested with immune fluorescent assays for anti-NMDAR antibodies. A non-specific method was used to test anti-brain antibody activity on monkey-cerebellum and rat-hippocampus slices.ResultsNeither the samples from the 40 patients, nor the samples of healthy controls contained anti-NMDAR antibodies. 14 of the patients’ and only 6 of the healthy controls’ serum showed positive reaction of the neuroendothelium. These results suggest that there is a difference between the groups, although the results are not significant.ConclusionsNone of the 40 patients proved positive for anti-NMDAR antibodies in agreement with previous studies. However, a higher proportion of samples from the FEP group showed activity in the neuroendothelium of non-specific immune fluorescent assays compared to healthy controls. Based on literature and on our experience, it is possible, that unknown autoimmune antibodies play role in FEP.DisclosureNo significant relationships.

P.034 Temporal lobe epilepsy associated with autoimmune conditions: a review

Background: Epilepsy mediated by immune cells must be identified early since immunotherapy has been associated with better clinical outcomes. This provides an overview of autoimmune TLE, emphasizing recent developments in its pathophysiology, imaging, and therapeutic interventions. Methods: Web-based research using advanced features of databases. Results: Epilepsy caused by immune dysfunction leads to inflammation of the brain. Inflammation play a role in the development of seizures. Proinflammatory molecules found to be overexpressed in neurons and glia of individuals with DRE, provoke a proinflammatory cytokines in the plasma and CSF. Autoimmune epilepsy is characterized by focal seizures refractory to ASMs accompanied by other neurological manifestations, as described by clinical scoring systems.Scoring systems are available to identify patients who are likely to be positive. The MRI findings include signal hyperintensities in the affected brain regions. EEG performed to exclude nonconvulsive seizures. Seizures resulting from autoimmune encephalitis are caused by antibodies to surface antigens and intracellular antigenes. Conclusions: Pathogenesis proposed to involve antibody-mediated ictogenesis. Immunotherapy is effective in autoimmune encephalitis with a positive prognosis if detected early. Limbic encephalitis has been shown to have a detrimental effect on cognition, mood, and behavior. Neuropsychology is an important outcome criterion for tracking disease progression and treatment success.

Paraneoplastic Limbic Encephalitis Case Report In A Patient With Suspected Conversion Disorder

Introduction. Autoimmune encephalitis is a difficult-to-recognize, complex disease that can present with various neuropsychiatric symptoms. N-methyl-D-aspartate receptor (NMDA-r) and anti-leucine-rich glioma-inactivated 1 protein (LGI-1) subtypes of autoimmune encephalitis may present with psychiatric symptoms.ObjectivesWe would like to present an autoimmune encephalitis case that can be confused with conversion disorder.MethodsA 54-year-old, female patient started to have forgetfulness ten months ago, and convulsions started five months ago. The patient had disorganized behaviors and contractions in the extremities. Diffusion MRI and brain CT images were normal. The patient had low blood sodium level. In the follow-up, her orientation was impaired and she could hardly make eye contact. As the patient’s contractions were evaluated as conversion in the first stage, 50mg/day sertraline was added to the treatment.ResultsAfter cranial MRI and EEG recordings were completed, the patient was referred to the neurology department due to the suspicion of autoimmune encephalitis. In the cerebrospinal fluid examination anti-LGI-1 and anti-yo antibodies were positive. Thereupon, IV pulse steroid was given. After that her orientation and disorganized behavior improved. Then, the patient was referred to oncology department.ConclusionsLimbic encephalitis may manifest as sleep disorders, short-term memory loss, conversion disorder, disorganized behaviors, slurred speech, non-epileptic seizures, sensory and motor defects. Delay in diagnosis may worsen the prognosis of possible malignancy. It should be kept in mind that the patient with a suspected conversion disorder may have limbic encephalitis.DisclosureNo significant relationships.

Psychiatric manifestations of paraneoplastic syndromes

IntroductionParaneoplastic syndromes (PS) result from indirect effects of neoplasms. In 50% of the cases the symptoms precede the diagnosis and run independently. PS may involve the peripheral or central nervous system, resulting in symptoms from sensory neuropathies to several neuropsychiatric manifestations.ObjectivesTo review the psychiatric manifestations of paraneoplastic syndromes affecting the nervous system.MethodsSelective literature review via PubMed search, using the keywords “paraneoplastic syndromes”, “endrocrine paraneoplastic syndromes”, “neuropsychiatric manifestations”, “limbic encephalitis”.ResultsThe prevalence of PS varies with the type of cancer (<1% for breast and ovarian cancers; 3-5% for small cell lung cancer; 20% for thymomas). The general mechanisms behind PS are related to the production of substances by the tumor that directly or indirectly cause distant symptoms, the depletion of substances or the host response to the tumor. Frequently there are autoimmune phenomena involved, with the production of antineuronal antibodies that recognise various antigens at the nervous system. Paraneoplastic neurological disorders include limbic encephalits that can present subacutely with symptoms of depression, irritability, hallucinations, cognitive impairment associated with sleep alterations, confusion and seizures. Others include psoclonus-myoclonus ataxia syndrome, neuromyotonia and cramp fasciculation syndrome. Metabolic and endocrine paraneoplastic syndromes (hypercortisolism, carcinoid tumors, pancreatic cancer) can result from the production of cytokines and hormones by the tumor and produce mood disorders, confusional states and psychosis.ConclusionsPS can be related to various neuropsychiatric manifestations affecting consciousness, cognition, mood and perception. The recognition of this association can alert for the possibility of a cancer diagnosis specially when facing a patient with unusual clinical presentation.DisclosureNo significant relationships.

Psychiatric symptoms in autoimmune encephalitis. A case report

IntroductionEarly stages of autoimmune encefalitis (AE) often present cognitive and neuropsychiatric symptoms such as personality change, irritability, axiety, depression, behavioral disorders, hallucinations, disorientation, sleep-wake cycle reversals, …). Thus often these cases are first treated as psychiatric disorders.ObjectivesA literature review throughout a case report presentation.MethodsWe present the case of a 25-year old female with a medical history of iron-deficiency anemia who arrives at the emergency service. She presents the following one week of evolution clinical picture: complex auditive hallucinations, behavioral disturbances, sleep disorder and short term memory impairment. Neurological examination, LP and craneal CT are all normal. CSF analysis has no abnormalities. Thus she entered the psychiatric ward. There she was treated with neuroleptics with no improvement of symptoms presenting a severe psychomotor agitation and language impairment. After neurology interconsultation AE is suspected.ResultsShe was performed an EEG (left temporal epileptiform activity), CSF (inflammatory pattern), MRI (bilateral temporal lobe hyperintensity). Suspecting limbic encephalitis the presence of anti-NMDAR antibodies was tested , which turned out to be positive. First she was treated with corticotherapy with mild results. Then she was treated with intravenous immunoglobulin improving significantly.ConclusionsAnti-NMDAR encephalitis is usually a multistage illness. Early in the course of disease psychiatric manifestations are not rare. Therefore the proper diagnosis and approach of AE may requiere a highly organized assessment, starting with detailed history and physical examination and an appropriate testing to exclude other possible relevant pathologies.DisclosureNo significant relationships.

Nivolumab-Induced Limbic Encephalitis Associated with Glutamic Acid Decarboxylase 65 Antibodies.

Nivolumab-Induced Limbic Encephalitis Associated with Glutamic Acid Decarboxylase 65 Antibodies.

Pathological emotionalism following limbic encephalitis: the neural foundations of a novel disorder

ObjectiveWe investigated pathological emotionalism in a large cohort of patients that had presented with autoimmune limbic encephalitis(a-LE).Methods38 patients in the post-acute phase of a-LE completed questionnaires probing emotion regula- tion. They all underwent structural/functional MRI post-acutely, along with age- and sex-matched healthy controls. We investigated correlations of questionnaire scores with demographic, clinical, neuropsycho- logical and brain MRI data across patients. We also compared patients with pathological emotionalism and those without, along with healthy controls, on grey matter volume, resting-state functional connec- tivity and activity.ResultsPathological emotionalism was reported by 50% of the patients. It was not associated with depres- sion, impulsiveness, or memory impairment. However, it correlated with abnormalities in specific emotional brain networks: volume reduction in the anterior hippocampus, fusiform gyrus and cerebellum, abnormal hippocampal resting-state functional connectivity with the posteromedial cortex and middle frontal gyrus, and abnormal hemodynamic activity in the fusiform gyrus, inferior parietal lobule, and ventral pons.ConclusionsPathological emotionalism is common following a-LE, is not a manifestation of other neu- ropsychiatric disorders, and reflects abnormalities in networks of emotion regulation including, but not limited to the acute hippocampal focus. This condition provides novel insights into the neural basis of emotion regulation and its dysfunction in disease.christopher.butler@imperial.ac.uk

Long-term evolution and prognostic factors of epilepsy in limbic encephalitis with LGI1 antibodies.

To characterize the evolution of epilepsy in patients with leucine-rich glioma inactivated 1 antibody-associated (LGI1ab) limbic encephalitis, including factors associated with drug-resistant epilepsy (DRE). Retrospective analysis of patients with LGI1 encephalitis managed at two tertiary epilepsy centers between 2005 and 2019 and whose samples were confirmed by the French Reference Center of Paraneoplastic Neurological Syndromes. Raw clinical, biological, EEG, and MRI data were reviewed. Two endpoints were defined: (i) Epilepsy remission: patients seizure free and in whom anti-seizure medications (ASM) have been stopped for at least 1year at the last follow-up visit (ii) DRE: patients with persistent seizures at the last follow-up despite at least two ASM used at efficacious daily dose. 39 patients with LGI1 encephalitis were included with a median follow-up duration of 42months (range 13-169). All of them reported seizures at the acute phase, with faciobrachial dystonic seizures (FBDS) in 23 (59%) and other focal seizures in 38 (97%), including 4 patients (10%) with de novo status epilepticus. At the last follow-up visit, 11 patients (28%) achieved epilepsy remission. Among the 28 patients with persistent epilepsy, eight (29%) fulfilled criteria of DRE. The only factor significantly associated with epilepsy remission was the time from clinical onset of the encephalitis to initiation of the first immunomodulatory treatment, with longer delay in patients with persistent epilepsy (7.5 ± 8.9 vs 2.4 ± 1.7months, p = 0.006). Evolution to DRE was only driven by MRI evolution. Eight of the 15 patients (53%) who developed hippocampal atrophy (p = 0.007) also suffered from drug-resistant seizures at the last follow-up. In patients with LGI1 encephalitis, rapid initiation of immunomodulatory treatment favors long-term epilepsy remission. Evolution to DRE might primarily reflect the anatomical lesion of limbic structures. Determining what modalities of immune treatment may alter these outcomes requires prospective studies with long-term follow-up.

Ovarian Teratoma-Related Paraneoplastic Neurological Syndromes.

Paraneoplastic neurological syndromes (PNSs) are a group of neurological disorders triggered by an underlying remote tumor. Ovarian teratoma (OT) is the most common histologic type of germ cell tumor in females. The most common PNSs associated with OT is anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, with the increasing number of new antibodies reported over the last decade, the clinical spectrum of OT-related PNSs is also expanding. Our knowledge of OT-related PNSs is still far from complete. Here, we provide a comprehensive review of the most recent findings in the field of OT-related PNSs, with a particular focus on their clinical and pathological characteristics. Overall, the description of neuronal antibodies in PNSs associated with OT strongly suggests that antibodies may be responsible for the clinical symptoms in some cases. OT-related PNSs are associated with various clinical manifestations, including anti-NMDAR encephalitis, limbic encephalitis, encephalomyelitis, progressive cerebellar syndrome and opsoclonus-myoclonus syndrome. The pathological characteristics of the OT suggest that the mechanism of PNSs is probably due to heteromorphic neurons in the tumor tissue, the ectopic expression of the antigens in neural tissue within the teratomas and patients’ unusual immune response. Despite the severity of the neurological syndromes, most patients with OT-related PNSs showed good neurologic response to early tumor resection combined with immunotherapy. To further advance the management of OT-related PNSs, additional studies are needed to explore this complex topic.

Construction of an Assisted Model Based on Natural Language Processing for Automatic Early Diagnosis of Autoimmune Encephalitis.

IntroductionEarly diagnosis and etiological treatment can effectively improve the prognosis of patients with autoimmune encephalitis (AE). However, anti-neuronal antibody tests which provide the definitive diagnosis require time and are not always abnormal. By using natural language processing (NLP) technology, our study proposes an assisted diagnostic method for early clinical diagnosis of AE and compares its sensitivity with that of previously established criteria.MethodsOur model is based on the text classification model trained by the history of present illness (HPI) in electronic medical records (EMRs) that present a definite pathological diagnosis of AE or infectious encephalitis (IE). The definitive diagnosis of IE was based on the results of traditional etiological examinations. The definitive diagnosis of AE was based on the results of neuronal antibodies, and the diagnostic criteria of definite autoimmune limbic encephalitis proposed by Graus et al. used as the reference standard for antibody-negative AE. First, we automatically recognized and extracted symptoms for all HPI texts in EMRs by training a dataset of 552 cases. Second, four text classification models trained by a dataset of 199 cases were established for differential diagnosis of AE and IE based on a post-structuring text dataset of every HPI, which was completed using symptoms in English language after the process of normalization of synonyms. The optimal model was identified by evaluating and comparing the performance of the four models. Finally, combined with three typical symptoms and the results of standard paraclinical tests such as cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), or electroencephalogram (EEG) proposed from Graus criteria, an assisted early diagnostic model for AE was established on the basis of the text classification model with the best performance.ResultsThe comparison results for the four models applied to the independent testing dataset showed the naïve Bayesian classifier with bag of words achieved the best performance, with an area under the receiver operating characteristic curve of 0.85, accuracy of 84.5% (95% confidence interval [CI] 74.0–92.0%), sensitivity of 86.7% (95% CI 69.3–96.2%), and specificity of 82.9% (95% CI 67.9–92.8%), respectively. Compared with the diagnostic criteria proposed previously, the early diagnostic sensitivity for possible AE using the assisted diagnostic model based on the independent testing dataset was improved from 73.3% (95% CI 54.1–87.7%) to 86.7% (95% CI 69.3–96.2%).ConclusionsThe assisted diagnostic model could effectively increase the early diagnostic sensitivity for AE compared to previous diagnostic criteria, assist physicians in establishing the diagnosis of AE automatically after inputting the HPI and the results of standard paraclinical tests according to their narrative habits for describing symptoms, avoiding misdiagnosis and allowing for prompt initiation of specific treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00355-7.

Seronegative autoimmune encephalitis: clinical characteristics and factors associated with outcomes.

Seronegative autoimmune encephalitis is autoimmune encephalitis without any identifiable pathogenic antibody. Although it is a major subtype of autoimmune encephalitis, many unmet clinical needs exist in terms of clinical characteristics, treatments and prognosis. In this institutional cohort study, patients diagnosed with seronegative autoimmune encephalitis with available 2-year outcomes were analysed for the disease course, 2-year outcome prediction system, effect of immunotherapy, necessity of further immunotherapy at 6 or 12 months and pattern of brain atrophy. Seronegative autoimmune encephalitis was subcategorized into antibody-negative probable autoimmune encephalitis, autoimmune limbic encephalitis and acute disseminated encephalomyelitis. Poor 2-year outcome was defined by modified Rankin scale scores 3-6, and the 2-year serial data of Clinical Assessment Scales in Autoimmune Encephalitis score was used for longitudinal data analyses. A total of 147 patients were included. The frequency of achieving a good 2-year outcome (modified Rankin scale 0-2) was 56.5%. The antibody-negative probable autoimmune encephalitis subtype exhibited the poorest outcomes, although the baseline severity was similar among the subtypes. The RAPID score, consisting of five early usable clinical factors, refractory status epilepticus, age of onset ≥60 years, probable autoimmune encephalitis (antibody-negative probable autoimmune encephalitis subtype), infratentorial involvement and delay of immunotherapy ≥1 month, was associated with poorer 2-year outcomes. Any immunotherapy was associated with clinical improvement in the patients with low risk for poor 2-year outcomes (RAPID scores 0-1), and the combination immunotherapy of steroid, immunoglobulin, rituximab and tocilizumab was associated with better outcomes in the patients with high risk for poor 2-year outcomes (RAPID scores 2-5). In patients with persistent disease at 6 months, continuing immunotherapy was associated with more improvement, while the effect of continuing immunotherapy for more than 12 months was unclear. In the longitudinal analysis of MRI, the development of cerebellar atrophy indicated poor outcomes, while the absence of diffuse cerebral atrophy or medial temporal atrophy indicated the possibility of a good outcome. This study provides information about the clinical characteristics and courses, the effect of immunotherapy and its duration, and prognostic factors in seronegative autoimmune encephalitis.

A case of new cognitive changes in a patient with seronegative paraneoplastic limbic encephalitis: encephalitis relapse or Wernicke’s encephalopathy?

ABSTRACT Wernicke’s encephalopathy (WE) and paraneoplastic limbic encephalitis (PLE) can both present with acute-to-subacute memory impairment and cognitive dysfunction. Both can lead to significant morbidity and mortality without rapid identification and treatment. Often patients with WE may not have the typical clinical triad of ophthalmoplegia, gait ataxia, and altered mental status. Furthermore, both WE and PLE may share similar MRI findings. Here, we present a case of a patient with a history of seronegative PLE presenting with acute-to-subacute cognitive changes and gait imbalance. Initially, it was felt to be a relapse of PLE but upon further history and testing may potentially have represented WE in the setting of a recent dietary change.

Unusual Presentation of Paraneoplastic Limbic-Encephalitis (PLE) with Acute Retrograde-Amnesia as Presenting Symptom. (P11-1.003)

Unusual Presentation of Paraneoplastic Limbic-Encephalitis (PLE) with Acute Retrograde-Amnesia as Presenting Symptom. (P11-1.003)

Nivolumab-Induced Limbic Encephalitis Associated with Glutamic Acid Decarboxylase 65 Antibodies (P8-1.003)

Nivolumab-Induced Limbic Encephalitis Associated with Glutamic Acid Decarboxylase 65 Antibodies (P8-1.003)

(PO-045) C-L psychiatrists Should Take Protein-binding into Consideration when Treating Neuropsychiatric Manifestations of Limbic Encephalitis in those Receiving Plasmapheresis

(PO-045) C-L psychiatrists Should Take Protein-binding into Consideration when Treating Neuropsychiatric Manifestations of Limbic Encephalitis in those Receiving Plasmapheresis

Anti-N-methyl-D-aspartate receptor encephalitis associated with chronic myelogenous leukemia, causality or coincidence? A case report

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most frequent autoimmune paraneoplastic encephalitis, and is primarily associated with ovarian teratomas. Here, we report the first case of a patient diagnosed with chronic myelogenous leukemia (CML) during the recovery phase of anti-NMDAR encephalitis.Case presentationThe patient was admitted with fever, headache, and seizures. Brain MRI revealed a cerebrospinal fluid (CSF)-containing arachnoid cyst in the left temporal lobe with no other abnormal signals. EEG showed diffuse background slowing in the delta-theta range. The patient tested positive for anti-NMDAR antibodies in both the serum and CSF. One year after the onset of encephalitis, the patient was referred to the Department of Hematology for extreme leukocytosis. Karyotype analysis showed the presence of Philadelphia chromosome t(9;22)(q34;q11). Quantitative reverse transcriptase PCR analysis further identified BCR/ABL1 fusion transcripts; thus, CML was diagnosed.ConclusionsTo the best of our knowledge, this is the first case of anti-NMDAR encephalitis associated with CML. This report should alert clinicians to consider CML as a malignancy that is possibly associated with limbic encephalitis.

Anti-LGI1 encephalitis recurring 3\xa0years after the first episode: a case report

BackgroundPatients with antibodies against leucine-rich glioma-inactivated 1 (LGI1) present with limbic encephalitis, which is clinically characterized by a subacute disturbance of memory and behavior, often experience seizures. Most patients have a monophasic course, often with hyponatremia.Case presentationHerein, we report a 67-year-old Japanese male presenting with involuntary neck movement, abnormal behavior and apraxia. He was disoriented to time and place and occasionally unable to follow directions. Laboratory tests revealed the patient had hyponatremia (131 mEq/L). Cerebrospinal fluid (CSF) analysis showed that the cell count (1/μL) and protein content (33 mg/dL) were in the normal ranges. Electroencephalography showed transient theta bursts in the right frontal lobe. Magnetic resonance imaging (MRI) of the brain demonstrated hyperintensities in the medial temporal lobe and basal forebrain on fluid-attenuated inversion recovery (FLAIR) without gadolinium enhancement. Anti-voltage-gated potassium channel (Anti-VGKC) complex antibodies were below the reference level for limbic encephalitis. Although the diagnosis was unknown, intravenous methylprednisolone therapy was effective. Three years later, the patient began to speak incoherently and became disoriented to time. FLAIR MRI of the brain revealed recurrence in the left medial temporal lobe. The patient’s serum sodium level was 131 mEq/L. After intravenous methylprednisolone therapy, he regained alertness. A CSF sample stored at the time of the first attack was assayed and the patient was found to be LGI1-positive and CASPR-2-negative, and the diagnosis of anti-LGI1 encephalitis was made.ConclusionsMonitoring serum sodium levels and the preserved samples from the first episode were useful for diagnosis.

Autoimmune Encephalitis and Other Neurological Syndromes With Rare Neuronal Surface Antibodies in Children: A Systematic Literature Review.

Neuronal surface antibody syndromes (NSAS) are an expanding group of autoimmune neurological diseases, whose most frequent clinical manifestation is autoimmune encephalitis (AE). Anti-NMDAR, anti-LGI1, and anti-CASPR2 autoimmunity represent the most described forms, while other NSAS are rarer and less well-characterized, especially in children. We carried out a systematic literature review of children with rare NSAS (with antibodies targeting D2R, GABAAR, GlyR, GABABR, AMPAR, amphiphysin, mGluR5, mGluR1, DPPX, IgLON5, and neurexin-3alpha) and available individual data, to contribute to improve their clinical characterization and identification of age-specific features. Ninety-four children were included in the review (47/94 female, age range 0.2–18 years). The most frequent NSAS were anti-D2R (28/94, 30%), anti-GABAAR (23/94, 24%), and anti-GlyR (22/94, 23%) autoimmunity. The most frequent clinical syndromes were AE, including limbic and basal ganglia encephalitis (57/94, 61%; GABAAR, D2R, GABABR, AMPAR, amphiphysin, and mGluR5), and isolated epileptic syndromes (15/94, 16%; GlyR, GABAAR). With the limitations imposed by the low number of cases, the main distinctive features of our pediatric literature cohort compared to the respective NSAS in adults included: absent/lower tumor association (exception made for anti-mGluR5 autoimmunity, and most evident in anti-amphiphysin autoimmunity); loss of female preponderance (AMPAR); relatively frequent association with preceding viral encephalitis (GABAAR, D2R). Moreover, while SPS and PERM are the most frequent syndromes in adult anti-GlyR and anti-amphiphysin autoimmunity, in children isolated epileptic syndromes and limbic encephalitis appear predominant, respectively. To our knowledge, this is the first systematic review on rare pediatric NSAS. An improved characterization may aid their recognition in children.

Histopathologic Characterization and Neurodegenerative Markers in Patients With Limbic Encephalitis Undergoing Epilepsy Surgery.

PurposeLimbic encephalitis is an increasingly recognized cause of medial temporal lobe epilepsy (mTLE) and associated cognitive deficits, potentially resulting in hippocampal sclerosis (HS). For several reasons, these patients usually do not undergo epilepsy surgery. Thus, histopathologic examinations in surgical specimens of clearly diagnosed limbic encephalitis are scarce. The purpose of this study was a detailed histopathologic analysis of surgical tissue alterations, including neurodegenerative markers, in patients with limbic encephalitis undergoing epilepsy surgery.MethodsWe investigated the surgical specimens of six patients operated on with mTLE related to limbic encephalitis (among them four patients were with GAD65 and one with Ma1/2 antibodies), and compared the findings to a control group with six patients matched according to age at the time of surgery without limbic encephalitis and without early inciting events.ResultsHistopathologic analysis in the group with limbic encephalitis revealed HS in four patients, while three of them also displayed signs of an active inflammatory reaction with lymphocytes. In one of the patients with GAD65-encephalitis who was suffering from a late-onset mTLE and a long disease course, neurodegenerative protein markers (β-amyloid and hyperphosphorylated tau) were found coexisting with inflammatory reactions and HS. Investigations in the control group did not reveal any inflammatory reaction or neurodegenerative marker.ConclusionOur findings suggest a possible link between long-lasting immune reactions in the medial temporal lobe, HS, and further toward the development of neurodegenerative diseases. Presently, however, a causal relationship between these entities cannot yet be established. Furthermore, our results suggest that an immunological etiology should always be considered in late onset (> 18 years) mTLE, also in cases of long disease duration and the presence of HS.

P 92 Limbic encephalitis with Contactin-associated protein like-2 (CASPR2) -antibodies: acute psychosis with late onset and abnormal EEG

Introduction: Contactin-associated protein like-2 (CASPR2)- autoantibodies are associated with distinctive syndromes 1 , such as agrypnia excitata, psychosis, neuromytonia and limbic encephalitis. All of them are highly responsive to immunotherapy. The target of these directly pathogenetic autoantibodies are surface-exposed domains of CASPR2 2 . Due to the fact of multiple variations of clinical presentations, it may be challenging to distinguish particular an autoimmune encephalitis associated with anti-neuronal autoantibodies, from primary psychiatric disorders such as psychosis. First medical treatment should be immediate immunotherapy, such as steroids, intravenous antibodies or plasma exchange given fast diagnosis of encephalitis is made. In our case the EEG showed focal slow waves with the clinical presentation of an acute psychosis which leaded to an admission to the neurology ward and further investigations. Patient and methods: A 75-years-old man was hospitalized on a psychiatric ward for psychotic symptoms characterized by psychomotor agitation, thought disorganization, persecutory delusions and auditory hallucinations with commanding voices and global insomnia. Cerebral Imaging with cMRI and cCT scan showed no acute abnormalities. EEG showed focal intermittent slow delta-theta wave activity (4-6 Hz) on the left temporal lobe, reactive to visual stimuli and provided focal cerebral dysfunction and pathology. CSF did not reveal any evidence of infection, but CASPR2- autoantibodies (1:10.000) were indentified and the diagnosis of limbic encephalitis with CASPR2-antibodies was made. Treatment with high dose dexamethasone and intravenous immunoglobulin (IVIG) was made and the clinical conditions improved. Conclusion: Fast and first medical treatment of autoimmune encephalitis should be initiated in early stages. To avoid an unnecessary delay in diagnosis and treatment, EEG, cMRI and expanded CSF examination should be performed as soon as possible to prevent severe disability in patients with limbic encephalitis with CASPR2-antibodies.